Dr. James Beck 00:00:00
Hello everyone, and welcome to the Parkinson's Foundation Expert Briefing. I'm Dr. James Beck, Chief Scientific Officer of the Parkinson's Foundation, and it's a pleasure to have you with us today. In today's expert briefing, we'll be discussing the thinking and memory changes that may occur in Parkinson's disease. This webinar will cover cognitive changes in detail and offer practical strategies to help manage daily activities. Our goal today is to increase awareness and provide you with the tools to support daily life with Parkinson's disease. Thank you for joining us.
Our next step is we'd really like to get a sense of who's joining us today. There's a lot of people on the call, a lot of people signed up, so we're going to post a poll that should appear on your screen, and it's going to ask a couple questions. Are you a person with PD? Are you a spouse or partner? What's your relationship to Parkinson's disease? If you're joining us on Facebook Live, feel free to put in the comment section your relationship to PD, and our colleagues will get a capture of that. In just a few more seconds, we'll be able to get the results up and see where people are coming from and how they are related to Parkinson's disease. Any second now, we'll see that.
Yep. Not surprisingly, most people here have a really close connection. They're either a person with Parkinson's or a care partner of a person with Parkinson's disease. We have some others joining us as well. Welcome, everyone, to our webinar today.
Before we begin the formal briefing, I think it's important to tell a little bit about the Parkinson's Foundation. As a nonprofit organization, we're dedicated to improving the lives of those living with Parkinson's by enhancing care and advancing research. Our efforts are deeply rooted in collaboration with the Parkinson's community, ensuring that everything we do aligns with your needs and priorities. Today's program is just another example of how we are working with you to meet these goals, and this will be the last one of our year. We'll talk about some feedback at the end to help us ensure we have a good one for the coming year.
Since our founding, the Parkinson's Foundation has invested more than $449 million in research and care to improve the diagnosis and treatment of Parkinson's disease. Our goals help to change lives and advance scientific breakthroughs. One of our key initiatives is PD GENEration. This is a global research effort that's offering free genetic testing and free genetic counseling to people with Parkinson's disease. By participating in PD GENEration, individuals can learn more about their personal connection to Parkinson's while also contributing to the research that could lead to tomorrow's treatments and, ultimately, we hope, a cure.
We invite you to share in this opportunity with your community and help us reach forward in the quest to end Parkinson's disease, because together we can make a difference. Feel free to follow this link when you have an opportunity to see how you can participate in PD GENEration, either locally or online through our portal as part of that process.
A friendly reminder that we're going to be recording this session today for our expert briefings, and we'll be making this recording available very shortly. Don't worry about that. If you've registered, there's no need to check back to see if it's been posted. We'll be certain to email you a link to the recording and other resources that are covered today to ensure that everyone who's registered has that information. Because it's recorded, let your friends know who may not have been able to join so they can watch this later.
Now I'd like to move on to our focus today and introduce our expert presenter. Dr. Greg Pontone is a professor at the University of Florida, where he holds the Louis and Roberta Fixel Chair and is the Division Chief of Aging, Behavioral, and Cognitive Neurology. He also serves as co-director of the Fixel Neuropsychiatry Program. With extensive training and expertise, Dr. Pontone completed his internship in medicine and residency in psychiatry at Johns Hopkins, followed by a specialized two-year fellowship in geriatric psychiatry and mood disorders focused on Parkinson's disease.
Dr. Pontone is an active contributor to the field. He serves on the editorial boards of the American Journal of Geriatric Psychiatry and Parkinsonism & Related Disorders. He's been a member of the Parkinson Study Group since 2008, where he's currently serving on the scientific review committee and chairing the cognitive psychiatric working group. Dr. Pontone's clinical and research focus has always been on understanding and addressing cognitive and psychiatric symptoms in Parkinson's disease. Dr. Pontone, welcome, and thank you for sharing your time with us today.
Dr. Greg Pontone 00:04:12
Hello. Thanks for having me. I'll go ahead and share my slides and get to the talk.
Okay. Hopefully everyone can see this slide. Today, I want to talk about thinking and memory changes in Parkinson's. I think in order to understand these changes, you need to know what's a normal change with aging before you can know what to attribute to the Parkinson's. That's the first place we'll start. I don't really have any disclosures relevant to the content of this material today, but here are my disclosures.
Today I want to help you understand the cognitive changes that occur in Parkinson's. Then it's important to know the difference between changes that may be very mild and almost inconsequential to your day-to-day life from what we call dementia, which is a much more severe condition. Then hopefully I'll show you some practical strategies to lower the risk of cognitive changes and progression to dementia across the lifespan. Then we'll discuss some research around new treatments and better understanding these symptoms along the way.
The first thing to know is that when we age, there are some changes to cognition, and there also are some things that are very well preserved. Among those are what we call procedural and semantic memory. Procedural memory is the memory of how to do certain actions or perform certain tasks. Literally, riding a bike is a type of procedural memory, and that's usually really well preserved even as we age.
