Nancy Nealon 00:00:00
Hello and welcome to Veterans and Parkinson's: Exercise, Nutrition and Wellness. I'm Nancy Nealon, Senior Community Program Manager for the Parkinson's Foundation New York/New Jersey Chapter. On behalf of all of us at the Parkinson's Foundation, welcome to everyone attending today. That includes more than 300 individuals who registered for the webinar and a special edition for today, webinar watch parties. I would like to give a big shoutout and hello to our first watch party.
This is a special gathering for veterans and their care partners to watch this webinar together. Hello to Gloria and everyone watching at the Friedberg JCC in Oceanside, New York. Also, a big hello to Paula and everyone who has gathered at the Utica Center for Development Veterans Outreach Center in Utica, New York. Last but not least, all those who have gathered at the Western New York Health Care in Buffalo, New York. Thank you to everyone who has made these watch parties possible.
Our program today will consist of two presentations from Parkinson's experts from the VA health system, as well as answering your questions at the end of the webinar. We collect all the questions during the webinar so you'll see them disappear to organize and ask our presenters at the end. A few webinar watch tips for you: We share a lot of information in these webinars and realize it can be kind of tough to take it all in at once. But not to worry, we have you covered. This webinar is being recorded.
And you will receive a link via an email from us in about a week, and then you'll be able to watch the recording, any parts or the whole thing, all over again at your leisure. Sit back and enjoy. While I say sit back, we also know two hours is a long time to sit. Please remember, get up, stretch, go get a snack, do what you need to do. You won't miss anything because you're going to have the recording to refer to.
I'd now like to share with you important information about the Parkinson's Foundation. We are the nation's leading community for people living with Parkinson's disease and the people who love them.
And we are all working to end this disease. Our mission is to make life better for people with Parkinson's disease by improving care, advancing research towards a cure, and empowering and educating our global community.
We offer an extensive set of resources. In fact, I'm going to show you a couple of them live in person here. These are just a few of the examples.
Parkinson.org, our free educational book series that you can download or order in hard copy, a library of recorded podcasts and webinars like we're doing today, our hospital safety kit called the Aware in Care Kit. In addition, our helpline staffed by Parkinson's specialists is ready to assist at 1-800-4PD-INFO. You can contact the helpline to order any of these materials as well that I've mentioned.
In addition to webinars such as this specifically for veterans, we also offer weekly webinars through our PD Health @ Home program. Join us for Mindfulness Mondays, Wellness Wednesdays, and Fitness Fridays. These webinars are recorded as well, so you can always go back and watch those. And I'd like to invite any care partners, caregivers watching today to please join us on Saturday, October 29th. If you live near Tarrytown, New York, please consider joining us in person, but this will also be broadcast live on Zoom.
Nancy Nealon 00:04:08
We'd love to have you sign up, register, and attend the Northeast Region's Care Partner Summit.
I'd also like to share with you that part of the foundation's, the Parkinson's Foundation's commitment is to reach every person living with Parkinson's disease. A critical way we do that is through our partnerships. With more than 110,000 veterans living with Parkinson's disease, the foundation has established a formal partnership with the Veterans Administration. With the overarching goal to improve the quality of life for veterans living with PD and their care partners through greater access to education, resources, and support.
We have created a webpage dedicated to veterans living with Parkinson's at Parkinson.org/veterans. On this page is the FAQ guide that provides an overview of Parkinson's disease and VA resources, benefits, eligibility, and access to care. Remember, we're going to send all this to you in our follow-up email as well. We are honored to support all of you during your Parkinson's journey.
And next, I'd like to give a big thank you to our sponsor for today's program, Genentech, which is a member of the Roche Group for their generous grant to support our series of virtual programs for veterans living with Parkinson's. Thank you so much, Genentech.
And now, as we get ready to introduce the first speaker, and Dr. Morley is going to come on camera now, we are going to ask for all of you to join us in getting to be able to cast your vote in our first poll. We'll have two of the polls today. If you can take a look, how many days per week do you get at least 30 minutes of exercise? And you can see that you have several choices.
And people are voting now, which is great. Thank you so much. Cast your vote. We'll get everyone's opinion on this. You can weigh in.
And it's coming in, the results are coming in. I think we're looking pretty good here. All right.
Overwhelmingly, well, close to overwhelmingly, five or five or more days per week, which is fabulous, followed by three to four days per week. Many, many of you, are already involved and we hope we can reinforce and provide even more information about exercise and Parkinson's.
Now I'd like to invite Dr. Morley to join me and we will have him come up. I'm not sure, perhaps we're having... No, there he is.
Dr. James Morley 00:07:14
Yep. I think I've clicked all my buttons.
Nancy Nealon 00:07:18
Alright. Excellent. There are a lot of buttons to keep track of. We're going to stop sharing our screen and I will give Dr. Morley just a second to get his bearings and be able to pull up his screen.
And then I will stop talking and turn it over to you, Dr. Morley. Thank you so much.
Dr. James Morley 00:07:39
Thank you so much, for the invitation. And I think I have to switch this. Correct?
Does that look correct now?
Nancy Nealon 00:07:47
Yes, it's perfect. Thank you.
Dr. James Morley 00:07:49
Super. Yeah, great.
Thanks so much for the invitation to do this and for having this important webinar and for all the work that the Parkinson's Foundation does and in particular, the partnership we now have between the VA PADRECCs and the Parkinson's Foundation. I think it's wonderful. I also want to thank the veterans who are here. Thank you for your service. Thank you for your interest in this topic and congratulations on exercising so much. I hope I'm not preaching to the converted here, but we'll try to make this informational and have some real-world impact.
Just to briefly go through an outline of what I'll talk about today, I'm going to talk about sort of the efficacy of exercise, what kind of effects it has on Parkinson's symptoms with the idea that maybe different exercises could have different effects. I'm going to talk about what we know about activity and exercise levels in people living with Parkinson's disease, in particular what drives activity levels in Parkinson's disease and what might we be able to do to increase them. And if we have a little time for it, I'll tell you a little bit about some of the work we're doing. And then I'll finish up with kind of a real-world summary of how do we prescribe exercise like a medicine for Parkinson's. One of the things I'll try to convince you of is that exercise is a very powerful medicine to treat Parkinson's disease.
And so how do we treat it like a medicine? How do we prescribe it? How do we get patients to take it?
This is an outline here of the components of a brain wellness program. You can see that it is multifactorial, involving exercise, diet, stress management, meds, social connection, adequate sleep. Our second speaker, Dr. Duda, is going to talk about a few of these, and so I'll let him kind of talk about the synthesis here and I'm going to focus in my talk on fitness and exercise.
We all know that exercise is good for you, it does a body good. There are well-documented risk reductions for cardiovascular disease, for all-cause mortality, and for many chronic diseases, we prescribe diet and exercise. The idea that these sorts of interventions should affect brain health, is supported by the idea that both dementia and depression, two brain diseases, are reduced by exercise.
And we know from epidemiologic and clinical trial data that if you look at cardiovascular fitness that it's related to scores on cognitive tests in senior citizens, that midlife exercise is related to a reduced risk of dementia, and there's even some imaging type data looking at functional MRI showing that connectivity between different brain regions is influenced by exercise. Clearly, exercise affects the brain.
And when we look in animal models where we can look in a little bit more detail in what's going on in cells and molecules, we know that important brain growth factors, markers of synaptic connections, and the ability of the connections between neurons, the cells in the brain to change, and also for the brain to even grow new cells are all influenced by exercise. And so there's good reason to think that exercise will influence brain diseases. This is not a new idea. This is a graph of how many publications there are looking at exercise and Parkinson's from 2000 to 2020. And you can see that there's a very, very rapid growth.
Dr. James Morley 00:11:13
So now we have more than 400 academic papers per year, talking in some way or another about exercise and Parkinson's disease. This is also to apologize in advance that obviously I can't possibly cover everything that's going on, but we can start to talk about, what does exercise mean? It can mean different things to different people. There's four main categories that people think about, and those are shown here with some some examples. Aerobic or endurance exercise, strength exercises that generally use weights or some sort of resistance.
Flexibility exercises like yoga is obviously is a very popular one among our patients, and also just static stretching or traditional physical therapy. And then more balance-based balance-based exercises with physiotherapy, tai chi and qigong. And we'll talk about some more of these in detail. And also there's obviously overlap between many of these that if you do hot flow yoga, you are also getting an aerobic workout, and many different aerobic or strength exercises can also influence balance. And so this is really great.
It means that there are there's kind of an exercise for everyone and we'll come back to that. But it makes it a little confusing to study in a in a scientific way because there's a lot of apples and oranges here in clinical trials in terms of what interventions are looked at and what kind of outcome variables about symptoms are studied. And so one way that we kind of compare apples and oranges in clinical trials is to do something called a meta-analysis. And I'll spend just a second talking about what that is because we're going to look at a few of these. And it's basically looking at studies that have used the same outcome And so in this case, it's in red, the UPDRS-III. The main sort of motor test for motor function that we do in Parkinson's disease. And then each of these studies, or each of these lines, is one study. And then on the right, there is a little graph that has zero in the middle. And if the lines tend to point one way, it suggests that there was a benefit of the exercise intervention, and if the lines were on the other side, it suggests that there was no effect or that actually the control group seemed to do better in this particular outcome.
And really the thing to focus on, if you want to ignore all of that is that there's going to be a larger colored, diamond, it's a black diamond here shown at the bottom, that shows you the sort of the overall effect, when you combine all of those different studies. Now circling back, this is a, a meta-analysis that came out a few years ago now and there have been other ones that, say much the same thing looking at, more than 18 randomized controlled trials of different kinds of aerobic exercise.
