Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

This podcast marks something of a milestone in our series, now having produced 100 episodes. We hope they're helpful, and we invite you to give us your input as we continue the series. Later, we'll tell you how diet and nutrition are central to a healthy lifestyle and to stave off serious illness. Even with a chronic disease like Parkinson's, people can help manage their symptoms and maximize their overall health by paying attention to how and what they eat. For example, fluid and fiber intake can help with constipation, and as they say, what's good for the heart is good for the head. So, a heart-healthy, plant-based diet may be good for cognition, and even stave off dementia.

In this second episode in our two-part series with Dr. John Duda of the Parkinson's Center at the Veterans Affairs Medical Center in Philadelphia, he gives us practical advice on what to eat, why, what specific nutrients you should be aware of, and possible laboratory tests that can be informative for good nutrition with Parkinson's disease. And since people with Parkinson's often have a diminished sense of smell, I asked him what kinds of flavorings can make foods more palatable, helping to fend off weight loss. The sense of smell is so intrinsic to the taste of foods, and in Parkinson's disease, people often have a diminished sense of smell. Does this affect their diet, affect their nutrition, their enjoyment of food, what they would be eating? I would think everything would be bland.

Dr. John Duda 2:28

Yeah, that's a very important question that has actually, obviously, been brought up with COVID-19 as well, because one of the early symptoms or prominent symptoms of COVID-19 infection is a loss of your sense of olfaction or smell. In fact, most of your sense of taste that we think of is actually smell. There are only five things or so that you can taste with your taste buds, but most of how you appreciate your food is through the sense of smell. And people with Parkinson's disease do almost universally lose their sense of smell to varying degrees, and it is a big problem that does affect how you appreciate the food and your appetite.

What I recommend to patients if that is the case—if they have noticed that everything tastes bland and they just don't feel like eating because they've lost some of the pleasure from eating—is to try to use foods that have really robust flavor profiles. So for example, using as many and as much spices, herbs, and things like that as you want, because number one, spices and herbs are loaded with things called antioxidants and anti-inflammatory compounds, so they have really good health benefits, but they also obviously are very strong-tasting in many cases. So, if you add more of those to your food, you can overcome some of the bland flavor, because for the most part, people with Parkinson's disease do not have no sense of smell, they have an impaired sense—and sometimes a highly impaired—but they can still taste things. They don't necessarily know exactly what it is they're tasting, but if you increase your food intake that way, it can be helpful.

Dan Keller 4:10

Do people with tremor burn more calories? Do they need more food intake and caloric intake than people without tremor?

Dr. John Duda 4:19

That's a great question, and there is some evidence to support that, including not just tremor, but dyskinesias as well. As you know, there are more than one symptom of Parkinson's disease that involve excess movement, and dyskinesia, which is a side effect of long-term levodopa therapy, is another one. There is evidence that, obviously, if you're tapping your foot on the ground day and night, or your arms are always moving from a tremor, you're burning calories. So your caloric balance will be shifted, and there is a high prevalence of malnutrition and weight loss in Parkinson's disease. It's not clear—some people actually gain weight, especially early on in Parkinson's disease, but weight loss is a common symptom, and so needs to be adjusted for.

And it is actually a big concern for a lot of my patients who do try to adopt more of a Mediterranean-style diet, where they're not eating a lot of highly processed foods that in general contain large amounts of sugar or fat and other high-caloric foods. So things that I recommend are increasing the amount of nuts and seeds, which have a high caloric density, and other kind of plant-based sources of lots of calories to make sure that you maintain your equilibrium and don't lose too much weight.

Dan Keller 5:38

I suppose that eating a lot of high-fiber food, you may feel full and satisfied, but those nutrients don't give you as many calories as a more processed diet might.

Dr. John Duda 5:53

Yeah, it is true. In general, a whole-food, plant-based diet, or foods like that, have a lower caloric density, and that's why it's one of the few diets that's actually been proven to help people lose weight and maintain a healthy weight. You can eat a whole plate full of broccoli and not get the same calories as you would get in a couple chicken nuggets or something like that, or some other highly processed foods. So that's the nice thing, also, about eating that kind of diet. You can eat basically as much as you want and not have to worry about weight gain. It's another one of the advantages of this type of diet.

Dan Keller 6:31

Oils carry a lot of calories. Are there good oils, better oils that people should be using?