Semantic memory is the memory for understanding concepts and things, and that's also well preserved. Vocabulary and general knowledge remain stable or even improve a little bit per decade through the seventh decade. Visual perception of objects remains stable. Actually, it's shown that older people might be a little more accurate in judging distances. Again, this is up to about that seventh decade. With advanced age, many things can change. Language is stable at least until age 70. Again, if prior to 70 you see changes, especially in these things, that would raise some concern that there are some disease-related changes going on, either Parkinson's or another disease of aging.
What changes? Again, this is what changes with normal aging. Attention decreases. That's both focused attention and our ability to attend to multiple things in our environment simultaneously. That's called divided attention. That decreases with aging with everyone. Working memory, that's the ability to hold some variable in mind and manipulate it, whether it's doing a calculation or problem-solving, degrades a little bit. Executive functioning degrades with aging. Processing speed changes with aging. As I mentioned earlier, in advanced age, most cognitive domains change a little bit. By advanced, right now we're saying seventh decade, but I think we're living longer and that may shift as well. People are aging more healthily now.
Dr. Greg Pontone 00:07:56
What are the changes that happen in Parkinson's? This graph from a paper by Aarsland et al., I think, really shows a good example of what you can expect. The first thing you'll notice from this graph, with time on the horizontal axis and the level of cognitive impairment ascending on the vertical axis, is that there's a lot of heterogeneity in what you can expect in Parkinson's. There are different trajectories.
I would say that there are people who have a very mild progression of cognitive changes related to Parkinson's, and you can see that represented there in the graph in the light green shades. There's no or minimal cognitive decline over the course of the disease. Oftentimes, we see this in the people who, ironically, have the early-onset Parkinson's. Sometimes you would think the longer you have it, the worse off you are, but it actually turns out that very often people who have a younger onset have a milder course, especially with some of these cognitive symptoms.
You can still see there's a good proportion of people who might have some mild changes throughout and do quite well. Then there's unfortunately a subset of people, and we think it's a minority, who will rapidly progress in the cognitive domains and become demented because of the disease. The other important aspect of this is, if you see that dotted, fluctuating line, there are times within the disease over the long term where people will experience a little bit of a decline, but then they'll recover from that decline.
This is shown in many longitudinal studies where people will have a decline maybe in a few domains of cognition, but then recover normal functioning. We see this in a number of studies that have followed people with Parkinson's over the years.
It's really important to have this appreciation that if you know someone who has this disease, or you're part of a support group and you see people who are in worse shape, that doesn't necessarily mean it's going to be you. If you've entered a period where you're not doing as well, there could be hope that you'll fluctuate and return to a higher baseline later in the disease. But what is important to know is that the disease does cause changes to cognition in the majority of people, and it's really just the extent of those changes. Now we're going to talk a little more specifically about that.
If you were to think about cognitive changes dimensionally rather than categorically, sometimes people think, well, there's unimpaired and impaired, or not demented and demented. That's probably not true. It's probably more dimensional. As we age, as the disease progresses, we see sometimes a change in cognitive functioning over time. If you think of mild cognitive impairment, this is a term you're probably hearing more about in the news media because of what's going on in Alzheimer's disease.
This really is a mild impairment in maybe one or two areas of cognition. You might have a change in memory, for instance, if you have early Alzheimer's disease, but then the rest of your abilities, let's say executive function and visual-spatial perception, might be relatively intact. That would still be called a mild impairment because it's really focused on just one domain of cognition, and it doesn't necessarily affect your day-to-day functioning, or at least doesn't affect your day-to-day functioning broadly.
When you accumulate more and more areas of dysfunction or impairment, let's say now you had memory and now you have some language difficulties, and then you start having trouble with organizing and sequencing, which is an executive task, and it starts to interfere with your ability to do things independently, that starts to head toward a threshold that we call dementia, which is a severe cognitive impairment that interferes with daily functioning.
Dr. Greg Pontone 00:12:18
A way to visualize this, and this is true of any neurological or neurodegenerative disease that leads to dementia, whether it's Alzheimer's or Parkinson's or other Lewy body disorders, is that as the years go by, there may be first a transitional period for some, where you have mild cognitive impairment that eventually progresses to become worse and turns into dementia. Now, there are people who get to that mild cognitive impairment level and plateau there for a long time, years and years, sometimes decades, just with mild impairments.
Remember, aging is playing a role here too. Age is going to, as I showed you earlier, play a role in certain domains, and then the disease could add to that decline that would be normal age-related decline.
I want to talk about what we call cognitive domains. I mentioned these different areas of cognition. I'll just throw out a few categories. People debate whether there are seven or nine different areas of cognition, but the ones that are pretty common and you've almost certainly heard about are attention, executive function, memory, and visual-spatial domains.