It may have been treadmill running, it may have been biking, but in one way or another it was an aerobic exercise intervention. And in this case, they looked at this UPDRS-III motor outcome. Across 18 randomized controlled trials, so these are all high-quality clinical trials looking at more than 900 patients to in and mostly in early and mid-stage PD. As I said, multiple different kinds of interventions looking over about a month to six months. And you can see that when you look at the overall effect of aerobic exercise on motor function in Parkinson's, there's a significant effect here. This...
Dr. James Morley 00:14:48
Black diamond is shifted well to the left of the of the of the unity line.
We also see that aerobic exercise, so this is looking mostly at different gait or walking type tests, so the six-minute walk, stride length, walking speed, walking cadence, a test called the timed up and go, so looking at all of these different measures of gait, pretty consistently you can see that in this particular study they put the or this particular graph they put the favors exercise on the other side, but for most of these there's there's significant effect or significant benefit of aerobic exercise on all of these different gait outcomes.
This is a meta-analysis that looked at eight different studies of resistance exercise, so weightlifting or resistance bands or something like that. And they looked at over 400 patients from early to fairly advanced Parkinson's disease. And not surprisingly, perhaps, there was a very large effect on strength when they measured muscle strength. This was in, mostly weightlifting studies. And but there were really sort of more moderate to even not really effects on on balance, whereas there was still a moderate effect on on the UPDRS.
So a little bit of different pattern, looking at resistance training versus aerobic training.
And now looking at, this is a meta-analysis looking at, different studies that studied Tai Chi, in different outcomes in Parkinson's disease. And this is probably one of the best characterized and studied balance exercises in Parkinson's because it can be practiced by patients with many different levels of function, from, early, highly functioning patients to patients that are more advanced and may have more, difficulty with balance and getting around.
And you can see here that there were large effects on overall motor function that were seen mostly in the medicated state but not as much in the unmedicated state, but that there was both with and without medication there was a much larger effect on balance. And so, to contrast with what we've talked about leading up to this, Tai Chi does seem to have more of an effect on balance than perhaps some other features.
We can't discuss fitness in Parkinson's disease without referencing the important role of our colleagues in physical therapy and rehabilitation. And specifically the big and loud, which is a voice therapy, but the big PD-specific training method. As you are all aware, one of the sort of common features in Parkinson's disease is the slowness of movements and that movements get smaller, and this is represented in speech by a quiet voice or what we call hypophonia, and with motor function with slow movements or what we call bradykinesia.
The Lee Silverman Voice Therapy, so the voice version of this BIG Program was initially developed for speech and it's an intensive therapy based on increasing the size or the volume of the voice, but it turns out that also improves articulation and even swallowing. The Big Physical Therapy Program was adapted principally for rehab focusing on increasing movement amplitude, but also in turn improves the speed of movement and coordination. And this has been examined in a number of clinical trials and it's clear that there are improvements in overall motor function associated with these programs.
Dr. James Morley 00:18:30
And even more than that, I think that we have lots and lots of positive real-world experience, for patients with Parkinson's disease, being referred to physical therapy, rehabilitation medicine, and often using, these PD-specific programs.
And one point that I want to make is there's, and we have to remember this as much as providers as as you do, as people living with Parkinson's disease or their caregivers, that there's not a reason to wait, to bring, physical medicine, physical therapy into, into the mix here for what we call prehabilitation, and helping you to, discover how to implement, physical activity and exercise into your life safely, no matter what stage of Parkinson's that you're at. And we'll we'll come back to that closer to the end.
Just to mention very, very quickly as a very very much an overview, folks will often ask about, things that people don't always think about as exercise but has some of the characteristics of exercise. Dance or water therapy or using virtual reality or Nordic walking. This is a meta-analysis that looked at more than 1200 patients with 20 randomized controlled trials using very diverse interventions but sort of falling into that kind of alternative exercise space. And it was clear that each of these has some benefit, but it's not clear that any one is better than any other. And then we'll we'll come back to that important question a little bit later.
To summarize this this first little bit of the talk, I think it's clear that multiple exercise interventions improve motor symptoms in Parkinson's disease, that different exercise types may target different types of motor symptoms, so overall motor function, balance, walking, and that aerobic exercise probably has the broadest effects. It's sort of the broadest spectrum of the exercise treatments. And importantly, we sort of have this data from clinical trials, but there are some important questions that we'll we'll talk about closer to the end about how do we translate this into a treatment for Parkinson's disease.
Excuse me.
We know a lot, that I summarized very quickly about the effect of exercise on motor symptoms, but as as I'm sure many of very, very well that the non-motor symptoms of Parkinson's disease, such as mood problems, sleep problems, cognition problems, are are common, and very important because they cause they cause significant disability. And importantly, the medicines that we use for Parkinson's disease to improve motor function very often do not improve non-motor symptoms and sometimes can worsen them. Employing non-pharmacologic therapies for non-motor symptoms is potentially very important.
And I think the top line header here is that we think that exercise is likely to improve non-motor symptoms, in particular, mood, sleep, and cognition.
We are not as sure about this because they're usually not the primary focus of most of these exercise trials. They are sort of measured as what we call secondary outcomes. And very often for these sorts of exercise trials where you're trying to get people to be motivated and exercise more or to show up to study visit appointments, they select for patients that don't have a lot of cognitive dysfunction or don't have a lot of mood problems. And so it's it's been a little more difficult to demonstrate that with the same level of evidence. But there's very good reason to think from the general population and mental health literature that exercise should help with many of these, but we really do need more targeted studies and I'd like to talk to patients about that.
Dr. James Morley 00:22:07
We can think of it as a good side effect of using exercise to try to improve motor symptoms if we get some benefit for non-motor symptoms.
Just highlight a couple of areas where we have the most evidence about exercise and non-motor symptoms. This is again a meta-analysis that looked at nine different randomized controlled trials, more than 250 patients with moderate or greater disease, and with sort of one- to three-month durations with exercise with a targeted outcome looking at cognition.
And it involved treadmill, dance, tai chi, Wii Fit, cognitive motor training, and standard physical therapy. Again, sort of a variety of types of interventions, but overall, when you combine these studies, there were significant effects on on cognition. And if you separate it out again, some of these more aerobic things like treadmill training, that's where sort of the biggest bang for the buck seemed to be or the strongest effect of exercise on cognition.
But again, this is limited by, apples and oranges, different types of interventions, different types of outcomes, but certainly there's emerging evidence and good reason to think that exercise is good for thinking and memory and other elements of cognition in Parkinson's.
This is just one relatively small study that was done or published relatively recently, but it's important because it was a high-quality randomized controlled trial that was designed specifically to look at the relationship between exercise and sleep in Parkinson's, which is a significant problem. They looked at a total of 55 patients that were divided relatively evenly between a three times per week supervised exercise program versus a counseling control intervention where there was no exercise, but they discussed with study staff about sleep habits and sleep hygiene and the like. And this was done over a period of about four months.
And you can see in the graph here, if you compare these objective measures of sleep function, such as how much total sleep time, sleep efficiency, or slow-wave sleep as as measured by an EEG, that there were significant improvements or significant benefits relative to the counseling group for the exercise group. Interestingly, there were subjective measures of sleep, so sort of asking what people thought about their sleep quality and if they felt better in the morning and rested and those sorts of things, that those also improved in the control group as well.
And then this is absolutely as hot off the presses as you can get. I saw this on my little sort of feed of literature that I might be interested in this morning, and threw this slide together real quickly. This is a meta-analysis that hasn't even really been published yet. It's been accepted by the journal and they've put a version of it online looking at a meta-analysis of exercise and depressive symptoms in patients with Parkinson's disease, looking at 19 studies over 1,300 patients.
And you can see again just to skip to the headline that this colored diamond down here shows that there was a significant effect of different kinds of exercise on on depressive symptoms in patients with Parkinson's disease.
Dr. James Morley 00:25:29
Kind of the holy grail, I would say, of research in Parkinson's disease is trying to, develop therapies that not only improve symptoms that somehow modify disease progression. And there's some reason to think that exercise might be might be able to affect disease progression. Some of the lines of evidence for that is that There's epidemiologic data, so looking at large populations, people who report exercising more in middle age, so years before you would normally get Parkinson's, there's a significantly reduced risk of developing Parkinson's. And people who do get Parkinson's, it happens at a later age. There's this idea of either protecting against getting Parkinson's or delaying its onset. If you look in animal models and you you do animal models of exercise in animals that have been given a version of Parkinson's disease, that actually slows down or protects against the changes that you can see in cells.
And again, that growth factors in these animal models are increased by exercise. And a relatively until recently limited clinical trials looking at disease modification in exercise, there's some hint that maybe there could be increases in dopamine receptors, dopamine being one of the main chemicals affected in Parkinson's disease, indicating that maybe there were new cells that could respond to dopamine, that were influenced by exercise.
A couple of clinical trials that recently came out, that don't demonstrate, that exercise, affects disease progression, but I think start to hint at that. So this is a trial called the SPARX trial that looked at high-intensity, treadmill training, and the influence on, motor symptoms of Parkinson's disease.
It was over a hundred patients that were randomized to either no exercise, kind of a moderate level intensity exercise, and we'll talk more about sort of exercise intensity, and then a very high-intensity exercise getting up to, greater than 80% of the maximum heart rate. And importantly, these were very early.
