Ellen Walter is an Acute Care Nurse Practitioner at the Cleveland Clinic in the Center for Neurological Restoration. She graduated Summa Cum Laude from Kent State University with a BSN and received her MSN from Case Western Reserve University Frances Payne Bolton School of Nursing.

She has worked for the last 23 years in neuroscience nursing in neurology and neurosurgery practices including caring for individuals who have had deep brain stimulation surgery for the treatment of their movement disorder. She works with a team of specialists in the Movement Disorders section of the Center for Neurological Restoration at the Cleveland Clinic.

Her position there, in addition to caring for those who have had DBS, involves a comprehensive approach caring for persons with Parkinson’s disease, dystonia, essential tremor and other movement disorders.

She has a special interest in exercise and community outreach for Parkinson’s disease as well as creating programs for the care partners.

La doctora Maria Cristina Ospina es neuróloga especialista en trastornos del movimiento, así como Profesora Adjunta de Neurología Clínica en la Universidad de Arizona. Durante su carrera médica, la Dra. Ospina se ha mantenido activa en la investigación médica, participando en diversos estudios clínicos patrocinados por la NIH y la industria farmacéutica. Se ha desempeñado como investigadora en el Grupo de Estudio de Parkinson y ha sido invitada como ponente sobre distintos temas relacionados con los trastornos del movimiento. Está capacitada para administrar la toxina botulínica para distonía y para aplicar Estimulación Cerebral Profunda. Cree en el uso de las modalidades complementarias en la atención del Parkinson y promueve el ejercicio para mejorar motricidad, flexibilidad y estado de ánimo.

Dr. James Beck 00:00:01
Hi everyone, and welcome to the 2022 Expert Briefing Series. We're very happy to start off the year with a really interesting topic today: Sight, Sound and Parkinson's Disease. I'm your host, James Beck, the Chief Scientific Officer of the Parkinson's Foundation, and I'm really excited, as I mentioned, for our topic today. For those of you who may be new to the Zoom environment, or at least new to our Expert Briefings, and for those who have come back, I just want to take a moment to re-familiarize everybody with how our Zoom layout is going to work and how you can interact and ask questions of our presenter today, Dr. Hamedani.

Right now, I've just advanced the slide, and you see a big red arrow pointing down. That's the chat feature, where my colleagues will push out information for you to take a look at. Right now, there's a welcome, as well as an option for texting your questions for those who are joining us live on Facebook to my colleagues, and we can ask our panelist about those questions. Next is the Q&A. For those of you who are joining us via Zoom, this is where you'll ask your questions, and you can put them in there.

My colleagues will take them in. If time permits, we'll hopefully get a chance to address them. If time doesn't permit, we'll ask our colleagues or our Helpline to assist and see if we can get an answer for many of the people. We do our best to get to everyone's question, of course. What's also nice is there's a new feature in Zoom that allows us to have a live transcript of what's going on. If you have a hard time hearing, or it's a noisy environment, you can turn this transcript on. It's computer generated, so it's not going to be perfect, but it should give you enough of a sense of what's going on and allow you to follow along, at the very least, with what we're talking about.

Of course, and as always, these sessions are recorded and archived. If you are unable to watch it all or you come in midway, in about a week's time, you'll be able to watch this recorded and capture what you missed and share it with others who you think might find it interesting as well. Also keep in mind that the slides being presented by our speaker are available for download. Again, this is in the chat feature. This is where you'll find a link to download the slides if you'd like to have them at a later time.

What we'd really like you to do is sit back and enjoy, listen to the presentation, and take some notes if you like, but know that we have a lot of this material ready for you if you want to refer to it again later on.

Dr. James Beck 00:02:49
As we talk about the Foundation, I just want to emphasize again what our mission is as an organization, and that's to make the lives of everybody living with Parkinson's disease and everyone affected by Parkinson's disease better. We're looking to improve care and working furiously to advance research toward a cure. We really build upon the Parkinson's community to do that. We will often engage in surveys and questions to really understand: what are the needs and priorities of those living with Parkinson's disease?

As stewards of other people's money, we can ensure that what we're doing is the best and meets the needs of the PD community as a whole.

As part of that, we have three goals with which to meet that mission. As I mentioned, improving care for everyone with Parkinson's, advancing research — we spend millions of dollars trying to better understand Parkinson's disease and hopefully reach a potential cure — and the third is to really empower and educate our community of those living with Parkinson's disease through sessions just like this one today, our Expert Briefing Series. The more you know about Parkinson's disease, the more you can have confidence when you go speak with your clinician, the more you know what to expect, and you can be a master of your own journey to the extent you can.

This is what we do, and I think we do very well as an organization.

I also want to thank our sponsor. For our 2021-2022 Expert Briefing Series, our Expert Briefing Series was supported by a grant from Genentech, a member of the Roche Group. Without their support, it's very difficult to put on these types of presentations, so I want to acknowledge them and thank them for their support. As I mentioned, recordings of our Expert Briefings will be archived and made available in about a week. Already, my colleague Danielle has made a link available for the slides to download. If you want to download them right now, feel free, or if you want to come back and do so, you can.

Dr. James Beck 00:05:00
Right now, I'd like to put a poll out there to understand who's here and attending. We have over a thousand participants here and really want to know who is watching today. If you're joining us via Facebook Live, go ahead in the comment section and tell us whether you're a person with Parkinson's, the spouse or partner of someone, or if you're a healthcare professional. It's helpful to understand who's joining us live today, and because we're doing this live, we can always make some slight adjustments to the presentation to ensure that we're presenting something for everyone to take in.

Again, if you happen to be a scientist, researcher, clinician, nurse or nurse practitioner, feel free to ask questions, and Dr. Hamedani will be happy to answer those as well. Let's see what we have for the results.

Not surprisingly, we have a lot of people here who have Parkinson's disease or have a loved one who has Parkinson's disease. A good number of healthcare professionals are joining us, which is really great — 6%. We really look forward to having a wonderful talk today as part of that.

Without further ado, let me move on and introduce our speaker, Dr. Ali Hamedani. He is a neuro-ophthalmologist and movement disorder specialist at the University of Pennsylvania. This is a really interesting mix of ophthalmology and neurology, and he can talk a little bit about that.

He obtained his bachelor's degree in biology at Yale University and his MD at the University of Maryland School of Medicine. He also holds a master's degree in epidemiology from Johns Hopkins Bloomberg School of Public Health. Dr. Hamedani joined the faculty after completing his neurology residency and fellowship training at the University of Pennsylvania, where he sees, as you can expect, patients with a spectrum of visual symptoms from neurologic disease. With a specialty in movement disorders, he has a clear interest in Parkinson's disease as well. His research is in epidemiology and uses national health surveys and administrative claims data to truly understand how vision affects outcomes and quality of life in Parkinson's disease and other patient populations. He is published in this area, and hopefully we will get a chance to touch on some of that.

I'm going to welcome Dr. Hamedani and turn off my video, and allow Dr. Hamedani to present his slides today so we can have that as well. Dr. Hamedani, welcome.

Dr. Ali Hamedani 00:07:40
Thank you, Dr. Beck, and thank you everyone for being here. As Dr. Beck said, my clinical practice is primarily as a neuro-ophthalmologist. What that means is that I'm a doctor who specializes in visual symptoms from neurologic disease, or you can think of it as anything behind the eyeball that affects vision. Parkinson's is behind the eyeball, in the brain, which is one of the reasons that I've become especially interested in this subject. Thank you for the invitation, and I'm really excited to be speaking to you all.

Before we talk about vision and Parkinson's — and I should back up and say that I know this talk is about sights and sounds. Because of my particular background, I'm focusing a lot on sights, although we will get to sounds and hearing toward the end. Before I talk about vision in Parkinson's, I want to spend a little bit of time talking about vision and health in general, because to a certain extent, the way that vision affects health in Parkinson's is a microcosm of how it affects health in the general population. Just because you have Parkinson's doesn't mean that you stop being another person.

One thing that I think helps to frame this discussion is to acknowledge that vision is our most dominant sense. In fact, about 40% of our brains are devoted to vision in some capacity, which means that any condition that affects the brain, such as Parkinson's, is almost guaranteed to affect vision as a result. We rely on vision for many of our daily activities, like reading, writing or driving. This is only becoming more prominent as technology plays a greater and greater role in our lives, like, for example, using text and email instead of talking on the phone or something like that.

We also know from studies of the general population in the U.S. and other countries that visual impairment is associated with poor health outcomes, regardless of whether you have PD or not. Specifically, people — and by people, I'm referring primarily to older adults — with visual impairment are more likely to have falls and injuries, such as hip fracture. They're more likely to suffer from depression or anxiety, and there's some evidence they may even be more likely to develop cognitive impairment and dementia too, for a variety of reasons. As a result, vision and the treatment and prevention of visual impairment are important for health in general.

Dr. Ali Hamedani 00:10:05
This is especially important because we know that at least half of all visual impairment is caused by eye diseases that are treatable or preventable to a certain degree. When we think about things that we can do to improve health or outcomes, many risk factors for disease are ones that are out of our control, such as age or genetics, but vision is one that, to a certain extent, is within our control or we have the opportunity to improve. Anything from needing glasses, which is what refractive error means, or some common age-related eye diseases like cataracts, glaucoma and macular degeneration, do have some treatments.

These are also all things that increase with age, as does Parkinson's. Some of the reason that visual impairment occurs in people with Parkinson's is at least in part related to the fact that these age-related eye diseases also track along with age.

As a result of all of this, it's important to see an eye doctor regularly, regardless of whether you have PD or not. Currently, the American Academy of Ophthalmology recommends that people over the age of 65 see an ophthalmologist every one or two years.

Moving now onto vision and Parkinson's specifically: we do know, based on a number of studies over the past 15 to 20 years, that vision is affected in Parkinson's. But it's affected in a number of different ways, and that experience is different for everyone. Some people may have one particular difficulty with vision, and others may have another one. As you all know, the experience of Parkinson's in general is very unique and different for everyone, and the same is certainly true of visual symptoms. An important thing to know about vision in PD is that it is something that can negatively impact quality of life. However, visual symptoms from Parkinson's generally do not result in overt loss of vision.

By loss of vision, I mean an inability to see certain letters unless they're very large, or blindness, you could think of it. The question I get sometimes from patients is, "Will I go blind from my Parkinson's?" and the answer to that is no, because the way that Parkinson's affects vision is in a little bit more subtle ways that are not as easily measured.

Dr. Ali Hamedani 00:12:21
The good news is that those symptoms of Parkinson's with regards to vision are treatable, but it's typically not by adjusting Parkinson's medication. Instead, the way that we would approach visual symptoms with Parkinson's is primarily looking at your glasses, thinking about certain eye drops if needed or other lifestyle modifications.

Another important thing to note is that visual symptoms from Parkinson's are very common, such that they might even happen to people without Parkinson's. With vision in general, it's very difficult to tell based on someone's symptoms alone whether they're related to Parkinson's or whether there's something else going on in the eye, like cataracts, for example. To a certain extent, we all experience difficulty with vision as difficulty doing something: I'm having difficulty seeing, or things are blurry. It's very hard to tell just from speaking with someone, is that Parkinson's related or is that something else that we should be worried about?

As a result, it's important for your doctor to be aware of these symptoms so that they can help to distinguish between Parkinson's and non-Parkinson's-related causes of visual dysfunction, since those might be treated differently.

There are five common visual symptoms in Parkinson's that I want to touch on today, although there are others. Later, during our question-and-answer time, if you think of any others, please feel free to ask. The five that I'm going to talk about now are dry eye, double vision, difficulty reading, impaired depth perception and hallucinations.

The first is dry eye. I'm going to begin this discussion with kind of a silly question, which is: why do we blink? It's something that you probably never thought to ask yourselves before, but the answer is that we blink in order to keep the surface of the eye moist.

Specifically, the cornea, which is the front of the eyeball, plays a big part in focusing our vision and protecting the eye. When we blink, we distribute, or we move, tears across the eye in order to keep it moist. If that didn't happen, it would be bad.

Dr. Ali Hamedani 00:14:22
It turns out that because people with Parkinson's blink less frequently than people without Parkinson's, they're prone to developing dry eye. In addition, some Parkinson's medications can worsen dry eye too, so it's important to know about that if you're someone who already has dry eye and to be aware of which medications you're taking or starting. Something that often goes hand in hand with dry eye is something called blepharitis, which is an inflammation of the eyelid skin caused by a buildup of oil and bacteria there. That often accompanies or precedes dry eye.

One important thing about dry eye to know is that it can cause a number of different symptoms. You might think that if the eyes are dry, then they'll feel dry, but it turns out that dryness feels very different to different people. Some people experience an actual feeling of dryness, but others might not experience that feeling and instead have blurring of vision, increased glare where bright lights blur your vision or are bothersome, or sensitivity to light. Those can all be symptoms of dry eye. Like I said, an actual feeling of dryness or irritation can happen, and what's underappreciated is how uncomfortable or painful that can be.

For some people, their eyes may be sore, stinging or aching, and that's also because of dry eye. People can have itching or redness in their eyes, sometimes going along with allergies, for example. It might feel like there's something in your eyes that shouldn't be there, like sand or some other foreign body.

A really important thing to highlight is that sometimes your eyes might actually water or tear a lot, and that is a sign of dry eye. It's a little bit counterintuitive because you think if there's extra moisture, if there's extra water and tears, how can they be dry? But it turns out what's happening is that when your eyes are dry, it stimulates your eyes to produce more tears, but they don't produce the correct type of tears. They're producing a different one that is not staying in the eye and doing its job. That's why your eyes water and there's a lot of discharge, but that's still a result of dry eye.

Dr. Ali Hamedani 00:16:36
Any combination of these can happen, or dry eye can actually be asymptomatic. It's not unusual for Parkinson's patients to go to their eye doctor and be told that they have dry eye even if they don't really feel it or notice it at all. But it's still worth addressing because untreated dry eye can cause some permanent damage, believe it or not. It can cause some scarring of the cornea, the outer layer of the eye, which can lead to some permanent problems with vision. Dry eye sounds very frivolous, but it's very common in Parkinson's and an important thing to take seriously.

If the main cause of dry eye in Parkinson's is reduced blinking, then you might think that the answer is to blink more often. Yes, that's theoretically true, although I find that it's very hard to consciously blink more frequently. Blinking is something that we do without thinking, and we have many other things to think about in our time instead. I think if you stopped what you were doing every 10 seconds to blink, you wouldn't get very much done, and it wouldn't be all that fun.

You're welcome to try, but I don't think that's a really feasible solution. One thing I will say, though, is that the blink rate does increase with stimulation or activity. The more that you're doing things, looking around, exercising, engaging with people, that sort of thing, you actually do blink more frequently as a result, versus things like watching TV, where you tend to blink less. Having a generally active and full lifestyle may help in that sense.

Like I said, be mindful of screen or reading time because we're blinking less when we do those. But really, the mainstay of treatment for dry eye is artificial tears, which are eye drops that are available over the counter. The important thing when you get artificial tears is to make sure that they're preservative-free. Specifically, you want to avoid anything that on the label says "get the red out" or "redness reduction" or anything like that. It's because the chemicals that are used to remove redness do remove redness, but they also irritate the eye and can worsen dry eye in the long term.

When you go to the pharmacy to buy artificial tears, you'll see some daytime and nighttime preparations. They're pretty similar, except that the nighttime preparation is a little bit thicker. That's because our eyes tend to dry out the most while we're sleeping, because we're not blinking at all while we sleep. You can use artificial tears up to four or six times a day. There's actually no such thing as too much of them. A general rule of thumb that I often give Parkinson's patients is to use artificial tears around the same time that you take your carbidopa-levodopa, which for many people they're taking three or four times a day or more. That will help you remember to use them.

I've listed a few examples of artificial tears here. There are others, and I don't endorse any one in particular, but just in case you see any of them at the pharmacy.

Dr. Ali Hamedani 00:19:31
I mentioned blepharitis earlier. That is treated a little bit differently, with something called warm compresses. What that is is when you take a clean washcloth or paper towel, soak it in warm water, close your eyes, and put it over your eyelids for about five or 10 minutes or so. That helps to loosen up the oils and to clean the skin. If these strategies don't work, then you should follow up with your eye doctor because there are some prescription treatments for dry eye that require an eye doctor, including a couple of prescription eye drops. There are even some procedures in the office that can be used to help promote lubrication of the eye.

All right. The next visual symptom in Parkinson's is double vision. Just to clarify, as I've shown you here, when I say double vision, what I mean is seeing two of the same thing instead of one. In these pictures, that might mean seeing a shadow of the fingers to the side, or a part of someone's face doubled up, or that sort of thing. Double vision in general can occur for one of two different reasons. One would be if there's a problem in the front of the eye that's causing difficulty focusing, such as needing eyeglasses or dry eye or something like that. When that's the case, that causes double vision that persists even when you cover one eye. You have double vision, you cover one eye, and the double vision is still there.

That type of double vision is actually completely unrelated to Parkinson's. But the type that is related is a little bit different. That's double vision where each eye individually is healthy and seeing well, but the eyes are pointed in a slightly different direction. In other words, they're misaligned. What happens is it causes each eye to see a slightly different image, and when your brain sees both of those, it sees double. That double vision will get better when you cover one eye or the other. That is the type of double vision that's related to Parkinson's. To summarize, if you're having double vision and you want to know, could it maybe be related to Parkinson's or not, you should cover one eye and see if it goes away. If it does not go away, that's not Parkinson's related; that's needing new glasses. If it does go away, then that might be Parkinson's related.

Dr. Ali Hamedani 00:21:39
Double vision from Parkinson's is actually quite common. Up to 30% of people in some of our recent studies have shown that. The most common pattern of double vision in Parkinson's is one in which you have double vision near, like when you're looking at something up close, like reading, but not when you're looking at something far away. That's something called convergence insufficiency. Like I said, it's common in Parkinson's in general, but one particular time to be on the lookout for it would be after deep brain stimulation. Sometimes it can emerge or worsen after deep brain stimulation. The main way that we treat double vision is with eyeglasses with prisms.

Prisms are a special type of lens. What they do is they don't cause your eye to move differently or strengthen it or anything, but they shift the image that your eye is seeing to meet where your eye is so that you no longer see double. You can also wear an eye patch as needed. I mentioned that covering one eye will get rid of the double vision. An eye patch helps you to do that. A question I often get from people is about eye muscle exercises. Unfortunately, these generally do not work, not only in Parkinson's but also in people who have double vision for other reasons.

The reason for that is that the eye muscles are fundamentally different from other muscles of the body in a way that means they can't really be strengthened or exercised more than they already do. In fact, our eyes are such that we use all of our eye muscles all the time. Right now, as I'm looking at my screen, I'm using all six of mine on each side, and you all are doing the same. There isn't a way to use them any more than we already do.

Next, I'll talk about reading. The reason I do this is to say that even setting individual symptoms aside, like dry eye or double vision, we know that as a whole, people with Parkinson's are more likely to have difficulty reading. That's because reading is a pretty complex and demanding task. It requires us to have clear vision, especially when we're looking at something up close. One thing that happens when we read, which you might not realize, is that every time you move from one word to the next, your eyes move too. I don't know if you've ever tried watching someone else as they read, but if you watch them, you'll see their eyes move from one word to the next.

Dr. Ali Hamedani 00:23:53
And that's important because we know that people with Parkinson's have difficulty moving their eyes quickly from one place to the next, kind of seeing where the next word is, knowing to get there quickly, and that sort of thing. But everything else really contributes to difficulty with reading, too. Dry eye and double vision also make reading worse.

Another thing to keep in mind, regardless of Parkinson's, is that everyone starts to need reading glasses after around age 40 or so. Many people will choose to wear progressive lenses or bifocals. What that means is that the top part of the lens is for distance vision, and then there's a different prescription in the bottom part of the lens for near vision, which is in this schematic here.

One thing we know is that bifocals and progressives can make it a little bit difficult for some people to read, and that's because there's a limited space that you can look through within the lens in order to see clearly up close. We know that people with Parkinson's are more likely to have difficulty finding that little area and moving within it. As a result, many people with Parkinson's benefit from having separate glasses for distance and separate glasses for reading rather than using bifocals and progressives. That's something to keep in mind when you see your eye doctor.

Another common visual complaint for people with Parkinson's is difficulty with depth perception. When I say depth perception, what I mean is the ability to perceive where things are in space in three dimensions, or to be able to look at something and get more about it than just things being side to side. The way this works is that each of our eyes only sees an image that's in two dimensions, but our brain combines those two images together in a way that produces a three-dimensional map of the space around you.

There are a few different reasons why someone might have difficulty with depth perception. One is that to have good depth perception, you need to see well with each eye individually. If one eye is not seeing well because of a cataract or because it needs glasses or something like that, then that, by definition, will affect depth perception.

Your eyes also need to be pointed at the same target. In other words, we can't have double vision because if things are doubled, then it makes it very difficult to combine them into a three-dimensional image. Finally, like I said, there are parts of the brain that are responsible for combining those two images together that each eye sees in order to see in three dimensions. We know that those parts of the brain are affected in Parkinson's.

Here are a few examples of how you might have difficulty with depth perception or how it might affect you. One is reaching for objects. People with Parkinson's might find that when they reach for something, they'll think that they're going for something, but actually it turns out that they didn't reach far enough, and it's a little further away than they thought. Some patients will tell me that they'll go to put a cup on the table, and they'll think that they're putting it in the middle of the table, safe away from any edges, but where they end up putting it is kind of close toward the edge of the table. Their partner may keep telling them, why are you putting it on the edge of the table all the time?

Driving, and especially parking, is another way that depth perception really comes to light. When you parallel park, for example, it's really important to be able to see and know how far away each car is from you.

Some people with Parkinson's experience a phenomenon called freezing, which is when they walk, especially when they first begin to walk, they may feel that their feet are stuck to the floor and they have difficulty initiating steps. We know that this is something that tends to happen, or is more likely to happen, within narrow spaces like doorways or hallways. We think there's something about space and the amount of space you see around you that affects walking and freezing.

Unfortunately, impaired depth perception is not something that can be readily fixed with either medication or glasses. The primary way of managing it is with compensatory strategies. For example, we know that depth perception improves with better lighting. When in doubt, turn the lights on. This is especially important if you're getting up in the middle of the night to go to the bathroom and are worried about navigating your steps or about falling. Lights on.

Another thing that can help with depth perception is providing some other sort of visual cues. For example, some people with Parkinson's will say that when they're going upstairs, they have a little bit of a hard time telling where the next step is. They feel like the next foot is fishing forward, and they can't tell how far away or how close that next step is. But if you have the steps brightly colored, in this example with a little yellow runner, then you can use the color to help guide you. It basically gives you visual cues for where things are to help compensate for impaired depth perception.

Just a note on driving, because I mentioned this earlier in the context of depth perception. Driving is a complex task. It requires a lot of different things, one of which is vision. In addition to vision, attention, coordination, and reaction time are also important. A question I get a lot is about vision with regard to driving in PD. The way I approach that is that Parkinson's-related visual symptoms can affect driving, particularly depth perception, as an example. But most of those effects can usually be managed just by caution.

I gave you the example of using paint or bright colors to help with depth perception on the stairs. Think of similar strategies while driving. Many patients with Parkinson's, however, do have to stop driving at some point, but that's usually not because of their vision. That's usually because of other things, such as coordination and reaction time or cognition. All that to say, driving can be affected by vision in Parkinson's, but it's usually not the main source of difficulty driving.

Dr. Ali Hamedani 00:30:07
Lastly, I wanted to talk about visual hallucinations, which you might not think of as a visual symptom per se, but technically they are because they involve vision. It consists of seeing something that is not there. Visual hallucinations are very common in Parkinson's, so up to half of people will experience them at some point in their life. What we know is that they're very frequently underreported. Many people with Parkinson's do not say that they have hallucinations unless their doctor specifically asks about them. That's because there's a lot of stigma surrounding hallucinations, and people may be afraid of being perceived as crazy or having dementia, when in reality neither of those things is true.