I think with Parkinson's disease, the one that we'll talk about the most is executive dysfunction because that seems to be, if not the most common, one of the most common areas of cognition that's affected specifically by the disease. Usually where this will show up is having trouble with tasks that require you to organize, sequence, or plan. Almost everything an executive in a company would do, right? This has been illustrated very well in some research.
Though this one now is an older study, it's still, in my opinion, one of the best demonstrations of how executive function changes with the disease. Remember, executive function is another domain that changes with aging. I said both focused and divided attention and executive function can be affected. This study we kind of call Let's Have Tea.
Basically, it was people who were involved in this mock trial where they would go to a kitchen and have a tray, and they would walk and recall a list of letters. It looked at how attentional demands during everyday functioning contributed to gait disturbances in people with Parkinson's. What they did is they studied about 20 people with mild to moderate Parkinson's and then 10 people who didn't have Parkinson's. They had four different levels of this task, with complexity increasing with each level of the task.
The first level, the simplest level of the task, was just to walk to the kitchen, and they would time you. Then the second level of complexity was what they called dual motor. You were walking and carrying a tray, so two movement or motor-type tasks, and then they would time you. Then they had something called dual cognitive. Now you're walking and recalling a memory. They would give you a list of words to recall after you walked to the kitchen. The final and most complex task was what they called multiple motor-cognitive task. Now you're walking, carrying a tray, and recalling a memory.
What they noticed is that for everyone, people with Parkinson's and controls, gait speed decreased. You slowed down with increasing task complexity. The lesson here is that everybody is vulnerable to impairment due to multitasking. We don't do our best when we multitask. But what really stands out is that the people who had Parkinson's slowed down even more.
Dr. Greg Pontone 00:16:41
The disease increases the deficit that's caused by attentional demands. What I tell people is, when you're doing something, in order to function your best with Parkinson's, it's best to focus on one thing at a time and to block out distractions. A lot of the new interventions and strategies are centered in what we call mindfulness, which is, in large part, this ability to focus on one thing at a time and to block out distractions. I think this is something you can do every day to function better. None of us multitask well, and people who have Parkinson's especially have this limitation.
I've even heard some of the patients I work with tell me that if they're walking in a group and they start carrying on a conversation, they'll fall behind the group. In order to keep up, sometimes they'll have to save the conversation until they sit down.
Memory impairment in Parkinson's is interesting. The memory impairment that is caused by Parkinson's is different in some ways than the memory impairment that's caused by Alzheimer's.
What I like to use is what I call the file cabinet example because memory, what we call memory, is a very complex process. It has more than one part. The two fundamental parts are what we call encoding and then retrieval. This example of the file cabinet is, I say, if we have two people, one who has Parkinson's and one who has Alzheimer's, and their wives tell them that their birthday's coming up and they want them to bake a cake for the spouse.
The person with Alzheimer's has an encoding problem. That's where their memory is chiefly failing. They can't form new memories. They take that six-page recipe and it really never makes it into the file cabinet, right? Two pages go behind, they throw the rest away. It just never gets encoded. The person with Parkinson's can generally encode very well. They take that six-page recipe, put it into the file, and close the file.
Now, both of them are going to potentially have a problem three days later, when it's their spouse's birthday. They're going to go to the file cabinet, open it, and say, 'Okay, bake me a cake.' Well, the poor person who had Alzheimer's never made the memory, never encoded the memory. Even if you give hints like, 'Go to file C for cake,' it's not going to help because either a partial recipe or no recipe is going to be in that file.
Whereas a person with Parkinson's has maybe a little bit of executive dysfunction, so their search strategy and their retrieval is a little clumsy. They might look in Z and L and all sorts of other letters, and eventually they'll stumble upon it. Or you can cue them or give them a hint and say, 'It's my birthday. I want a cake. Look and see,' and they can go right to C, and they'll have, most of the time, a fully formed memory of the event.
This is important in two ways clinically and in life. One is I tell people, when you're interacting with someone with Parkinson's, just let them take their time when you're talking or reminiscing because it's very likely that whatever they're trying to think of will float into their memory, just given time. Or give contextual cues.
In fact, one of the tests that we use in the office, the Montreal Cognitive Assessment, or MoCA, uses this distinction to discriminate between types of memory dysfunction in the clinic. It has a section for cueing by category and by theme, and by multiple choice if people fail to remember by category or theme. This is really, I think, a hopeful message because it means that a good portion of memory is still working for most people with Parkinson's. Now, the underpinnings of this are also kind of interesting.
Dr. Greg Pontone 00:21:20
Recognition memory, free recall memory, essentially most, if not all, of memory function is really bad in Alzheimer's, and so you see those double downward arrows. It turns out that recognition memory in Parkinson's is actually largely intact, and free recall is only modestly corrupted in most people. They benefit from hints and cueing. Again, this is an important distinction.
The thing I do want to mention here, because this is becoming, as technology advances, a more and more important concept, is the fact that at least for Alzheimer's, we can now visualize some of the misfolded proteins in the brain. In the case of Alzheimer's, these proteins are beta amyloid, or amyloid beta, and tau. Right now, we have clinically approved ways to look at amyloid in the brain. Soon, I think we'll have tau scans. We have them for research, so certainly I think we'll have them clinically soon.