Unmedicated patients. They were not taking levodopa, they were not taking dopamine agonists, they were not taking an MAO-B inhibitor or, Selegiline, something like that. That's important because one of the problems in detecting changes in disease progression is that people who are taking medicine are getting the benefit of their medicine. And so it's sometimes hard to sort out the benefit from the medicine from the benefit that you might be getting from the intervention. But here, exercise is the only intervention. These folks are not taking medication. If they're getting better in a randomized controlled trial, we'd argue that it's the exercise that's doing it.
And what we see here is that if you compare the change over six months in the UPDRS motor score, if your motor score gets higher, that means that there are worse symptoms. Not surprisingly, over six months, in the control group, there was a little bit of increase.
Sorry, I'm pointing at the wrong screen here. That there was an increase in the UPDRS score, so motor symptoms got worse on average. If you looked at the moderate intensity exercise group, there was a hint towards less progression, but it was not statistically significant. Whereas if you look at the high-intensity group, while there's some variation here, overall, there was essentially no disease progression over six months. Now it's a short window and changes in the UPDRS motor score are not A direct index of disease progression, but it certainly is as interesting and hopeful and it's hopeful enough that this trial has now moved on into another phase and is currently ongoing.
Dr. James Morley 00:29:15
This is another study there. There was a basically an aerobic Exerbiking study where that was done in the Netherlands where they kind of gave their patients Pelotons. It's good to be Dutch if you have Parkinson's disease. And then performed a randomized controlled trial of this Exerbiking, which importantly was done in the home. And not, patients didn't have to come in and go to study visits and things like that. Previously they've reported in well over a hundred patients that this exercise intervention significantly improved motor symptoms.
Dr. James Morley 00:29:54
In this study that I'm illustrating here, they looked at a subset of the people in that original study who had MRI studies of their brain and also underwent some different cognitive testing, and then compared how things looked at baseline compared to a six-month follow-up. They found — I'm not going to belabor the details here — that there were changes in connectivity between two different brain regions.
Importantly, the amount of change in connection between the brain regions was directly related, in different individuals, to how much they improved their fitness during the study. Again, not demonstrating or proving, but suggesting a relationship between this high-intensity exercise, changes in cardiovascular fitness and changes in brain connectivity that certainly could be related to changes in the progression of Parkinson's disease.
I alluded to this earlier: What's the right kind of exercise? What kind of exercise should I be doing? What's the best exercise? These are questions that frequently come from people living with Parkinson's disease. This is an example of one study — there are more — that tried to compare different forms of exercise, including aerobic exercise, stretching and resistance exercise. In this case, many outcomes were improved by all of the exercises, and there really wasn't any group difference between one exercise and the other.
That's good because it suggests that all of these exercises are helpful, but it also highlights that it's difficult to compare what might be smaller or different effects in these exercise studies, which generally involve relatively low numbers of people because they're hard to do and hard to get people to do.
Another recent study tried to address this question. This was an epidemiologic study, again looking at high-level patient databases rather than individual patients.
There was a Korean-based population study with more than 10,000 Parkinson's patients. That's one of the benefits of these so-called epidemiologic studies: you can look at many, many more people than you can in interventional clinical trials. These patients filled out a questionnaire where they said how frequently they exercised and whether they did high-, moderate- or low-intensity exercise. Then the investigators looked at the relationship between the intensity of activity and all-cause mortality.
Again, in an epidemiologic study, they can't do motor function testing on these individual patients. You have to look at data that's available in databases, such as when patients passed away. In these different graphs, you're comparing, in the dark line, folks who did not report doing this kind of activity, and in the yellow line, people who did. The lower line means that in each of these different cases, the rates of mortality were lower in association with activity. This was true whether it was light activity like housework, moderate activity like walking your dog or more vigorous activity such as treadmill running or high-intensity interval training.
Dr. James Morley 00:33:35
Importantly, any of these was good at reducing mortality in people with Parkinson's disease. When you looked at the relationship between intensity and outcome, basically the more intense activity was associated with a stronger effect on mortality.
We've talked a lot about clinical trial data, so how does this work in the real world? Importantly, the Parkinson's Foundation has done a wonderful large QI study where they've looked at care patterns and outcomes in Parkinson's Foundation Centers of Excellence. These are two papers that have come out of that study looking at exercise and different outcome variables. The first showed that exercise improved quality of life and self-rated mobility in Parkinson's disease over time. Importantly, exercise was also associated with decreased risk of hospitalization for patients with Parkinson's disease. Important real-world outcomes are affected by exercise in Parkinson's disease as well.
Moving on to the second part of thinking about this: if we assume that exercise, in some way, shape or form, is efficacious — meaning it showed benefit in a clinical trial setting — how can we make it an effective medicine? How can we actually get it into the hands of patients living with Parkinson's disease and derive the benefits? You could have the most effective drug in the world in a clinical trial, but if it's too expensive, has terrible side effects or can't get in trucks to pharmacies, it won't be effective because patients won't take it and they won't get better. As part of that, I think there are two questions. One is, how do we prescribe exercise like a medicine? And B, will patients take it if we prescribe it?
I'll talk about the second part first. This is one of our former fellows, Sneha Mantri, who's now at Duke, who did an interesting study and looked at self-reported exercise in the Parkinson's Progression Markers Initiative, or PPMI. PPMI is a large longitudinal study over time looking at Parkinson's disease progression and markers of progression.
These patients had filled out a questionnaire about how much they exercised and how intensely they exercised. Sneha compared that to guidelines that existed at the time by the American College of Sports Medicine about how much and how intensely to exercise. Shown here is a comparison of controls to people with Parkinson's disease for moderate activity, vigorous activity and strength training. Interestingly, Parkinson's patients reported just about as much exercise for moderate and vigorous activity overall, and less for strength training, but fewer than 40% of patients met these goals for the American College of Sports Medicine exercise guidelines. More than 50%, if you look at these graphs, basically reported never exercising.
This was an early population with Parkinson's disease, and they were already involved in a clinical trial, so they might be highly motivated. It might even be worse in other populations. I don't have time to go through it, but Sneha did a second study in veterans where she showed that self-reported activity levels were even lower. Importantly, she also included a questionnaire to try to understand something about the attitudes of our veterans with Parkinson's disease toward exercise and to start to get a handle on why some people do or don't exercise.
Interestingly, this is showing motivators of exercise, and I've highlighted two that were outliers compared to the others. In our study, veterans actually said, 'I did not prefer to be in a scheduled exercise program,' and, 'I did not prefer to exercise with others,' which we were a little surprised by given the popularity of things like Rock Steady Boxing or other group exercise classes.
When we looked at barriers to exercise — what kept people from exercising — our veterans were particularly affected by conditions outside of Parkinson's disease, such as their general medical health and factors like pain. The takeaway from this is that we have to take these factors into consideration, not just think about Parkinson's disease status. We need to take a more holistic approach to motivating our patients to exercise and designing interventions for exercise in Parkinson's disease. Very importantly, we have to make this individual. The motivation to exercise is individual, so we have to develop programs that are tailored to individuals.
Dr. James Morley 00:38:52
This is a more qualitative analysis that Sneha did on open-ended questions rather than rating scales. Among the health domain, fear of falling was a barrier to exercise, and several other groups have reported this too. Other medical comorbidities probably lead with motivation, which are prevalent in Parkinson's disease. A motivator to exercise was the desire to maintain independence and increase health.
In terms of the social domain, exercise partners and PD-specific programs were things that motivated exercise. That is in seeming conflict with our observation that veterans did not want to exercise in groups or be part of scheduled programs. What we learned from the more free-form answers was that it was really the stigma associated with exercising in a large group with Parkinson's, and that people with Parkinson's felt much more motivated to exercise if they were exercising with other Parkinson's patients. That's important to remember and probably explains much of the success of things like Rock Steady Boxing and PD-specific exercise interventions.
I'm going to take just a second here to tell you about one of the things we're trying to do to increase physical activity levels in people with Parkinson's disease. It's derived from a concept called nudging in behavioral economics, which is changing behavior through simple changes in the way you present information — not large, heavy-handed interventions. One of the ways this has been done in a variety of settings is through something called gamification.
Gamification applies game elements, such as levels or points, to a particular intervention. These are collaborators, Nitesh Patel and Kim Waddell, who work in what's called the Nudge Unit at Penn. They've used these sorts of interventions to increase activity levels in a variety of disorders, such as diabetes and obesity. We're currently doing a study now to try to use these types of interventions to increase physical activity levels in people with Parkinson's disease. It's interesting in the era of COVID because we're able to use wearable sensors and digital health platforms. This is a touchless clinical trial, so people in this trial never have to come into the office.
If you live in the Philadelphia or tri-state area and you're a veteran with Parkinson's disease, I think my email contact should be on here, so please feel free to reach out if you'd be interested in something like this. We recruit folks with Parkinson's disease who complete all of their consent, demographics, surveys and assessments online. We send folks a Fitbit that they can wear to track their activity levels.
You get linked up with a digital health platform at Penn called Way to Health that automatically collects all of this fitness data. Then we're enrolling folks in what's called a gamification intervention. Basically, we measure step counts for two weeks at baseline. We ask participants to increase that step count by 20% over a six-week gamification intervention where, if you meet your goals, you level up. If you don't meet your goals, you level down. Then there's a little bit of a prize at the end.
Then we do a four-week follow-up period where we get rid of the intervention to see if there are increases in activity levels during this gamification intervention, and if they last after the game ends. We're using another wearable sensor that some of you may be familiar with, the Parkinson's KinetiGraph. It's a commercially available watch-like device that can measure tremor, slowness and other things with Parkinson's disease.