Dr. John Duda 6:37

A great question. You know, every time I get asked, "Is there something in particular that I should be eating or not eating?" I always remind people that you have to ask compared to what. So oils are good sources of fat and calories, which is an advantage for certain things and a disadvantage for others. The oils that we think are more anti-inflammatory and antioxidant-related are oils that have a high omega-3 fatty acid content. There's several different types of fatty acids, which are the building blocks of oils, and omega-3s are the ones that we think are helpful in the long term for health. They tend to come from fishes, as well as some nuts and seeds, so there are certain oils that are better than others.

Fish oil as a source of omega-3 is a reasonable addition to your diet, but then for cooking, there are different questions that again, compared to what? So everybody talks about extra virgin olive oil as being a healthy fat, and in many ways it is, but it's still a high-caloric food, and the one problem with extra virgin olive oil is that it breaks down pretty quickly under heat, so it depends what you're using it for. I think good choices for cooking are avocado oil, and perhaps canola oil, or rapeseed oil. For non-cooking purposes, then extra virgin olive oil and grapeseed oil, and some of these other ones that have a high quantity of phytonutrients are a good choice. When I say phytonutrients, so extra virgin olive oil compared to olive oil or non-extra virgin olive oil...

There's a lot of people who ask me about coconut oil, and in general, I think coconut oil is not a terrible choice for cooking because it is relatively heat-stable, but the coconut oil has a lot of saturated fatty acids. And saturated fatty acids are the things that we are pretty sure are causing some of the detrimental health effects of animal-based fats like butter and lard and things like that. So, coconut oil and palm oil are the two plant-based oils that are more likely to have a larger percentage of saturated fatty acids, which we know are bad for long-term cardiovascular health.

Dan Keller 8:58

If someone is about to take steps to change their diet, or has already started to adopt things, are there specific lab tests that would be useful?

Dr. John Duda 9:08

Yes, I think there are two, for sure, and then many others that you could consider. I think two tests that I think everybody with Parkinson's disease should have drawn by their clinician—but they are not routinely drawn in many instances—are vitamin D and vitamin B12. We know that both of these vitamins in people with Parkinson's disease are often low. There's debates about why that might be, but vitamin D, which is the sunshine vitamin, may be related to the fact that people with Parkinson's disease don't spend a lot of time outside, but it's probably more complicated than that. And almost everybody I test with Parkinson's disease has low vitamin D and ends up getting supplemented, because it's actually pretty hard to eat enough leafy greens and beans and things like that to get adequate levels of vitamin D.

And vitamin D is an interesting compound because it functions almost like a hormone in many cases, and so it likely is involved with cognitive function and mood and things like that. So, there's a particular level of vitamin D that we know will help prevent rickets, which is the classic vitamin D-related bone dysfunction, but there's higher levels that we think are actually more conducive to overall health, and those are the levels that I tend to aim for on that 50 to 70 range that almost always requires supplementation with pills.

Vitamin B12 is kind of similar. It is a vitamin that for the most part only comes from animal foods, so anybody adopting a vegan or entirely plant-based diet should almost certainly be on a vitamin B12 supplement. It is water-soluble, so it doesn't hurt you if you take too much of it, and it is involved with many different processes in the brain as well. And actually, one of the byproducts of B12 metabolism, a compound called homocysteine, is actually increased in people who have insufficient levels of B12 or folate, and also increased in people who take levodopa to a certain extent. So it is particularly worthwhile checking in people with Parkinson's disease and supplementing B12, folate, and perhaps pyridoxine, if necessary, to get homocysteine levels down.

Dan Keller 11:27

From what you've been saying, just in general, it sounds like color in food is a good indication—dark green leafy vegetables, orange things, red things, blue things, blueberries, peppers, things like that, carrots. Should people just, as a simple guide, should they look for color?

Dr. John Duda 11:45

Yeah, one catchphrase is to "eat the rainbow." The compounds that make all of these fruits and vegetables the different colors that you mentioned are, for the most part, the same compounds that we believe have antioxidative and anti-inflammatory properties, so eating a diet that is loaded with different colors is a great idea. And in general, if you have a choice—again, compared to what?—if you want to eat cabbage, well, red cabbage is a better choice compared to white cabbage, and red onions are a better choice compared to white onions, and blueberries are a better choice compared to other berries that aren't so bright in color. So that's a great general rule, that you want to eat the rainbow on your plate, and the more bright-colored foods of every color, the better.