We don't yet have alpha-synuclein or Lewy body scans that we can do, but again, I'm very hopeful that these will be something that technology in the future will allow us to visualize. The reason this is important is that you probably have heard that we have antibody infusion therapies that can remove amyloid from the brain of people with Alzheimer's, and the hope is that will slow down disease progression.
We're also very hopeful that we'll have therapies that either inhibit the misfolding of protein in Parkinson's so that maybe there won't be as much Lewy body formation, or maybe even the removal of abnormal alpha-synuclein in Parkinson's. Again, this is all aspirational at this point, but what we know is that from autopsy studies, people with Parkinson's often have more than just alpha-synuclein and Lewy bodies. Sometimes they have the same changes, the amyloid and the tau tangles that we see in Alzheimer's.
If we see memory failing early or failing in a way that's more global like we do in Alzheimer's in a person with Parkinson's, we might suspect that they have two pathologies: that they have Parkinson's, maybe as the primary disease, along with a little bit of Alzheimer's. If you think back to that slide I showed you of the trajectories, where some people just seem to stay about the same with very mild decline in Parkinson's, that might be the people who just have the Lewy bodies and just have the alpha-synuclein misfolding, whereas the people with a more aggressive course may be the ones who have that combined pathology with some Alzheimer's changes along with some Parkinson's changes.
That's actually a big part of my currently funded studies in Parkinson's, to understand this better and see what we can do to change that and maybe mitigate that people are having more aggressive courses.
What's the impact on day-to-day functioning of some of these changes? With memory loss, you may see things like repeating the same question or asking about something that you had known the answer to earlier in the day. That's rapid forgetting. Difficulty learning new information has to do with that process of encoding, where you learn something and you should be able to incorporate that going forward, but that doesn't happen. Of course, forgetting appointments can also be a key to memory loss.
Sometimes people have insight that their memory is failing, and they'll tell you. They say, 'I can tell I can't remember.' But other times people don't really have the insight to know that their memory is failing, only the people around them.
Dr. Greg Pontone 00:25:23
Another change that could impact day-to-day functioning is difficulty performing familiar tasks: no longer able to use a remote control, microwave, computer, smartphone; can't organize medications. Things like this, for the most part, can be related to executive dysfunction when they're mild, and that can be very common in Parkinson's. You just have a little trouble organizing medications. But things like forgetting how to use a remote control, microwave, or computer, those are typically more than one domain of cognition failing and are usually a more advanced symptom.
Language deficits: we don't see those a whole lot in people who have Parkinson's, but we do see word-finding difficulty, where you might have trouble remembering your niece's name because you only see her twice a year. Some of that can be normal for aging, and so we always tell people, don't panic. But some of that can be the Parkinson's, where it just takes you a little longer to recall these facts that you do know and that are encoded.
Time and place disorientation, getting lost in familiar places: again, I don't see this a whole lot in Parkinson's, but when we do, maybe that's a sign of either more advanced disease or one of those combined processes where maybe there's some Alzheimer's with the Parkinson's. Poor judgment, being a little irresponsible, things like that are a combination of all of these.
The other important message is, if someone was a good person for most or all of their life and all of a sudden you notice these changes, don't blame them or attribute this new behavior to their character. This is probably the disease changing their habits and behaviors and not an intentional thing that's happening. I always tell people, have a little grace if there are changes. It doesn't mean you can't challenge people to try harder and do better, but sometimes it's not through lack of effort that these things are happening.
It's a fine balance to recognize what you can do in terms of motivating someone and supporting them versus just pushing for something that's potentially beyond their limits as the disease goes forward.
Now, I want to talk about something that's a little more proactive. A lot of times we give these talks and we talk about the medications and the science, and all that's interesting. I mean, that's the stuff I love and wake up for every morning. But what does that science tell us about what you can do day to day to have better outcomes in your life while you manage this disease? The first thing I want to say is everything I'm about to talk about isn't just a soft recommendation or my opinion. It's supported by research in people with Parkinson's disease and other diseases and in people who don't have any disease about what's the best strategy to support cognition as we all age.
This concept of wellness is, again, you can call it anything you'd like. Right now, the common term in the healthcare literature is wellness. This is that idea of a proactive strategy of changing your behaviors so that you're moving in a positive direction. This is wellness for people who don't have a disease, wellness for people who have any disease. It's the idea of operating at the top of your license wherever you are in life. If you're 50, your capabilities are in one place physically. If you're 70, they're somewhere else. If you're 70 and have Parkinson's, they're somewhere else.
Dr. Greg Pontone 00:29:21
Either way, wellness is the actions you take to operate at the top of your license. Sometimes it's physical things you do, and sometimes it's learning and optimizing your choices. You can see in here that there's awareness of issues, education, and growth throughout the process. The disease will change over time, so this is an evolving process. Each time, your ceiling may change for the better or worse, but you're going to keep going forward, and that's really what wellness is about. It's not just defeating a symptom. It's about achieving your highest level of function.