I just wanted to make you aware of a study like this. I should not have used the word advertised. That's not what I'm trying to do, but I think this is an interesting and exciting approach to increasing physical activity levels in Parkinson's, and we really have to learn how to do that in the real world.
Dr. James Morley 00:43:24
All right. In the last few slides, I'll talk about how I hope I've convinced you that exercise can be as beneficial as medicines that we prescribe by mouth for people with Parkinson's disease. I think we have to think about how to prescribe it like a medicine. I'll make the caveat, with this cartoon, that I've been talking about a lot of different evidence and clinical trials. We are leaving that realm, and we are now firmly in the realm of this is my opinion, for whatever it's worth. Your mileage may vary.
Here's a prescription. I'm sure many of you have seen a prescription like this for carbidopa levodopa. You probably have never seen a prescription that says, 'Carbidopa levodopa: make sure you take some.' We don't do that. What we do is prescribe 25/100. We want you to take one pill by mouth three times a day. We're going to do that for 30 days and check in and see how things are going. We have a type of medication, an amount of medication, a frequency and how long we're going to do it for.
I think we very much have to start thinking about exercise in the same way. Rather than saying, 'Get some exercise,' we have to say, 'I want you to do power walking for two miles. You're going to do that on foot. You're going to do it once a day, and then after 30 days we'll check in and see how you're doing with it and think about refilling that prescription or seeing if we have to alter it.'
If we're going to do that, are there guidelines about what people with Parkinson's should be doing as far as exercise? This is a little cutaway of recent Parkinson's Foundation guidelines that were developed in concert with the American College of Sports Medicine. The upshot is very similar: we'd like folks to be getting 150 minutes, or two and a half hours, of moderate-to-vigorous exercise per week. You want to use different modalities such as aerobic activity, strength training, balance and agility training, and stretching.
Importantly, you should use physical therapists to think about safety, and you have to continuously think about how this program is working for you and modify the routine over time. I think that's also illustrated in this little cartoon that I've made here. Exercise is a medicine that's appropriate at most, if not all, stages of Parkinson's disease, but we have to differ in the way that we prescribe it along the disease continuum, very much in the way that we change the way we prescribe medications.
For example, aerobic exercise can probably help with most symptoms. We would like people to get aerobic exercise at all disease stages. For early patients, it's a little easier. We can say, 'Go do whatever works and whatever feels good. Get on a bike, get on a treadmill, swim laps — whatever works,' at early stages of disease when physical capacity is not as much of a limitation.
Similarly, with strength training, you may be able to do whatever you want in early Parkinson's disease — do kettlebell training, do whatever you'd like — but as you move into later stages of Parkinson's disease, you might have to modify that. It might be resistance bands for weight training, aqua aerobics or just using a hand bike pedal to get your heart rate up and achieve aerobic exercise.
Similarly, balance and flexibility exercises like tai chi are probably beneficial along the entire disease continuum and probably start to become even more important as gait and balance become more prominent features of disease in later-stage Parkinson's, and aerobic and strength training may become somewhat more difficult.
Again, it's this idea that we have to change the prescription for exercise over the disease course to target different symptom types and accommodate different levels of physical ability along the continuum of Parkinson's. At any stage, we probably want to use a multi-domain approach where you're attacking this from different angles.
While, for an early-stage patient, we might prescribe high-intensity treadmill training for two miles, as mobility becomes more of an issue, maybe it changes to a stationary bike or getting in the pool and doing aqua aerobics, where you don't rely on balance as much. At different stages of disease, you may need a targeted intervention like speech therapy or Big physical therapy to target balance and gait. In later stages, it might be more tai chi than treadmill. In all of these times, we should be thinking about how to specifically target exercise prescriptions to individuals and to the individual disease stage.
I'll finish up with my conclusions. Exercise and physical activity are good medicines for Parkinson's disease symptoms at any stage. I think there's emerging evidence that it might be something that could modify disease progression, but we're still holding out for real concrete evidence on that.
In terms of what's best, there are more studies, and I don't really know that this is going to get resolved. I think the real answer is whatever you can motivate yourself to do is the best exercise at any stage. In the meantime, it's really important while we're waiting for these answers to work with your provider, but also physical therapists, to help determine the right exercise prescription for you.
It's one thing to say that your neurologist or Parkinson's provider should write you a prescription for exercise, but we really have to do that with the input of physical therapists who can spend more time than is available in most office visits to talk about your motivation, your abilities and what is the right and safe exercise for you. The last thing is that, just like your medication prescription changes over the course of disease, we have to think about changing our exercise prescriptions to target individuals and to target the disease state.
I'll stop here and see if we have questions that have appeared in the chat or anything else people are interested in. This is just a little cartoon that we'd all love to have an exercise pill where you get all the benefits of exercise. There is an exercise pill. It's just that you have to take the pill and then take it out for a jog, take it to the gym and get on a bike with it, and it'll work just fine. Thanks very much again for the opportunity to talk to you today. It's really a treat to do this and be part of this. Thank you.
Nancy Nealon 00:50:20
Thank you so much, Dr. Morley. Really great cartoons. I need to offer you a huge apology because, in my quest to get our poll up before you even started, I neglected to tell our wonderful audience that you are the co-director of the Parkinson's Disease Research, Education and Clinical Center at the Philadelphia VA Medical Center and also an assistant professor of neurology at the University of Pennsylvania. I'm sure people are not surprised by that astounding title. We are going to include both you and Dr. Duda's bios in our follow-up email to everyone.
Thank you so much for all of you tuning in. Dr. Morley, although we're saying goodbye to him right this second, will be back at the end for our Q&A. Dr. Morley, go have a break. Thank you so much for your great presentation.
Dr. James Morley 00:51:14
Okay, thank you.
Nancy Nealon 00:51:15
Now it is my honor to ask — and Dr. Duda will be coming up here in just a second. Hello, Dr. Duda. Thank you so much for joining us. I'm going to get it right this time. You are the director of the Parkinson's Disease Research, Education and Clinical Center and co-director of the Center for Neurotrauma, Neurodegeneration, and Restoration at the VA Medical Center in Philadelphia, and also professor of neurology at the University of Pennsylvania. Thank you so much for being here.
Before we ask you to bring up your slides, we are going to check in with our audience again and ask everyone to participate in this poll. In case anyone is having difficulty seeing it, the question is: What is your opinion about how your diet can affect your Parkinson's disease? If everyone watching from our watch parties or from home would please cast your vote, we'd love to know what you think about our question: Does your diet affect Parkinson's disease?
This is great. We have a lot of people casting their votes right now. We'll have results in just a moment. Thank you to everyone participating. We'll give it just another second or two. We've got great participation happening here. Interesting.
Okay, our results: a good number, 36% of respondents, think that eating healthier helps to treat some of their Parkinson's symptoms. Dr. Duda, you've got a great audience. I'm sure you're going to provide them with even more information. With that, I'll invite you to share your screen and take over. Thank you so much.
Dr. John Duda 00:53:11
Thank you. Let's see, one more click.
Nancy Nealon 00:53:27
There you are. Thanks.
Dr. John Duda 00:53:30
Thank you, Nancy. Welcome to everybody. As Dr. Morley mentioned, I am very grateful to the Parkinson's Foundation for inviting me to participate in this symposium, and even more grateful to all of you who are in attendance, especially those of you who are veterans. I just wanted to take a moment to express my appreciation for your service and sacrifice.
This is going to be a little bit of a whirlwind tour of the rest of this chart. Some we will delve into a little bit deeper than others, but this is part of what I try to get my veterans with Parkinson's disease to practice, which is a whole program of lifestyle choices that we believe can affect your brain wellness. They certainly can improve your wellness in other ways, like reducing the risk of heart disease, cancer, stroke, hypertension, diabetes and just about every other chronic disease we suffer from. They very well may improve your PD symptoms and perhaps even your PD progression. Some of that we're still doing the studies to prove, but we think it's entirely likely. Like I said, the side effects are mostly all good things.
Starting out with diet and nutrition, this schematic shows — and please don't try to read it or understand it; just take my word for it — that this is a fairly up-to-date representation of what we think is going on in the cells of people with Parkinson's disease that may be problematic. There are a lot of different problems here, and we don't have any magic pill that stops one part of this chain of events and stops the disease.
There are obviously many clinical trials underway, but we've been trying to do this for, I don't know, 20 or 30 years, and unfortunately we haven't come up with anything that clearly stops the progression. In addition to all those pharmaceuticals, there are innumerable compounds that are found in food that can affect these things as well. Most of this evidence is from test tubes, animal models and things like that, but the food we eat has more than just sugar, salt, fat, protein and vitamins. It has innumerable compounds that, when taken orally, are a lot like drugs and can have similar effects to drugs.
Dr. John Duda 00:56:15
All of these components of the chain of events that occurs in the cells of people with Parkinson's disease can be affected by these compounds. Frankly, I think it's unlikely that any one of these compounds is going to end up being a silver bullet that cures Parkinson's disease. But just like in our treatment of HIV, cancer and a lot of other really tough problems, it's likely going to take a battery of different compounds treating different aspects of a condition to really slow down or stop the progression of Parkinson's disease.
In my humble opinion, until we figure out what that combination may be, I think it makes sense to flood your body with these compounds in levels that we know are safe, because they're normally eaten by millions of people around the world on a daily basis, by eating foods that are high in these types of potential therapeutics.
Why do I think that might help your Parkinson's disease? This is a study from a friend of mine, Laurie Mischley at Bastyr University in Washington. It's called the CAM Care in PD study. CAM is complementary and alternative medicine. What she's doing is trying to find out what people with Parkinson's disease are doing to treat their disease themselves, something that is not very well studied. The way she's doing that is through an online study.