Hallucinations are a result of Parkinson's itself, but they can appear or worsen with certain medications, which is important to know about. They can come in a variety of different flavors. For some people, mild hallucinations from Parkinson's might consist of the feeling that someone is standing next to you or that something is moving in the corner of your vision, but you turn to your side and look, and no one's there. Some people will see a brief shadow or the shape of something passing but can't tell what it is. Often, hallucinations in Parkinson's have a familiar appearance.

They might look like animals. You might see a childhood pet or children who used to live next door playing outside. Sometimes hallucinations from Parkinson's can be very distressing. People might feel that others are trying to break inside their home or to harm them in some way. While they may initially be mild and not very bothersome, they can be very troublesome.

As I mentioned, sometimes Parkinson's medication can worsen hallucinations, so adjusting medication may be helpful. There are some other medications that can be used to treat hallucinations, too, although we generally reserve them for hallucinations that are significantly bothersome, just because we want to be mindful about potential medication side effects.

Another reason I mention hallucinations in the context of vision is that there is growing evidence that reduced visual function may be a risk factor for hallucinations. The reason I say this is that you can think of hallucinations as a balance in visual information between information that comes from the outside world, images of the world around us, and information that's stored in our brains, like images from previous memories or dreams. There is a constant balance in our brains between external and internal visual stimulation. Hallucinations essentially represent an imbalance in those two things: having too much internal stimulation.

One thing this means is that having good vision, having clearer images of the outside world, is important for suppressing or preventing hallucinations. In fact, you may not know this, but there are some people who have vision loss because of an eye disease like macular degeneration, and they can have hallucinations that are just like the ones that happen in Parkinson's, even though they don't have Parkinson's. Hallucinations in Parkinson's, we think, involve the visual centers of the brain. To a certain extent, this may also be true of hearing loss, too.

Just a note on contrast or color vision, because if you do any googling of vision and Parkinson's, you might come across this. There have been a number of studies looking at contrast acuity and color vision. I thought I'd take a second to show you how these are measured because these are things that are usually not measured when you go to the eye doctor. But if you see, for example, a news article about contrast acuity in Parkinson's, what they've done is something like this here. They've taken a chart where there are letters of the same size, but they become progressively dimmer as you move down the chart. What they're doing is asking people with and without Parkinson's how far down the chart they can go. Color vision is tested using something like this.

This is called an Ishihara color plate, and it shows a number in one color against a background of a different color. People with Parkinson's do have some difficulty with color vision when tested in this way, although again, color vision can be affected by other problems, too, not just Parkinson's.

The reason I mention this is that if you do any reading, you will come across some articles that talk about how both contrast acuity and color vision are reduced in Parkinson's compared to people without Parkinson's. But I actually find that this is largely asymptomatic and not a source of all that much difficulty with vision, although, for what it's worth, having difficulty seeing things under low conditions of brightness can come out when driving in the evening or something like that.

Just a brief discussion of hearing in Parkinson's. Hearing, in general, is less well studied than vision when it comes to Parkinson's disease. There are some studies that suggest that people with Parkinson's may have mildly reduced hearing compared to people without Parkinson's. That's especially true of early-onset PD.

Independent of actually being able to hear things, we do know that people with Parkinson's may also have some difficulty telling where those sounds are coming from. When you hear a car approaching, you can hear that it's coming from one side, so you know to look to that side and look out for it. But people with Parkinson's may hear that car just as well, but they may not tell exactly which side it's coming from.

Like I mentioned earlier, like vision, hearing impairment may also be associated with hallucinations. The mainstay of treatment for hearing loss is hearing aids. Again, there's a certain amount of stigma around that. Some people are self-conscious and may not want to use hearing aids because they're visible, but I think that's outweighed by the benefits that better hearing has on your health overall.

Finally, I want to conclude with a couple of questions that I get often from my Parkinson's patients about vision. One is, when I take my glasses off, I can't see well, but then when I put my glasses on, I see fine. Is this related to Parkinson's, or is this the sign of a concerning eye problem at all? The answer to this is no. Needing glasses is related to changes in the shape of the front of your eye and nothing else. It does increase with age, but as long as your vision can be corrected with glasses, that's fundamentally reassuring against it being Parkinson's-related or related to any other eye problem, for that matter. Needing glasses is not anything to be concerned about.

Another question is that patients might say their eye doctor told them they have another eye problem, like cataracts, glaucoma, or macular degeneration. Is that condition related to Parkinson's in any way? The answer to that is also no. Those conditions that I mentioned earlier are all associated with age, and because Parkinson's is also more common with age, they are pretty common in people who have Parkinson's, and they do cluster together a lot.

Some of these diseases, like glaucoma and macular degeneration, are technically neurodegenerative conditions of the eye. Parkinson's is also a neurodegenerative condition, but of the brain. As a result, there has been the suggestion that there might be some underlying causes for the two that are the same, but this isn't something that's really been shown for sure yet. In general, we think of these as mostly unrelated.

Finally, a reminder that cataracts are correctable with minor surgery, and it's important to know that Parkinson's doesn't disqualify you in any way from any sort of eye treatment, such as cataract surgery. If anything, I think that having better vision is even more important for your overall health if you have Parkinson's.

With that, I'll conclude here. This is a picture of Pennsylvania Hospital, which is the oldest hospital in the U.S. and is where our Parkinson's clinic is located. Thank you all again, and I'm happy to take some questions.

Dr. James Beck 00:38:17
Thank you very much, Dr. Hamedani. That is a tremendous amount of information, and I think it's going to be really a lot of gristle for people to mull over. I know that having the opportunity to download the slides and look at them later is going to be quite helpful. Hopefully people are seeing my screen. I think that just stopped one second, and I'll start again, just because we have some other things to share as well.

Questions are pouring in. Lots of people have some things naturally related to vision because I think that's what a lot of people are experiencing. It's amazing, when people can experience all kinds of problems, but as soon as their vision gets affected, they really are very aware of it. It's very clear that we're really dependent upon our vision to get through.

You mentioned the vision problems that people experience with Parkinson's are subtle. It's very clear that we're generally not talking about the front part of the eye. I thought you made it very nice when you mentioned one example of how to differentiate some of those issues, which is covering one eye. I think it's important probably for the audience to know that it's not closing one eye. It's actually covering one eye, because when you close it, I think that can affect your vision as well when trying to understand this stuff.

Do you recommend that if people are experiencing some vision problems at home, and they're listening to this and say, I've got some vision problems, what's your first recommendation? Chances are, because they have Parkinson's, they probably have dry eye. Is it worth them going out to the drugstore and investing five to ten dollars in some drops to see if that helps? Or should they do this kind of thing and say, well, my double vision is still happening, so that is a stronger indication to try, or when do they make that leap to say, I should go see a specialist about this?

Dr. Ali Hamedani 00:40:14
It's a great question. The part that I said about covering one eye or covering the other is specific to double vision only. That doesn't really help with other visual symptoms quite so much. If you're seeing double, if you're seeing two of the same thing, then you can try covering one eye or covering the other and seeing what happens.

Artificial tears are essentially harmless. There's the inconvenience of putting them in, and that's about it. It certainly doesn't hurt to give them a try. But in general, I think if you're having any difficulty with vision of any kind, it is a good idea to see an eye doctor. Like I said, pretty much everyone, especially over the age of 65, should be seeing an eye doctor every year anyway.

That starts sooner if you have certain conditions. If you have diabetes, you need to see an ophthalmologist every year, period. If you have a strong family history of glaucoma, then you should be seeing an eye doctor every year, period. I think seeing an eye doctor is always a good place to start first. If you've seen them recently and are still having these problems, then yes, maybe giving eye drops a try is a good start.

If you've seen your eye doctor and you don't have a good explanation for your visual symptoms yet, or things aren't quite adding up, then that would be the time to think about seeing a neuro-ophthalmologist, or that's usually when an ophthalmologist would be referring someone to me.

Dr. James Beck 00:41:38
Okay, great. That gets to my next question then. Should someone who's having trouble, and this is coming from one of our viewers, can a regular ophthalmologist diagnose some of these vision problems? When do we go see a specialist? Do they wait for a referral, or should they go straight to someone with your unique expertise?

Dr. Ali Hamedani 00:42:00
That's a great point. All of these things, everything I talked about, is something that a general ophthalmologist should be able to diagnose and treat. Double vision is the one symptom that some ophthalmologists may not be comfortable prescribing glasses for, but usually, if that's the case, they'll suggest that you see a neuro-ophthalmologist.

Most patients who come to see me have seen their eye doctor and have discussed it with their neurologist first. I'd say start with your regular eye doctor. Most things they should be able to take care of. If there's anything they can't, they'll point you in the right direction.

Dr. James Beck 00:42:38
Great. Thank you. One of our viewers, Penny, brings up a really good point about Parkinson's and eye drops. It's one of those things that requires precision motor control. Trying to get the drops into the right spot is not always easily done. Do you have any suggestions on how a person with Parkinson's can maybe more easily, if not easily, get the drops in?

Dr. Ali Hamedani 00:43:00
That's a great point. I don't have Parkinson's, and if I ever have to put eye drops in, it's a huge struggle, too, so I can only imagine. Yes, it is challenging. One other thing that can make it even a little bit harder is that not only is there the coordination involved in putting the eye drop in, holding this small tube, and squeezing it in the right way, but you also have to keep your eyes open while you're putting eye drops in. That's very hard for us to do as it is.

When you see something coming at you, your eyes want to close. We know that the urge to close the eyes actually becomes stronger in people who have Parkinson's. It's normal to want to close your eyes when something gets close to your eye. To a certain extent, we can overcome that. We can kind of force our eyes to stay open, but our ability to do that does get harder if you have Parkinson's.

All that to say, I definitely understand that it can be challenging. This is the sort of thing that it might be a good idea to ask someone to help you with. You can lie down in bed and ask someone to help you with the eye drop.

What you can do in that scenario that would help is two things. Number one, you can, with your finger, hold the bottom of your eye and pull it down a little bit. That helps. The other is, when you're trying to keep your eyes open for an eye drop to come in, don't think, I have to keep my eyes open. Instead, think, look up. It turns out when you look up, your eyes will stay open, but you'll be looking away from the dropper, and it'll be a little bit less threatening of an image. If you're enlisting someone's help, you lie in bed, from the top of your cheek pull down a little bit, and look up. That will help your eyes stay open for the person who's putting the eye drops in.

Dr. James Beck 00:44:47
That's fantastic. Not to get super technical or really get down into details here, but does it actually need to fall right into the eye, or can it fall into the little inner part of the eye and go in? Because maybe that will help as well.

Dr. Ali Hamedani 00:45:04
The corner is also an option, actually. We do that in young children who need dilating drops in the office but aren't going to cooperate. You can put them in the corner and then blink a few times, and they will flow in as long as they get in there in some capacity.

The other thing, too, is remember, because there's no such thing as too many artificial tears, you don't have to put just one or two drops. You can put several. If some of them don't make it in, that's okay. As long as one of them does, then you're good. You don't have to ration them or worry about putting too much in. Squeeze it a bunch of times. Eventually, one of them will get there.

Dr. James Beck 00:45:42
Okay, that's fantastic. People with Parkinson's, as you mentioned, may be more likely to keep their eyes closed. Marge, one of our viewers, mentions her husband has a hard time keeping his eyes open except when he's reading or eating. They want to stay closed more often. Is that like a dystonic problem with the eyelids, or is that just something unique and she should really take her husband to see a neuro-ophthalmologist to investigate a bit further?

Dr. Ali Hamedani 00:46:17
That's a great question. That's something I didn't talk about here, but what you're describing sounds a little bit like something called eyelid opening apraxia. Eyelid opening apraxia means difficulty initiating and maintaining voluntary eye opening. In other words, someone is totally awake, but the eyes just have a tendency to want to close, and it can be a struggle to keep them open.

It is considered to be a type of dystonia, or there is a type of dystonia called blepharospasm, which can sometimes happen to people with Parkinson's, although it's more common in other conditions like progressive supranuclear palsy. We think eyelid opening apraxia might be a type of blepharospasm.

There are a couple of things you can do about that. One is, if it's not that bothersome, some people are not bothered by it, and that's okay. Your eyes are closed sometimes. As long as people know you're awake and are talking to you, that's fine.

Some people do find it bothersome because their eyes close when they want to be reading, watching TV or talking to someone. There are a couple of strategies you can try. Sometimes people find that wearing a headband around their forehead can help encourage the eyes to stay open. Wearing goggles can even help.

I mentioned that we think this might be a type of blepharospasm. Blepharospasm, which is involuntary squeezing and closing of the eyes, is treated with botulinum toxin injections into the eyelids, and that also can work sometimes for eyelid opening apraxia. For that, I would say talk to your neurologist because your neurologist may be able to do that. If they don't provide that treatment, they can point you in the right direction, whether that's with a neuro-ophthalmologist or another neurologist.

Dr. James Beck 00:47:55
Fantastic. That was great advice.

You mentioned that having the lights on is important because there could be a relationship with changes in cognition, and certainly that vision may impact hallucinations. For people whose family members are impacted with Parkinson's, and in an older population that is more likely to have other vision problems like cataracts, should they be aggressive in trying to get those vision problems corrected?

This is a question coming from Facebook. Should they be aggressive in trying to get those vision problems corrected, or if their physician says, 'Maybe we should just wait and see until it gets a little worse,' what's the approach? Because Parkinson's is in the background, should we really work on maintaining optimal vision quality all the time, or do cataracts progress slowly enough that it's not an issue and can wait until the threshold is met?

Dr. Ali Hamedani 00:48:53
With regard to hallucinations specifically, there haven't been any studies yet to show for sure that people who get more aggressive or upfront treatment of eye disease, like cataracts, have fewer hallucinations or do better. We're starting to do some of those studies to see if that's the case.

Personally, I think that it is true, so I would recommend being a little bit more aggressive about treating reduced vision, especially if you think someone is at risk for or is having hallucinations. But that's not something we can really say for sure at this time.

When it comes to cataracts, one thing to keep in mind is that cataracts are not something that happen overnight or even within a period of a year. They're something that develop over the course of many, many years. Essentially, everyone by the age of 60 or so, if not sooner, is starting to develop them to a certain degree.

In other words, cataracts are not like a disease or abnormality per se. It's a normal aging of the lens. For some people, it happens more than others. The reason I say that is that there's no such thing as cataracts being not ready one second and then all of a sudden ready to come out, or now we need it the following year. It's something that happens over time.

The threshold for how bad someone's vision is and whether it's enough to merit cataract surgery is one that is very vague, individual and up for interpretation. There are some guidelines or requirements when it comes to insurance for how bad someone's vision has to be for them to pay for cataract surgery.

All that to say, whether someone's difficulty with vision is due to cataracts can be a little difficult to tell in the beginning. But I think the most important thing is to advocate for it as a consideration, especially if someone has hallucinations.

If the ophthalmologist says they're there but they're not ready yet, maybe ask for a little bit more clarification about what that means. As long as someone's vision can be corrected with glasses, usually that means you don't need cataract surgery. But if we think it's not, then that's when you start to think about cataract surgery.

Dr. James Beck 00:51:02
Okay, fantastic. Again, thinking of some of these other vision problems, I know that a lot of times people think about small floaters in their eyes. What are those, and do people with Parkinson's have a predominant issue with those?

Dr. Ali Hamedani 00:51:19
Floaters, which you're describing, Dr. Beck, are something that's benign and generally unrelated to Parkinson's. There is a gel inside the eye called the vitreous. Over time, that gel develops little condensations in it, and those cast a shadow in your vision. Usually, people will say it looks like a strand or a little dot, kind of like a fly or something like that.

They aren't more common in Parkinson's per se. I will say, though, there is a certain amount of... everyone gets them, but not everyone is bothered by them all the time. Part of that is because our brains learn to filter out that image or ignore it. It's possible that people with Parkinson's may have a harder time ignoring the image of that little dot there. For that reason, it might seem like it's more common, but I don't think it actually is.

Dr. James Beck 00:52:13
Okay, fantastic. We've spent a lot of time talking about vision, and vision is so important, but so is hearing. I just want to touch on some of the questions coming in about hearing. I don't know if you addressed this in your talk, but can you talk about tinnitus, people hearing background noises or background sounds as part of hearing? Is it unique to Parkinson's? Is that part of aging? Regardless, how might people deal with that?

Dr. Ali Hamedani 00:52:43
Tinnitus, as you said, just refers to ringing in the ears. For many people, it's a high-pitched ringing. For some, it can be a little bit more low-pitched. In general, it's not something that we think of as being more common in Parkinson's. It is something that happens with age.

Essentially, tinnitus can happen to anyone who has difficulty hearing for any reason. It's kind of the equivalent of blurriness of vision, right? It's a little extra something that's not there. It's common in Parkinson's, but I think just as a result of the association with age.

As far as what to do about it, unfortunately, it can be very challenging. One thing that can help is, if you're having difficulty with hearing, hearing aids would be helpful. The reason for that is, like I was telling you earlier with hallucinations, we think that the better you see, the less likely you are to have these internal images.

Not to say that tinnitus is an auditory hallucination in any way, but hearing better may help to drown out, if you will, the tinnitus. Other things can help, like ambient music or plain background noises. Seeing an audiologist or an ear, nose and throat doctor may be helpful, too.

Dr. James Beck 00:54:00
Okay, fantastic. It clearly sounds like having good vision and good hearing is important, so people who have those issues should seek treatment to get that addressed with hearing aids if necessary. I understand they can be rather compact these days compared to what they have been in the past, so that's hopeful for those who might be self-conscious of that.

You mentioned that people with young-onset or earlier-onset Parkinson's may have more issues with hearing compared to the broader PD population. Jen reports that her husband is having these issues, as you described. He's having a harder time with louder and punctuated sounds. Is he becoming sensitive to that? Is that something that's unique to Parkinson's, or what can you talk about there?

Dr. Ali Hamedani 00:54:56
That's a good question. I'm not sure. The difficulty in early-onset PD that I mentioned, the studies primarily look at how well someone hears. But it sounds like you might be describing something a little bit different, which is sensitivity to sound.

That's something I don't think has been very well studied in Parkinson's. But what I will say is that, as many of you know, people with Parkinson's have a tendency, when they speak, for their voice volume to be softer. There is some evidence that how loudly we speak has something to do with how loudly we perceive outside noises to be.

It may be that people with Parkinson's, especially those who become used to speaking very softly, become more sensitive as a result. You're used to hearing yourself speak very softly, so now sounds from the outside sound much louder than they should be, or something like that. But that's one where we don't totally have all the answers.

Dr. James Beck 00:55:51
Okay, interesting. Again, thinking about hearing, is there anything you recommend as far as assistive devices beyond hearing aids to help people? Is there a special type of phone that people can use? Are there other things like that? Parkinson's is isolating enough, and not being able to hear and engage in conversation is certainly compounding that.

To still talk with loved ones, is it as simple as using something like AirPods or some other type of device where you can keep the sound right at your ear? What would you recommend?

Dr. Ali Hamedani 00:56:27
I think hearing aids, or as you said, earphones where, if you're plugged into your phone, you can turn the volume up, are going to work for most people. Special assistive devices that really amplify noise are typically reserved for people with very, very severe hearing loss, which would be completely Parkinson's unrelated, and that would definitely require seeing an audiologist to get.

Those would be for people who are approaching the level of deafness. Yes, there are some special devices there. There are even some surgical devices, but again, that's for exceptionally severe hearing loss. For most mild to moderate age-related hearing loss, hearing aids are the main thing for that.

Dr. James Beck 00:57:11
Okay, fantastic. I know we're coming to the top of the hour, and I just want to finish up and thank the audience again and thank you for your time.

First, you hear a lot in the popular press about different colored lenses, either filtering colors or perhaps yellow lenses or blue lenses. Are those helpful at all for people with Parkinson's? Do they improve contrast enough that, for instance, orange or yellow lenses can be significant enough that people should use them, or is it more of a beauty-is-in-the-eye-of-the-beholder type of assessment?

Dr. Ali Hamedani 00:57:53
That's a great question. You're right that there is a lot out there about colored lenses or tinted lenses, and there's way more advertising than there is research on those things. A lot of it, we don't know for sure.

In general, those lenses are primarily geared not so much toward quality of vision or being able to see clearly or have better contrast, but toward comfort. Specifically, some people with migraine, or people who've had a concussion, report a lot of sensitivity to light, and they may find that certain tints reduce their headaches or eye strain. Again, it's not so much about improving the ability to see clearly, but more about comfort.

The one exception is the condition I mentioned earlier called blepharospasm, which is involuntary squeezing or closing of the eyes. That is a condition in which many people who have it report sensitivity to light, to the point where we think that condition represents oversensitivity to light, or the parts of the brain that are responsible for closing your eyes in response to bright light are oversensitive.

In that condition, there actually are some studies that show that a specific type of tinted lens, called FL-41 — the letter F, letter L, dash four one — may improve the severity of blepharospasm. If someone has Parkinson's and blepharospasm, then that might be worth looking into. Aside from that, whatever helps you see best and is most comfortable.

Dr. James Beck 00:59:22
Got it. Are those tinted lenses like sunglasses?

Dr. Ali Hamedani 00:59:23
No. FL-41 lenses are not that dark like sunglasses. They have a slightly red tint to them because they filter out blue light, so they look a little more red. They actually look pretty similar to regular glasses, but just slightly pink. You would get them from your eye doctor.

Dr. James Beck 00:59:50
Rose-colored glasses, then. It's nice to look at the world through rose-colored glasses.

Then a final question, and this is kind of a big one, so I'll throw it at you. We've talked about two senses here, vision and hearing. Is there any kind of general comment you can make about some of the other senses and how Parkinson's might impact them?

Dr. Ali Hamedani 01:00:14
Other senses? Smell is certainly affected in Parkinson's. We know that even before people develop Parkinson's, they may start to notice some difficulty with smell beforehand. Usually, taste is not a major source of difficulty in quality of life, although you may find that foods don't taste as good or need more seasoning than they used to.

One thing to know is that we often draw a distinction between smell and taste, right? Smell is when you're breathing in, and taste is when you put something in your mouth. But actually, it turns out most of what we think of as taste is actually smell, too.

The thing that lets you tell whether something tastes like chicken or fish or broccoli, the distinctive taste that things have, is actually largely smell. Taste itself is limited to things being sweet, sour or salty, things like that. All that to say, we know smell is affected, and what we think of as taste is largely smell.

Dr. James Beck 01:01:19
Okay. With that, I think we're going to thank you again for your time. Thank you to the audience for joining us today.

I just want to let you know we've completed our first expert briefing of 2022. We have a lot coming up ahead and have an opportunity to speak with everyone again on March 2, when we have a conversation about complementary therapies with Dr. Diaz, and then continuing on throughout the rest of the year. We certainly look forward to that. Don't forget to register, as you've done here, at Parkinson.org/ExpertBriefings.

We have lots of resources available for those who may need them. Our Aware in Care kits are fantastic if you may be thinking about having to go to the hospital, hopefully voluntarily as opposed to involuntarily. We have wonderful resources, including our library of materials and PDFs to download.

For those who are interested in whether their Parkinson's may be genetically related, I encourage those individuals to participate in PD GENEration, where we offer free genetic testing and counseling to people with Parkinson's. Penn Hospital is one of our PD GENEration sites.

We also have other ways to educate the community, including podcasts for those who like to do this while driving. Our PD Health @ Home series has webinars throughout the week to address many issues in Parkinson's. For those of you who are coming to us with a clinical background, we will be launching professional education opportunities as well, CME credit in particular. One of our first ones will be on genetics, which is really fantastic.

If we didn't get to your questions today, I'm sorry. We had a lot coming in and limited time. But our colleagues at our Helpline, 1-800-4PD-INFO, as well as Helpline@Parkinson.org, are ways you can send in questions to get them addressed, whether it's about vision and hearing or other issues with Parkinson's disease.

Lastly, when this ends and we're in the Zoom world, it's just going to go to black. What will happen is that your web browser will open up with an opportunity to provide feedback on your thoughts about this webinar, so please complete that evaluation.