What are some of the core wellness behaviors? I really like to talk about four. This pyramid, I always like to show this because it's sort of the National Sleep Foundation making a joke, and they say sleep is as important as diet and exercise, only easier. Exercise, diet, and sleep are three of the core wellness behaviors that really people can make a difference by optimizing. There's one more that isn't on this pyramid, but I think certainly many people would include, certainly CMS, our government CMS would include, and that's socialization and being socially connected.
We'll talk about all of these. I want to talk about exercise in Parkinson's, not the way you usually hear it, where you hear about how it's going to help your walking and your stability and balance and all of that, and decrease your risk of falls. All that's true. But what I want to talk about is what physical exercise does directly for your cognition. I pulled 18 studies. There's more now because I pulled this about a year and a half ago.
Dr. Greg Pontone 00:31:16
Eighteen studies directly showed that aerobic or cardiovascular exercise in particular improved attention, processing speed, reaction time, executive function, and language. They showed improvement in stability because of exercise in these specific domains. This could be almost anything that gets your heart rate up and your blood pumping: walking outside, walking on a treadmill, swimming, a stationary bike, almost anything you can think of that's called aerobic exercise. In addition, it also improved mood.
It reduced the severity of depression in those who had depression. Again, this is something that's been studied in a very rigorous scientific way, and we know that right now, believe it or not, compared to the available medications, exercise makes as much of a difference as the best available medications, if not more and more enduring. This is absolutely something to add if you're not currently doing it.
There are other types of exercise, though. I'll give you another example. This is what we call resistance exercise, where either using weights or bands or your own body weight, you move against resistance. Of course, it helps walking and balance just like most other exercise does. It especially, in women, improves bone density, which again lowers the risk of fractures in the case of a fall. But when you look at its role in cognition, again, there are studies that show it improves executive function and attention.
Remember, we said that the two most common domains affected by aging and Parkinson's both, and we've got both going on—we're all aging, and if you have Parkinson's, you have two things—the two domains that are most likely affected are attention and executive function. This improves both of them. Again, right now some of the guidance that's out there is that you do 150 minutes of moderately intense exercise each week. You accumulate 150 minutes in whatever you like doing, and then at least two of these sessions should be resistance training, which is the current guidance from the American College of Sports Medicine. We think that's relevant to Parkinson's as well.
There are other types of exercise: stretching, yoga, mobility exercises. We think all of those are good as well and should be incorporated. They just haven't been studied as rigorously yet, but we think they probably have benefit as well. The important thing is that you're doing something.
Dr. Greg Pontone 00:33:50
Now, I want to talk a little bit about diet. There's actually going to be some great guidance coming out of the International Movement Disorder Society's journal soon that should be publicly available on specific diet recommendations in Parkinson's because of the protein and absorption of levodopa issue.
For overall health, especially in conditions that affect the brain, I would recommend, and it's in the guidance that I mentioned that should be coming out within the next year from the Movement Disorder Society, the MIND diet. The MIND diet is a combination of the Mediterranean diet, which is probably, in terms of health promotion, the most recommended evidence-based diet currently out, and the DASH diet, which is a diet that helps mitigate and control risk factors for cardiovascular problems like heart attack and stroke and high cholesterol, diabetes.
It combines those two. You can go on the internet right now and download this little flyer and put it on your refrigerator. While you can read about the MIND diet, the truth is, if you more or less follow what's on this single page, you've got the core of this diet. This is what's on my refrigerator. We think it can be very helpful in many conditions, and certainly as something that will lower your cholesterol and mitigate your glucose levels.
Anyway, that's one suggestion there. The one other issue that might be relevant is how you distribute the protein in the instances where it might be interfering with absorption of your medications. That isn't a major issue for everyone, but when it is, that might be the only other thing to consider.
Dr. Greg Pontone 00:36:04
Now, sleep. Sleep is tough as you age in general, but it's especially tough for Parkinson's because there are many things that impinge upon your ability to sleep restfully. The first thing we tell people is, you don't want to get so focused on sleep that that actually becomes part of the problem, where you're waking up every couple of minutes looking at the clock, getting more frustrated and less able to fall back asleep. What we coach people to do is to give themselves at least an eight-hour sleep opportunity. In part, you do that by habit.
One of the core habits, and again, this is all over the internet, you can look this up in many places, is called sleep hygiene. It's a collection of behaviors that get you in the optimal state to relax and be able to fall asleep and stay asleep. It's things like having a routine before bed, not stimulating yourself before bed by having a lot of screen time or caffeine or activating foods or drinks.
Sleep is really important again for cognition, and it's most important for attention and executive tasks. You can see, I think, now with exercise and sleep that the domains that are most affected by aging and Parkinson's are the ones that are most helped by these wellness or health-promoting behaviors. That's why I really want to keep reinforcing how important these things are that you can do.