If you just Google CAM Care in PD, you will find the website, and you can join it yourself. It's a voluntary study that is all online. As an outcome measure for how well your symptoms are being managed, it uses another instrument that she developed, the patient-reported outcomes in PD measurement scale, or the PRO-PD.
There are 28 questions that involve all different aspects of Parkinson's disease symptoms, things like falling and rising from a seated position, dressing, eating and grooming. Online, at www.propd.org, you can go and take this scale yourself. You take these sliders and say, for falling, if I never fall, you leave it here. If I fall occasionally, you move it somewhere over here. If you fall daily, move it somewhere over here. Then she totals up these scores and gets an overall assessment of the severity of your PD symptoms without ever seeing you in person or laying hands on you to assess your symptoms. It's a patient-reported outcome, which is gaining in popularity in clinical trials.
Using that PRO-PD score and thousands of people who are already in the study, she can generate figures like this. This is looking at your score in that PRO-PD score. If you have zero symptoms, you'd be down here. If you got 2,800, I guess that would be the highest because you got up to 100 on each one.
Dr. John Duda 01:00:08
All these dots are one person with Parkinson's disease who has had the disease for this number of years. This person has had it for a little over five years and has very minor symptoms. This person has had it for 17 years and has a lot of symptoms. What she is trying to do is find out what is going on with what she calls the positive deviants: these people who have had symptoms for 10, 15, 20 or 25 years, and yet their symptom burden is still good to excellent - low amounts of tremor and falling and depression and things like that - and seeing if there's some magic combination of lifestyle choices they're making to affect their outcome.
One of the things she has already looked at is their diet, using a food frequency questionnaire that asks people how often they eat this and how often they eat that, and how those scores affect the PRO-PD score. She has come up with lists of foods that seem to protect or affect it in a positive way, meaning you generally have a lower score on that outcome if you eat fresh fruits and vegetables, nuts, fish, olive oil, wine, turkey, coconut oil, fresh herbs, spices and things like that.
Again, it's an observational study, so we can't say for sure about cause and effect, but in general, people who eat more fresh vegetables have a lower score on that symptom severity scale. Alternatively, there are certain things that are typically associated with raising your symptom burden on that scale, including canned fruit, diet soda, canned vegetables, fried food, beef, soda, ice cream, yogurt and cheese, and some things that don't have much of an effect either way.
If you look at all of the things that seem to be beneficial, they resemble something like the Mediterranean diet, which I think most of you have probably heard about. It's a diet or nutritional pattern where you focus mostly on whole foods, like whole grains, fruits and vegetables, lower amounts of olive oil and high-fat foods, lots of seafood, and smaller amounts of cheese, poultry, meats, desserts and things like that. The things that seem to be associated with lower symptom burden fall in line with this type of dietary pattern. Based on that and a lot of other studies, which I'll go into a little bit, I do suggest that people eat something like the Mediterranean diet.
Dr. John Duda 01:03:23
One of the big side effects, if you want to call it that, of the Mediterranean diet is that it almost certainly reduces your risk of getting dementia or cognitive impairment. Obviously, one of the main concerns of a lot of people with Parkinson's disease, in addition to limitations in mobility, is limitations in thinking. There's overwhelming evidence that dietary patterns like the Mediterranean diet reduce your risk of developing that. I think that alone is a good enough reason for me to eat a diet like this.
If it slows down my Parkinson's progression if I had it, then great, but this is enough for me. General rules about nutrition: for varying reasons, evolution and other things, we get a lot of pleasure out of food, and that's important. I certainly don't want you to slow down or stop the progression of your Parkinson's disease if you're going to be miserable for the rest of your life. Food gives us pleasure, so eat what you need to eat to be happy. If you have to have a cheeseburger every week to be happy, then have a cheeseburger every week. If there are certain foods you don't like, don't eat them.
There are plenty of healthy choices out there. The main note is that food is also supposed to nourish us. The rest of the time, if you're not eating food to be happy - and I think people would do well to find other sources of entertainment other than their food - then eat the things that make us healthy. That means eating mostly a whole, unprocessed plant-food diet.
That includes nuts, seeds, vegetables, fruits, beans, other types of legumes, whole grains, teas, spices - anything that comes from a plant, basically. Eat more of those and eat them as unprocessed as possible. The problem with processing foods is that you lose nutrients when you do that. Eating them as close as you can to the way they come in the produce aisle is probably a good idea. Eating more variety and color is probably also a good idea.
All of these compounds that we get from plants tend to work together in synergistic ways. If you're trying to take turmeric to get some curcumin, something many of you know about, if you just take turmeric, you're not going to absorb very much of it. But if you take it with a little bit of pepper, there's a different compound in pepper that increases the absorption of curcumin by about 1,000%. Eating a variety of different plant foods at the same time and at different times is great.
Dr. John Duda 01:06:39
We also like to say, eat the rainbow. The more color, the better, because often those colors are generated by the compounds that are giving the beneficial effects. If you have a choice between a red onion, a green onion and a white onion, eat the red one. Red cabbage versus white cabbage, eat the red cabbage. Try to eat all different colors on your plate every day.
In general, following something like the Mediterranean diet or the MIND diet - which is a combination of the Mediterranean diet and a diet originally called the DASH diet, developed for the prevention of hypertension - may be the best choice currently. Any one of those two, or what's called a whole-food, plant-based diet, will almost certainly be helpful. If you want to eat the MIND diet, I like it because it's fairly straightforward. You don't have to count calories, and you don't have to keep track of all kinds of different ingredients. There are 10 things you try to eat more of and five things you try to eat less of.
This was developed essentially to help people prevent getting dementia, which is something really important for all of us, including those of us with Parkinson's disease. The 10 things you want to eat more of include green leafy vegetables, six or more servings per week, so once a day. Other vegetables: at least one other vegetable in addition to the leafy ones once a day. Berries twice a week. Berries are loaded with antioxidant and anti-inflammatory compounds, two classes of compounds that we think are very important. It says at least twice a week, but eating them every day is probably even better.
Most people in America don't eat enough nuts, and there are a lot of healthy components in nuts, including healthy fatty acids, fiber and other things. Eating a handful of nuts is a good idea, depending on the situation with your weight. If you're having trouble keeping your weight down, then eating a handful of nuts and not more is probably a good idea because they are high in calories. But many people with Parkinson's disease have difficulty maintaining their weight, so eating lots of nuts and seeds, nut butters and seed butters are great ways to increase caloric intake and maintain weight. If you're using oils, using olive oil as your main oil is part of this diet.
Dr. John Duda 01:09:32
Then whole grains. Rather than eating white bread, white pasta, white pizza dough and things like that, eating foods made out of whole wheat or other whole grains, or just eating the whole grains themselves, is a big part of the diet: three servings of those per day. Eating fish at least once a week is recommended. If you're going to eat fish, eat fish that are high in omega-3 fatty acids, including salmon, sardines, mackerel, anchovies and things like that.
Eating more beans is important - at least four servings per week of beans, and I tell people to eat even more than that. They do say to try to eat chicken or turkey at least twice per week. I think you can argue about whether adding chicken or turkey to an otherwise plant-based diet definitely gives you more benefit. It may be that this is partially to eliminate more of the red meat in the diet, but that's part of the recommendation.
Then drinking no more than one glass of wine a day. For a lot of people who eat a diet that's not so good, drinking a glass of wine gives you exposure to some resveratrol and other compounds in wine that you wouldn't get normally if you're eating a standard American diet. But alcohol is a toxin, and it's not clear that wine is actually good for you if you eat a really healthy diet. For the average person, drinking one glass of wine may be a good idea.
Then there are five foods they suggest limiting. They want you to limit processed oils like margarine, avoid trans fatty acids and keep things like butter to less than a tablespoon a day. Cheese should be less than one serving per week, which I think a lot of people find difficult, but there are good reasons, with the saturated fat and other parts of cheese, to try to avoid it. Red meat: no more than three servings per week. Again, I think you could argue that there's nothing you can get out of red meat that you can't get out of other plant foods, so eating even less than that may be an even better idea.
Fried foods, obviously, have lots of problems with them, so eating them less than once per week is a good idea. The same thing with sweets. Again, these are treats, and if you have to eat them to be happy, then of course do it, but if you don't, try to avoid them. If you want more information, just Google the MIND diet online and you'll find all kinds of sources. The one from Healthline.com is a nice resource for finding out more.
Dr. John Duda 01:12:44
If you want to learn a lot more about nutrition and Parkinson's disease, I encourage you to look for this previous webinar that I did with the Parkinson's Foundation about five years ago, where we talked for a whole hour about nutrition, the gut microbiome and more recommendations about what I suggest people with Parkinson's disease eat. Obviously, it's hard to copy this web address down, so if you go to YouTube and search for Parkinson's Foundation Expert Briefings, the title is Nutrition, Parkinson's Disease and the Gut Microbiome. That will be the first thing that comes up.
The second part of this all-around wellness program that I wanted to talk about was stress management. We all have stress, and we all know that it probably leads to some of the chronic diseases that we suffer from. There's a really interesting paper out of a Dutch group headed by Bas Bloem talking about how stress and mindfulness may affect Parkinson's disease. It includes hypothesizing about how chronic stress elevates glucocorticoid levels, the stress hormones we express when we're under stress, and how those things change processes in the brain and may affect the cells in your brain, leading to things like Parkinson's disease. It's an interesting attempt to explain why it's a good idea to decrease your stress levels if you can and find better ways to deal with them if you can't.