Again, as I said at the top of the hour, we really value the input of our colleagues and our community who are living with Parkinson's disease and those who are affected by it. Please let us know what you thought of this webinar. We share it with Dr. Hamedani and with all our speakers and use that to keep improving what we do, so what we're offering remains relevant to those living with Parkinson's.

With that, I'll bid Dr. Hamedani adieu. Thank you again for your time today, and I look forward to talking with everyone again come March. Until then, take care.

Dr. James Beck 00:00:02
Hi there, everyone. My name is Dr. James Beck. I am the Chief Scientific Officer at the Parkinson's Foundation, and I want to welcome you to yet another Expert Briefing. Today we're going to be talking about conversations about complementary therapies and Parkinson's disease. I'm very excited about this. It's something that our community was interested in, and as you know, we always survey our community, trying to come up with ideas for each Expert Briefing series. This is going to be a good one.

Before we begin, I know that many of us are familiar with Zoom, but I just wanted to provide some reminders about what to expect in the Zoom interface that you're experiencing right now. At the bottom of your screen, there are three different icons, and I'm going to tell you what each of those are for and what they mean. The chat icon is actually not where you'll send information to us; it's where we can send some information to you. In the chat icon, my colleague Danielle will be giving you some information, whether it be links to download a PDF or information about what's going on, and you can see that there. In the next spot is the Q&A.

This is where our Parkinson's community can ask questions of our speaker, Dr. Natalie Diaz. If you're coming from Facebook, don't worry, that won't work for you, but you can send questions to us via the comments section in Facebook, and we'll be able to answer those as well. The next one is something that's relatively new in the Zoom world, and that is the live transcript. This is a closed-captioning-like experience for those of you who may be in a noisy environment and want to hear what's going on. It's computer generated, so take what comes through with a little bit of a grain of salt. It's not perfect, but it can be better than nothing, depending upon where you are and where you're listening to our presentation.

Just a little bit about the Foundation for those of you who may be new to us. The Parkinson's Foundation is a nonprofit that's really focused on improving the lives of those living with Parkinson's disease, both through improving care and advancing research. Importantly, everything we do is done in close concert with our community to ensure that our actions are aligned with the needs and priorities of those living with Parkinson's disease. We have three main goals that we use to achieve our mission. We're focused on improving care for those living with Parkinson's disease, advancing research towards a cure, and empowering our global community.

I think our Expert Briefing series nicely fills our objectives here. It is but one way with which we are there to advance our mission and achieve some of our goals. We're able to do this in part through our sponsors, and I'd like to give a shout-out and a thank you to Genentech. Genentech has provided an unrestricted educational grant to the Foundation to support our 2021-2022 Expert Briefing series. Genentech is a member of the Roche Group, for those who may not know. Thank you to them.

Dr. James Beck 00:03:14
For those of you who may not have been able to attend the entire one, are coming in late, or want to share this with others, this Expert Briefing, like all our Expert Briefings, is being recorded, and it should be available in about one week. For those of you who want to download slides and have that ready, my colleague Danielle just put a link into the chat where you can download the slides as a PDF for today's presentation. Then you can have them there in front of you, refer to them, and come back to them later.

First, I'd like to do a poll just to get to know who our audience is. On your screen is a poll. Please fill out your relationship to Parkinson's disease, whether you're a person with Parkinson's, a scientist, a physician, a healthcare professional, or you have a family member with Parkinson's. Again, if you're in Facebook land, please feel free to put in the comment section your relationship to PD. It's helpful to know. The nice thing is these are live, and our speaker, Dr. Diaz, can respond to them as appropriate. We'll leave that up there for just a little while longer, and hopefully we'll get some results in and see where we are.

Not surprisingly, most of the people attending are people with PD, at 72%. Thirteen percent are spouses and partners. Again, as we've always seen, a sizable portion, about 5%, are healthcare professionals, so thank you for joining our call today, our Expert Briefing. This should be, I think, very interesting for everybody.

Now I'd like to turn over the screen shortly to our presenter, Dr. Natalie Diaz. Dr. Natalie Diaz is a board-certified neurologist with fellowship training in movement disorders at the Pacific Neuroscience Institute in Torrance, California. That's just outside LA. Her clinical practice focuses on the evaluation and management of patients with Parkinson's disease, atypical parkinsonian disorders, Huntington's disease and other choreiform disorders, as well as dystonia and ataxia. She has also specialized training in the evaluation and programming of deep brain stimulation for Parkinson's disease, essential tremor and other dystonic disorders.

She also can therapeutically administer botulinum toxin for non-cosmetic indications, such as dystonia, hemifacial spasm and limb spasticity. Her research focuses on industry-sponsored clinical trials in Parkinson's disease and other collaborative clinical projects in the field of neurodegenerative disorders. She's often been a speaker for the Foundation and does a fantastic job. It's really my pleasure to welcome Dr. Diaz to our Expert Briefing series. Dr. Diaz, I'm going to turn off my camera and turn it over to you. I look forward to your presentation.

Dr. Natalie Diaz 00:06:15
Thank you, Jim, and thank you to the Parkinson's Foundation for inviting me to come and speak today. I'm going to go ahead and start with a quick poll, asking people a little bit about their use of complementary therapies and their comfort level in speaking with their physicians. If everybody could just take a moment to answer these.

Right. I'm going to go ahead and share my screen. Hopefully everybody there can see my screen a little bit. Just to share the results of the poll, 26% of patients, or people on today's call, shared that they do have a conversation with their physicians about complementary therapies, whereas 35% don't. We'll talk a little bit about where that is on the national average.

I'm going to start today's presentation with some typical disclosures and also a disclaimer. As Jim mentioned, I am a clinician, a neurologist. I trained in movement disorders, and I spend 80% of my time in the clinic seeing movement disorder patients, the bulk of which is Parkinson's disease. The other 10% or 20% of my time, over the last decade or longer, I have been involved in clinical trials with pharmaceutical companies as multi-site, large trials to try to bring new compounds to market. I have in no way ever spoken on behalf of any one product or received monies from companies to speak about their product or have gotten research monies for independent research.

In relation to this talk as well, I received no monies or have any affiliations with any companies or institutions that work with complementary therapies. My talk today comes from me being a clinician, working with patients every day and learning about some of these complementary therapies as we go.

Dr. Natalie Diaz 00:09:09
I am in no way trained in complementary therapies or in integrative medicine, but I learn from this every day. I always tell my patients, I'm not here to dictate your therapy. I'm here as your advisor and to give you recommendations and have discussions about what I know and what you learn. My patients often know that if they ask me questions that I don't know the answer to, I'm going to go look it up, and we'll talk about this, or I'll give you a call back and I'll tell you what I think. That is my approach for today's talk.

My goal today in discussing complementary therapies is to discuss what they are and how we define them. What is their appeal? I'll talk a little bit about what I call the good, bad and ugly of complementary therapies. If people are considering using them, what should you be thinking about?

Let's start first with definitions. The National Institutes of Health defines complementary therapies as those products and practices that are outside of what we call mainstream traditional medications or therapies. These are usually not prescription products or practices by the doctors, but they're taken alongside traditional therapy. They complement traditional medicine and are taken alongside. This is different from what we call alternative therapies, where people forgo traditional medicine or push off taking traditional medicine and take them instead.

As we become more comfortable using these therapies as the scientific medical community and the patient community learns more about these products, they start becoming more studied by the scientific community, and we learn more about their efficacy, their use and their safety. We're seeing more of a trend towards what's called integrative medicine. That's where practicing providers actually bring these two worlds together and use both traditional medicines and complementary therapies. Doctors now are incorporating this more into medical schools, and it's now a certified area of medicine where people can get certified fellowship training in integrative medicine.

It's a very important thing because this is a huge topic that's taking over. In this country alone, the global market is over $80 billion in the last couple of years in the use of complementary therapies. It's projected that by 2027, 2028, it's going to be globally a more than $300 billion industry. It is very important for doctors and the scientific community to know about this. We're seeing more and more patients who feel comfortable with this.

Dr. Natalie Diaz 00:12:07
We definitely see that studies have shown there are geographic differences in the use of these therapies. In America, there tends to be more of a use of vitamins and dietary supplements, herbs and botanicals. In Europe and Scandinavia, there tends to be more of a preference for body-based practices such as acupuncture, yoga and massage. In Asian and African countries, there has always been more of a pull towards their traditional medical systems that incorporate a little bit of all these practices: herbs, botanicals, foods, as well as some of the body practices. There definitely is a geographic preference.

In terms of Parkinson's disease, there have been a couple of studies that have shown somewhere from 30% to 40% of patients with Parkinson's in this country use complementary therapies, and more in other countries. It tends to be more women than men as users and consumers of these products, and we definitely see that there's a socioeconomic difference, too. The higher the socioeconomic level, the more use of these therapies as well.

Interestingly, there are several surveys published that show more than half of Americans don't consult their treating doctors when they're taking these therapies or before taking these therapies. It's very important because doctors are getting more comfortable with this. There are a lot of doctors now that actively practice this, and still there are doctors that are reluctant to discuss this and see this as a threat to traditional medicine.

The literature on this is kind of all over the place. In academic centers, there was this interesting study published back in 2006 from the Mayo Clinic surveying doctors of all specialties. Back then, they found that only a quarter of doctors actually discussed complementary and alternative therapies with their patients. Only about a quarter of doctors actually talked about the potential risks and harms of complementary therapy, but all of those who did say they had conversations said that the conversation was initiated by the patient.

It's very important because not all doctors feel comfortable talking about this, so they won't bring it up. But most doctors these days, I think, if you bring up the conversation, are willing to at least say, I don't know, but here are some resources, or I'll go look it up, or I've heard of that. It's a discussion because, as I'll go on and talk about, these therapies can have their drawbacks. They also can have their interaction with other medications that people take. It's very important for people to be informed consumers when they're considering taking these.

Dr. Natalie Diaz 00:15:11
Another study that was published in 2020, and this one looked more at community physicians, found that more than 50% of physicians were recommending complementary therapies. Again, more female physicians than male physicians, but it tended to be more in primary care specialties where doctors were more comfortable discussing these, as opposed to specialists. It is definitely a growing trend where physicians are becoming more comfortable not only discussing it but recommending some of these therapies.

Why do people seek these therapies? There have been a number of studies that have tried to look at it, and there's a myriad of reasons, I'm sure, why people seek complementary and alternative therapies. A lot of the studies have shown people really are looking for more benefit from therapies. A lot of people may be dissatisfied with the traditional medication they're getting. I think, as all physicians that treat Parkinson's disease understand, we have medications that are purely symptomatic at this point. They can be really good for some people, especially in the early part of the disease, and really get people's functionality improved, mobility improved, but they don't work as well for other people. They can have a lot of side effects for people. Over time, they can lose their effect, requiring people to take them more frequently or have some long-term complications.

I understand the dissatisfaction with what we have available in our traditional medications. We do have an arsenal of medications these days. We have more than 20 medications that are available for the treatment of Parkinson's disease, and we pick and choose them depending on the individual, but they're very imperfect medications.

Other reasons that people seek these complementary therapies include a sense of empowerment. It's a sense of, I'm doing something for myself, rather than something that is coming from the medical world. These are all things that most of us understand why people seek.

Dr. Natalie Diaz 00:17:14
I'm going to talk a little bit about what I call the good, the bad and the ugly of complementary therapies. The good is that these therapies tend to inspire a sense of wellness for people. They're a positive feeling. They probably do provoke a sense of a placebo response, a sense of reward. They tend to look at and focus on treating the whole person. They're not just focused on the symptom that somebody is having or the condition. They're looking at trying to address the person as a whole: their mental, emotional, spiritual and physical health. That's very appealing to people.

We talk about these therapies trying to focus on some of the body processes that are thought to go awry in a lot of conditions: inflammation, oxidative stress, the buildup of proteins and gut problems. These are things that are generally affected in many conditions, and these therapies try to focus on those mechanisms rather than one condition. It does give people a sense of empowerment. They do the research. They talk to other people about it. It gives people a sense of, I'm in control. It makes people feel good. That's the good of complementary therapy.

To be honest, most of these, if they're taken in moderate doses, used with practitioners who know what they're doing, and people do their research and understand the medications that they're taking alongside, have relatively few potential risks and side effects. That's the good thing. A lot of them can be very useful for things that a lot of people, not just those with Parkinson's, experience: problems with sleep, problems with nausea, constipation, and they help reduce stress. These are good things that we get from complementary therapies.

The bad thing is that unfortunately, as you'll hear me talk about today, we have not been able to prove these really in human studies. There's a lot of lacking evidence and research support that we have as clinicians to say, yes, absolutely, you should go do that because the studies really point us this way. As clinicians, we're always sort of like, yes, let's talk about the pros and cons. I don't have a lot of research evidence to say you should definitely do that, but most of them, as I mentioned, have low risk. They can be costly. This is a big business, so some of these supplements, herbs and practices can be costly. Most of them are not covered under insurance.

Dr. Natalie Diaz 00:19:59
Because these are not considered drugs, supplements, herbs, vitamins and dietary supplements are not really regulated by anybody. The FDA doesn't really follow them. There's always the question of labeling: is what it says on the label truly what you're getting in the bottle, and is that pure? Are there no impurities in there, or other things? There have been reports of people selling things where, when there's an investigation, there is absolutely nothing of the product.

I think a lot of the large retailers, Target, Walgreens and a number of others, got in trouble for selling supplements a number of years back that had zero or very little of what was in the bottles. Now a lot of those companies use third-party companies to vet the supplements that they're selling, so there's some quality assurance there. But with a lot of products that people get online, you don't really know what you're getting or whether it's safe.

These herbs and supplements also use the same metabolic systems that drugs do. They're metabolized by the liver, the kidneys and different processes in the blood. If people are on prescription medications that use those same metabolic processes, there can be interactions. If you're taking an herb that's metabolized by the same liver enzyme that your blood thinner or your cardiac medication is, then there's the possibility that it could increase or decrease the effectiveness of those prescription medications that you're on.

That's an important reason why you should do your research and discuss these with your physician. If you're on a blood thinner that is there to prevent clots, and you're on one of these therapies that could decrease the effectiveness of that clot prevention or increase your risk of bleeding, that can be very dangerous.

Also, there isn't a lot of reporting of side effects and toxicities with these. Again, because it's not regulated, when drugs go through this approval process, it's mandatory that they log adverse effects and toxicities. Whereas these are nutritional supplements, herbs and practices, there's no requirement to log toxicities. When you're looking at the data, and people take advantage of this, there is this real imbalance of a lot of data of toxicities and side effects with pharmaceuticals and a lack of data with the other, because people aren't reporting. There's no requirement, and people take advantage of that and say, hey, look at the difference in toxicities.

Dr. Natalie Diaz 00:22:29
That's what I call the ugly of this because companies take advantage of this. This is a multibillion-dollar industry. When we don't have a lot of scientific support, where there isn't a lot of regulation, and there is a need for people to find things that work, there are companies and institutions that unfortunately take advantage of this and make false claims of things being curative for Parkinson's, or being proven to slow down the process in humans, and portray traditional medicines as toxic and these other alternative or complementary therapies as the cure.

I can assure you, and the scientific and medical community will tell you, we have not been able to prove anything yet that is curative for Parkinson's or truly, truly with a lot of scientific confidence, neuroprotective. Companies have gotten in trouble across this country for making these false claims, and people have to be very careful with that.

I understand, though, there is interest in this in the scientific community. We don't deny that there is potential for all these practices to help with Parkinson's. There are a lot of things that we see in the brain of Parkinson's disease where these complementary therapies mechanistically could be of use. In the brain of Parkinson's, we see inflammation. We see oxidative stress and the formation of free radicals. We see problems in the functioning of the powerhouse cells in the brain and the body called the mitochondria. There is a buildup of abnormally folded protein. There's poor communication between the brain and other systems, especially now the gut. Then with all this going on, neurochemicals go awry, and there are certain chemicals that become upregulated and cause more damage.

Mechanistically, complementary therapies are meant to try to help with that. A lot of these therapies have, in the lab or in animal models of Parkinson's disease, proved that they do have an effect in those systems. We just haven't been able to prove it in human trials as of yet or have had very inconsistent results.

Dr. Natalie Diaz 00:25:05
I understand why there's this promise and this real look to that, because our traditional medicines really just affect here. They're really just trying to help the symptoms once all this has taken its toll, and we're having a low level of neurochemicals because the brain cells have atrophied, and we're trying to supplement all these neurochemicals. There is still a lot of promise for these therapies, but we're still in the really early stages, and people have to be careful.

Why is research so hard? The truth is we don't quite know yet what causes Parkinson's disease. We see all these changes in the brain, but we don't know if these changes are the cause of or the result of another injury. We don't know if we just hit one process, or do we have to hit them all across the board? If it's one of these therapies that only works as an antioxidant or as an anti-inflammatory, is that enough to turn the car around and make sure that we can stop this?

When they do show effect in the lab or in animal models, very often, and this is the same case that we have with pharmaceuticals, it doesn't translate to human trials. That's because we're a much more complex animal than rats or monkeys. We also think there's a lot of variability in people genetically, what they've come across in their lifetime, symptoms and maybe even in their brain processing. There's always been this idea in the scientific community when things fail: are we just not looking at this right? Would it fail for everybody, or are there certain groups of people that could actually benefit from some of these products, but maybe not everybody would benefit?

We also don't know if we're studying Parkinson's very well. We have crude ways to rate changes in motor function and people's symptoms, but maybe that's not across the board the best way to do it. We don't have a specific blood test or imaging tool or other type of biomarker that we can say we can follow effectively for changes in Parkinson's to help us in these trials.

With such a big research engine in this country, there is a lack of interest in studying these. When we talk about limited funding, private companies go for things that they can patent, make money from and bring to market. Unfortunately, natural products can't be marketed, so they kind of fall to the wayside by private companies. When there's limited funding for investigators that are interested, a lot of funding gets shifted to pharmaceuticals.

The National Institutes of Health, a couple of decades ago, saw this growing trend and the interest in it both from the scientific community as well as the patient population, and they developed the National Center for Complementary and Alternative Medicine. They are responsible for trying to generate funding and have an idea of where the federal government and government funding agencies want to target in some of these therapies. Every five years, they come up with a strategic plan of how best to move the science needle forward in these therapies.

Dr. Natalie Diaz 28:26
Then they got renamed as the National Center for Complementary and Integrative Health. They also do a lot on the patient side, so they have in their web portal something called Know the Science to help patients learn about what we mean by evidence-based medicine and how to vet a study that talks about benefit in the use of some of these therapies. What should you be looking for in these studies? How many patients are in it? Is a placebo being used? Is it vetted by peers? Is it thrown out to the scientific community to see if it truly is a good effect? There is also something called the herb list.

It's still rudimentary. I sometimes use it, but it's a mobile app that can be downloaded on your phone, and it's got a list of popular herbs that people can look at. It talks a little bit in general, not Parkinson's, about what the herbs are, how they've been looked at, and what some of the potential safety and toxicity issues are that people should be aware of. All those are available for patients.

Now let's focus a little bit on complementary therapy. The National Institutes of Health kind of breaks it up into five categories, and there can be a lot of overlap between them. We talk about biologically based therapies. These are herbs, vitamins, dietary supplements, and foods that are thought to play a role in medicinal therapy. There are mind and body techniques, things like biofeedback, meditation, relaxation techniques, and guided imagery. These are self-taught and self-administered most of the time.

Manipulative and body-based methods look at things with a practitioner who does these: massage or chiropractic manipulation, reflexology, and whole body vibration. Then we talk about energy therapies. These are more in ancient traditional medicines, with the idea of balancing energy within the body and its symbiosis with energy in our environment. I'll talk a little bit about some of the alternative medical systems that use a little bit of all of these.

I'm going to talk a little bit about biologically based therapies, and I'm not going to focus on just one because I think it would take up the bulk of this talk and really spread out into multiple talks. I can say this is probably what Americans focus most on: vitamins and dietary supplements and functional foods. There have been a number of studies that have looked at these. As I mentioned, mechanistically they make sense. A lot of them have antioxidant properties. They have anti-inflammatory properties. Some of these have shown in animal studies that they help with dissolving or preventing some of these abnormal protein clumps that we see in the brains of Parkinson's disease, or help maybe with the communication of the brain with other body systems.

Mechanistically, and sometimes in the lab or in animals, we see that this could possibly work. Unfortunately, for a lot of these, we have not had consistent positive results. A few of them, in early studies with humans — coenzyme Q10, creatine, vitamin E, and even glutathione — those are the ones that have probably been the most studied and did show some early results in humans that were positive. But as they were more studied and more effectively studied with placebo response and with bigger groups of people, the research evidence just didn't pan out, or we got mixed reviews. At this point, the medical community can't, with good science behind us, really recommend it.

Dr. Natalie Diaz 32:29
Having said that, most of these that I put up here are pretty safe to use if people are using them. It is always important for people to make sure where they're sourcing them from. I put here a couple of things that people need to be worried about. One of the big risks, as I mentioned earlier, was blood thinners. People who are on aspirin, Plavix and blood thinners, some of these can interact with these vitamins. They can interact with other medications as well. Some of them can cause side effects as well: facial flushing, nausea, dizziness, headaches. A few of them can also affect you if you're on cholesterol medications that also act on the liver.

It's very important to understand the potential side effects and toxicities of some of these vitamins. But I think most of us feel that if people want to try them, they want to spend the cost, they know the potential side effects, and are taking them reasonably, meaning they're not taking whopping doses, but they understand the pros and the cons, I think most of us in the medical community are like, okay, and let's see how you feel.

The same thing with herbs and botanicals, or what we call phytochemicals. These have probably been less well studied than vitamins and dietary supplements. They've been around for millennia that people have used them, so these are things that a lot of the ancient medical systems tend to use. There's been a lot of interest over the years in ginkgo biloba, curcumin, which comes from turmeric, different forms of ginseng, which most commonly in this country is Asian ginseng that we're using, the Camellia sinensis plant, which, depending on which part of the plant is being used, black, green and oolong teas come from, and then a number of other herbs and botanicals. None of these are exhaustive lists of things that I've heard people trying.

Unfortunately, there isn't a lot of evidence. Some of them have never been studied. Some of them have been studied very radically. Some of them have not had placebo groups with them. Some of them have shown mild benefit in different things — cognitive function, sleep, gastrointestinal things. They just haven't been studied in a consistent way, with the right preparations consistently and the doses consistently with placebo groups. For us as scientists and clinicians, we have a hard time, unless we have proof, really recommending.

But like I said, if people understand the potential side effects that they should be looking for, potential risks with some of the medications that they're taking, and really isolate, I'm going to take this, let's see how I feel, and I'm going to get it from a reputable source, most of us are like, okay, let's go ahead and try it and let's see how you feel. As I mentioned, in the studies that have been done, there are patients that feel better. If you look at all the blogs and the patient websites, people do feel better with these therapies. If people want to give them a try, as long as they understand the lack of good evidence, but also understand the potential side effects and toxicity, and as physicians, if we understand that most of these can possibly help, we just can't prove them, then I'm all for these most of the time.

I'm going to talk a little bit about Mucuna because this is one that is very popular with people. This is a legume that's actually found in tropical and subtropical areas of the world, especially the desert plains of India. It is a legume where the seeds of the legume actually contain levodopa. It's the precursor to dopamine. Roughly, and again, it's not a precise science, they have anywhere from five to ten percent of levodopa in the seeds. This has been used as part of Ayurvedic medicine, a traditional medicine system, for millennia.

Dr. Natalie Diaz 36:35
Actually, there's a lot of literature on people using this for a number of medical conditions, as it's thought to have antioxidant, anti-inflammatory, maybe even work with diabetes, maybe work as an antidepressant. It is definitely documented in ancient texts for its help on what sounds like Parkinson's disease. It has been studied, so there is not a tremendous amount of literature out there, though good literature.

But it has been studied. In a couple of good studies that looked at single doses compared to traditional levodopa, it may actually kick in faster than traditional levodopa, may have more of a stable effect than levodopa, and may even last longer than levodopa without necessarily kicking up as much dyskinesia in people that have that propensity. Unfortunately, a few studies that have looked at more longer-term use of Mucuna have shown that people do run into potential side effects, the same ones we see with levodopa: dizziness, nausea, gastrointestinal issues.