Sleep also plays a role in memory stabilization and integration. There have been tons of studies that have shown that people who memorize something in these studies and then have a nap or go to sleep perform better on recalling that information later and learning that information for having good sleep than those who don't. Clearly, sleep also plays a role in that domain of cognition. We've got information that it helps attention, executive tasks, and memory.
Dr. Greg Pontone 00:38:18
Sleep is important for brain metabolite clearance. Not only metabolite clearance; there are studies that show that abnormal proteins like amyloid, remember we mentioned that could be involved in Alzheimer's, are cleared better when you sleep than when you don't. People who have disrupted sleep accumulate more amyloid, and they can sometimes show that change even in as little as one night's disrupted sleep. If it's doing that for amyloid, what might it be doing for alpha-synuclein and Lewy bodies in Parkinson's and other proteins like tau? We think that sleep and maybe something called the glymphatic system, which is like the lymph system of the brain, could be really importantly affected by the quality of sleep you get.
Again, the reason I'm telling you this is because the science is interesting, but also because, if you don't already, I want you to prioritize this sleep opportunity and sleep in general.
Sleep is also when the gains of exercise are realized. Your exercise tears down the body, and it's when you sleep and rest that the rebuilding and the gains of exercise are realized. The other thing is, if you exercise during the day, you're typically going to sleep a little better.
Again, there are many ways to go about this. There are formal consultations you can have with sleep experts if it's problematic, and I do recommend that. There's even a cognitive behavioral therapy for improving your sleep quality.
Dr. Greg Pontone 00:39:49
Now, let's talk about this fourth behavior in that pyramid that isn't painted on all pyramids yet. This is the idea of staying socially connected. There are two concepts within that. Social isolation, which is an objective lack of connection to people, whether it's families or friends or the wider community, and loneliness. You can be lonely even when you're connected. Loneliness is more subjective. It's associated with a perceived lack of a specific desired companion or a wider social network. You feel like you're missing out. I think both are important.
I want to show you some research that was done in the general population, not just in people with Parkinson's. One of the things that really was shocking, and I think the pandemic really taught us a lot about social isolation, but this work has continued to go on even after the pandemic. What they found is that social isolation significantly increases your risk of a premature death. In fact, it rivals the risk. Social isolation is on the same level of risk as if you smoke, are overweight, or are completely physically inactive.
It increases the risk of heart disease and stroke by about 30%. This is the one that I think is most relevant to our talk today. This is for everyone and maybe especially for people with Parkinson's: social isolation is associated with a 50% increased risk of dementia. There's something about the interaction socially that protects the brain.
Dr. Greg Pontone 00:41:28
In terms of studies directly carried out in Parkinson's, we know that being isolated increases the risk of anxiety and depression, and people report poor well-being more often.
When people are isolated, they're more likely to report episodes of confusion, to have delusions, and problems with memory and problem-solving. One of the most common times for hallucinations to occur is when people are alone or isolated. In fact, we hear a lot fewer reports of hallucinations in people with Parkinson's when they're in groups of people and stimulated. The other thing is, when you're isolated, the hours of caregiving at home and caregiver burden increase. It puts stress on the system too.
There are many reasons, even beyond the individual suffering from Parkinson's, to promote social interaction.
The last thing I want to talk about before I take some questions is what your doctors might do. Just to give you some context, because when I say that these behaviors—sleep, exercise, staying social, and diet—are important, these medications that I'm going to talk about, the two classes we use in Parkinson's to treat cognitive changes, are very modest. Their benefits are very modest, and I think most people would argue that the combination of behaviors—sleep, diet, exercise, and socialization—does more than the medications and is more enduring.
It doesn't mean you shouldn't take the medications. It's just that if you really want to fight as hard as you can, these behaviors are at least as important as these medications. That said, we are developing new medications and new interventions all the time. Like I said, even my own research is looking at new things to help with memory and thinking in Parkinson's.
Dr. Greg Pontone 00:43:07
Let's start with the most common class of medications. These are called acetylcholinesterase inhibitors. Acetylcholinesterase is an enzyme that breaks down the brain chemical acetylcholine. Acetylcholine is important for memory and other brain functions. You've already got less of that because of Parkinson's, and you have much less of it if you have Alzheimer's. One strategy to keep more of the acetylcholine around is to temporarily disable that enzyme, acetylcholinesterase. That's what these medications do.
You can see that donepezil is disabling acetylcholinesterase so that it doesn't break down the acetylcholine. Rivastigmine, also called Exelon, that's a brand name, is the one that's FDA approved for Parkinson's. You can see that it both inhibits acetylcholinesterase but also butyrylcholinesterase. So two enzymes that break down acetylcholine, it partially disables both of those.