They looked at the literature to date on mindfulness, which is one way to reduce stress. Of the eight trials that have been done in Parkinson's disease and mindfulness, six out of eight showed an improvement in depression, and four out of seven showed an improvement in anxiety scores. Motor symptoms were only studied in three different studies, but two of them reported significant improvements after starting a practice like mindfulness.
The same group put out another study where they surveyed 5,000 patients, similar to the study Dr. Mischley was doing, and asked them about their stress and mindfulness. Not surprisingly, people with PD experience more stress than controls, and they had higher levels of anxiety and depression, and lower scores on the state level of mindfulness. I think most of you know that when you're stressed, your tremor gets worse, your stiffness may get worse and other symptoms get worse. They confirmed this in the study as well.
Dr. John Duda 01:15:14
A couple of interesting things came out of it. Of all the people in the study - 5,000 people - there were different things that we know can help decrease your stress level. We know that physical therapy and physical exercise can decrease the amount of stress you're feeling, and many people were taking advantage of these and getting benefits from them. Relaxation exercises, like yoga or stretching, can help. There are all kinds of different things that could be included in that. Then mindfulness, which is a type of meditation that I'll explain in a second.
Lots of people are doing these things, and I encourage you to as well. This is self-reported, so obviously people know if they're doing physical therapy or mindfulness meditation, but according to them, the effects of mindfulness on their PD symptoms were positive in nearly every example, decreasing anxiety, depression, tremor, walking problems, sleep problems, slowness and dyskinesias to varying amounts, but all of them in the positive-effect range.
More importantly, or equally important, is that the more you do, the more benefit you get. In this graph, they show how many times you're doing a particular relaxation technique and how much you think it improved different symptoms. For depression, if they practiced mindfulness less than once a month, they had a certain level of depression. But as they increased from a few times a month to weekly, several times a week, daily and several times a day, the amount of benefit they perceived increased in nearly every symptom. The main reason people hadn't done it was because they hadn't thought about it or didn't know anything about it, but they were interested.
One other study that supports this came out a couple of years ago looking at an actual mindfulness intervention in PD. They had 138 subjects randomly assigned to either eight weeks of mindfulness yoga or stretching and resistance. They had one session with a leader and were asked to do two other 20-minute sessions per week. It was not a terribly big burden, but they saw good improvements in depression, anxiety and quality-of-life scores.
Dr. John Duda 01:18:43
Maybe most intriguingly, they saw fairly robust decreases in overall motor function. The MDS-UPDRS is the way we measure motor symptoms in Parkinson's disease, and they showed about a one-third reduction in those, which, if you had a medication that did that, would get FDA approval immediately. Again, it's open label, so you have to take it with a grain of salt. You don't know if they just felt their symptoms were better because they knew they were doing these interventions, but it was compared to a stretching and relaxation exercise program, and that didn't have the same magnitude of effect. There may be something special about mindfulness meditation.
What is mindfulness? You can define it as the basic human ability to be fully present, aware of where you are and what you're doing, and not overly reactive or overwhelmed by what's going on around us. That's a definition from Mindful.org. Essentially, it's the ability to be aware of what's going on in this present moment without judging it.
I do this with all of my patients. I tell them to close their eyes and try to focus on their breathing for as long as they can. Within seconds, literally, most people realize that they're thinking about something else other than their breathing. That proves that we're not really too good at focusing our attention on something for very long without having other thoughts pop up. A lot of times, those thoughts aren't very helpful. But all of us have the ability to be mindful.
When you're focusing really hard on something like a sport or driving, we're usually more mindful. Obviously, some people aren't very mindful when driving, but this state of being aware of what's going on right here, right now, without judgment can be strengthened with training, and that's called mindfulness meditation. There are many different forms of mindfulness meditation, either focusing on your breathing, walking, eating or anything that's happening right now. If you focus on that instead of worrying about what happened in the past or what's going to happen in the future, you're being mindful.
Dr. John Duda 01:21:11
There are other types of practices within the mindfulness tradition as well that can help with other things, like improving your compassion, quality of life and outlook. If you just Google mindfulness, you'll find a million different resources. Some of them are better than others, but I encourage all of you to look into it and try to find something that you think may be helpful. If you want, in the discussion, I can give some recommendations for apps that are particularly useful, or webpages or whatever.
Next is sleeping. I think most of us know and recognize that sleep is very important for our mental and physical health, and people with Parkinson's disease have a problem because they often don't get enough. There are a number of sleep problems that happen in Parkinson's disease, some fairly specific to Parkinson's disease and some not so much. These include insomnia, having difficulty falling asleep, and having your medications wear off at night, so you have difficulty turning over in bed and wake up because of that or other symptoms.
There's something called sleep fragmentation, where you fall asleep okay - you don't have insomnia at the beginning of the night, and this is probably even more common than insomnia - but after a certain amount of time, you wake up and feel like it's morning. You feel wide awake and can't get back to sleep. There's something called REM sleep behavior disorder, where you act out your dreams, often punching, kicking, yelling or hurting yourself or your bed partner, which is a fairly specific symptom of sleep dysfunction in Parkinson's disease.
Then restless leg syndrome. There are more people with restless legs who don't have Parkinson's disease than people who do, but a lot of people with Parkinson's disease express symptoms like that as well. Sleep apnea is very common in the general population, so it's going to be very common in the Parkinson's population as well. We know that untreated sleep apnea has detrimental effects on your vascular system, your heart and your brain, so getting that addressed is important too.
Dr. John Duda 01:23:23
Excessive daytime sleepiness is also a problem. Obviously, if you don't sleep well at night, you're going to be sleepy during the day. But some people sleep through the night and feel restored. I ask my patients, when you wake up in the morning, do you feel like you've had a good night's sleep? If they feel that way, I'm less concerned that they have a primary sleep disorder. Most people with PD don't, so I often refer them to sleep specialists, but some people do sleep well and still feel sleepy. There are different ways we can manage that as well.
Don't forget to talk to your physician about sleep. Most good movement disorder neurologists will talk about sleep problems, but often general practitioners or general neurologists will not. It's up to you to bring up whatever symptoms you're having with your sleep and discuss them. Consider involving a sleep specialist if you think you're not getting an adequate response from your typical provider, because many of these problems have good treatments. Some of them are pharmaceutical, but many are not.
If you have sleep that is non-restorative, meaning you don't wake up feeling refreshed, I think most of those people should have a sleep disorder referral and a sleep study. If you have insomnia, especially beginning-of-the-night insomnia where you lie in bed for hours trying to get to sleep, try something like the CBT-I programs. If you're a veteran, you can easily get this in the VA. It's cognitive behavioral therapy for insomnia. In fact, it's the number one recommended therapy for insomnia in the VA before you try medications and things like that, and it often helps.
Dr. John Duda 01:25:20
For everybody who is having trouble with their sleep, learn about and practice sleep hygiene. Just like if you didn't shower and clean yourself regularly, your personal hygiene would suffer. If you don't practice certain things regarding sleep, then your sleep hygiene suffers. This is a quick list of some things involved in typical sleep hygiene programs, including maintaining a regular sleep schedule.
Basically, all of these are intended to train your brain that when you're going to sleep, you're supposed to sleep, and when you're not in bed, you're not sleeping. Improving the atmosphere around where you're sleeping, and improving the likelihood that you're going to fall asleep and stay asleep, is the idea. If you just Google sleep hygiene, you'll find many good references.
It's things like not exercising, drinking alcohol or having big meals soon before you go to sleep, because those things tend to impair your sleep. Lowering the light, and often the temperature, as you approach bedtime can be helpful. We all know about blue light and how it can affect your sleep. Not using a screen, like your phone, TV or computer, for at least an hour or more before you go to sleep is important. When you're doing that, you're telling the parts of your brain that used to wake you up in the morning when the sun came up that it's time to get up. Your brain doesn't know the difference between sunlight and the blue light coming out of your iPhone. It's important to limit that before bedtime. I encourage you to try those things.
Dr. John Duda 01:27:33
Social connection is the last one of these that we're going to talk about, but there's a growing recognition that it is very important. Obviously, COVID led to some of that recognition because of all the disconnection we experienced during COVID. This is a study from my colleague Indu Subramanian using data from Dr. Mischley's CAM Care in PD study. It looked at things other than diet, like exercise. The more you exercise, the lower your score on that PRO-PD symptom severity score.
If you exercise 30 minutes a day, three days a week, you have a very good benefit. If you exercise seven days a week like that, you have an even better benefit. But if you have lots of friends, it's almost as good as exercising three days a week. If you practice stress management, like mindfulness meditation, it's a good benefit. It's like eating a lot of fruits and vegetables. But if you have a lot of stress, or especially if you self-report as being lonely, you have a very detrimental effect on your symptom severity as assessed by this one study. It's difficult to untangle all the effects of all the different things we're looking at, but suffice it to say that there's good reason to believe that if you're lonely, your PD symptoms are going to be worse, and if you have a lot of stress, they're going to be worse as well.
Dr. John Duda 01:28:57
Maybe even more importantly, every symptom you have is going to be worse. This blue outline is for people who do not feel lonely. This is the severity of their symptoms. For sexual dysfunction, they have this much. But the people who do feel lonely report having this much - 34 compared to 47 - and this is visual disturbances. Every one of these symptoms is worse in people who feel lonely. Depression is a big one, and it's possible that depression can make other symptoms feel worse, so sometimes it's difficult to untangle that. But people who are lonely are often depressed.