Some of the studies show that a good percentage of patients stop just because they worsen their motor function. It's complicated using Mucuna because we don't know yet, while in the moment it can be really good, from the long term — people usually require more levodopa as the years go on — how good it is at keeping up with patients' symptoms, how to titrate it to patients' symptoms. There's a lack of evidence to that. And what are some of the long-term side effects of being on Mucuna? We also have to make sure that people don't go out and eat the seeds or even the extract. The extract can be very potent as well.

Most of these are boiled, roasted, cooked so that the percentage that you're getting is a lower percentage. A lot of people use the powder, which people can then weigh and get a better idea of how much levodopa they're getting in. But again, it's not well regulated, so we don't know that exact content, and it can vary from the source that people are getting.

It also can interact. If patients are taking diabetes medications or antidepressants, it can interact with those and can also lower blood pressure, just like levodopa does. People do have to be careful.

I'm going to talk a little bit about cannabinoids because that is something that comes up a lot in my discussions in clinic. Cannabinoids are one group of hundreds of substances that we find in the Cannabis sativa plant. There are more than 100 cannabinoids that are known. The Cannabis sativa plant is known as marijuana. The dried plant is called marijuana. The main cannabinoid that we find in the Cannabis sativa plant is tetrahydrocannabinol, THC. This is the one that has the euphoric effects that make people feel high, as opposed to cannabidiol, which is CBD. This is still psychoactive, but it tends to be more of a calming effect rather than causing euphoria and a high.

There are a couple of other cannabinoids that are gaining in popularity. There's, cannabigerol, cannabidiol. I'm stuttering on those.

Dr. Natalie Diaz 40:44
These are also gaining. These are usually less potent forms of THC that are becoming more available. It's a loaded political subject because CBD products, because they don't cause euphoria, because they don't cause psychoactive highs, tend to be available in most states in this country legally. They need to have 0.3% or less of THC to be able to be legally available in this country.

THC-containing products are still legally regarded as Schedule I products, and people need to have a medical use to be able to use these. Parkinson's disease in a lot of states can be something that people can apply for. Physicians unfortunately can't prescribe for it, but can help in the process if people meet that criteria. It is approved for certain medical uses: seizures, cancer chemotherapy, nausea and vomiting, and weight loss in HIV and AIDS. There are small studies using these products, again not very well done studies, but they have shown improvement in anxiety, depression, pain and anxiety, and maybe even help sleep.

In the realm of Parkinson's disease, there have been a couple of decent trials that have looked at its effect in Parkinson's disease. They have shown some mild benefits, and some have shown no benefit. Pooling them together, we really don't have much direction yet because what happens is there are varying compounds that are used, there are small studies, and some of them don't have real good placebo-controlled groups. While there's promise in these, we still don't know. The consensus is we still don't know how well they work and, long term, how they do with Parkinson's disease.

There are always safety concerns that I talk about with my patients. One is we usually don't recommend that people vape these products, especially products that have THC, because they can cause lung injury. There are problems with absorption and effect in edibles. These edibles take a while to get their effect, and so sometimes people keep taking more because they don't quite feel the effect right away. With the constipation of Parkinson's, where these products stay in the gut for a while, all of a sudden that effect kicks in at one time and can be toxic. People have to be careful with edibles, especially with Parkinson's.

These cannabinoids and cannabis-related products do use the liver as their metabolism, so they can interact with other medications as well. They can also be associated with side effects. They can lower blood pressure, cause fatigue, dizziness, mood or cognitive changes, especially with THC, but there's some data that suggests that even with CBD, some people can have cognitive changes. Because they can have sedating effects, they can affect balance and hallucinations.

Again, we don't have a great governing control over these products. CBD products, people can get online and different places, and there's nobody to regulate the quality or the labeling of what you're getting. There have been shown to be contaminants in some of these products: microorganisms, pesticides from growing these, and other toxic substances within some of these that are sold online. There is no good regulation that tells us what's the right content of cannabinoid if somebody is following these.

The Parkinson's Foundation came out with a consensus statement back in 2020 that talks a little bit about this, some of the limitations we have had as physicians as well as the scientific community, and what we know. Right now, most of us just can't promote it. But again, it's accessible to patients, so it's a discussion that I always have. I have a number of physicians that feel more comfortable with it. I have people that dabble in this that know better the dosing and the different products that are available for purity and safety. It's good to talk to your physicians because some people are gaining a lot of interest and expertise in this.

Dr. Natalie Diaz 44:49
There are a number of other useful supplements that I sometimes recommend in my clinic. I use a lot of melatonin to help with sleep-onset insomnia and what we call the REM sleep behavior problem in Parkinson's. Chamomile teas or extracts can be very useful for helping people sleep and can help a little bit with anxiety. Passion flower, both in the tea and the extract, can also help with that. There's also valerian root that, again, has been used for millennia but can also have some side effects. Ginger, either tea or oral, can help with things like diarrhea, heartburn and indigestion.

Peppermint oil as well. Flaxseed or flaxseed oil. I use flaxseed every day. I put it in my oatmeal. It can help with constipation and has some antioxidant effects. Some of these can be useful, but again, you have to be careful with these. Cranberry extract is something that's been looked at and can sometimes help in those people that have a tendency towards recurrent urinary tract infections.

I'm going to pivot a little bit because I see that I'm running out of time. This is an area, mind-body practices, where I'm a big proponent. I practice this myself. These are practices that people can self-teach themselves. They practice, they can do them as part of a bigger group or associated with practitioners that do it, but they can be free, they can be self-taught, and this is where we train our mind to be more conscious of our body. We use mental focus, deep breathing and imagery to help us in reducing stress and feeling more in tune with our body.

There have been studies that have shown that mindfulness meditation, yoga and tai chi can actually be very useful for things like stress relief, relaxation, improving anxiety and improving sleep. These are all practices that people should be doing, and I'm a big proponent of these. Things like tai chi, also some other medical communities have been suggesting as part of, say, a pain program.

The American Academy of Rheumatology actually recommends tai chi as part of a larger plan to help with osteoarthritic pain, especially knee pain, that tai chi can be very useful for that. Qi gong is something similar to tai chi, again where we use slower, less intense body movements, but a lot of deep breathing to help with that. Again, there's some growing interest and evidence showing that these can be very useful for some of those body feelings.

Manipulative and body-based practices are a little bit different. These take a practitioner who does these, but there is some evidence that some of these can help with similar things: stress reduction, pain relief, anxiety, things like osteopathic practices, especially craniosacral therapy where there are pressure points that are stretched and pressed on, especially at the occipital cranial area and the lower back, where these can have some relief of pain and stress. Massage as well.

Again, we don't have a lot of evidence for massage, but if people are going to reputable places that are clean and they're doing gentle massage, there is some evidence that it does help with things like muscle tension, neck and back pain, and may even help circulation. Whole body vibration also, a lot of physical therapy studios use vibrational therapy. There are some studies that they may help with some of the physical motor symptoms of Parkinson's at least temporarily and can also help with gait and motor function.

Dr. Natalie Diaz 48:52
There are physical therapy studios that use vibrational therapy either focally in certain body parts, or there are machines people can stand on for a few minutes of vibrational therapy. Unfortunately, the studies have been inconsistent with it, but some people really do feel that it helps along with other therapies.

Energy therapies are part of more traditional cultural therapies. One that I always get a lot of questions about and interest in is acupuncture. Acupuncture has actually been studied. There are studies that show that in animal models, acupuncture can actually be helpful in these animal bodies, and we don't really know why, what the mechanism is. The idea from a traditional cultural standpoint is that we have a body force called qi — I think it's chi, actually — that flows through our body through channels, what we call meridians. When there's disease or conditions, there are blockages of flow of our energy force, and so acupuncture is specified points that help release some of these blockages.

Unfortunately, there have been studies in humans, and the results have been mixed. The ones that have actually been done with a sham procedure, with a placebo group, did show that there is a big placebo effect. Looking at all the literature collectively, the AAN in 2006, that's the American Academy of Neurology, and then the Movement Disorder Society in 2015 kind of pooled all these studies and felt we really can't recommend it. The study criteria, the evidence, is just not strong enough.

But most of us feel that if patients want to give it a try, as long as they're going to a place that's clean and is reputable, there's not a lot of drawback in trying these therapies. I definitely have had patients who feel that it has helped, whether it's pain or whether it's just a sense of feeling better. If people want to try these, I think most of the medical community will say it's okay.

There are other therapies, what we'd call touch therapies. There have been no significant studies done in Parkinson's disease. There have been some limited studies done in general in different conditions or in people in general that may help with stress, pain relief and mood. This is the practice where people either use light therapy or they use touch or hover their hands over people with this idea that there's a force that helps people feel better.

Traditional medical systems, things like traditional Chinese medicine and Ayurvedic medicine, have been used for millennia. Most of them do cover a mix of herbs and botanicals and some of these mind and body practices and manipulative practices. A lot of people outside of this country, in Asian countries, have been using these for a long time. There is something to it in the studies; we just have not been able to prove it. Native American culture also has their traditional practice. This involves a combination of prayer, healing touch, use of herbs, teas, tinctures and rituals, which some people feel has been helpful.

Dr. Natalie Diaz 52:30
I'm going to end there and just, in summary, a few key points. When we talk about complementary therapies, these are defined as natural products and practices that can be taken alongside traditional medicines. I usually don't recommend that people forgo therapy if they need it. Many times I have patients who come to me, they don't quite need medicine yet or they're sort of at that cusp and they want to try it. They're like, I don't feel that I'm ready for medicine yet. Sometimes I'll say, okay, I agree with you. You're still doing everything you need to do. You're not really suffering too much. Let's go ahead and try it and see if it changes the course.

What I hate to see is sometimes when patients are really suffering, having to pull away from work, having to pull away from family functions because they're not doing well, but they're so anti-medicine that they look for these. Unfortunately, for all the drawbacks that we have from pharmaceuticals, there is no doubt that they have helped people over the 50 years that they have been in use. If we look at the natural history studies before we developed levodopa and after we developed levodopa, most patients with Parkinson's can live almost a normal sort of lifespan with Parkinson's. It's usually not Parkinson's that is the fatal flaw; it's some of the complications that people can have with Parkinson's. But again, there's no doubt that pharmaceuticals can help, and I hate to see people forgo it.

We do have, most of us understand, these have promise. They do have promise. Mechanistically, they have promise. They have shown some data in animal models, but we just don't have a lot of great data in humans for us as scientists and clinicians to say, absolutely, go give it a try because this is what it shows. But it is a conversation that you should have with your physicians because most people, I think most people in the medical community, are open to it. If we don't know about it, we'll go read about it, and it should be a conversation that we have, not a yes or a no, but a conversation with us advising you what are the pluses and what are the minuses of using these.

Dr. Natalie Diaz 54:44
In general, most of these, as I mentioned, have relatively few potential risks and toxicities if you're trying to get them from a reputable source. I usually recommend that people really try to go to naturopaths or physicians who practice integrative medicine, or really do their research and try to find some of the larger brand-name companies. Target, Walmart, all those now use third-party companies that try to vet the supplements that they're selling, so there's some assurance of quality that they're getting, or at least of content.

Always remember that just because it's natural does not mean that it's safe. These therapies can have their side effects, they can have their toxicity, they can interact with other medications that you're taking, and even with each other. Herbs can interact with each other and with other vitamins. They're not regulated, and so you don't always know that what you're getting is quite what you're getting.

But what can you do? Always be aware that there is no miracle cure out there right now for Parkinson's. We're working on it both on the complementary and the pharmaceutical side, but there is nothing yet that we have been able to say, with good evidence, that cures Parkinson's or significantly slows it down. Some people do get benefit from these, so again, I don't rule them out.

It is very important for you to talk to your healthcare providers about these. Always remember, if you're going to try them, do your research, talk to your physicians, and do one therapy at a time so you can isolate if you have side effects. It's the same thing I always tell my patients with traditional therapies. Let's do one thing at a time because if we throw too many things into the recipe and something goes wrong, we don't know which one is the culprit. We don't know which one caused the problem.

Always check for verification. There are a couple of companies that will put their verification on the labels, that they've vetted the quality, purity and content. The federal government has something called the U.S. Pharmacopeia. You can go onto their website, and they have discussions about vitamins and herbs. There's something called ConsumerLab. This is a nonprofit separate company that tries to look at the quality and content of some of these herbs and dietary supplements. Then there's NSF International. Some of these supplements that you'll read out there have this on their label, which gives an extra level of security that what you're getting might be more honest than something that you buy on the internet that doesn't have that.These are some of the useful resources that are available to people to learn more.

Dr. James Beck 57:38
Thank you very much, Dr. Diaz. That was a fantastic presentation. You really covered a tremendous amount of material here. For someone who says they're not an expert, I think you certainly are pretty close to doing justice to this subject area.

A lot of questions have come in, but one of the ones I just want to start off with at the top, because you mentioned this, just for clarity for our listeners: you mentioned sometimes traditional medicine. I think you're referring to medicine you practice, American-style medicine, Western medicine, versus the culturally based, what some people often think is traditional medicine too. Is that correct understanding?

Dr. Natalie Diaz 58:18
Yeah, yeah. I apologize because that term is used for both, right? Conventional medicine, I guess, is a better term for it. It's the convention that we have in our medical treatment in this country, which is through a doctor, prescriptions, most of them. That's what we call conventional medicine, sometimes referred to as traditional medicine.

But that term, as you mentioned, is also used for cultural tradition, right? A lot of countries outside of the U.S., in Asia and Africa and even parts of Europe, there are supplements and foods and herbs that have been used and passed down for generations as useful for treatment of ailments. Yes, I talk about culturally traditional therapies as opposed to more conventional medical treatment.

Dr. James Beck 59:11
Got it. Thank you very much. As I mentioned, lots of questions coming in. I know we're almost at the top of the hour, but I think you said you could stay for a little while longer, so I appreciate that. For those of you who may have to sign off, this is recorded, so you can always come back and catch the Q&A afterwards as part of that.

If you've been listening to this, and there were a number of people who didn't really know what complementary therapies are and now their interest has been piqued, how do they go about trying to find someone to talk with about complementary therapies? Should they go to their doctor first? Is there a complementary therapy doctor that they should consider? Do you find those who specialize in PD? What would be the first step you would recommend for someone who's listened to this and says, I'm willing to see if some of this may help as part of the overall care for my Parkinson's?

Dr. Natalie Diaz 1:00:01
Absolutely. I don't tell people to go out there and reinvent the wheel and go out and get themselves a whole new set of doctors to treat their condition. I would always first start, if you have a good relationship with your doctor, that's always the first place to start: talk to your doctor, right? As you saw, I highlighted some of the problems that can come with these: toxicities, potential side effects, interaction with medications. It is always very important for your doctors to know that because they're writing your prescriptions. If you're taking something that's counteracting with a medicine that they're giving you, and there's a complication and they don't know what you're taking, it's very important to know that.

I always start my day when I'm meeting patients for the first time or even when I'm seeing them in follow-up, I always tell them, okay, what are the medications you're taking? What are the changes in your medications? Are there any new supplements or supplements that you're thinking of talking about? Knowing that this is a growing trend, I think you're going to see more and more doctors asking those. When you check in, they're always asking you to put down everything that you take because you may not know if it's important or not, but it could be important. Always start first with the physicians that you already have and try to have that conversation.

Of course, there are physicians with all levels of knowledge and comfort with these, right? Sometimes you will come across physicians — traditionally, we're not trained in this — you will come across physicians who say, I wouldn't take that, or, I know nothing about it. Then you're left with, well, where do I go? There are some useful resources for you to do your research that I mentioned. There's fellowship training, so there are institutes of integrative medicine where doctors can get fellowship training, and some of those have listings of integrative medicine doctors. Most of them are primary care doctors, but there are specialists as well who take that a little bit further and try to bring these two worlds together.

First start with your own doctor. Then start with some of these national organizations of integrative medicine, the NIH, different things that give you more information and things for you to learn yourself, but also to help identify. Also ask your doctor. I have colleagues that I work with who, in certain things, are much more well-versed in things like this. I will dole out to other doctors. I have emergency room doctors and internists who feel really comfortable with CBD products, with Mucuna, all that. I am by far not an expert in these. I will dole out and say, I really can't tell you too much, but I do have colleagues who work in that. Let me give you a referral or let me give you their contact information.

Dr. James Beck 1:02:57
Okay. That's fantastic. If your doctor is, as one listener said, dismissive of this approach, is it worth going out on your own, as you said, trying to establish these relationships? But even then, you should always be telling them what you're taking, just so that they know.

Dr. Natalie Diaz 1:03:17
Absolutely. You don't necessarily, sometimes you have a good relationship with your doctor on other terms, and you think that they're a wonderful doctor, but maybe that doctor just doesn't feel comfortable or doesn't know too much. It doesn't necessarily mean you have to go changing your doctor. But you have to be in control of your own ship. We're there to help guide you on the road, but ultimately, you have to be aware that there can be problems with this, and so your medical team needs to know everything you're on. It's okay if they don't approve. It's okay if they don't, but I need to tell you what I'm on so that you're aware.

Then a discussion. If they don't feel comfortable or they don't know other physicians or other providers, then like I said, there are accessible resources through some of the national organizations and some of the government websites that have listings of people who do have more training in that.

Dr. James Beck 1:04:14
Fantastic. I've gone through this process, and I want to take some of these complementary approaches, especially with the biologically based ones. Supplements and herbs and whatnot, things you would probably ingest. How long would you expect to see some effects? When would you say, this isn't really working out? Is it just a matter of people will know it's not worth the effort? Because it does sound like this is a little bit really on the cutting edge of things where, for those early adopters of technology, things don't work quite as you expect and you have to do a lot more fiddling. It's not going to be turnkey, and so it requires a lot more effort on the behalf of the patient or the person with Parkinson's who's doing this.

What do you advise somebody who says, I'm going to try this, and you say, well, yeah, you should try a couple weeks or a couple months? What do you say?

Dr. Natalie Diaz 1:05:08
Yeah, I mean, it's similar to pharmaceuticals, right? People, if they want to try them, you try them, right? You give it a little bit of time. Side effects, most of the time you're going to feel first, right? Those are things that you always have to keep in the back of your mind. Know what you're taking. What are the potential risks? Like I said, always vet out yourself or definitely with your physician: am I on medications that are going to interact with something that I want to try? That's the first and foremost thing to do. Is this appropriate for me to try?

Then if I'm going to try it, as I mentioned on one of my slides, do one thing at a time. It's the same thing with pharmaceuticals. Like I said, if you throw too much into your recipe and you don't feel well or you have some toxicity, we don't know. You might have lost out on something potentially good because we aren't able to sort out which one was the culprit, right? If you're going to change something, always change one thing at a time. I have patients who dabble in bacopa, dabble in CBD, dabble in these, and we have this discussion. I think maybe you need a little bit more levodopa. I want to try this first. Okay, well, let's just do one.

Let's do one, and we talk about the pros and cons of both. If we decide we're going to do the complementary therapy adjustment first, we do that, and we'll leave the conventional medications the same because we want to see how this works. Ideally, you want to give it some time. If you looked at some of these processes that the complementary therapies are trying to get at, these inflammation, oxidative stress, changes in your stress level, pain, all that, it's not going to be immediate. You do have to stick with them as long as you're feeling okay. I usually say give them a couple weeks, a couple of months.

If financially it's feasible, some of these are not cheap, right? You have to take that into account too when you're balancing this. I definitely don't recommend that people waste a fortune or their savings on these, but if they're financially feasible and people really want to give them a try, like medicines, you have to really give them a few weeks, maybe even a few months, to see if you notice an effect.

Some of these effects, again, we don't know. That's the problem. We don't know without them being properly studied. These studies that we do are very short-lived. There's no way that we follow these supplements for months and years. Could it have an effect of something that you're taking now and you take it for a couple of years, then maybe we look back then and say, well, it did make a difference, right? I usually say stick with it for a while. If you're going to give it a try, stick with it, maybe three months, maybe six months. But it becomes a problem if we need to adjust conventional medicines, right? Again, we say give it a try, but we may have to do something in the interim.

Dr. James Beck 1:08:03
Yeah, I do know that we surveyed the Parkinson's community a couple years ago, asking their experience with medical cannabis. What was interesting is we found a lot of people tried it, but a lot of people also stopped using it because they, for various reasons, didn't find it as effective as they had hoped.

Thinking about why people try this, you had that nice slide which showed different things people were looking at, more holistic, big-picture stuff. But do you find — and this is a question from one of our listeners, Wayne — do you see specific symptoms as a trigger for people to try complementary medicine, particularly pain? Is it one of those more intractable issues with Parkinson's?

Dr. Natalie Diaz 1:08:43
Yeah, absolutely. As I mentioned, holistic and looking, but a lot of it is over time people have these things, and whether part of it is aging and part of it is Parkinson's disease, there are symptoms that just don't get covered with a lot of the therapies that we have available, both Parkinson's treatment as well as pain management. Sleep issues are so prevalent as we get older. Constipation issues, right? When our therapies aren't there or we've tried them and they've given people side effects or we've reached a ceiling, that's where a lot of people turn to some of these.

I do, like I mentioned, the mind and body practices, I think that's probably the one area that I promote the most. I'm actually a consumer of that. I find it very useful. I have a bunch of free apps on my phone to help with mindfulness meditation. I do yoga, dabbled in tai chi and qigong. Those are the areas where I think really help people with pain, with stress reduction, can help with sleep, and can sometimes help people focus a little bit more.

But yeah, I think it's those symptoms like that: pain, sleep, stress, focus, mental fog. These are the things that sometimes we don't get at with our conventional medicines that people turn to that.

Dr. James Beck 1:10:07
Yeah, absolutely. I'd just alert our listeners that every Monday we have Mindfulness Mondays hosted...

Dr. Natalie Diaz 1:10:14
Wonderful.

Dr. James Beck 1:10:14
Yeah, it's a form of — thank you for saying so. We're way past our time. I appreciate it, but just if I give you some shotgun questions real quick, rapid-fire, if I may. We talked here, we're talking about Parkinson's disease, but people have atypical Parkinson's. This applies to them as well, right?

Dr. Natalie Diaz 1:10:33
Yeah, these are across the board. These are not specific for Parkinson's. The ones that have been studied have been looking, trying to single out just Parkinson's disease. As far as we know, a lot of these studies don't go through some of the same criteria that we do for pharmaceutical trials, where we really try to isolate out real Parkinson's and not some of these other Parkinson's conditions. We don't know if those are in there. But these are general therapies, right? They really are therapies that not only Parkinson's patients, atypical Parkinson's patients, but the general community also can try.

Dr. James Beck 1:11:10
Fantastic. Another question has come in about functional medicine. I'm not familiar with that term. Is that different than integrative medicine or complementary medicine? Are you familiar with that term?

Dr. Natalie Diaz 1:11:21
I'm not sure. I'm wondering if they're talking about functional foods. When we talk about things like Mucuna and actual foodstuffs, protein and things like that, these are actual foods and not supplements that people take. I don't know if the listener was referring to that, functional foods rather than functional medicine.

Dr. James Beck 1:11:42
Okay. One last one, if I may. Reflexology. You mentioned that in one of your slides. That question has come in about what is it? I'm not familiar with it either. What is reflexology briefly?

Dr. Natalie Diaz 1:11:53
Yeah, again, it's one of those manipulative practices, right, where you actually have a practitioner. There are certain areas of the body, and this again is an ancient practice. There are books that date back to I don't know when, where touching and pressing, similar to acupuncture but not acupuncture, certain areas of the body seem to help, at least by ancient texts, release digestion, improve digestion, help sleep, all those sort of things. The pressure areas release some of these body flow of energies and have traditionally, in ancient texts, helped.

I don't know that there's a lot of evidence to them. If you think about them, they're similar to a lot of these mind-body practices and manipulative practices. I'm sure they help with pain. They help with stress relief. Anytime you have one human touching another human in areas where you've got stress and discomfort, it can be useful. If people want to try it and they're going to places that are clean and have a reputation, I have no qualms about it. I just don't know that there's a lot of literature on it.