Dan Keller 12:35

It seems that most physicians don't have a great grounding in nutrition. Is it worth it for someone with Parkinson's to see a nutritionist who works with people with PD?

Dr. John Duda 12:49

That's a great question, Dan. I think the general population doesn't realize how little training doctors get in nutrition, and most doctors really do not know that much about how nutrition can affect Parkinson's disease. I only learned because I was interested and learned it on my own. I think there are some nutritionists out there that can be helpful, but in general, many nutritionists do not have that much training either in some of the things we're talking about.

There are good sources out there you can find online for whole-food, plant-based information. One website that I encourage people with Parkinson's disease to check out is called The Science of Parkinson's Disease. It's a blog that Simon Stott puts together that is actually very informative and very approachable, presenting highly complex material in a very layman-friendly way, and a great source of information. I often check out his posts to learn new things. If you find a nutritionist who's a strong believer in either whole-food, plant-based nutrition or the Mediterranean diet and things like that, then I think those would be a good choice. There are a lot of nutritionists out there who haven't had as much of an education in the benefits of those types of diets, so you have to be careful what you get.

Dan Keller 14:10

Have we missed anything important or anything interesting to add?

Dr. John Duda 14:14

One question that I get a fair amount when I'm speaking to patients and caregivers with Parkinson's disease is, "What about organics?" There's a fairly robust body of literature suggesting that exposure to pesticides may increase your risk of Parkinson's disease, and we don't honestly know if eating organic foods and decreasing your exposure to pesticides once you get Parkinson's disease will make a difference in the progression of the disease. However, I think for Parkinson's disease and for health in general, I think it's reasonable to try to reduce the amount of pesticides you're being exposed to.

And one, I think, worthwhile way to do that is to go to the Environmental Working Group website, who have developed something called the Clean 15 and the Dirty Dozen. It's a list of 12 different fruits and vegetables that they believe you should try to eat organic if possible, and in general, these include fruits and vegetables that use a lot of pesticides in their production and you eat the outer layer, so like apples and berries and things like that, and lettuce. And the Clean 15, on the flip side, is a lot of fruits and vegetables that it doesn't make that much sense to try to eat organic because either they don't use much pesticide in the production of those foods, or something like a pineapple, where most of the pesticide will be bound up in the outer layers that you don't consume, or oranges and things like that, or like asparagus, because as soon as it sprouts out of the ground, it's harvested, and it's not really exposed to pesticides. So, I think, in general, that's a reasonable way to approach it—not trying to eat everything organic, but being smart about it and eating the things that would likely expose you to higher levels of pesticide if you did consume them.

Dan Keller 16:07

I suppose it's worth noting that not all pesticides can be washed off. Some plants will actually incorporate them into their tissues.

Dr. John Duda 16:15

Yeah, certainly. I think, in fact, there's little evidence that washing makes a huge difference in the pesticide levels, even the ones that are on the surface. There's some studies that have suggested that bathing them in salt water—fairly high concentration salt water—and then rinsing off the salt water may be helpful. But for things like berries and stone fruits, like nectarines and apples and plums and things, I think it is worthwhile trying to find organic sources of those.

And I always encourage people also to try and find, you know, local sources of their foods, so that they can actually talk to the farmers and find out how they're producing them. I mean, there are certain chemicals we know are potentially involved in the risk of Parkinson's disease. They're allowable in organic agriculture because they're natural products. So, just because something says it's organic doesn't mean it doesn't have pesticides, and doesn't mean it doesn't have pesticides that are potentially worrisome for people with Parkinson's disease.

Dan Keller 17:19

Finally, in a nutshell—and maybe it really does involve nutshells—what do you recommend that your patients eat? Is there any way to summarize a lot of what we've just been talking about?

Dr. John Duda 17:31

In general, I recommend people eat seven to nine servings of fruits and vegetables a day, which to most people sounds crazy, but it actually isn't that hard because you can get many servings in one meal if you focus most of your food on fruits and vegetables. I think increasing consumption of nuts and seeds, eating a lot more spices, herbs, and high-antioxidant compounds like that, cruciferous vegetables—which are broccoli, cauliflower, kale, cabbage, things like that—have sulforaphane, which there are many different ways that sulforaphane may help people with Parkinson's disease. So, increasing your consumption of those vegetables, beans, and greens are two things that I think most Americans don't eat enough of, and basically any bean or bean product that you like, which includes lentils, split peas, beans, chickpeas, tofu, anything like that, as well as any kind of greens that you like. I mean, iceberg lettuce is the least helpful, but it's better compared to some other foods.