Improving social connection, the number of friends you have and how often you see people seems like it may be helpful in reducing your symptoms. What should you do? Things like this. Right now, you're not really seeing other people other than me, but at least you're seeing me and you're not doing something that's completely impersonal.
Joining a support group nearby, either in person or virtual, can be beneficial. Staying connected to family and friends is very important, especially as mobility changes. That can be a real problem for people. They feel embarrassed to get out and see their friends and family because they don't want to be a burden and other things, but it's detrimental to your health to do that.
Volunteering in your community, if you don't have a lot of family and friends to hang out with, is a great way to increase your interpersonal connections. As many of you know who have lived a life of service or served our country, service clearly improves mood, self-worth, quality of life and many other things. I think that's a great idea.
Jumping in with what Dr. Morley was saying, joining an exercise group can help. There are many online. If you search exercise groups for Parkinson's disease online, you'll find innumerable ones. Many are free. Some have small monthly fees if they include a physical therapist or trainer. I think it's a great way to connect with people. You can also go to your Rock Steady gym and do those classes or other fitness classes.
I'm going to stop there. I forgot exactly when I was supposed to stop. I think I actually saved some time for questions. These types of talks always come up with innumerable questions, and I would be happy to start answering them if that's where we're at. I'm sorry if that's not exactly where we're at.
Melody McLaughlin 01:32:43
You're spot on, Dr. Duda. Thank you so much for that fantastic presentation. We will be taking questions from our web audience now, and I also warmly welcome Dr. Morley back on our Zoom screens to help answer questions from his presentation. I will say in advance, we get a lot of questions, so if we're not able to get to yours, please call our helpline. We'll also include the VA number for their help service as well. There's no shortage of people who can help you, so if we don't get to your question, it's not that it's not important. Time is always of the essence in these Zoom meetings.
Dr. Morley, welcome back. Thank you both for your presentations. They were so fantastic. I have not introduced myself yet. I'm Melody. I'm Nancy's counterpart in the New England chapter as a community program manager, so I'm happy to moderate this Q&A session here.
We did already get a lot of great questions, and if you haven't already submitted your questions, or maybe a question inspires you to ask another, that Q&A button is still open on the bottom banner of your screen. Feel free to type it there, and we will try to include as many as we can. It always feels like a lightning-speed round, doctors.
Melody McLaughlin 01:33:57
Here we go. We have this first question here for Dr. Morley, and at any point, feel free also to chime in on each other's questions. I'll assign them the best I can based on your presentations.
Dr. Morley, what are your thoughts on wearables and smartphone apps like the StrivePD app or watches? How might that impact a fitness routine and health status?
Dr. James Morley 01:34:22
I think it's a great question because there are so many and so many to choose from, and it's hard to know what to make of it. I think they can be very useful. Just something as simple as a Fitbit or step counter gives you a way to compare yourself over time and say, am I really making progress? Am I really hitting the goals that I want to? I think those are great. They can be used to design interventions to motivate you to do more and more, whether it's in the setting of a clinical trial or not.
I think wearable sensors in terms of monitoring symptoms are also really, really interesting. They're maybe not as well studied, and I worry sometimes that patients get a little too attached to them: are my symptoms this much better today or that much worse today? I would encourage people not to get too wrapped up in it. But I think anything that gets people engaged and interested in participating in their own care, and interested in how they can take control in their Parkinson's disease, are good things.
Melody McLaughlin 01:35:35
Thank you so much. Dr. Duda, that kind of prompted me in Dr. Morley's answer. I know on some different phones there are sleep apps to track sleep. What are your thoughts on things like that?
Dr. John Duda 01:35:49
I don't know of any research on that in Parkinson's disease. There are some studies, I think, that are trying to look at that. I think, as Dr. Morley said, if you try it and you find you're sleeping better, then sure. I also would be hesitant to have people focus too much attention on nitty-gritty scores - I'm 97% sleep value versus 94%, or whatever.
I would probably steer them more toward the CBT-I and other treatment-focused apps and programs rather than the monitoring ones, especially if you feel like you're sleeping well. I don't think there's a great reason to do it. Even the ones that do very well, people who study them find that they're perhaps not as accurate as we would like to think they are. If you're into gadgets and you like it, give it a shot, but don't put all your eggs in that basket. If you're having problems, talk to your doctor about it, get referred to a sleep specialist, and try something like CBT-I or sleep hygiene tips.
Melody McLaughlin 01:37:36
Thank you both. Dr. Duda, this next question is for you: Since my Parkinson's diagnosis, I've noticed I've lost weight. Do you have any suggestions for ways to gain weight healthily while not just eating donuts and sweets and high-protein foods?
Dr. John Duda 01:37:53
Great question. Like I said in the talk, it's not an uncommon problem. Obviously, someone who is moving all the time with tremor or dyskinesia is at risk of burning more calories than they're taking in. For most people, it's a good thing that it's hard to eat too many calories on a healthy diet. If you're not eating much oil, fried food or high-caloric-density foods, then you tend to lose weight, which for the majority of Americans is a good thing.
For people who are already at a normal weight or are trending low, that can be a problem. Healthy choices for weight maintenance, high-caloric healthy choices, are focused mostly around nuts, seeds, nut butters and things like that. Sometimes healthy pastas or healthy sources of carbs can have a lot of calories in them. It is a problem on occasion.
Now there are so many good choices for plant-based alternatives for dairy products. Compared to certain things, vegan mayonnaise and vegan cheese are not as healthy, but they are a good source of calories. Things like that, I guess I would suggest as well.
Melody McLaughlin 01:39:43
Awesome, thank you. Dr. Morley, we have some questions here about exercise and whether or not it can really help with balance or freezing problems. If not, or if so, what else can people do to help with these challenges? Who can they see?
Dr. James Morley 01:40:03
That's a really good question because it's an example of two things that don't always get better with medication and become much more difficult to treat the longer folks have had Parkinson's. I would say they're not exactly the same thing. Balance is one thing, and freezing, this getting stuck, I think about a little bit separately.
I talked about studies looking at specific exercise programs like tai chi, qigong or physiotherapy prescribed for Parkinson's disease, and those are useful and evidence-based interventions to try to improve balance. Certainly, do any of this in consultation with your neurologist and/or physical therapist to make sure that, if you're at risk for falls because you have bad balance, you're not engaging in activities that are going to put you at higher risk.
Freezing is tough. It's really, really tough. I think Dr. Duda would agree that clinically it's one of the more challenging things we face. For freezing, we talk a lot about when it happens. Is there some correlation that we can do something about between medicines wearing off, with off freezing, or is it happening with on freezing? Some people experience that. If you learn that, then you can hopefully make adjustments to medications or perhaps use a rescue therapy for situations where people get stuck or frozen.
When there aren't those obvious relationships, it's a little trickier. I think what we will do is refer our patients to physical therapy because sometimes physical therapists can mimic real-world situations a little better than we can in the office. Is it corners? Is it stairs? Is it doorways? Then they can work with patients to develop strategies to get out of a freezing episode. Among this group of veterans, often a count-off and starting a march is something that some people find very helpful, or picking out a target and stepping over it. There are even studies with little lasers that shoot out of canes or other visual targets. For freezing in particular, working together with physical therapy and rehab is really, really important.
Melody McLaughlin 01:42:28
Awesome. Thank you. That's really helpful. Thanks for distinguishing those two very different symptoms. Dr. Duda, can you speak a little bit more about the timing of medications with meals and the protein factor as well?
Dr. John Duda 01:42:47
Yes, thank you. Great question and something that, when I have a full hour to talk about, I certainly include. If you Google my name and nutrition and videos, you'll find several online for different organizations that I've done over the years that go into great depth about this.
For those of you who don't know, Sinemet is two compounds: carbidopa and levodopa. Levodopa has the same shape, or is similar, to certain types of amino acids that you get when you eat protein. It is absorbed into the body and into the brain by the same receptor that absorbs those amino acids. The thought is that if you take your Sinemet, which has levodopa, at the same time when you have a lot of amino acids from a high-protein meal circulating in your blood, it's going to have a hard time first getting into your blood through your gut and then getting into your brain.
Some people will notice a difference if they take their Sinemet half an hour before they eat. They have a certain amount of benefit. If they take it during or after they eat and have protein in the meal, they may not see as much benefit because not as much of it is getting into the brain where you need it. Early on in the disease, that's unusual. Usually there's enough reserve of levodopa in the brain to avoid that, but particularly later on, as more cells have died or are having trouble, you're more reliant on the blood level of levodopa. In that case, it can make a big difference.
What we typically ask people to do is take their Sinemet 30 minutes before or an hour after a meal. If they're having a lot of problems with fluctuation, in addition to the pharmaceutical treatments that we use for motor fluctuation - a feeling that your medications kick in and work pretty well and then, after a delay, are not working anymore - one thing to try is a protein redistribution diet, where you take the vast majority of the protein you're consuming in that day in the evening meal.
In the evening, you're not moving around as much. There's no great evidence that you need to be eating protein all day, so it's fine nutritionally and can help your synapses work better throughout the day. The vast majority of people in America eat too much protein anyway. The meat and dairy industries and others have led us to believe that we have to eat a hunk of meat every meal, every day, and it's just not true. There's no evidence that you need that much protein to be healthy. Ninety-seven percent of Americans, or something like that, get enough protein, whereas 93% of Americans don't get enough fiber. Instead of asking me, the guy who doesn't eat meat, where I get my protein, I'll ask you where you get your fiber. If you're only eating meat and cheese and standard American diet kind of stuff, you're almost certainly not getting enough.