Dr. James Beck 1:13:06
Yeah, understood. Dr. Natalie Diaz, thank you very much for your time today. Wonderful presentation. I also want to turn this over and say thanks to our community. I really appreciate you taking the time to tune in and to listen to our presentation today. This closes on two of six presentations for 2022. Look forward to April 6, Parkinson's Awareness Month, about whether we can put the brakes on progression for Parkinson's disease with Dr. Lazarus.

We have discussed a lot of different resources and material. Dr. Diaz mentioned some in her slides. Again, those slides are available for download, so you can take a look at that. Also, have our own Aware in Care kit, something for people to keep in mind as they consider visits to the hospital. We have an extensive library of resources and our PD Health @ Home series, where you can find out about our Mindful Mondays. Then we also have some other digital materials, like this podcast, Substantial Matters, which is really fantastic for those who like to listen to it. For those who don't know what a podcast is, it's basically the radio on the internet. You can download and listen to it when you want to.

We have professional education, so for those allied health professionals who joined us, we've just launched CME programs. Certainly take a look at that for those of you interested in it, particularly in genetics and Parkinson's. Speaking of which, PD GENEration is our large study that we're looking to test as many people as we can to understand whether they have a genetic basis to their disease. The hope here is that we'll have enough people who are identified and be willing when the time comes, which we think will be soon, where people can participate in clinical trials that are targeting people with specific genetic forms of Parkinson's disease.

That said, we are here for you: Parkinson.org, 24/7, and during business hours, we have our Helpline, 1-800-4PD-INFO. If people are busy, they return calls, so feel free to leave a message. They will call you back. Also, Helpline@Parkinson.org. Last, before we go and fade to black, when this Zoom call is over, a window will open up from your browser. It's an opportunity for you to give feedback to the Foundation, feedback to Dr. Diaz. Let us know how we did. Give us feedback. We take it, we listen to it, and incorporate it to always make certain that we're bringing you the best material that's possible.

With that, I will bid everyone adieu and look forward to talking to you again in April, and hopefully the spring will be warm for everybody. Thanks again and until next time.

Dr. James Beck 00:00:01
My name is Dr. James Beck. I'm the chief scientific officer at the Parkinson's Foundation, and it's my pleasure to welcome you to another session of our Expert Briefings. Today's topic is "Can We Put the Brakes on Parkinson's Disease Progression?"

I'm just going to go over a little bit to familiarize you with our Zoom interface. I know we have many people who know this quite well, but we always have new people each time, and I just want to make certain everyone's comfortable. At the bottom of the screen, you'll see a red arrow that highlights our chat. This is where my colleagues will share information, so this isn't where you would ask questions. We'll get to that in just a second.

My colleague Danielle will be sharing information about resources that the Foundation provides, a place to download slides, information on calling, and other details you may need to know. On the next slide, we show you the button for the Q&A. That is where you will actually click and ask your questions. If you're on Facebook, don't worry, you won't be able to click on the button, but you can send questions to the Foundation via the comment section.

This is a way that my colleagues will be looking for questions that come in so I can ask them of our speaker today. The last thing to point out to you is the live transcript. This is a relatively new Zoom feature that will provide a closed-captioning-like experience. If you're having a little trouble hearing, or you're in a noisy environment, you can see closed captioning at the top of your screen. It is computer-generated, so it's not going to be perfect, but it should give you a good sense of what is being discussed.

On the next slide, I just want to talk a little bit about the mission of the Parkinson's Foundation. The Parkinson's Foundation is a nonprofit that's focused on improving the lives of those living with Parkinson's, both through improving care and advancing research. I think it's important that everything we do is done in close contact with our community to ensure that our actions are aligned with the needs and priorities of those living with Parkinson's.

On the next slide, we outline our goals here. It's important to note that we are focused on improving care for those living with Parkinson's disease, advancing research toward a cure, and empowering our global community. I think our Expert Briefings series is but one way we do that. We certainly rely on the Parkinson's community to inform our structure and our agenda for the year for the Expert Briefings. But our Expert Briefings really wouldn't be possible without the support of our sponsors, so I want to take a moment to give them thanks.

Dr. James Beck 00:02:27
Our Expert Briefing series for this year is supported by a grant from Genentech, which is a member of the Roche Group. We're supported by the Light of Day Foundation, whose generosity has made our PD Health @ Home programming possible as well, and by support from Kyowa Kirin. Thanks to all three sponsors for our Expert Briefing series this year.

I just wanted to mention that our Expert Briefings are recorded and archived. Within a week, you should get an email, if you've registered for the Expert Briefing, that it's available for download. That's something to look forward to. In case you're not able to take notes, or you want to share this with others, it's available online. We also make the slides available for download. If you want to have those separately, you can. There's a link in the chat. Click there, and you can download a PDF version of that.

What I'd like to do next is get to know who our audience is. I always like to do that. If you're viewing on Facebook Live, just use your comment section to let our colleagues know who's listening. We're just trying to get a sense of what our audience is like. We have a lot of people with Parkinson's, as I suspect. Sometimes we have a good selection of nurses, scientists, clinicians and people who are really interested in Parkinson's disease. Let that go for just a brief moment, and hopefully we'll see what our breakdown is in just a second.

Not surprisingly, we have a lot of people with Parkinson's who are listening, and we welcome them, as well as their care partners and a good number of people who have family members with Parkinson's disease. Welcome to everybody.

Next, I'd like to introduce our presenter, Dr. Joash Lazarus. Dr. Joash Lazarus is a graduate from the University of the Witwatersrand Medical School in Johannesburg, South Africa. I hope I pronounced that correctly. Following a primary care internship in his home country, he joined the movement disorders section at Emory University to pursue research training in neurology and genetics.

Dr. Lazarus completed neurology residency training, as well as a clinical fellowship in movement disorders. He is board-certified by the American Board of Psychiatry and Neurology and has that specialty focusing on movement disorders. His clinical and research interests revolve around the evaluation and management of balance disorders, such as those seen in multiple sclerosis, Parkinson's disease and other movement disorders. It's my distinct pleasure to welcome Dr. Lazarus to our presentation, and now I'll turn it over to you. Thank you.

Dr. Joash Lazarus 00:05:34
Thank you, Jim. Thank you for the invitation to present today, everyone.

As Jim mentioned, the title of today's talk is "Can We Put the Brakes on Parkinson's Disease Progression?" Just as a summary leading into this, Parkinson's, of course, is caused by an aggregation or accumulation of essentially a toxic protein called alpha-synuclein in very strategic areas of the brain that results in a depletion of dopamine. Dopamine is that messenger that's very important in controlling, among other things, smooth and coordinated movement. The consequences of that are all the symptoms we typically see in Parkinson's.

But we have to be mindful that everyone's experience with the disease itself is very different. There are no two similar disease experiences, and with that in mind, there are no two identical treatment approaches that are typically used. As a general paradigm, this is often the algorithm or the set of tools that we use when approaching either a newly diagnosed patient or when confirming a patient with a diagnosis of Parkinson's disease. That current therapeutic approach draws on one or more of these modalities at any given time during the entire experience.

It's often a new diagnosis, followed by some form of either in-clinic and continuing patient and community education. We're very quick right now to emphasize early pharmacotherapy. The pharmacotherapy, or the drug therapy, is really aimed at controlling motor symptoms, and to a lesser extent the non-motor symptoms, with the goal of improving function, preventing disability and improving overall quality of life. Those three things — improving function, preventing disability, improving quality of life — really remain the cornerstone of managing Parkinson's disease. That's the goal in treating the symptoms related to this disorder.

There are different modalities and different ways in which we can approach that. Pharmacotherapy is listed very high on this list as one option. The others are support groups, social support, mental health support — mental health in terms of prevention of mental health complications — and participation in clinical trials. All of those are really geared toward addressing the underlying biochemical disorders.

Other forms of therapy are very useful and have proven benefit in this disorder. For gait and balance problems, for example, we have very specific evidence-based treatment options now. Things like BIG therapy and LSVT therapy, for example, have shown that they can really improve not just symptom control, but with it, the quality of life and function that patients can have.

Dr. Joash Lazarus 00:08:19
Massage therapy, mindfulness-based therapy — there is a plethora of complementary therapies that really help the clinician form a more comprehensive approach to managing these symptoms. We also have the benefit of more advanced pharmacotherapies now. Continuous dopaminergic stimulation, for example, a Duopa pump, and then DBS surgery, which has become more common because of its efficacy, which I will underline a little later.

If you look at all these therapies as a whole and across the spectrum, often we are looking at it through different perspectives and we're asking different questions. In the scientific fraternity, so to speak, we're looking at the disease and the disease process. In other words, the degree to which that protein accumulates and the degree to which dopamine is depleted. The holy grail of any neurodegenerative disorder is the concept of neuroprotection. Can we discover or develop a therapy that's effective enough in actually slowing down that process in the brain?

To date, and I will go through several examples that highlight this, none of the pharmacotherapies, none of the medications or none of the complementary therapies like DBS surgery have overwhelming weight of evidence to support that it actually does that. It actually slows down the process in the brain.

But that's okay, because really what's more pertinent on a day-to-day basis for patients, and in terms of our interaction as clinicians in a clinic visit, is: how are you doing functionally on a day-to-day basis, and how are you progressing, if at all? The types of things that we're really interested in, and patients find most relevant, are from a functional standpoint: are they able to cope or manage as efficiently or effectively as they did three months ago or six months ago? Is there any degree of disability or discomfort that's disrupting their life now compared with previously, and how do we manage that?

Symptom control, kind of masking the symptoms and the process that's there, is a little bit different from controlling disease progression or neuroprotection. Often, in the clinic, it may seem like we use those interchangeably, but they're a little bit different. This goal of neuroprotection, of slowing down this disease process, has been the focus of research for many, many decades. The question is: how do we determine or answer whether any intervention, whether it's a medication or a lifestyle change, is actually effective in slowing down this process in the brain, or if it's merely covering up the symptoms, which is still very potent, still very useful and not trivial at all?

Dr. Joash Lazarus 00:10:50
This is a good example of how we would design a study to do that. This study was called the ADAGIO study. It was published in 2009, and essentially it was to look at the efficacy of rasagiline, or Azilect, in symptom control, number one, but also whether or not it actually impacted that disease process. To answer that question, there were two groups of patients in the study. Apologies for that.

There was an early-start group. This was the group of patients in this lower bar here, who started the active ingredient, the rasagiline, very early on at the start of the study, and they were followed for 72 weeks. During that process, they had neurological examinations. The examination we use is called the UPDRS. It's a way of us quantifying all the motor deficits that we see on exam that's relevant to Parkinson's. Of course, a higher score is relevant to less controlled symptoms as a whole.

Then there was a second group of patients who started on a placebo, so an inactive substance, until 36 weeks before they were switched to rasagiline.

To summarize, there were a few important endpoints here, but if a medication were truly effective in slowing down the disease process, then the trajectory would be very similar between the two groups when they were both on the active medication. In other words, they would both respond to Azilect, as they did here. But the group that started later, which is the placebo group, would never quite catch up to the first group. It would never quite reach the same degree of disability control because they started later, which means the sooner you start, the better it is, and that's likely because it's impacting the disease process as a whole.

If you look at the trajectory of this graph, you see that the placebo group steadily got worse, as you'd expect, because they were untreated for the first 36 weeks. When it was then switched to rasagiline, they did much better out to 48 weeks, and it was similar or parallel to the group that was on rasagiline. At 72 weeks, you notice that the delayed-start group, the group that started later, never caught up to the group that was on the active medicine from the beginning. They didn't do quite as well, although they had some improvement from the time they started the active medication.

Dr. Joash Lazarus 00:13:07
Those were optimistic features that suggested the possibility that Azilect, or rasagiline, could perhaps alter the progress of the process that's involved in Parkinson's, with the caveat that two doses were studied. There was a 2-milligram dose and a 1-milligram dose. Although the 1-milligram dose met the criteria, or the features that we look for in a so-called neuroprotective or disease-modifying agent, the 2-milligram dose did not.

It remained uncertain. There was not overwhelming evidence, unfortunately, that rasagiline was neuroprotective or could protect the brain from the processes that were underlying the development of Parkinson's disease. There is still ample evidence from this that patients who are on rasagiline do better. Their symptoms are better controlled, and it's still a very effective symptomatic treatment, which is why it's used as an adjunct to the gold standard levodopa even today.

Speaking about levodopa, or Sinemet, this was the equivalent study — a delayed-start study using the same kind of methodology in 2019 — to try to answer that question related to levodopa. The background to levodopa, which is Sinemet by brand name, or by generic name comes in different formulations, is that the science behind it was well established in the 1960s. It's been a mainstay in terms of oral treatment for Parkinson's disease ever since then.

In early 2004, there was a study that showed that potentially levodopa therapy either had a prolonged symptom effect or could potentially attenuate the disease process, or be neuroprotective. The way that study was done is that patients were either on placebo or levodopa for four weeks and then taken off medicine for two weeks. Even two weeks later, patients who were in the levodopa-treated group still did a lot better than those who were in the placebo group.

But the study design was very similar to the one that I'm about to show you, because this really is the best way of elucidating whether a medication or any intervention is covering up the symptoms and is symptomatic, or is slowing down the process.

Dr. Joash Lazarus 00:15:09
In this study design, if you look at the first graph, the delayed-start group here compared to the early-start group, once the delayed-start group began an active medication at around 40 weeks from randomization, they caught up very quickly to those who started earlier on. That suggested that there wasn't a real benefit in this study design for patients who delayed starting Sinemet or levodopa until later on. They both had the same symptomatic benefit.

The same was true if you look not just at the motor features like tremor, dyskinesia or stiffness, but if you look at the quality of life that was self-reported using the scale we call the PDQ-39 total score. This was a great study that was done three years ago that showed that levodopa, unfortunately, probably does not have the disease-modifying and neuroprotective effects that we aim for, but it's still very much the gold standard in terms of medication management because of the symptomatic benefit it confers.

Deep brain stimulation, of course, is a great adjunct therapy. It's more than just an adjunct therapy. It has really transformed the way we control motor features in Parkinson's disease. The FDA approval of the label for DBS in Parkinson's patients is roughly around four and a half years — four to four and a half years — of symptom onset, with about six months of motor complications.

Those complications are things like uncontrollable involuntary movements, such as dyskinesia; wearing off, when the medication kind of loses its effect sooner and sooner; or just tremor that never gets better, even on an optimal dose of levodopa medication. Several studies have shown a profound benefit for DBS and shown that it's very safe in the correct clinical setting, and that the long-term outcomes are also very relevant and well-established.

One of the questions that needed to be answered was whether starting patients on DBS, or proceeding with DBS early on, would alter the long-term outcomes and perhaps hint at the possibility of some neuroprotective effect.

This study, which was published two years ago from the Vanderbilt group, looked at patients between six months after diagnosis or six months after symptom onset to four years, so really early on in the disease process. Here they were randomized to two groups. They were randomized to early DBS, which is the black line, in addition to medical management. If patients were on Sinemet plus Azilect, they remained on the medications, of course, versus those who were randomized to only aggressive and the best possible oral medications that they could be on.

Looking across the five-year follow-up period, you notice that those patients who were randomized to the DBS group had an improvement in their overall motor scores, or had a lesser degree of worsening over the five years than patients did with just medical management. If you look at tremor specifically, the impact of DBS on tremor is really very effective, and that's been shown in several blinded randomized controlled studies in the past.

Even in this study, which is consistent with that, you notice that the tremor continues to improve and shows long-term efficacy, a long-term response to DBS, out to five years.

Dr. Joash Lazarus 00:18:13
Patients with oral optimized drug therapy followed the natural history of that. The expectation, in other words, is that symptoms generally progress a little, and in this group there was worsening of tremor in the five years after study enrollment and improvement of tremor in the five years after study enrollment in the DBS group.

Another way of looking at the efficacy is patients' total levodopa daily dose. Again, patients who had DBS early on had a lower increase in the total amount of dopamine they were taking out at five years, whereas patients who did not have DBS were likely to have a much higher increase, a much higher total daily dose of levodopa five years later in comparison. The same is true of using other medications.

The red bar here represents patients who did not have DBS early on and only had optimized drug therapy. A higher percentage of them needed two, three or four categories of medicines — so polypharmacy — in comparison to those who had DBS, in which they were much more likely to remain either on one medication treatment option or fewer medication options. The one graphic I did not include here was dyskinesia, but dyskinesia follows a very similar trend to that of levodopa dose and tremor, in that, in general, patients who had early DBS, as well as optimized drug therapy, generally did better with dyskinesia control.

Now moving away from that, we spoke about two of the pivotal neuroprotective trials, which were unfortunately unsuccessful but still very positive in terms of symptomatic benefit. We spoke about surgical management. Other areas of focus are the holistic approach to managing Parkinson's symptoms, and that includes evaluating lifestyle strategies, including nutrition and exercise, which we're going to focus on a bit.

This is a study from 2017 from Dr. Laurie Mischley, and it's a self-report scale. Patients completed this scale at different intervals during the study and at baseline, noting the quantities of how much of each of these food types they consumed during the 12-week study and beyond. There was an extension phase as well, correlating that to quality of life and functional symptoms measured by something called a PRO-PD score.

This PRO-PD score looks at different complexes of symptoms. It looks at overall motor function, like tremor, fine motor dexterity and balance. It looks at cognitive scores from a subjective standpoint — so how patients and their caregivers feel like they're doing — including energy, and then non-motor symptoms as well.

Dr. Joash Lazarus 00:20:45
You notice that I'm including really the positive symptoms here. A lot of these components that fall under the Mediterranean diet had a significant p-value, so had a positive impact in patients' function as self-reported at the 12-week and six-week mark. It's growing evidence, which had been established previously, of the benefits of the constituents of a Mediterranean diet in symptom control.

Again, the manner in which the study was done may not have been robust enough to look specifically at neuroprotection or disease progression in the way we think of it from a preclinical scientific basis. But in terms of patient-reported outcomes, patients basically felt better and did better at a time point of 12 weeks, which is very reassuring and something we can definitely use on a clinical basis.

We spoke about medications to begin with, and we tried to broaden our approach into how we look at therapeutic modalities in Parkinson's disease. By beginning with that, we really focused on a couple of things. The medications are very often very specific, but they're very effective in dealing with the neurotransmitter and the biochemical dysregulation that occurs in Parkinson's. DBS is really very exquisitely effective in terms of targeting circuitry that's involved in both symptoms and side effects.

In doing so, both of those can help to modulate behaviors, and motor behaviors being the predominant target here — things like tremor, mobility and overall global motor function. But this is a bidirectional circuitry, a bidirectional relationship. Patients' adaptive motor behavior can also have an impact on the circuitry, on general brain health and possibly on the neurotransmitters and different synapses as well.

When we look at other lifestyle changes, one that has recurred across the literature for neurodegenerative disease has been exercise.

Of course, trying to summarize a plethora of research findings here, a take-home point from much of that literature is that exercise has what we call pleiotropic benefits. It has benefits that extend to more than just one circuit in the brain that may be relevant for Parkinson's, and more than just a couple of neurotransmitters. It really has diverse benefits that we'll go into on a clinical basis, and diverse benefits on brain health as a whole, as well as a behavioral health perspective.

But let's stop before we get to the clinic and before we get to patients. What about any evidence or any proof that this actually works in Parkinson's disease? Here's a summary, and this is a very brief synopsis of a wealth of evidence that's been done in the lab looking at different lab models of Parkinson's disease. There are rodent models, and there are primate models as well.

Dr. Joash Lazarus 00:23:15
For example, there have been studies by Gerecke et al. that showed that, in a specific animal model, those that were forced to do high-intensity exercise, when you induce Parkinson's in these animals using a toxin called MPTP, the amount of damage that was incurred in those animals was less than in the lab rats that were not forced to exercise, basically. Exercise could modulate the amount of MPTP-induced damage. We know that this concept right here, neurotoxin-induced damage, is often used as a disease model, as a surrogate to try to understand the disease process in humans as well.

In a similar type of experimental design, it was shown that dopaminergic balance and glutamatergic balance in the striatum were restored somewhat. What that basically means is that we know in Parkinson's you lose some dopamine; that's one of the messengers for movement. In some of the circuits that overlay Parkinson's, there's an excess of another messenger called glutamate. That balance is disrupted.

Glutamate excessively can cause some of the tremor or lead to some of the downstream consequences that result in things like tremor and dyskinesia. Restoring the balance between the two may, down the line, help to open up avenues in which we can understand and maybe manage those symptoms a little bit better.

A more consistent finding across both animal and clinical data is that certain neurotrophic factors, certain proteins and certain molecules in the brain after exercise are upregulated. They're expressed to a higher degree, so you have higher levels of them. One of those is called BDNF, which I will speak about later. All of these are really on the molecular level, even within individual cells as well.

Mitochondrial dysfunction and oxidative stress are things where, with time and exposure to different stresses, the power plant, the energy supply to the neurons of the brain, becomes dysfunctional. Exercise has a means of trying to reduce that damage within models that try to replicate the Parkinson's disease process.

The benefits of exercise are seen across the age spectrum, of course, but also in elderly patients. Here's some of the reasons why. One of the biggest unmet needs in the clinical practice of Parkinson's is, of course, falls and trying to prevent falls. They're very common not just in the PD population or in the geriatric population as a whole, but in PD patients, the fall frequency is about three times that of the general population on an annual basis, and half of them can result in a major injury. Of course, the number of falls doesn't really matter on a personal level if you have one severe fall. Preventing that is really at the top of the list of the healthcare demands in terms of movement disorders.

If you quantify the cost to the healthcare system in fall-related injuries, they're one of the leading causes of morbidity and downstream consequences, like the loss of independence and the increased healthcare costs that emanate from them. Preventing falls in the elderly, and especially in this subpopulation with neurological disorders, has naturally become a priority in a lot of healthcare systems. Exercise is one possible solution to that.

Dr. Joash Lazarus 00:26:11
It does that through a number of different targets. It's really well known how exercise has good benefits for the heart, so in preventing cardiovascular complications. We also now know that it can slow down osteoporosis. In general, it can improve cognitive function and prevent things like depression and anxiety, things that have become even more prevalent with the pandemic. Those can have rebound effects on sleep and energy as a whole.

If you look at the last three or four bullet points here, these are all non-motor symptoms that are even better represented, even more common in the Parkinson's disease population, and so could be of relevance here in terms of how we manage them. Things like constipation and fatigue, we know that they are not uncommon among PD patients. Overall functional motor performance — that's the hallmark of the disease process that we're trying to manage.

Specifically, what has been done in Parkinson's? How do we know the relevance of the overlap between the two? There is this suspicion that those populations that have a higher exposure to exercise have improved drug efficacy. Also, optimization of dopaminergic transmission, meaning that dopamine that's there, with or without improving the levels of dopamine, the efficacy with which it's used could be better, and some suspicion of neuroprotection, which we had spoken about briefly previously, that I'll go into in the next couple of slides.

What about those pleiotropic effects that I mentioned before? Exercise improves brain function in many ways. We know that it improves cardiac function and, of course, lung function, and in doing so, it can really have a positive impact on overall motor function, attention and cognitive processing speed. We know that aerobic exercise specifically has very well-described benefits and characteristics in neurocognitive profiling.

Patients who are involved in aerobic exercise on a frequent basis, compared to those who are involved in other forms of exercise, really show benefit in terms of attention and executive function — things like multitasking, for example — as well as memory. Even in those with a specific disease process, not necessarily Parkinson's, but this study looked at Alzheimer's, those aspects were improved: memory and executive function. Those are hallmark dysfunctional areas in patients with Alzheimer's. As expected, with it, so did their balance.

Dr. Joash Lazarus 00:28:40
If you look at non-neurologic patients, so patients who don't necessarily have the title of the process of a neurologic disease, patients with depression also show benefit from this, in that their working memory, processing speed and a certain type of learning or memory called visual learning were improved. Even though these are different patient populations, they share a lot of characteristics and challenges that characterize the Parkinson's disease process. It is very interesting to look at whether this could help the PD population in general.