And again, eating less processed foods, so starting more whole foods. Eating more mushrooms—there's a very interesting compound in mushrooms that can't be found in any other food sources, called ergothioneine, that may be helpful in general. I recommend that people eat a tablespoon or two of flaxseed a day. If you can make one change to your diet, I would recommend that because it's a great source of fiber and lignans and omega-3 fatty acids, so just eating one tablespoon of ground—has to be ground up, or it'll go right through you—is a good choice.

And then again, eating like whole-grain foods. So there's a lot of people who ask me about the "grain brain," and "Is gluten bad for Parkinson's disease?" And I don't think there's strong evidence to suggest that gluten is bad for most people with Parkinson's disease. A couple percent of people are truly gluten-intolerant, and a couple more percent may be gluten-sensitive, but for the vast majority of people, whole grains are a beneficial part of a healthy diet, including lots of fiber. So shifting from processed flours to whole-grain flours and whole grains themselves is another great choice.

Finally, drinking adequately. Other people have noted that a lot of people with Parkinson's disease don't drink enough fluids, and that's probably one of the reasons they get constipated. But I think drinking four ounces every two hours throughout the day is a rough estimate, and you can actually find cups and bottles online that help you do that. It'll help you because most of that will be absorbed. You won't be running to the bathroom all day, and staying adequately hydrated, as I said, improves your constipation, but also probably improves your cognition and other things.

So in a nutshell, those are the kinds of recommendations that I make, and most importantly, to not stress out if you really desire to have some other kind of food that isn't on that list that makes you happy. It's okay to cheat every once in a while, just to try to eat healthy choices the majority of the time, and then you'll be winning the battle.

Dan Keller 20:42

Excellent, thanks a lot. For more from Dr. Duda and other experts, search our website at parkinson.org for diet. There you'll find an article by Dr. Duda called The Latest in Nutrition and Parkinson's Disease that summarizes many of the points in this podcast. You can also find this article, as well as an expert briefing, by searching the site for Duda, that's D-U-D-A. His first podcast episode on diet and nutrition was titled Nutrition Advice, Part One. Another podcast of interest is called The Importance of Good Nutrition for People with Parkinson's. More on nutrition is available by going to our website and clicking on Living with Parkinson's, and then selecting the tile called Managing Parkinson's. Much of this information can also be reached by going to parkinson.org/library and in the topic list selecting nutrition and digestion. Nothing can substitute for nutrition advice based on your own situation. You may be able to find a nutritionist with expertise in PD through your Parkinson's care team, or by calling our helpline at 1-800-4PD-INFO.

As I mentioned earlier, this being our 100th episode in our podcast series, we want to continue to bring you news and information most relevant to your managing and learning about Parkinson's disease. As always, you can leave us feedback at parkinson.org/feedback, but we also would like to solicit your input for future podcasts through a survey we're running. You can find it at parkinson.org/podcast. Please take a look and help provide feedback for our podcast series by sharing your experience tuning in.

If you have questions about today's topic or anything else having to do with Parkinson's, our information specialists can provide answers in English or Spanish. You can reach them at 1-800-4PD-INFO. News and updates about future events and resources are available by joining our email list at the bottom of our website's homepage. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts, or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

John Duda, MD is the Director of the Parkinson's Disease Research, Education and Clinical Center (PADRECC) and Co-Director of the Center for Neurotrauma, Neurodegeneration and Restoration of the Cpl. Michael J. Crescenz VA Medical Center and a Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. For the past 19 years, he has worked with his colleagues in Philadelphia to provide state-of-the-art care for thousands of Veterans with PD and related disorders.

His research activities have included basic science investigations into the role of Lewy pathology in the pathophysiology of Parkinson’s disease and related disorders as well as investigations into the mechanisms involved in traumatic brain injury. He has also conducted clinical research in Parkinson’s disease with studies of deep brain stimulation therapy, transcranial magnetic stimulation, the benefits of a plant-based, whole food diet, and the use of olfaction as a biomarker of disease diagnosis and progression. He has received research grants from the Department of Veterans Affairs, NIH, the Michael J. Fox Foundation for Parkinson Research, and the Department of Defense. He has been recognized as a BLR&D Senior Clinical Research Scientist and authored more than 120 scientific publications including articles in JAMA, Science, Neuron, The New England Journal of Medicine and Neurology.