Then there's a third one called galantamine that does a combination of things, but all with, again, the intent of keeping more acetylcholine around. This helps very modestly. It's the best available currently, and usually the first thing we'll try when you reach the level of needing a medication. But exercise, sleep, diet, and socialization seem to work even before medications are indicated, and after medications, they have modest benefit.
Dr. Greg Pontone 00:45:03
The second medication that can be used in combination with the acetylcholinesterase inhibitors is a unique molecule called memantine. It works through NMDA receptors. Basically, what it tries to do is reduce the level of an excitatory neurochemical called glutamate. It does this, and we think it just quiets the neurons down and helps them function better. Again, very modest and usually reserved for later in the course of the disease, but it can be used in combination with drugs like rivastigmine. You have a sort of one-two punch because they work by different mechanisms.
The point I wanted to give you is that, in addition to these health-promoting behaviors, we do have some medications that help. I think new interventions are on the way. Let me stop there and go ahead and take some questions, if anybody has anything that they'd like to ask.
Dr. James Beck 00:46:06
Thanks very much, Dr. Pontone, and that was a fantastic presentation. Really great information covered, and I appreciate some of those specific details that you provided as part of that process. Just a reminder, if you've got questions, put them in the Q&A. If you're on Facebook Live, put them in the comment section, and we'll do our best to get to them. A lot of people are joining us today, and I don't know if we'll get to them all, but my colleagues on our Helpline will certainly do our best to follow up. So, questions for you.
We've talked a little bit about procedural memory. There's a concern, as you can appreciate with our older population that is living with Parkinson's, about driving. Is car driving a procedural memory? Is that one of the things where you mentioned basic things like operating a microwave or a remote control? I presume it's not a procedural memory, which is why it's not working. Where does that fit into things? Is that really just a function perhaps of the executive function losses that you talked about? I will have to say, we have one person who came in, and I think it's worth repeating: if you can just cover what executive function might be again, just so we can place this in context. So it's a lot.
Dr. Greg Pontone 00:47:22
Yeah. Oh no, absolutely. Executive domain changes are the most likely to happen in Parkinson's, and that's been well studied. It's usually behaviors that require you to organize, sequence, or plan. That's a lot of different things we do. Any complex task has some element of executive function in it. Car driving is a very complex task. The first thing I always tell people is, depending on the trajectory you're on, there are two things to consider: there are the movement or motor changes of Parkinson's, and then there are the cognitive changes of Parkinson's.
I think both are relevant to driving a car because there's the judgment of spatial distances, there's the reaction time, there's the cognitive processing time. It's not just how quickly can you move motorically; it's how quickly can you process these visual-spatial cues that you need to react to. Independence is a big issue when you're living with any disease. For the individual, we want to prioritize the maintenance of independence, but we don't want to jeopardize the individual's safety or the community's safety.
Sometimes people have tons of insight, and they know when it's time to get evaluated. You can get evaluated. There's a process to get evaluated for driving through occupational therapy within a medical context, or you can go right out to the Motor Vehicle Administration and take the test that all of us take. Frankly, that's a good way to do it in some cases. Sometimes things can be more subtle, so it really kind of depends. I've seen people get the right answer through either alternative.
Dr. James Beck 00:49:11
You bring up a good question. This is one our listener Robert had brought up. Some people don't have insight. How do you approach that with your loved one to let them know that they may have this issue without really upsetting them? Because I imagine it could be startling for people to realize that they're having these issues and they're not aware of it.
Dr. Greg Pontone 00:49:34
Absolutely. The issue of insight can be very problematic. We've all heard the stories of a grandparent or older loved one who has to have the keys taken from them versus surrendering them, as an example. When you go about having a conversation about a loss of function, whether it's for driving or anything else, especially where safety can be involved, I do think that it's good to be direct. I do think that it's good to involve multiple people.
As part of the healthcare team, I always encourage people proactively, at different stages of the disease journey, to involve me in particular and my team. Sometimes as a spouse, family member, daughter, niece, you don't want to be the bad guy, or there's a different level of authority within a family structure, and there are cultural differences. I think a good central player in any decision where insight might be an issue is the healthcare team.
Dr. James Beck 00:50:46
Yeah, fantastic. As we think about these issues of memory changes that occur, you brought up a really interesting context in which to think about it. Based upon your age, if you're younger than 70, the changes, if they're experiencing them, really could be related to the disease. But if you're over the age of 70, how do you, and maybe you can't, determine whether this is my Parkinson's disease or some other issue that's going on? Unfortunately, Parkinson's doesn't protect you from getting Alzheimer's, or I'm just getting older. As an individual, you aren't worried about that. You can just accept, I'm 75 and there's going to be some changes that happen. How do you advise people to think about that?
Dr. Greg Pontone 00:51:42
That's a great point, and I think something that families struggle with all the time. One heuristic rule of thumb that we give people is, if you look at your peer group and you're more or less either having similar or the same complaints or performing at a similar level to most of your peer group, that's a good indicator of where you are. If you're out of step, if you're looking at your peers who are similarly aged and you're having deficits that are unique, or you're more impaired and there are things you can't do, and it's not just because your movement isn't as good, those are indicators that there might be something more there.