If you look at cognitive functioning, one of the hallmark features of cognitive dysfunction in PD is a frontal cognitive dysfunction and something we call mild cognitive impairment. Essentially, things like multitasking and processing speed are affected. We know that, in terms of cognitive dysfunction, it correlates, it tends to go hand in hand, with some of the gait dysfunctions and balance impairments that happen in patients with PD.

If you had to characterize from a lab basis how patients with Parkinson's mobility and walking change, a consistent theme is that their speed and the quality of gait are negatively impacted early, but also negatively impacted even more by a dual-task activity. What that means is that if you had to give a patient a cognitive task — count backward, tell me the months of the year — and a gait task at the same time, that it becomes almost overbearing at times, and you can unmask deficiencies, you can unmask problems in a gait pattern.

Dual tasking is a good lab-based technique to separate out gait and balance dysfunction, but it's also a very good target in terms of rehab programs to try to address some of the dissonance that we see in Parkinson's disease. A better way to think of that is that in PD, because the multitasking and executive function aspects can be very prominently affected early on, things like walking, which were previously on autopilot, now become very conscious, and you really have to think about your movements. You have to be purposeful about them in order to prevent falls or in order to be effective in doing so.

Even more concerning, often, is that performing more than one task at a time can lead to falls. Often, this is impossible to ignore.

Downstream, the longer-term effects of exercise on Parkinson's are well established in terms of the degree of disability. The two pyramids are very similar in content here, but the size of them differs. If you compare the pyramid on the left, for example, it's a group of patients — a simulated group of patients — without exercise. Those on the right, you notice that the second or the top portion of the pyramid is smaller in the group on exercise. That's meant to communicate that all the secondary disability that's derived from Parkinson's is often attenuated with exercise in comparison to a group of patients who do not have that.

What do I mean by primary and secondary disability? We think about the disability that emanates from direct symptoms of Parkinson's as being a primary one. So the slowness or the stiffness, more commonly the tremor, dyskinesia and postural instability, cause a lot of disability in patients. But even in mild primary dysfunction, long-term consequences of that include things like deconditioning, a loss of muscle strength and muscle bulk, some proximal weakness and contractures. Those are all complications of long-term primary symptoms of Parkinson's.

Dr. Joash Lazarus 00:32:12
There's good evidence to show that early exercise and an appropriate amount and type of exercise can attenuate not just the primary disability, but the degree of secondary disability and its impact. This data was from a group of patients who had stage 3 PD, so symptoms on both sides of the body and were already starting to have some balance and gait problems.

We spoke about the generic effect in which exercise can improve brain function in the general population, Alzheimer's, the elderly population and even patients with depression. But we also know that, in both healthy adults and in PD, one of the molecular changes we mentioned was an increase in BDNF, which may be neuroprotective.

How do we provoke those changes, possibly? Although not done in the same study, if you aggregate the clinical data that has been done to date, we notice that moderate-intensity aerobic exercise at least three times a week, of about an hour duration, has a positive impact on executive function. We know that things like resistance exercise of slightly longer duration twice a week can improve not just executive function, but also working memory and attention.

More recently, there was a large randomized controlled trial of high-intensity exercise looking at two possibilities, either very high intensity — 80% to 85% of maximum heart rate — or more moderate intensity, 60% to 65%. That improved mobility compared to either the moderate intensity or just usual care with medications or physical therapy.

It's a lot to take in, but I will summarize the types of exercise that I think are very practical and the benefits they do have. If you have to sum this up, there's really good evidence that early exercise of moderate or severe intensities — so high-intensity exercise frequently — has a good benefit on cognitive function and mobility in Parkinson's. And that this vigorous exercise, because of the data that we have to date, appears to maybe have a neuroprotective impact, not just covering up the symptoms. We’ve shown that it has a symptomatic benefit and a quality-of-life benefit, but potentially, it could impact the process as well. The evidence for that, of course, comes from people with PD who had regular exercise and had less cognitive decline after one year in a study that was published in 2016. The proof of that will have to be shown in a long-term study that’s prospective, where we look ahead and randomize two groups, like was done in the two medication trials and in the DBS study we discussed earlier.

But this was a really interesting study published in 2018 called the SPARX study. It was a national, randomized, single-blind study. Here, patients were divided into usual care, in which they were really treated with optimized medical therapy. A third of them actually had DBS as well. A second group had moderate-intensity exercise, so the exercise programs were geared toward elevating the heart rate to about 60 to 65% of expected maximum heart rate, which is age-dependent. And, of course, a third group was to elevate the heart rate to between 80 and 85%. The outcome we looked at here was the degree of motor symptoms, that UPDRS score again, at around the six-month mark.

You can see that those who had the highest-intensity exercise had no change at all in the UPDRS score. Those who had moderate intensity had a smaller change, and it was the group that had usual care, the clinically standard of care, that had the highest change in overall symptom severity. This helped establish the case for high-intensity exercise as being really effective early and throughout the spectrum of Parkinson’s disease. There’s another study following up on this called the SPARX3 study, which is the first and largest randomized, double-blinded controlled study in which patients will be randomized to these two groups or just optimal care.

Dr. Joash Lazarus 00:35:53
Apart from just the UPDRS score, a DaTscan will also be used to look at the actual dopamine transporters in the brain, and spinal taps will be done to look at inflammation and the degree of inflammation in the brain as well. So a number of different outcomes are being used. But in addition to pure clinical trials, which provide really good information about whether an intervention is effective, there’s also registry data that we have looked at. This study, for example, included 4,886 people with PD, and almost half of them, 44%, did more than 150 minutes of exercise a week, compared to a fifth of them who did less than that, and 36% who did no exercise.

The important findings to summarize here are that the group of patients who did regular exercise did better in terms of overall physical function. They had less depression, as measured by really well-validated scales, and overall, a better quality of life at the one-year mark. More importantly, compared to those who had poor physical activity at baseline, there was improved cognitive function, which was objectively measured, and also better quality of life, mobility and physical factors one year later. So not only did exercise matter, but the take-home point from this registry data was that the dose matters as well, much like when we talk about medication regimens and brain stimulation, for example.

So we started with a general template and the state of affairs right now as to how we approach a newly diagnosed Parkinson’s patient and how we try to be as comprehensive as we can. But one caveat was that we kind of relegated complementary therapies and things like exercise to later on, after optimizing medication management. Based on the growing body of literature and really good studies that have been done now, it’s provided good impetus for us to institute that much earlier on. There’s good evidence to show that, number one, dose matters, but timing also matters.

Dr. Joash Lazarus 00:37:44
Early high-intensity exercise is definitely going to have a benefit whichever way we phrase that, both in a symptomatic sense — in terms of day-to-day functioning, how patients are feeling and how their experience of disability and function progresses over time — and even more excitingly, the possibility that it could actually attenuate the disease process, which several studies are looking at validating or establishing right now. Moving forward, this is definitely something that will enter our conversations on a clinical basis as to whether, what mechanisms and in what way exercise and different physical therapy programs impact the disease process as a whole.

Putting everything into context, we spoke about how different forms of exercise have been evaluated. They all, as a whole, have some form of benefit across differing subsets of cognitive function, motor function and non-motor function. It’s hard to kind of distill together, but as a summary, a total of 150 minutes per week has been shown to have really good benefit in Parkinson’s patients, and to really get the heart rate elevated. So the high-intensity group, those patients who got their heart rate up to between 80 and 85% of the maximum heart rate, generally did better.

Of course, it’s hard to measure that without equipment or a heart rate monitor, but you’ve got to get a good sweat and get the heart rate up, to feel kind of fatigued at the end of the workout. If you get a total of 150 minutes a week, there’s good reason to believe that’s going to have a positive impact on the disease process. But at the very least, we know without a doubt that it shows some really good benefit in controlling symptoms in Parkinson’s disease. I know there’s a lot of information to go through. I want to leave plenty of time for questions, and I’m happy to take any questions now.

Dr. James Beck 00:39:32
Thanks, Dr. Lazarus. That was a great presentation. I appreciate you giving this information about the importance of exercise in helping to moderate Parkinson’s disease symptoms, even though it may not be clear that it may be stopping the disease directly. But certainly, I think improved quality of life is going to be critical and maybe difficult to disambiguate — significant changes in quality of life and function versus actually stopping the disease, I would suspect. Speaking of that, Joe and Amy have a question that I think is a real fundamental one that many people in the Parkinson’s community hear: What’s the difference between neuroprotection and neurorestoration? I don’t know if you could define that for us.

Dr. Joash Lazarus 00:40:24
Sure. That’s a really good question to try to distinguish, and there’s a lot of overlap between them. Unfortunately, the process involved in Parkinson’s, and the reason we call it a neurodegenerative disease, is that its natural history, its expectation, is that those processes will continue to evolve. It’ll get worse. The changes we see in the brain will get worse. The dopaminergic neurons will die off, essentially, and degenerate, and you’ll have less dopamine. The goal of neuroprotection is to slow that process down, to slow down the rate at which that area of the brain degenerates, the rate at which dopamine is lost, potentially to stop it if possible.

Neurorestoration would be to try to restore, to get back to baseline, the function that was lost. So while a therapy like exercise, for example, may actually slow down that process in the brain, it may not bring a patient back to where they were before the diagnosis, or two or three years ago.

Now, DBS is interesting. DBS has some of the neurorestorative features from a patient perspective because it can completely control tremor and improve their function to close to baseline, nearer to baseline or even baseline levels. But it would be interesting to see whether that overlaps with a neuroprotective mechanism, preventing things from getting worse.

Dr. James Beck 00:41:42
Yeah, absolutely. You bring up an interesting point about DBS, and you highlighted some of the potential benefits of it, especially for people considering it earlier than later. How do you advise your patients to consider DBS? I think in the U.S., a lot of people have had Parkinson’s a while before they get DBS, I understand.

Do you see a trend for people going earlier? I know there have been studies, and you highlighted some of it, but would that be out of the mainstream? Could you say to someone who’s been newly diagnosed and who has a tremor — and this is kind of along the lines of the question that Linda asked — let’s start with DBS? Has that ever crossed your mind, or where does that fit in the recommendations within your practice and your colleagues?

Dr. Joash Lazarus 00:42:40
That’s a great question. When I presented the data early on, the approach I highlighted was the potential positive impact of early DBS, and we defined that as less than four or five years, at the FDA level four years. I’m actually going to take a different approach right now. In the clinic, we really want to focus on interventions and timing that are well established. By well established, I mean a meta-analysis, several years, a decade of research that’s been replicated. We know that it’s very safe and it’s very effective.

When you boil DBS down to those characteristics, which you should because it is a major intervention, then the best approach to take is a minimum of four or five years after symptom onset, and I’ll explain why in a second, and for symptoms that are not adequately controlled with medication. The reason for that is because DBS essentially does exactly what levodopa does without the complications, so with less dyskinesia or no dyskinesia, hopefully, and without the wearing off. So instead of the medication dipping three or four hours later, you have a more consistent response.

But it shouldn’t give you any more benefit than levodopa, with the exception of tremor. Tremor is one symptom where patients who don’t respond to levodopa can rarely respond to DBS surgery. The reason I wanted to emphasize the importance of the timeline being four or five years is that there’s a group of disorders that we call atypical parkinsonism. Without being too detailed here, things like Lewy body dementia can often be hidden in the background of a Parkinson’s disease diagnosis. There are other cousin disorders, related disorders of Parkinson’s, that behave in a different way. Some of them are a different protein that may or may not respond as well to levodopa.

Dr. Joash Lazarus 00:44:24
But the important thing is they all take a different trajectory. They do not respond as well, from what we know, to DBS. Some of them may actually get a little bit worse. It’s important for us to have a good handle on what the exact diagnosis is, and it really becomes apparent around the four- or five-year mark. Patients who looked a lot like Parkinson’s disease after three and a half or four years may unfortunately develop balance problems or problems with vision that point to something called PSP, and those are patients who would not respond to DBS based on current literature. The same is true of Lewy body dementia. Patients may develop hallucinations or cognitive issues.

Jumping the gun and going for DBS too early may unfortunately include patients who will actually do negatively from DBS, number one. And number two, you probably would get very good benefit from medication management for the first four or five years. You won’t see a benefit in terms of quality of life, and that’s the goal — function, quality of life and disability reduction — within the first few years. It’s something I don’t typically broach until that point is reached.

Dr. James Beck 00:45:28
Yeah, understood. It seems like the safer and better approach is to wait because, as we all know, Parkinson’s disease is not a disease where you get a blood test or brain scan and you have PD for certain. Many people in our community have that frustration, and I’m sure you do too, trying to confirm someone’s diagnosis is exactly Parkinson’s and finding the best therapies for them as part of that process.

One last question about DBS. Does it impact other parkinsonian symptoms? People, I think, would certainly hope it would help with stiffness and the rigidity that people experience. What about freezing of gait? Does it help with that? Or any issues with cognition, fogginess? Does it help or hurt?

Dr. Joash Lazarus 00:46:21
The best way to separate the symptoms is kind of motor symptoms, or movement symptoms, and non-motor symptoms. If you look at the motor symptoms, DBS is absolutely, exquisitely effective for tremor and for dyskinesia. Those, without a doubt, generally get very much better and can improve to the point where patients’ function gets better, they’re much happier and they’re doing overall much better from a disability standpoint. Freezing is a little more complicated. The best way to summarize it — it’s an overly simplistic answer, but the best way to look at it — is that if those episodes of freezing get better with levodopa dosing, we call it dopa-responsive, then there’s a good likelihood they would also get better with DBS surgery.

But often, unfortunately, a small group of patients can have freezing even when they’re on. So even when they take the levodopa and the tremor is controlled, and the medicine is kicking in at a high dose, they still freeze. Chances are those episodes of freezing do not get better with DBS, and depending on the frequency, how often they’re happening and how bad the freezing is, that may not be the best treatment option for that patient at that time because they may not see a benefit if they still feel freezing.

The non-motor symptoms are also very interesting. Most of the DBS studies, the outcomes that were followed, in other words what they were targeting, were the motor dysfunction, the very visible symptoms. As a rule of thumb, we always say we don’t try to address the non-motor symptoms with DBS as a whole. In other words, if patients are suffering from depression, we wouldn’t go to DBS as a targeted therapy.

Dr. Joash Lazarus 00:47:55
It is, however, very safe. In the beginning, we would follow very closely cognitive function and mood function, so depression and hallucinations. As exclusionary criteria, we had a kind of high threshold. If patients had a minimal amount of cognitive dysfunction or depression, we would try to lean them away from DBS, but it’s become very clear over the last decade that from a cognitive standpoint, DBS is very safe, especially in patients who have relatively well-preserved cognition. From a mood standpoint, it may not worsen depression, which can be controlled with medication management.

Completely off topic, DBS has also been studied extensively now as a primary therapy for depression, other mood disorders like obsessive-compulsive disorder and even for addiction. Different areas of the brain, different disorders entirely, but just something to look out for.

Dr. James Beck 00:48:35
Interesting. A tool can be used for many issues when it comes to the brain. Moving on to some other questions regarding exercise, I think a person with Parkinson’s wants to know which might be more effective for slowing PD progression: medications, pharmacology or exercise?

I would hazard, from what we just talked about today, to say nothing is really slowing progression that we can definitively say, but it seems like you’re making a good case that exercise is probably one of our best bets.

Dr. Joash Lazarus 00:49:17
Yeah, and I don’t want to phrase it as an either-or paradigm. Many patients will only see the benefits of exercise — in fact, the majority of them — if they reach the high-intensity level, which, if you strictly define it, is 60 to 65% of your heart rate. You’ve really got to get sweating. In order to do that, for a patient with tremor or freezing, it’s only going to be possible if you’re on a good dose of medicine to allow you to reach that. The motor problems really hold back your performance in a workout or in a physical therapy session.

So it’s really the combination that proves best, and that combination is individually determined. Optimal drug therapy in all those studies that are highlighted — there’s no specific dose or frequency that we can reference because it’s really dependent on the patient. The ultimate best treatment strategy is a combination of the two. But I would say that, regardless of the status of the patient, any Parkinson’s patient should include some form of mobility protocol, either exercise, physical therapy or both. And that’s regardless of how much disability you’re starting with, what stage of Parkinson’s you have, whether you have symptoms or not, really. It’s a more consistent form of intervention that we should emphasize a little bit more frequently, I feel.

Whereas the pharmacotherapy tends to be a little, for lack of another word, niche, in that there are certain circumstances, certain very targeted goals and certain targeted effects that we would follow and think of.

Dr. James Beck 00:50:43
Yeah, absolutely. I think your slide was really appropriate. It’s a prescription for exercise, right? And like other medications, you have to take it on a regular basis in order to see an effect.

I guess it gets to the question we’re seeing: the two different heart rates that you suggested from the SPARX study, and there’s a phase three trial I think that’s going to be recruiting soon for that. Do you think there’s a dose response for exercise? When we talk about intense, as you said, 60%, maybe 80%, is that sufficient? And do you have to be on a bike, or is it just a matter of working hard to get your heart rate up?

Dr. Joash Lazarus 00:51:26
Great question. From the first SPARX study, it looks like there is a dose response. It looks like dose in terms of heart rate and total duration more than exercise duration per session, for example. That’s very practically hard to break down. How do you establish a really good dose response? Well, that’s the purpose of SPARX3, which is randomized and placebo controlled. In other patients, it’s been shown that if you get the heart rate up to 80 to 85%, some of the molecular changes — that molecule BDNF in the brain that we spoke about — the amount is increased thereafter.

In healthy studies, there was a new study in healthy athletes, actually, that if you reach that heart rate for as low as 10 to 12 minutes, you can trigger an increase in the BDNF. Then it didn’t matter whether you exercised for 12 minutes, 40 minutes or 50 minutes; the impact on the brain was still beneficial after 10 to 12 minutes. It wasn’t a dose-response curve in terms of time or duration. It was in terms of volume of BDNF, which is intensity. We’re not sure if the same is true or applicable in Parkinson’s, but this study will tell us because we’re segregating both based on heart rate and duration, and different measures.

So it’ll be interesting to see whether it’s purely a function of how hard you work and how much you sweat, or if it’s a question of how long each session is, or both. Does it really matter what type of exercise? Is it a question of stressing the cardiac system enough because this is just a good surrogate of how well the workout is doing? Or, as we pointed out in multitasking and dual tasking, do workouts that include a cognitive task — a great example of that are boxing workouts, and there are several that are well established in Parkinson’s — confer their benefit because of this dual-tasking component more than just getting the heart rate up? There are so many questions to really look at.

Dr. Joash Lazarus 00:53:12
But the takeaway message I think is really important for patients is consistency is the key. Just like consistency for medication dosing, at least three to four times a week and at least 150 minutes, and to stick to something that you really enjoy because that’s really the only way for any of us to be consistent with an exercise program.

Dr. James Beck 00:53:29
Okay, great. I see we’ve got a couple more minutes of your time before I know you have to go and before we’ll have to go on to the closing slides. So let me just ask some quick questions, if I may. Maybe this is not so quick, but Chance asks, how do you exercise when you have problems with balance and you have a risk of falling down? Related to that, should you go to a physical therapist, or should a doctor prescribe your exercise regimen?

Dr. Joash Lazarus 00:53:58
That’s an excellent question. I would say that physical therapists are the experts right now in doing that. It’s an aspect of medicine, an aspect of neurology, that’s been neglected. I’ll honestly admit that even as physicians, we have so many constraints and our focus is often narrowly geared toward the medications, surgery and aspects like that. Physical therapists, especially those who are BIG therapy-certified, are really good at structuring a mobility program. I say mobility because it’s either therapy or then the transition from therapy to exercise.

That’s a very good question because the risk of falling is high, and in high-intensity or stressful exercise it’s going to be even higher. So having guided therapy leading into guided exercise programs is a great way to do that. There’s a paucity of really guided, assistance-driven exercise programs right now. In fact, the Parkinson’s Foundation has an accreditation process that was recently established to look at a couple of boxing programs. One of the criteria there is that there are enough assistants and enough trained, certified help to prevent patients from falling, which means it can cater to more disabled patients, those with a greater degree of motor dysfunction, those who are prone to fall. Expanding our avenue to look at programs like this and expanding access to programs like this is going to be really great.

Dr. James Beck 00:55:17
Fantastic. Two quick questions, and I think I know the answers, but does DBS make exercise more difficult?

Dr. Joash Lazarus 00:55:24
No. It really should make things better, and that’s a good point because it should not exclude exercise. DBS is not this magic bullet to control DBS. It really should draw attention to maximizing our function. So don’t stop exercising after DBS. If anything, really evaluate your exercise program to maximize how much you can do.

Dr. James Beck 00:55:47
And then the last one before you go, and again thank you for your time. It sounds like if someone is able to exercise and get involved in their program, they might be able to alter their medication doses with the help of a physician. Is that what you would expect, where symptoms seem to be better under control and they can then adjust perhaps their medication dosage?

Dr. Joash Lazarus 00:56:09
Absolutely. One of the studies, when you follow patients for six months, those who did consistent exercise either stayed on the same dose or had fewer increases in medication. Our tendency as neurologists, and not just neurologists but as a medical fraternity, is to add medications on, not necessarily take them off. But I think that we can see more and more instances, with things like surgery for sure, but with more comprehensive physical therapy and complementary therapies, that if you have an MDS specialist who’s really attuned to your experience, it’s very possible to start coming down off the medications like we see in other consequences of exercise-related health benefits. Insulin doses gradually decrease.

People come off their cholesterol medicines. High blood pressure medication decreases. Those are all chronic illnesses that are modulated in one way or another by exercise. We said exercise has pleiotropic benefits, including the brain. There’s no reason not to be optimistic that we can at least consolidate, when patients who are on three or four different Parkinson’s medicines will have less wearing off now because of exercise and may not need an adjunctive injection or something like a COMT inhibitor. Those, I think, are very positive goals to aim for.

Dr. James Beck 00:57:16
That’s fantastic. Exercise is the rising tide that raises all boats. Dr. Joash Lazarus, thank you very much for your time.

I really appreciate it. And I want to thank everyone here as well for their time and the audience for listening. I also want to thank again our sponsors, Genentech, the Light of Day Foundation and Kyowa Kirin, as part of that.

On our next slide, we show that we’ve knocked out three of our expert briefings so far this year. We’ve got three more to go. We’ll be taking a bit of a break as we move over the summer and get ready for the impact of physical activity with Dr. Miriam Rafferty in September. But we’ll certainly be thinking about questions that may come in, and we’re here to help as part of that.

We have lots of resources and supports. The Aware in Care kit is fantastic for those who may be going to the hospital, just to help communicate their needs within the hospital setting. We have our library resources as well, of course, as our regular presentations on PD Health @ Home for everyone there. We also have other resources for people who like podcasts: Substantial Matters. I encourage everyone to listen in. For the few professionals I saw who joined us today, we have opportunities for CME. The Foundation is now providing accredited education units for clinicians. We have CMEs and CEUs as well.

And at last, I always encourage people to think about participating in PD GENEration. It’s an opportunity to get an understanding of whether you have a genetic risk, a genetic form of Parkinson’s disease. It’s rare, but this is the first step to knowing and having the potential to participate in clinical trials, which I think will be coming, targeting those with genetic forms of Parkinson’s disease.

Dr. James Beck 00:59:19
Last, we’re here for you in case you have any questions: Parkinson.org, 24/7. We have our 800 number, 1-800-4PD-INFO. We’ve got colleagues standing by who are very experienced at helping to answer questions. If you prefer, you can send it by email Helpline@Parkinson.org.

But before we go, I just wanted to say that your feedback is always important for us. When this Zoom call abruptly stops, a window will pop up on your browser, giving you an opportunity to provide feedback for this webinar. We certainly utilize it, and we share it with our speaker as well. So please take the time to give us some feedback on your thoughts about this expert briefing evaluation.

I wish everyone a good Parkinson’s Awareness Month in April and look forward to seeing everyone at the next presentation come September. Until then, take care.