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

Clinical researchers are intensely interested in finding treatments and lifestyle modifications that may slow down or eventually stop the progression of Parkinson's disease. While proof of their effectiveness would require controlled clinical trials, or at least in the case of lifestyle changes, population studies over time, some modifications may be worth trying now. Diet falls into this category. The medical field already knows that healthy foods can have beneficial effects, and there is no harm in eating better before proof emerges that it can slow Parkinson's progression. We have all heard about heart-healthy foods that are low in saturated fats and about high-fiber foods for gut health. Lately, research has connected the populations of microorganisms in the gut with various health conditions. Dr. John Duda of the Parkinson's Center at the Veterans Affairs Medical Center in Philadelphia notes that what you eat is what gut bacteria feed on as well. Dietary changes can affect the mix of microorganisms, and while it is still a developing field, the so-called gut microbiome has been shown to have wide-ranging effects in the body. In this first episode of a two-part interview with Dr. Duda, I asked him why nutrition may be especially important for people with Parkinson's disease.

Dr. John Duda 2:15

That's a great question. As we try to develop novel therapies that will slow down or stop the progression of Parkinson's disease, many of us are interested in other potential therapies that may do the same thing. We know that exercise may be capable of slowing down the disease progression of Parkinson's disease, as you've discussed with Bas Bloem and others on other podcasts, and many of us feel that nutrition may have a similar role. We don't know for sure if changing what you eat is going to slow down your disease progression, but we do know fairly convincingly that it'll affect the way that you experience Parkinson's disease by changing the symptoms that you have, possibly preventing some symptoms, and overall improving your overall quality of life by decreasing your risk of things like heart disease and stroke, diabetes, hypertension, dementia, and things like that.

Dan Keller 3:18

You advocate a plant-based whole food diet. What do you mean by whole food?

Dr. John Duda 3:25

The diet that I recommend, it comes out of a lot of research that suggests that the standard American diet, which some people abbreviate SAD for a reason, is loaded with food that's processed. So the American food industry takes a lot of natural whole foods and processes them into meals and other foods that makes it very convenient. It saves us time and food preparation, but that process of taking those whole foods and changing them changes the nutritional value of them as well. And so what we suspect is that as you take, for example, a whole grain and process it into something like white rice or white flour, you're taking away certain components of that grain that have health benefits—the bran, the fiber, things like that. The idea is to get back to the natural whole foods and start with natural whole grains, whole vegetables, whole nuts, seeds, greens, beans, all these things, and prepare food. It does take a little longer to prepare a whole-food, plant-based meal, but we do believe that the phytonutrients, which are nutrients that are found in plants only, will help you in many ways, including possibly helping your Parkinson's disease.

Dan Keller 4:58

You mentioned that it's not certain whether Parkinson's disease can be prevented by eating whole foods or a good diet. There does seem to be some epidemiological work in terms of environmental factors. Caroline Tanner at the University of California, San Francisco, and Bas Bloem in the Netherlands, and Ray Dorsey in Rochester have come out with a lot of stuff about environmental pollutants. But now, since we're talking to an audience with people who already have Parkinson's disease, is there evidence that it can actually help them?

Dr. John Duda 5:35

That's a great question. I think it is important, a very important distinction to recognize that much of the research we have to date has been focused on the risk of developing Parkinson's disease and nutrition, and it's pretty clear that there are certain foods that decrease your risk of getting Parkinson's disease and certain foods that increase your risk. There's much less evidence, especially quality evidence, on how changing your diet can affect your Parkinson's disease if you already have it. It's obviously a very difficult study to perform to take people who have Parkinson's disease and have them in some sort of blinded way eat some food that other people are not eating over a long term and follow them to see how their disease progresses. So that kind of evidence is clearly not as robust as some of the other epidemiological evidence.

There is one study called the CAM Care in Parkinson's Disease study, which you can find online from Dr. Laurie Mischley, which is a naturalistic, prospective study. So she's taking over 1,000 people with Parkinson's disease and following them prospectively, meaning into the future, and asking them now what kinds of things are they doing with their lifestyle and alternative therapies and supplements and things like that, and then seeing how they progress over time. And so some of the evidence from that suggests that the people who eat basically a Mediterranean-type diet, which is a whole-food, plant-based diet essentially, plus a little bit of seafood, red wine, not as clearly restrictive for all animal products, but that kind of diet does seem to be associated anyway with less symptoms in Parkinson's disease.