Melody McLaughlin 01:46:19
Thank you so much. I think that could be a whole other discussion. You're so right. Forty-five minutes is just not enough time to get into the timing, the protein, fiber, everything. Thank you.
Similar question for you, Dr. Morley, about timing and exercise. Is there a better time of day to implement an exercise routine, morning or afternoon, before or after medications? I don't want to complicate things for our viewers in trying to get this puzzle together, but it's an important question.
Dr. James Morley 01:46:54
I think it's a really important question, and I will definitely keep it simple with maybe a couple of caveats. Just like the best exercise is whatever will get you to exercise, the best time is whenever works for you to exercise. There are morning people, night people and afternoon people. I know for me personally, if I don't exercise first thing in the morning, it's probably not happening. I have to focus on scheduling it then. Some people need to do whatever they need to do in the morning and exercise in the afternoon.
One caveat you brought up is medication. Certainly, if you're going to be doing anything complicated that involves balance and risk of injury, you want to do it when you feel like you're in a good on state. If you know you have more trouble in the afternoon, then exercise earlier in the day.
The other caveat is sleep. In the sleep paper that I put up there, I focused on the fact that chronic exercise helped a lot of sleep variables they measured, but they also looked at the acute effect of one exercise session, depending on when you do it. If done too late in the day, some people find that exercise interrupts their sleep. People have to pay attention to their own body. But from a physiologic basis, is there a morning, afternoon or night time when you get the biggest benefit from exercise, or where it has effects it otherwise wouldn't? I don't think there's any good evidence for that, as far as I'm aware.
Melody McLaughlin 01:48:42
Thank you. Actually, you just answered our next question about whether an exercise routine can impact sleep. I'll rephrase it a little bit for Dr. Duda. What about mindfulness practice? Can that help with sleep? Do you recommend doing it before bed?
Dr. John Duda 01:49:02
Good question. First, from the last question, it's important to recognize that exercise can affect sleep if you do it late in the afternoon or evening, as Jim said. But for the most part, people who have a regular exercise program have better sleep than people who don't. That's a good reason to do it.
For mindfulness practice or other stress reduction techniques, like yoga, prayer, tai chi or whatever your choice is, I generally tell people to do it when you will do it. The problem with waiting too long to practice mindfulness is that, in sitting and focusing on your breath, if you're tired, you can fall asleep. Is that the end of the world? No. If you're tired enough that you're going to fall asleep while trying to do something else, then maybe you need a nap.
I'm a believer in naps, particularly for people who are older and have Parkinson's disease. It's much better to take a nap that is not a long nap. If you sleep too much during the day, you're going to have trouble sleeping at night, and there's a lot of day-night reversal in Parkinson's disease where that happens. But fairly brief naps of 30 minutes or so can be very restorative and better than some other alternatives.
You probably want to practice mindfulness when you feel fairly awake and on, but more importantly, find a way to make it a habit. There's good evidence that even five minutes a day can make a real difference. If you do that for a while and slowly increase how much you're doing, you'll get even more benefit. It has a lot more benefit that way than doing all 30 minutes in one day. So much of our life is habit and routine. Find a slot where it can fit into your routine and become as routine as brushing your teeth or anything else. That's a great approach.
Melody McLaughlin 01:51:26
Thank you. This next question looks like it's for you too, Dr. Duda. We talked a little bit about fibers and proteins. What about the vegan diet? How might it compare to the Mediterranean or MIND diet, and similarly, the keto diet that's popular right now?
Dr. John Duda 01:51:48
Good question. A vegan diet is a diet that does not include any animal-based foods. It doesn't include meat, poultry, seafood or dairy. A vegetarian diet is the same thing except that it allows dairy products.
A ketogenic diet, strictly speaking, is one that puts your body into ketosis, where your carbohydrate consumption is so low that you're not generating enough energy for your body to do its normal functions and you start burning your own fats to produce something called ketones, which are also used by brain cells in an emergency, if necessary, to function. I think it's a complicated story. Some people feel a whole lot better on a ketogenic diet. They feel less mental fogginess and other things. There are some small studies of ketogenic diets in Parkinson's disease that suggested an effect in an open-label fashion.
For people who are younger, I worry that a ketogenic diet, which is high in meat products, saturated fat and things like that, may have long-term consequences for brain function regarding vascular supply. It's not clear that a ketogenic diet is great for your heart and brain if you're clogging the arteries by eating so much saturated fat.
A vegan diet can be healthy because it's mostly plants. However, the difference between a whole food plant-based diet and a vegan diet is that French fries, Twinkies, potato chips and soda are all vegan, but they're not health foods. That's why there are so many unhealthy college-aged vegans out there. They're doing it perhaps because they don't want to harm animals, which is a great reason, but they're not being smart about it and they're eating junk food that happens to be vegan but isn't healthy.
A whole food plant-based diet means eating plant-based foods in a less processed way. A potato is actually a healthy food. If you take a potato, bake it and eat the skin and everything, there's nothing wrong with it. Eating a lot of it can bring in a lot of calories, but it's mostly when you slice it up, deep fry it, put cheese on it and add other things that it becomes unhealthy. The less processing, the better. The way we prepare foods can make a difference as well.
Again, I always say compared to what? A vegan diet is much better in most cases than the standard American diet, which is abbreviated SAD for a reason. But it's not necessarily a healthy diet. Go back to some of my previous videos or look online and you'll find out the difference. I encourage people to increase the amount of plant foods they're taking in. It's harder to get rid of something than it is to add something, so adding more healthy plant foods is a better approach than trying to eliminate unhealthy animal foods and other foods. Eventually that will happen because you'll feel better and you'll continue to decrease the amount of animal foods you're eating. For most people anyway.
Ketogenic is hard to say. If you're young, I would discourage it. You also lose weight on a ketogenic diet most of the time because you're not taking in enough calories to maintain your weight. That can be a problem for people with Parkinson's disease. If you're older and you're not at all worried about your vascular function, then it's possible that it may be helpful, but it's no miracle treatment that some people suggest it is. At least, the evidence is weak for that.
Melody McLaughlin 01:56:36
Awesome. Thank you so much. I know we got a few questions about that diet in particular. We are almost at time, so we have just enough time for two more questions. I want to make sure people are getting information about their local VAs. Dr. Morley, I know you shared a lot of different research happening. We will share those slides again, folks, so the information for those studies is on the slides and we will get those to you in an email. This question can be for either of you: How can someone find out about the research that's happening at their local VAs?
Dr. John Duda 01:57:17
All VAs have a research department. If you're looking in particular for Parkinson's research, go to the neurologist if you have one. Some VAs don't even have a neurologist, but go to the clinicians there and ask about research opportunities. If you don't get any answers, ask if there's a research department. They often have research fairs once a year or so where they bring in patients and talk about different research programs that are going on.
In general, it's the bigger VAs that are affiliated with universities that have the broadest reach of research opportunities. There's no easy way, no website that I'm aware of where I can say, go here and you'll find out which ones are available. ClinicalTrials.gov is a good place to look for clinical trials in general, for Parkinson's disease or for anything else. It's a website run by the government where almost all clinical trials are listed, and they will often list the sites where they're being performed. If you're looking for clinical trials in particular, that's where I would go.
Dr. James Morley 01:58:35
I was just going to mention that I think you could probably select keywords for veteran and your city in ClinicalTrials.gov. You might be able to do something similar with the Fox Trial Finder.
Dr. John Duda 01:58:46
Use a general resource for clinical research and then try to tailor it to your geography. There is also our website, www.parkinsons.va.gov, which is a good place to get more information about ongoing research. We have newsletters that come out talking about research. There are six of these Parkinson's Disease Centers around the country and 50 to 60 satellite sites. There are ample opportunities, and the Parkinson's Foundation and VA collaboration that started a couple of years ago has done a great job of expanding awareness and access to those opportunities.
Melody McLaughlin 01:59:36
Awesome. With just about a minute left, I want to thank you both so, so much for your fantastic presentations and for joining us for this Q&A session. Again, our viewers' questions are so important to us. If we did not get to your question, please do call our helpline, 1-800-4PD-INFO. I see my colleague queuing up our final slides. Again, Dr. Duda and Dr. Morley, thank you. We also have Gretchen Glenn here, who has been such a great support to this program as well.
For our viewers, please know you're not alone. Our respective organizations are here for you, and we look forward to connecting with you. If you have a question that was not addressed, please reach out to our helpline. It's staffed by my colleagues and Parkinson's specialists at 1-800-4PD-INFO. You can also call the VA at 1-800-949-1001, extension 205769. Thank you again for your service to our country. We hope you enjoy the rest of your day.
Again, thank you, Dr. Morley and Dr. Duda, for sharing your time and expertise with us and the veterans Parkinson's community. Thank you to all of our attendees joining us today. We hope you find today's discussion really helpful, and you can review those slides at a later date. Thank you, Gretchen Glenn, social worker and associate director of the Philadelphia Parkinson's Disease Research, Education and Clinical Center, for all your assistance. Many thanks to Genentech for your support of our mission in serving the Parkinson's veterans community.
Immediately following today's program, you'll see a survey pop up on your screen. Please try not to ignore it. Take a moment to complete the evaluation. This really helps us know how to improve our programs to better serve you, and your feedback is so important to us. One final reminder that this program was recorded, so you'll get a link with the video in an email, and the slides. You'll have everything there for you. Thank you so much for joining us. Hope you all have a great afternoon.
Dr. John Duda 02:01:41
Thanks, Melody. Thanks, everybody.
Melody McLaughlin 02:01:44
Thank you. Thank you.