Dr. James Beck 00:00:11
Hello everyone, and welcome to our new season of the Parkinson's Foundation Expert Briefing Series. I'm Dr. James Beck, the Chief Scientific Officer of the Parkinson's Foundation. Today, I'm delighted to welcome you to our winter/spring series for 2021. This past year, my colleagues at the Foundation have produced a number of excellent online educational opportunities for everyone in the Parkinson's community. Our Expert Briefing Series today is no exception. The series for this winter and spring is devoted to the issue of PD symptom management, where we ask the question: Is it Parkinson's, is it medication, or is it aging?

Today is the first of three webinars in this series where we will dive deeper into this theme. Today's expert briefing will highlight the question of motor symptoms. As always, we want to bring useful information to our audience, and our presenters will be discussing a co-management strategy between occupational therapy and neurology. But before we begin, I want to share some exciting news and a new option for how to listen to our Expert Briefing Series. Starting with today's webinar, we will be making our Expert Briefing Series available in Spanish on our YouTube channel, Canal en Español.

It takes about four weeks for our team to get the translation ready to view, but keep an eye out for being able to listen to this in Spanish. Let's take care of some housekeeping. First, let me share with you how to navigate around the screen. Many of you are familiar with Zoom, but just a reminder that if you want to ask a question, you'll go to the Q&A in the lower right-hand corner. Also, you'll see as part of the chat, my colleague Camelia will push information on how to, for instance, download the slides. Look into the chat, and there'll be a link there on how to download the slides.

You can look at them as we discuss them today or save them for later reference. Also, if you are an allied health professional and are interested in taking this and listening to this expert briefing for continuing education credits, you can receive free CEUs for watching this webinar. There's a link here also in the chat on how to do that. You're eligible for one free CEU from the American Society on Aging for viewing this webinar. Click on the link now and it'll open up in another window. This will be your way to register and get your CEU.

We'll also be sending an email later to follow up on this. And if you're looking for a CEU, remember you have 30 days, and that's until March 9, 2021, to collect this free CEU.

As always, this Expert Briefing Series has been recorded, and it's going to be available on demand later this week. All those registered for today's webinar will receive an email with that link as well. So if you didn't catch everything that's going to be provided today by our presenters, you can go back and watch again or let your friends know about it as well. Right now, I want to ask everybody where they're from. We're going to put a poll available on the screen to ask who you are. Just take a moment to fill out this poll to see what your relationship to Parkinson's disease is as part of this process.

Give people a few moments to do so. If you're following us on Facebook Live, go in and type in where you're from, and we can keep track of that as well.

Okay. We're waiting for people to come in. We got the results. We've got most of the people in here are people who are living with Parkinson's disease, which is great, and a lot of their spouses and partners. About 10% of the people here are healthcare professionals. That's really fantastic. Really looking forward to providing some useful information to everyone as part of that.

Dr. James Beck 00:04:02
Let's get on with today's topic. As part of our symptom management series, with motor symptoms and co-management, occupational therapy and neurology, we'll be hearing not only from our expert presenters, Dr. Michael Okun and Lisa Warren, but also from Gretchen Rosswurm, who chairs our Parkinson's Foundation People with Parkinson's Council. We have them on the screen. Let me just give you a little bit of background about each of our presenters.

Dr. Okun is the executive director of the Norman Fixel Institute for Neurologic Diseases at the University of Florida, and he also chairs its department of neurology. He is the co-director of the US Center for Movement Disorders and Neurorestoration. Dr. Okun is a friend of ours and has been long dedicated to the interdisciplinary care concept that the Parkinson's Foundation champions through our Center of Excellence program. He currently serves as our national medical advisor and has worked closely with our 43 national and international Parkinson's Foundation Centers of Excellence to help really foster the best possible environments for care, research and outreach to the Parkinson's community.

He focuses on Parkinson's disease, dystonia, Tourette's and movement disorders in general.

Ms. Warren is an occupational therapist and rehabilitation manager at the Norman Fixel Institute for Neurologic Diseases, also in Gainesville, Florida. She has participated on a number of expert panels at the World Parkinson's Congress, co-authored posters that have been presented at major neurology conferences, and has provided Parkinson's treatment lectures at the local and international level. She has been a contributing author in the ongoing research on Parkinson's care. We're happy to have her today.

Gretchen Rosswurm, as I mentioned, is chair of our Parkinson's Council. She was diagnosed with PD in 2017 at the age of 52. Her commitment to the Parkinson's community really springs from a deep history of PD in her family, while at the same time believing that what seems as an impossible challenge that many people with Parkinson's face creates an opportunity for connection, healing and hope. Professionally, Gretchen's work experience centers around corporate philanthropy. She also blogs and writes some short fiction.

She lives in Dallas with her family and joined our Parkinson's Council in 2018 and was elected as chair this past year in 2020. It's my pleasure to welcome them each to our presentation. I will turn it over to Ms. Warren.

Lisa Warren 00:06:30
Thank you so much, Jim, and thanks to the Parkinson's Foundation for having us on today. Hi, everyone.

My name is Lisa Warren, and thank you for joining us. We hope to share some information with you today that maybe makes your lives a little bit easier if you're living with Parkinson's, or helps those of you who work in this field or have loved ones with Parkinson's. Hopefully, we help you to better understand the lives of those living with Parkinson's.

These are disclosures of Dr. Okun's National Institutes of Health research.

Our learning objectives today, what we're going to talk about, are the four motor symptoms most often associated with Parkinson's. By motor symptoms, we often mean movement symptoms. We hope to help you learn new strategies for managing these symptoms, and participants will learn how the physician, the therapist and the person with Parkinson's can integrate all the recommendations that you're given for better function and, hopefully, an improved quality of life.

We'll get started. The four cardinal motor symptoms of Parkinson's are listed here on the screen. Again, these are often referred to as the movement symptoms, the motor symptoms of Parkinson's. Tremor, which is shakiness, often we see that in our hands. It can be in the legs, can be in the chin, can be in all of the above. Bradykinesia, that's just a fancy word for slowness. Slowness of movement is also considered a motor symptom of Parkinson's.

Rigidity simply means muscle stiffness. That, again, is another one of the cardinal motor symptoms of Parkinson's. And then postural instability, which is balance changes. Your balance may not be quite as good as it was before.

I want to take a poll here quickly. I want you to tell me, vote on what you consider to be the most challenging motor symptom between tremor; bradykinesia, the slowness; muscle rigidity being stiffness; and postural instability being balance difficulty. What do you consider to be the most challenging? If you're joining us by Zoom, you can vote on Zoom. If you're on Facebook Live, you can make comments as to what is your most challenging symptom.

Dr. Okun, while we're getting these votes in, can you tell us what it means, what cardinal symptoms mean?

Dr. Michael Okun 00:09:15
Yeah, it'd be my pleasure, and great to be with you, Lisa, and great to be with you, Gretchen, today. The word cardinal actually is a Latin word that means important. You may have actually heard of four other cardinal things before, and we often refer to the cardinal signs of the zodiac, right? Aries, Cancer, Libra and Capricorn. But when we talk about cardinal symptoms in terms of a disease state such as Parkinson's, usually we're talking about things that help us to make a diagnosis.

Lisa Warren 00:09:52
Terrific. And that was my next question: How do you get diagnosed with Parkinson's? Are these symptoms a big part of what helps you, as a movement disorders neurologist, diagnose someone with Parkinson's?

Dr. Michael Okun 00:10:05
Absolutely. We are keyed in, and these four cardinal symptoms are part of the criteria that we use to try to decide whether we're dealing with somebody who may or may not have Parkinson's, or just has symptoms but may not qualify for a diagnosis of Parkinson's disease. But it all starts here. Now, we're going to be a little bit focused here on what are called motor symptoms.

So movement-related symptoms and stiffness and slowness and postural instability, but we don't want to forget that there are also non-motor symptoms, things like depression, anxiety and sleep deprivation. Although we won't cover those, those can also pop up. And then finally, just to make sure that we're being well-rounded, there are these prodromal symptoms. Some people act out their dreams or have problems with smell or constipation. Today, we're going to focus on the four cardinal, or as we say in Latin, important symptoms of Parkinson's.

Lisa Warren 00:11:12
They are indeed very important. It's interesting on our poll that tremor and postural instability are really neck and neck. There seem to be a few more people that consider postural instability to be more challenging, but tremor is right behind, and then rigidity and the slowness being the least of what you find the most challenging.

Let's start our discussion with tremor. Let's talk about that shakiness that many of you may experience. The majority of folks with tremor with Parkinson's experience this tremor mostly at rest. As I mentioned earlier, it can be shakiness of the hands, the legs, the chin can even tremor. It typically affects one side of the body, at least initially, may very well move to the other side, and it may fluctuate throughout the day. It may be worse at one point, better at another, and from day to day, it's a little bit different.

We talk about what's Parkinson's and what are age-related changes. We don't necessarily consider tremor an age-related change. There are multiple types of tremor that we can experience, but a Parkinson's tremor is a rest tremor that is seen most often when you aren't using your hands. That's why it's called a rest tremor. When you activate the muscles of your hand, it often helps to settle the tremor. Doesn't mean it goes away completely. You can still have a little bit of tremor with movement, but movement tends to help it to suppress or help to suppress the tremor.

Often folks with tremor find it more irritating or fatiguing, more so than actually debilitating, because to use their hands, they often get a little bit of tremor suppression. As I mentioned in the beginning, it often starts on one side of the body but can move to both sides. Then using both hands can become much more challenging if both of your hands are trembling, or more fatiguing, quite honestly, if you're trembling throughout the day.

Dr. Okun, when a person with Parkinson's comes to you and they're telling you that this tremor is really bothersome, what can you as a movement disorders neurologist do to help them with this tremor?

Dr. Michael Okun 00:13:36
Yeah, thank you for the question. We, in general, spend a lot of time actually talking to folks, and that might surprise you to hear in this day and age as we rush people through. But it is super important that we understand your tremor. We understand if it's at rest. We will check to see if it's at rest, as you mentioned. That's the most common for Parkinson's. Sometimes you get a little bit of what's called a postural action tremor when you're intending to do things, and that might change our strategy a little bit.

Some people have tremors from when they're younger, and we need to separate those out and decide: are we dealing with somebody who had a little bit of tremor throughout their life and now they have Parkinson's, or maybe they were put on a medication and got a little bit of tremor? We want to be very sure that we're dealing with Parkinson's. We, of course, want to explore the idea of could we suppress this tremor by using medications or a cocktail of medications. The most common is dopamine replacement pills, sometimes called Sinemet. Sin means without, emet means vomit, so that's why we give both Sinemet together.

There are two components to that pill, and we want to treat the tremor there with dopamine replacement. If you're in Europe, you may have Madopar, which is another formulation of dopamine, and there are others like Rytary. But fundamentally, dopamine replacement is one strategy. We can tickle the receptors in the brain with something called a dopamine agonist, or we can use those in combination together. Of course, we watch out for side effects like passing out, or when you stand up, you get a little light-headed, or perhaps you may start buying a lot of things or shopping a lot on the internet.

We watch for impulse control disorders if we start those or in combination. Some folks will use other medicines occasionally, a medicine called amantadine, not super effective against tremor. Sometimes other medications may add a little bit, like monoamine oxidase inhibitors, but it's mainly those two. If you block a receptor in the brain that's called acetylcholine with drugs that are like Benadryl-like drugs, you can also suppress tremor, but we do that at the price of thinking problems. We try to create our best cocktail of medications to see if we can suppress the tremor.

If we can't do it with medications, then we start thinking about other things like deep brain stimulation.

Lisa Warren 00:16:12
Thank you.

As an occupational therapist, if you go to your OT with this same complaint, one of the things that we're going to discuss is managing your stressors. Your symptoms can increase, especially your tremor, with stressors. We all experience some type of stress. There are emotional stressors and there are physical stressors, and either one can increase your tremor. The emotional stressors being upset, frustrated, anxious, nervous, all the things that we all experience, can certainly increase tremor.

The physical stressors that we talk about are fatigue, being in pain, hungry, those types of things can also increase your tremor. Tremor fluctuates throughout the day. Certainly, managing your stressors to the best of your ability, and your occupational therapist can review some strategies with you. If the medication does help, as Dr. Okun had mentioned earlier, trying to time some of your activities with the medication on time when the medication's working really well. Try to time some of your activities where the tremor's most bothersome to a time when the medication's working.

The other thing that occupational therapists can help you with are adaptive devices. Many folks come into the clinic and have heard about or are interested in weighted utensils, so heavier utensils. My advice on that is try them, because it just depends. If you don't have much tremor with action, these devices may not be that helpful. If you do have more tremor with action, then it could be that they're helpful. So I would say trial some of these things with your occupational therapist before you purchase them. There are special pens.

There are a lot of different things that can help you with your task if tremor is interfering. Gretchen, as someone with Parkinson's, has tremor been a concern of yours or something that you've had to manage?

Gretchen Rosswurm 00:18:38
Yes, definitely.

I think it was one of the things that I first noticed when I thought perhaps there was something going on more than just what I hoped it wouldn't be, I guess. What I'm saying is that was when I thought I had Parkinson's, when I saw the tremor. I had seen that with members of my family, so it's a difficult thing for me. It is a signal that something's wrong, and also really, from my standpoint, I felt very vulnerable, and I still do with the tremor, because it's something that anyone can notice.

I really relate to people who also have a tremor and feel a sense of vulnerability that comes with it. But I also believe I have found ways for myself to improve it every day.

Lisa Warren 00:19:36
Excellent.

That's a really good point because I do hear that quite frequently, that people are a little more self-conscious. Sometimes people are embarrassed by it, but just feel like people may notice the tremor because it is something that you can see. Each of us has come up with a take-home tip on managing tremors. Dr. Okun, if you'll review yours with us.

Dr. Michael Okun 00:20:02
Yes. A couple of points here. First of all, remember that one in five folks with Parkinson's actually don't have tremor. Okay, that's one.

Two, as for the live chat, if you do have a lot of postural action tremor, someone asked on the live chat, that may be something a little different, or sometimes we have subtypes of Parkinson's that mix that in. We might have to use different medicines like beta blockers or anticonvulsants like primidone. Remember that 20% or more, and in some series even more, folks have resistant tremor. That means it's resistant to medications or partially resistant to medications. In these cases, we consider deep brain stimulation.

There's also an FDA-approved therapy called focused ultrasound for one side of the brain that could also be a treatment option.

Lisa Warren 00:20:58
Thank you.

I think that's a really good point, that not everyone with Parkinson's has tremor. I think a lot of folks may not be as aware of that. We associate tremor so closely with Parkinson's, but not everybody does. Unfortunately, the medication doesn't always help with tremor, so that's a really good point. For me, just remembering that tremors fluctuate, managing those stressors, emotional and physical stressors to the best of your ability, can really help to reduce the tremors as well as timing your medication if you're getting benefit from your medication and suppressing tremors.

Gretchen, what would you say as a take-home message?

Gretchen Rosswurm 00:21:40
Well, I've tried a few different things. One is definitely managing stress. For me, that means staying within my body and taking deep breaths, just continually being aware of how I can manage that since the mention of tremor through this deeper breathing in particular. Meditation helps as well. I also meditate a few days a week, and that seems to help. Exercising takes the edge off of anxiety and therefore helps tremors as well.

I think talking with friends about things you might be experiencing that could be causing some anxiety also will help with the tremor. Finally, one of the things that I enjoy doing, for example, is coloring in these adult coloring books. I've noticed I have no tremor when I'm doing that. I think that just really helps me chill out and take my mind somewhere else. By having hobbies, meditating and deep breathing, that helps my tremors quite a bit.

Lisa Warren 00:22:53
I think those are all great strategies. On to our next symptom, the next motor symptom that we're going to talk about is bradykinesia, so slowness of movement. With this, when you're moving slower, everything takes longer. You may have difficulty starting movements. You may have stillness, decreased facial expression, everything may slow down. This is one of those things, too, that as we age, we get a little bit slower. Those without Parkinson's tend to slow down as they age.

When we get older, just in the general population, we often choose accuracy over speed, and often it's a wise decision to be more accurate than to be faster. We do see slowness with everyone, the general population, as we age, but then bradykinesia is a little bit different. This is an exaggerated slowness. Your neurologist or your therapist can watch your speed of movements and really recognize when movements may be abnormally slow for your age. Doctor, when a person with Parkinson's comes to you and they're struggling with the bradykinesia, the slowness of movement, what can you do to help?

Dr. Michael Okun 00:24:09
Yeah, so bradykinesia, as you mentioned, Lisa, brady means slow in many languages, not just in English. Bradipo is a sloth in Italian. We think about these slow movements being some of the most disabling that we see, and sometimes heartbreaking. One of the things that I've kind of picked up over time, been taught by folks that I've seen in the clinic, like Gretchen and others who have taught me, is paying attention not just to the cocktail of the dosages that we give, but paying attention to the timing, because a lot of times there are good hours during the day.

We need to figure out when the good hours are and when the not-so-good hours are. If we can optimize the medicine, sometimes simply by moving them closer together, using cocktails and then trying to create a complementary approach, we can speed people up. This slowness that we get can also affect things like eating at the dinner table, can affect other things in their quality of life. While we're doing medication optimization, we're sending all those patients, all those persons with Parkinson's, to you, Lisa. And then I'll just say, back at you, that one of the questions online was whether you could move a little closer to the microphone and talk a little bit louder.

Lisa Warren 00:25:42
Absolutely. That I can do. All right. Thank you, Dr. Okun.

One of the things that I often share with persons with Parkinson's is slow is not always bad. Now, I know there's an extreme slowness, and that's very frustrating and absolutely affects our quality of life. But moving a little bit slower isn't always a bad thing. Moving at the rate of speed your body's prepared to move at will make you more accurate. As I was saying before, we often will choose accuracy over speed as we age. But one of the best strategies that I have for this is medication timing. If the medication that Dr. Okun is talking about allows you to move a little bit easier, a little bit quicker, certainly make sure your medication is on before you're doing many activities during the day.

Plan extra time for your tasks. It may take you longer to get ready in the morning, so definitely prepare and allow more time, because if you get frustrated and try to rush, then your symptoms may increase, tremor may become worse, those types of things, and it may actually take you longer because you're trying to rush. Gretchen, is this something that you have had to deal with? And if so, what have you found to be helpful?

Gretchen Rosswurm 00:27:00
Yes, I'm familiar with being slower than I'm used to. I find it frustrating. I feel like sometimes a turtle trying to cross the road, and you know how long it takes the turtle to get across the road. But as with this one, we'll talk about it. There are things I think that, at least things I found, have helped me be able to manage some of the bradykinesia fairly well.

Lisa Warren 00:27:28
Okay. Thank you. And so our take-home tips, Dr. Okun?

Dr. Michael Okun 00:27:34
Yeah, one of the things that I always say to folks, and I just got a question about someone having trouble with guitar, is there isn't an exact formula to be successful in Parkinson's. If you're a person with Parkinson's, you have to work with your team to figure that out. One of the things that our team has, over the years, taught me, and the persons with Parkinson's like Gretchen have taught me, is that you have to be flexible.

We've learned that there are some tasks, whether you're a professional athlete or professional musician, if you take a little bit of Sinemet or Madopar or a dopamine replacement like Rytary 30 minutes before the task, you may be able to do better with the task, particularly if it's fine dexterity. That's just a little tip and a little pearl. Of course, you want to make sure you've optimized dose and timing.

Lisa Warren 00:28:32
Absolutely. My take-home is just to allow extra time to accomplish some of those bigger tasks, getting ready in the morning, showering, dressing, those types of things. Gretchen, what would your message be?

Gretchen Rosswurm 00:28:46
One of the things that has helped me a lot is exercise, exercise that is specifically for people with Parkinson's, because this is one of the things that the group that I work with focuses on every time, which is how to increase not only how well we can stretch and fully bring out our arms, for example, but also can we punch? Can we make a quick movement and really focus on working against the bradykinesia? I found that to be really helpful.

I love tossing a ball. I toss a ball almost every day, so that helps me work on my right hand to be able to catch a quick ball that's coming at me. And I mentioned the coloring; that's been good. And mancala is a great thing for bradykinesia as well. Mancala is a very old game that involves taking small pieces of glass, polished glass, and moving it around. Those are the kinds of things that I've been doing with bradykinesia that have helped me fight back.

Lisa Warren 00:29:59
Those are great tips. Great tips. On to our next symptom: rigidity.

Muscle rigidity is muscle stiffness. These two go hand in hand, the bradykinesia and the rigidity, and really work to make life a little more challenging. This is stiffness. It can be throughout the body. It usually occurs on one side, at least initially, will typically move to the other side, and it may cause pain or cramping.

Cramping in Parkinson's, we call that dystonia. It's not unusual to have some toe curling, or a foot turns in, or your hand gets fisted, or around your neck you may have some muscle cramping. You may experience dystonia with your Parkinson's. That is muscle stiffness that makes it really, really difficult to move. When muscles are tight, it takes more effort to move those muscles, and so you fatigue a bit quicker.

You put the same amount of effort into moving a stiff muscle, you're not going to get the same results that you do when you're moving a relaxed muscle. As I mentioned, these can cause pain. Often folks with Parkinson's have low back pain. They can have pain anywhere, quite honestly, but stiff muscles can certainly cause some discomfort. Again, as we age, we associate stiffness with the aging process. More often with aging, we have joint stiffness. But we also lose some flexibility.

It is hard at times to differentiate between what is rigidity related to Parkinson's and what is just age-related stiffness. Your neurologist or your therapist can move you around, move your relaxed arms or legs around, and feel the resistance in the muscle or the lack of laxity that you might have in your muscle to grade the amount of muscle stiffness, muscle rigidity.

Dr. Okun, when the person with Parkinson's comes into your clinic and they're having a lot of difficulty with muscle stiffness, what can you do to help them?

Dr. Michael Okun 00:32:11
Yeah. When we think about this, we typically take the approach that there are things that are important that you can't see. Not all of the world is Zoomable, and so when we have the opportunity to see you in person, a good neurologist, in my opinion, a reasonable neurologist, will actually touch you when they examine you. One of the things that they do is move your wrist very slowly back and forth. It's called, in French, a pronation maneuver.

You may feel some ticking as you move it. It's kind of like with old-fashioned trains as they go up the hill. You imagine sometimes they have to have a cog in the track. They drop the cog, and it goes click, click, click. It's the same thing like a roller coaster as you're going up. You hear that click, click, click, click. When you hear that or you feel that, when you feel it in Parkinson's, we call that cogwheel rigidity, where you can actually see the tremor blending in with the stiffness or the slowness.

You can have rigidity in your neck, you can have it in your arms, you can have it in your legs. One of the most important things is that you check for it because it can be disabling, it can be painful, and sometimes it can even have dystonia, where the symptoms happen, muscles fight against each other and the hands clench or the toes push down.

We will optimize medications, but also make sure that we're giving medicines on time every time and not letting them wear off for a symptom we can't see. So we have to do a lot of education and a lot of back and forth. One of the online questions, too, was about whether there are things you can do online for rigidity and for other things and exercise classes. There are, actually. There's a great free Helpline that we use all the time, 1-800-4PD-INFO, that the Parkinson's Foundation has. 1-800, the number 4, PD-INFO. For those of you that aren't old enough to know this, there are letters on each number of your telephone, 1-800-4PD-INFO, and they can hook you up with those resources through the Parkinson's Foundation.

Lisa Warren 00:34:34
Thank you, Dr. Okun. One of the comments that you made is so true, talking about we can't see rigidity; we have to feel it. I often find that's true for the person experiencing it. It's harder to recognize the rigidity because you can't see it. You can see a tremor, you can tell when your balance is off, you can see slowness of movement, but you can't see muscle stiffness. And it creeps in slowly. Often, it becomes our new normal. I do find that when you're living with it, it's a little bit harder to recognize it than when we move you around and we can feel it.

What do you do about it? Certainly, exercise is really, really important. Stretching can be beneficial with stiff muscles. The biggest help with all of this is medication on time, as Dr. Okun has talked about. If the medication gives you benefit with this muscle stiffness, taking it on time will certainly help you to move. These stiff muscles will reduce some of that tightness.