People with Parkinson's disease can improve, for example, constipation, which is a big problem for a lot of people with Parkinson's disease, by changing their diet. People always ask me, as someone who eats a whole-food, plant-based diet, where do I get my protein? Well, it's very hard not to get enough protein, as long as you eat a varied diet, no matter what you eat. So as long as you're not eating the same two foods day in and day out, it's hard not to get enough protein. But about 97% of Americans don't get enough fiber, and fiber is crucially important for maintaining good gut health and avoiding constipation.

I did a small study a number of years ago where we taught 13 patients with Parkinson's disease how to eat a more whole-food, plant-based diet, and one of the things we saw was a clear reduction in their constipation scores. It was a small enough study that it was only ever published in abstract. I think, in my experience, it happens routinely that people report having greater frequency of bowel movements, and importantly, less trouble in passing a bowel movement if they adopt a whole-food, plant-based diet and increased fluid consumption as well.

There are other symptoms that aren't as clearly well documented to improve in Parkinson's disease, but very likely do. For example, memory function. Obviously, one of the most troublesome and scary symptoms of Parkinson's disease is dementia, and a lot of people want to know from me how to reduce their risk of getting dementia. And it is very clear from other studies that what diet you eat affects your risk of getting dementia. And people eating a Mediterranean diet—and there's other versions like the DASH diet, or the MIND diet, or a whole-food, plant-based diet—are significantly less likely to get dementia, and almost certainly whether or not that dementia is coming from Parkinson's disease or not. There are other symptoms that may benefit, because even treating constipation actually may increase the absorption of your medications. If you have erratic transport through your intestines, your levodopa, for example, may not be absorbed well or the same way with each dose. And so just improving your bowel habits can actually improve your motor symptom response by improving the absorption of levodopa.

Dan Keller 10:01

If I remember correctly, the study that you did that you alluded to was only for about 14 weeks, and you measured people's symptoms and constipation over that time. It seems it's really hard to get people to change their dietary habits in the long term, so it would have been interesting to follow up once they were off study. I'm wondering, is it better to try to get people to make incremental changes or just say you've moved to the Mediterranean, it's a whole new way of eating? I think possibly people respond differently.

Dr. John Duda 10:37

That's a great point. I think the motivations and desires that people have vary, and people who study psychology and things like that have looked at this, and it's kind of interesting. Some studies suggest that incremental changes are better, and that's essentially what I try to do in my clinic. In addition to my regular Parkinson's disease clinic, I have something called a brain wellness clinic, where we bring in people with Parkinson's disease, and we discuss all of the choices they're making in their lifestyle that we think could potentially affect their brain health. Those include dietary choices, exercise, sleep habits, stress management, and things like that. And each visit we discuss potential changes, and over time I have seen many, many patients make kind of incremental changes—changing one or two things this visit, and then changing more the next time, and ending up with big changes, with, you know, significant reductions in their weight, being able to come off hypertensive or diabetic drugs, and things like that.

But there are actually other studies that suggest that if you ask people to do a large number of things all at the same time, they're actually more likely to do a few more than they would have if you only asked them to do a couple. So I think it depends a lot on the person you're talking about. I have some veterans I take care of who are young and really committed to doing anything they can to fight back against Parkinson's disease, and that's kind of the theme of the Brain Wellness Clinic, where we're empowering people by teaching them how to fight back against Parkinson's disease, and these vets will do anything that I ask them to. And it's really rewarding because they come back with clear health benefits and a sense of, like I said, empowerment and well-being that comes out—what, you know, regardless of underlying physiological changes, they just feel better because they feel like they're doing something, and you know they're sleeping better and getting exercise and everything, so certainly they're going to feel better.

Other veterans in my clinic are interested in making some changes, but perhaps not wholesale changes. And I always say that it doesn't do you any good to live to 100 if you're miserable the whole rest of the time you're alive. When people hear about the recommendations that I have for how to live a healthy life, I let them choose which ones to do and which ones not to do. I mean, if you have to eat a hamburger a couple times a week to be happy, well, I want you to be happy. I think the changes that can be made are at least as robust by teaching people to do healthy things in addition to the unhealthy things they do, rather than trying to just make them help them stop doing the unhealthy things. So if you have to eat some things that we know aren't the healthiest, that's okay, as long as you know some of the other time you're actually eating things that are healthy. And teaching people to eat the healthy things is a big part of what we do and have success with.