Really, I tell people it's just a matter of going again to your healthcare team and getting evaluated, because sometimes these can be things that can be addressed, or there are workarounds that can restore function.
Dr. James Beck 00:52:37
Are the changes that people see going to be gradual? Because you showed a graph where it kind of goes up and down. It can be episodic. Are those changes generally slight, and when do you become concerned about major changes?
Dr. Greg Pontone 00:52:53
I'm going to borrow a saying from one of the nurses who used to work with us for a long time at our Center of Excellence, Becky Dunlop. Becky would always say, 'There are no cliffs in Parkinson's disease.' What she meant by that is any sudden change is usually a medical issue that requires urgent attention and not the disease. The disease should progress very gradually over time. Anything that changes suddenly, if someone goes from clear one day to confused the next, that's likely an infection or a medical issue that can be reversed. But if you don't catch it, it can lead to bigger problems. I think that's a great point, and sudden changes should bring you to your medical doctor.
Dr. James Beck 00:53:39
Yeah, absolutely. I remember we had one of our presenters, Dr. Melissa Nirenberg, someone you may know. She talked about one of these myths of Parkinson's disease, and in her personal experience, her clinical experience, a lot of her patients had a UTI that was undiagnosed. It's so important to, as you point out, not see your movement disorder neurologist but your medical doctor, who you see on a regular basis. They can order those tests and really follow up on that. It's a nice way to think about it. There are no cliffs in Parkinson's disease.
People who have Parkinson's disease, they have a couple other things going on with their health. I wonder, those medications could impact cognition. How do you disambiguate, is this medication I'm taking now or a combination of medications causing this issue, or is it really a PD change?
Dr. Greg Pontone 00:54:33
That's another kind of usual suspect: medications. There are certain medications, in fact there are several categories of medications, that can change cognitive function for the worse. There's a list that, again, you can find on the internet. It's called the Beers List. Some of these things are even over the counter. Usually you'd think your doctors are the custodian of these medications and that they're going to make sure that I don't get exposed to medications that can worsen my cognition. But there are actually things that are over the counter that can be problematic, or as-needed medications that have been prescribed that you may take inappropriately or at inappropriate times.
Just to give a quick short list: medications that are anticholinergic. Unfortunately, a lot of allergy medications, things like Benadryl, which are not just allergy medications but over-the-counter sleep aids, can really have an outsized adverse impact on cognition in Parkinson's disease.
Opioid pain relievers: it's completely appropriate if you have a fracture of some sort to take strong pain medication, but just be aware they can cause confusion, delirium, or lower cognitive function.
Alcohol, and in some cases even in amounts that you tolerated before, can slow cognition or change cognition. Anytime there's a medication change, whether it's a Parkinson's medication or something else, I've seen bladder medications have some of these effects. Just keep that in mind: if you notice a sudden change, it could be medication related too, even over the counter.
Dr. James Beck 00:56:16
Yeah, thanks. I think one of those four things you bring up—socialization, exercise, diet, and sleep—seems so critical. I think the point you're bringing home is, regardless of the nature of your cognitive issues, whether it's Parkinson's or Lewy body disease, or you have some Alzheimer's going on, these activities seem to help raise the boat for all cognitive issues. Is that a fair interpretation?
Dr. Greg Pontone 00:56:48
Absolutely. They seem to have a global impact, regardless of where you are in the disease or what disease you have, or whether you have a combination of things at the same time. It helps in those domains across the board.
Dr. James Beck 00:57:03
Yeah, fantastic. Well, I want to thank you very much for your time, Dr. Pontone. The information you provided was fantastic. I want to thank everyone who was able to join us today. Not surprisingly, we had tons of questions, so we weren't able to get to them all. If your question wasn't answered, I want you to call our Helpline at 1-800-4PD-INFO as part of that process.
Also, you can go online and learn more and register about our Health @ Home programs, and there's a nice little QR code that's on the screen. If you have your phone handy, and hopefully you're not watching this on your phone, you can just hold it up to that QR code, or you can follow the website link down below and learn how to register for these programs. They're wonderful programs, and we have a little something in the link about them as well.
In the meantime, we're here. This may be the last expert briefing of our season. We'll start again in the spring, but come to our website, Parkinson.org, or reach out to our Helpline. My colleagues are amazing. They field all kinds of questions and reach out to others if they are unable to answer them, so feel free to do that as part of the process.
Lastly, before we go, I just want to remind you this whole expert briefing series has been tailored to you. The way we're able to do that is by your feedback. When this Zoom webinar ends, the screen will go black, and then what will happen is a page on your web browser will pop open and allow you to fill out our survey. Give us feedback on what you thought of Dr. Pontone's presentation and our series as a whole. We welcome anything you'd like to share. We look forward to hearing from you.
I'd like to thank everyone, and take care. We'll see you in the next expert briefing.