A couple of the things that an occupational therapist might suggest to you: people who have muscle rigidity, muscle stiffness, have difficulty getting on a jacket, getting on a shirt that buttons up the front. One thing you want to remember is the stiffest arm, the one that's the hardest to move, needs to be the first one in. First one in, last one out of a shirt or a jacket. Those are the easiest. Save the arm that's the most mobile, that's the most flexible, to do the reaching behind into the jacket. So the stiffest side, typically it's the side your Parkinson's started on, that needs to be the first one in and the last one out.

One of the other things that is often problematic is spilling food off the utensil. Certainly, tremor can cause that to happen, but as we talked about, tremor is mostly a rest tremor. It doesn't tend to cause too much trouble with eating, but certainly the rigidity does. I mentioned it takes more effort to get the same result. Often what we see with eating is you scoop your food, but you don't rotate the forearm quite enough to level off the utensil, so food slides off.

If that's happening to you, give it a little more oomph, an exaggerated movement, a little more effort to rotate that forearm to get the utensil level. Some strategies like that, the occupational therapist can take a look at what's going on, what you consider to be most problematic, figure out exactly what it is, and then offer some suggestions to help manage. Gretchen, is this something that you've had to deal with? And if so, what's it like for you?

Gretchen Rosswurm 00:37:23
I have experienced rigidity, and for me, what it feels like is not myself. I don't feel like myself because I feel like I walk differently and am not presenting myself as I normally would. That's how it feels to me. It's like, I don't like this. We'll talk a little bit about what we can do about rigidity.

Dr. Michael Okun 00:37:54
And Lisa, I think one of our listeners would like to get a little bit of direction as to where they can purchase heavy utensils for tremors. They have that up in the chat.

Lisa Warren 00:38:07
One of the best locations is Amazon, which has a lot of different options. I will tell you that my favorite weighted utensils are not the ones with the fat handles. Everyone has seen the ones that have the built-up handles, the ergonomic handles. Just a brief tip on that is that when you get the built-up handles, your grip on the utensil is different. Once you change the grip, you change the entire mechanics of the spearing, the scooping and bringing the utensil to your mouth.

There are weighted utensils that look more normal, if you will, look like standard utensils, and those are also on Amazon and some of the durable medical equipment companies' websites. Those are my preference because you can hold them just like you hold a regular fork. They look much like a regular fork. They are a little bit thicker, but they don't have the black built-up handles, which are fantastic if you have arthritis in your hands.

But if you're just trying to get something to manage tremors, give you a little more assistance with eating, I would say go for the handles that look like regular utensils but have some weight to them. On any of those sites, it will tell you the weight of the utensils, and most of them are pretty similar in how much they weigh. That's a really good question.

For my take-home tip with rigidity: stretch. Warm up the muscles. If things are getting slow and labor-intensive, stretch the muscles. Warm up the muscles before you start doing something. If you are on the computer typing and it gets slow, it gets labor-intensive, you're feeling that stiffness that Gretchen was describing, stretch. Stretch the muscles in your hands and your arms, and it will help you move a little bit easier. It's temporary. You may have to stretch again, but just stay at it and keep moving. Gretchen, what is your take-home tip for us?

Gretchen Rosswurm 00:40:11
Well, I have several. Just reiterating, the stretching is so important. I stretch every day, and I stretch anytime I have a free moment. I'll focus on something that might be bothering me, or just knowing that, okay, I need to keep this arm, for example, my right arm, in good working order. So that is one way, obviously, is stretching. If you need to be able to sit, there's a lot of videos and other workouts that are specifically yoga-oriented, but they're from a seated position. If you prefer to sit for your stretching, that's a great way to do that.

And then for me, again, I've been focusing on my gait and my arm swing, and that is helping me a lot. I'm literally seeing my gait get better. I believe it can happen. It just takes constancy of purpose. Finally, another one of my early symptoms was minuscule handwriting. I work on my handwriting almost every day, and it takes really big motions, and I think it addresses a number of the symptoms that we're dealing with. I don't enjoy, but I do my handwriting frequently as well.

Dr. Michael Okun 00:41:39
I'll also mention, in the chat, we have a question about whether we commonly use muscle relaxers like baclofen and others that are quite sedating in Parkinson's. The answer is actually no. We try to optimize folks with more dopaminergics and cocktails, and we very rarely use those. It's not that we won't, but it should be a last line and very rare. And then one other question or comment is they want us all to speak a little bit louder and lean into our microphones. So thank you.

Lisa Warren 00:42:19
Dr. Okun, I think I may have skipped your take-home tip. What is your take-home tip for rigidity?

Dr. Michael Okun 00:42:25
Well, I'm a pretty redundant guy, and so on time, every time with medication is the one that's really going to give you success in this area.

Lisa Warren 00:42:38
Absolutely. Thank you. All right.

That brings us to the last cardinal symptom that we're going to be talking about today, and that is postural instability. That simply means balance changes. It certainly can lead to falls, and then often if people are falling, they become reluctant to participate in activities, and we know it's super important that you remain active with Parkinson's. Balance and balance reactions also change with age. We do have age-related changes that are happening at the same time our postural instability with Parkinson's is happening. This is a tough one to manage.

You certainly want to exercise, stay active, work on core stability, and as Gretchen has mentioned before and a couple of times, just the importance of stretching, of exercise and being present. She thinks about how she's walking; she thinks about her balance.

Often our posture becomes slumped forward. Now, a lot of us sit that way, especially those that are on the computer all day, and so many of us are in that slumped posture. With Parkinson's, you want to stretch. You want to stretch those core muscles, arch your low back, and sit up straight or stand up straight throughout the day. You can't maintain that all day long. That would be just about impossible to do. But when you notice that you're slumped, fix it. Arch, sit up straight, straighten your back, and try to prevent those postural muscles from shortening into that position.

Dr. Okun, here again, what can a movement disorders neurologist do to address postural instability?

Dr. Michael Okun 00:44:21
Right. The first thing that we do is, again, we will touch the person with Parkinson's. I know that sounds crazy because many of you probably don't get touched by your physicians, but what we will do is we will actually stand behind the person, pull on their shoulders and ask them to try to maintain their balance with a quick jerk on their shoulders. We'll give them some practice and even allow them to take a step backwards. We should be doing this at every visit. If you're not asked to do this, you might want to remind your practitioner to do this.

By judging how many steps you'd have to take or whether you can correct your balance, that tells us whether or not you have what's called a postural reflex. This is the areas of the brain, many of which are deep in the brain stem, but there are also other areas that are important to this, that allow you to maintain your balance, and when things change around you and your environment changes, the curb changes, you can maintain your balance. We must, as a first step, identify whether you have any balance problems and whether you can recover, and track that over time.

Once we've developed that, we have to give a lot of counseling for preventing falls. We want to prevent as a key word here. If you have any postural instability, we want to prevent falls. We do want to optimize medications, and so it is a bit of a myth to say that medicines never help with balance or walking. They actually can help in some cases, particularly earlier and in the earlier and mid portions of the Parkinson's diagnosis, but sometimes even later on as well.

We want to optimize those medicines, we want to assess the postural reflexes, we want to counsel the folks, and we want to get them over to your shop in rehabilitation and begin to work together. And we're hopefully working together. We wrote about this in the JAMA review article in February of last year. We believe that these are first line. We should be working together with our physical and occupational speech and swallow therapists right from the diagnosis. We should be tracking these symptoms together and trying to optimize medications and optimize the behavioral and rehabilitative therapies.

Lisa Warren 00:46:48
Excellent. I couldn't agree more. That is one of the comments I wanted to make, is it is never too early to see your therapist. We'd rather see you before it becomes a problem, and maybe we can prevent it or at the very least delay it. Certainly, it's never too late to see the therapist either.

One of the things, or some of the things the occupational therapist is going to address in this area, is talk to you about removing some of the hazards in your home, like throw rugs; making sure that you have proper lighting; maybe use of night lights at night to help you see where you're going; having grab bars in the shower, around the toilet, areas that people are likely to fall or can fall, where falls most likely happen.

Multitasking becomes difficult. We're going to talk to you about minimizing the number of things you're doing at once, or maybe you sit to do things instead of standing so we don't have to worry about balance. Talking about dressing, we want you to sit down to put your pants on. Standing on one foot to thread the other foot through a pant leg, there are no bonus points for standing to put your pants on. So sit, put your feet into your pant leg, stand up, and then go work on your balance. We don't mind you standing on one foot, but don't do it while the other foot is hung in a pant leg. Just some tips to minimize the fall risk. Gretchen, how have you managed the symptom of postural instability?

Gretchen Rosswurm 00:48:12
This is something I've been working on proactively for some time. I was diagnosed in 2017, and I've been working on balance throughout that time. For example, I got a balance board pretty early in my diagnosis and started using that, and that has helped me quite a bit.

I want to do the best I can with myself, especially as it relates to balance, because I know so much that can happen to your life if the balance is off and continues to get worse. For me, it's been very much a proactive stance.

Lisa Warren 00:49:00
Very good. And so our take-home tips for dealing with postural instability, Dr. Okun.

Dr. Michael Okun 00:49:08
Yes. The tip here is that it's not always in the cocktail, right? So don't depend on just your medications. Integrate. Be early with your interventions, have your team together, integrate your care, and then the last tip is one that we've learned the hard way in the school of hard knocks, and that's don't take your therapies as bursts of therapy.

Parkinson's is a disease of cueing, which means if you start a therapy like physical therapy or something for your balance, you do six weeks of it. Just like if you had a stroke, you might come out of the hospital, do six weeks of therapy. That might be how Medicare wants to reimburse it. That's not the best approach for Parkinson's. You want to have a regular daily exercise program, and you want to spread those physical therapy appointments out and have them consistently throughout the year. So you want to make sure that you're not doing bursts of therapy, and you're staying preventative and using assistive devices when you need to.

Lisa Warren 00:50:12
Excellent. Good point. For OT, certainly minimizing multitasking. Standing to put your pants on is multitasking. So minimize that when you can. Focus on walking when you're walking. Focus on moving safely.

I couldn't agree with Dr. Okun more about spreading out your therapy. We need to see you through the duration, through the changes. Seeing you in six weeks and discharging is not as beneficial as if we see you throughout the year as you're changing. And Gretchen, what is your take-home message for this?

Gretchen Rosswurm 00:50:46
Well, a couple of things. As I mentioned, the balance board, and that's something that a person with Parkinson's might want to utilize to improve their balance or maintain their balance. You probably want to have someone nearby who can perhaps hold your hands or be nearby in case they're needed, but yeah, the balance board is very helpful. Focusing, for me, taking big steps, walking with big steps and confidence.

And then the other thing I would say is that I think it's important for anyone who has Parkinson's to know if they're going to take a fall, if they're feeling that that's going to happen, they know how to get back up. And so I think that's an important element that can come through, whether it's an exercise program that does that or through, I guess, perhaps OTs, if I'm right about that. And so that helps as well. And exercise that helps us be stronger, especially in our legs, which is what helps us prevent falls as well. So those are my tips.

Lisa Warren 00:51:58
Absolutely. Yep, excellent advice. So that brings us to the end. I would like to thank you all for being a part of this program today.

Dr. James Beck 00:52:09
Yeah. Thank you, Lisa, Dr. Okun and Gretchen. That was a fantastic presentation. Really, I think, super useful advice, and kudos to Dr. Okun, who was getting in there into the chat and starting to answer some of the questions directly. Didn't quite get to them all, so we still have a lot of questions to go through, and I've seen some of them come through.

Just a reminder, and I'll ask my colleague to push it through again into the chat, this presentation is being recorded. If you want to download slides, you can do that right now. She can push that link again, and information for CEUs is coming through. It takes about a week for this to go from today to being made available online again, and we're going to be translating this. It's going to be overdubbed in Spanish in about a month. So we'll have that information available for everyone as well in a little bit.

First, let's tackle some of the questions that have come in. And if we can just for a second, because we've got a really broad audience here, people from Facebook, which is fantastic, sending in questions, and people who are new to the Foundation. A basic question that's come through, I've seen this one came from Mumbai on Facebook, is, how is Parkinson's disease diagnosed to begin with? I know it's a very general question, but let's get to that, and I think we can really dive into some of these other questions as well. Maybe, Doctor, if you want to tackle that one.

Dr. Michael Okun 00:53:37
Sure. Well, it's great to have a question from Mumbai. It might surprise you that the answer is still based on a good clinical examination, meaning that we need to check for particularly those cardinal motor symptoms that we talked about: tremor, stiffness, slowness, the rigidity. And we need to quantify how much of those that you have, and we can apply criteria to decide whether or not we think you have Parkinson's.

But also, we tell folks not to jump to conclusions right away. Yogi Berra used to say, don't hit all your home runs in spring training. And so for those of you who are Americans, you don't want to jump to a diagnosis too quickly. It's also helpful to see how you respond to therapies like dopamine and dopamine agonists. And so we put that into the equation.

We also recognize that there are symptoms that may appear many years, sometimes 10, 20 years, before the diagnosis of Parkinson's. Some people have referred to them as prodromal symptoms or symptoms that occur before Parkinson's. And we mentioned that those might be loss of smell, those might be acting out your dreams or constipation. And so those aren't 100%, but that might be the clues that you're headed in that direction.

In the United States and in many areas around the world, there is a test called a DaTscan, a dopamine transporter scan, that's been approved to help in the differentiation between Parkinson's and another disorder called essential tremor. That's that tremor that you get when you intend to move. So it doesn't tell you that you specifically have Parkinson's. It tells you there's something wrong with your dopaminergic system and can sometimes be helpful to sort things out if there's a little bit of concern.

We do have some research modalities that are out there, some special MRIs, some PET scanners, and depending on the experts, we are getting better, and hopefully Dr. Beck will have some better diagnostic tools as we get along. But as it goes, the neurologist still gets to use their hands and their eyes to do this with their bag of tricks.

Dr. James Beck 00:55:59
Yeah, excellent. This still remains a diagnosis where having a good clinician is so important. And I'm glad that our Foundation is able to sponsor a number of fellowships to ensure neurologists are getting trained in this area as well.

Another question, Dr. Okun, just to follow up with: you mentioned the importance of taking medications on time, every time. And I think that can help with a lot of people who are maybe seeing changes and variations in their PD perhaps during the day. But you also mentioned the issue around if there's a special event that's coming up, about taking medication for that. How do you generally counsel your patients in that area? Is this something that they should be talking to their doctor about, or is this something that, having enough experience with something like Sinemet or some of the adjunct therapies, they could do on their own?

Dr. Michael Okun 00:56:55
Yeah. So thank you for that question. What I found over the years in attacking problems in a very multidisciplinary way, so you've got your therapists and you've got your prescribers — I call us drug dealers, the ones that are giving out the drugs — and thinking through the strategies for individuals, it didn't occur to me earlier on in my career that everything wasn't a one-size-fits-all.

Then as we get wisdom and we move forward, we realize that perhaps the majority of folks with Parkinson's are going to be just fine with the regimens. We'll adjust them. But we do have people that want to go out on these super long bike rides or who are struggling when they're going to the gym to work out every day, that they are playing a gig and they're the drummer in the gig and they need to be able to have the rhythm be on pace with the rest of the musicians.

And we have found, whether you're a professional performance athlete or not, sometimes you can work out a regimen and a deal with your doc where you can control your symptoms during times when it's a little bit more intense by just taking a little bit more dopamine, maybe a half a tablet of levodopa before things. And maybe Lisa wants to comment because I know you've seen some of these folks come through occupational therapy.

Lisa Warren 00:58:18
I think what's really important to remember is the best thing the medication does is it helps you function. And so if you think about it that way, it helps you do the things you need to do or want to do during the day. And so, as Dr. Okun said, timing your activities or, in this case, timing the medication with your activities can be really beneficial.

Dr. James Beck 00:58:46
Excellent. And so just one last question regarding medication. I know we've talked about rigidity and, I think, the very clear way of testing it among people with Parkinson's. There's some discussion I've seen in some of the questions coming through where people are wondering, are muscle relaxers really the solution to rigidity, or is it really making certain people have enough Sinemet as necessary in order to help reduce the rigidity? What's your thoughts on that?

Dr. Michael Okun 00:59:16
Well, from a neurologist's perspective, we will see when folks come in, particularly when they're not diagnosed appropriately with Parkinson's, and maybe they're not shrugging their shoulder as much or they have a little bit of shoulder pain or something. And they'll go through the motions. They might even have an inappropriate orthopedic surgery on their shoulder or on the wrist, and so we see that as well. And so that's where we most commonly will see the use of muscle relaxants, when the diagnosis isn't correct. And so I just want to point that out.

It's not that muscle relaxants can't be useful to try to get those muscles to tense down and how they contract and how those fibers in the muscles, just to get them a little bit looser for folks. But by far the number one way to address this in Parkinson's is to adjust the medications, the dopaminergics and the regular dopamine replacement or dopamine agonists, and then in some cases using botulinum toxin.

The other issue with the muscle relaxants is they're quite sedating, and they can actually contribute to folks having balance problems and falling problems and having trouble doing activities. In fact, if we start them, we've learned from wisdom that sometimes we send them to the therapists, to Lisa and to our speech therapists and also to our physical therapists, and they just can't function well enough to get the gains.

Dr. James Beck 01:00:59
Wow, that's something good to know. And speaking of issues around falls, Ms. Warren, a question's come through, a person who really likes to exercise, they like to play tennis. Their balance isn't great, but exercise is so important, and something like tennis where you've got that switching, which I think would be great to improve balance overall. What is your advice to people like that who are looking for ways to maintain that activity, maintain that muscle strength and yet still combat the problems they face with Parkinson's?

Lisa Warren 01:01:30
That's a great question. And we want them to maintain these quality-of-life activities. So these are things that are important to people. If you enjoy playing tennis, we want to keep you playing tennis as long as possible. We do fear falls, and we want to be very aware of that. And so having a therapist that you see frequently, as Dr. Okun was talking about earlier, as we mentioned, throughout the duration of your diagnosis will help you stay on top of those balance issues.

In our clinic, it's not unusual for us to see a patient once or twice a month, but throughout the year. We may only see them 12 to 24 times total, but it is throughout the progression. It is throughout the duration of the diagnosis. So if that day comes where playing tennis is a little too risky because of falls, then let's look for an alternative.

Pickleball is very big in Florida. I know it's big in California too, which is sort of a mini version, I suppose, of tennis. The court's a bit smaller. The net, I don't think, is quite as tall, so you don't have to move quite as much. But a lot of our folks really enjoy playing pickleball. So maybe there's an alternative that still keeps you active, is something similar, but might be safer. But again, our goal is to keep you doing the activities that you enjoy as long as possible, but also as safely as possible.

Dr. James Beck 01:03:01
Absolutely. I think that's great. And I'll just continue on this issue around falls because it's such a pervasive one that many people with Parkinson's fear, and I know there's a lot of anxiety around it. Gretchen, hopefully — she just went off camera — but a question to her and maybe to you, Ms. Warren, is how do people deal with anxiety around falls? Again, it's an activity issue. It's something that's not well controlled, but we want people to be moving and not stuck in their chair because they are afraid to get up and move.

Lisa Warren 01:03:36
Absolutely. I was going to give Gretchen a chance to see if she was still available to answer.

Gretchen Rosswurm 01:03:42
I'm here, but I can't find my camera at the moment.

Lisa Warren 01:03:48
Well, we can hear you.

Gretchen Rosswurm 01:03:50
Okay, that's fine. Oh, there we go. Start my video. Thank you, some lovely person on the other side. Okay.

Lisa Warren 01:03:59
Did you hear the question?

Gretchen Rosswurm 01:04:01
No, I didn't.

Dr. James Beck 01:04:02
Sorry. So, Gretchen, we were just asking about, there's a lot of anxiety people may feel around falling. And I didn't know how you've been able to, because you've mentioned it's an issue, thinking about getting back up, but that's certainly part of it. How do you wrestle with anxiety around this?

Gretchen Rosswurm 01:04:20
Well, my approach has been to be proactive. So I, knock on wood, have not had a fall since I was diagnosed with Parkinson's. And I have really counted on exercise, staying as strong as I can, and doing those kinds of things that will help prevent a fall.

But at the same time, early on I had worked with someone who taught me how to fall safely, if you can, and how to get up, especially if you're by yourself. And I think everyone should have that basic and fundamental skill as someone with Parkinson's.

Dr. James Beck 01:05:07
Absolutely. Ms. Warren, anything to add?

Lisa Warren 01:05:10
Yeah, I'd just like to say we know it's important that you stay active, and this is a common problem that after you experience a fall, people are very fearful and have a lot of anxiety about falling again or falling in public and being embarrassed about that.

If an assistive device is recommended to keep you safe, it's better to utilize that assistive device and be active than to choose not to do either. If it means a walker or a cane or whatever it takes to get you safe, if that allows you to be active, to do the things you enjoy, to visit family or the grandkids' sporting events, then by all means, utilize that assistive device, stay safe, and get out and enjoy life. Stay engaged in life.

Dr. James Beck 01:05:59
Excellent. We're a little bit over time, but I just wanted to get one last question for Gretchen. A couple of people have asked, one on Facebook, what's your handwriting program? You mentioned that as such a real practical issue to deal with. So, love to hear what you're using to tackle this.

Gretchen Rosswurm 01:06:17
Paper and pen. It's not too complicated. It takes more guts to do it, to be honest with you, than it does anything else because it's facing one of my worst fears, not being able to use my hand or write.

I've been taught through occupational therapy to do these extremely large motions so that we're getting to this place where we can create legible handwriting and also continue to create use in that hand. I write like this on just a big piece of paper, and I color, and that seems to help quite a bit. And it has to be done on a consistent basis.

Dr. James Beck 01:07:05
Absolutely. And this one, is there a website or example? Are you just transcribing stuff down, or are you just writing your thoughts down? I mean, is there any specific plan with which to do it?

Gretchen Rosswurm 01:07:19
I've done different things. Yes, I've written things out of books. I have been given, okay, here's an example of something, blah, blah, blah, write it. So nothing, yeah, nothing. You could pick up anything. You could write the alphabet, write your kids' names, those kinds of things that just give us the opportunity to really find a confident measure on our handwriting.

Dr. James Beck 01:07:54
Excellent. All right, well, I think we need to end there. I want to thank everyone again, Dr. Okun, Ms. Warren, Gretchen, for presenting to us today. It's been a fantastic presentation, and thank everyone for listening. But I don't want anyone to leave just yet. Just want to remind you again, this has been recorded and it's available for everyone to look at in about a week.

Theravance Biopharma has really been able to help put this presentation on, so we appreciate their support and giving us funding that's necessary to do that, as is required for all our things that we do. Just want to remind everyone again, CEUs are available, recordings available on demand in about a week, and in about a month we'll have it in Spanish as well for those people who would prefer it in Spanish.

We've just completed check mark for today's symptom management seminar or expert briefing. We've got two more. The next one is Tuesday, March 9th at 1:00 p.m., and then the last one will be April 20th. Looking forward to learning about some of the non-motor symptoms when it comes to symptom management.

We've got a number of resources available for everyone. Our website is very rich. Our 800 number, 1-800-4PD-INFO, as has been relayed to people in the chat who are asking questions, is a great resource. We have wonderful colleagues on the Helpline who can answer questions. We have other resources as well. We have our Health at Home series, which is three days a week providing live programming for people with Parkinson's.

For those who I saw come in who've mentioned that they may have a family history, as Gretchen does, or maybe even early diagnosed, I certainly recommend the PD GENEration study. This is a clinical study that we're offering to people with Parkinson's. You have to have a Parkinson's diagnosis, but please take a look on our website about that: Parkinson.org/PDGeneration. And our Aware in Care kit is very helpful for those who may have a planned hospital visit or even unplanned hospital visit.

And as we end, what will pop up is a new window asking you to complete an evaluation. This is really important for us to give feedback to our presenters, but also understand where we are doing things right and maybe doing things not so right. So really appreciate your advice on that. And with that, I will end and thank everyone for their time today, here on our Expert Briefing series, and wish everyone a good week. Thank you.

Gretchen Rosswurm 01:10:42
Thank you. Thank you.