Dan Keller 13:52

Let me ask you about the bacteria in the gut known as the gut microbiome. These microorganisms, it seems that studies have shown people with Parkinson's disease tend to have a different kind of population of bacteria in their gut from healthier people. Going on a diet, gradually moving to a diet like you advocate, does this change the gut microbiome? And it seems that not only would it have an effect locally, but now they've connected the gut microbiome even with things like depression and the immune system, and all sorts of stuff.

Dr. John Duda 14:31

That's a great question, Dan. The whole field of the gut microbiome and other microbiomes in the body has just exploded in the last couple of years. Now that we have advanced techniques of really identifying what bacteria and other organisms are in these environments, the story with Parkinson's disease is that there does seem to be a difference in the gut microbiome of people with Parkinson's disease compared to people without it. And a lot of the changes are actually similar to the changes that we see in a lot of other chronic kind of diet- or lifestyle-related diseases, like diabetes and arthritis and things like that, and that is that there are certain bacteria that tend to produce compounds that we think are beneficial to your gut health and to your overall health, and there are certain bacteria that we think are producing compounds that are not beneficial or detrimental to your health.

The big difference between these two populations of bacteria, for the most part, is what they eat. And so there are certain bacteria that eat primarily fiber and plant-based residue from your diet. Those bacteria end up being the ones that produce the short-chain fatty acids and other compounds that we absorb and help maintain our gut health. The bacteria that produce detrimental compounds, in general, are eating animal protein and things like that. So it's really premature to say for sure that changing your diet will affect your Parkinson's disease, but it is pretty clear that people who are eating a standard American diet with high amounts of processed foods and animal products, including dairy, can clearly change the microbiome in their gut within a relatively short period of time—within a couple of weeks, for sure. Some people believe within a meal or two, and it makes sense, because if you think about it, there are billions of bacteria in your gut, and the ones that are getting fed are the ones that are going to thrive and multiply. If you are feeding the bacteria that primarily eat dairy products and protein and things like that, they're going to thrive. If you start feeding the ones who eat primarily plant residues and fiber, they're going to start thriving.

Sometimes, when you change to a whole-food, plant-based diet or a Mediterranean diet, there are changes in your gut bacteria that you can feel. You can sometimes feel some GI side effects, including increased flatulence and things like that, but these changes tend to subside over time. And what you're left with is a gut bacteria that we think is healthier, and it, like you said, is associated with mood state, and weight gain and weight loss, and your risk of other chronic diseases, including heart disease, diabetes, arthritis, almost anything you can think of. So that's a really fascinating story that we're really just starting to scratch the surface of, but I think it's pretty clear, and one of the best reasons, I think, for people with Parkinson's disease right now to start eating a healthier diet that includes a lot of plant-based sources of food.

Dan Keller 17:50

Little did we know how prescient Grace Slick was in singing White Rabbit, saying, "Feed your head." It seems like your gut bacteria only eat what you eat, and it has ramifications for possibly neurologic disease and mood and all sorts of things, so...

Dr. John Duda 18:08

It is a really fascinating field.

Dan Keller 18:20

In our next episode, we'll continue our conversation with Dr. Duda, and he'll have some practical tips on diet and nutrition, specifically for people with Parkinson's. In the meantime, you can find an expert briefing that he presented on the subject by searching our website at parkinson.org for his name, Duda, that's D-U-D-A. It's called Nutrition and Parkinson's. The link is at the bottom of the page. You can also find this webinar in our archived expert briefings page linked on parkinson.org/ebs, and we'll have a new expert briefing in March 2021 on non-motor symptoms, including gastrointestinal issues. You can find the details at parkinson.org/eb.

For more, you can hear a previous podcast in our series with Dr. Bas Bloem of the Netherlands, called The Importance of Good Nutrition for People with Parkinson's. That same page has links to more information, including a webinar by Dr. Heather Zwickey and a fact sheet about nutrition. Two other podcasts, one with Dr. Ai Huey Tan of the University of Malaya, and the other with Dr. Ali Keshavarzian of Rush University in Chicago, both titled The Role of the Microbiome in PD, may also be of interest.

If you would like dietary advice for yourself, you may be able to find a nutritionist or dietitian through your Parkinson's care team, or by calling our helpline at 1-800-4PD-INFO. If you have questions about today's topic or anything else having to do with Parkinson's, our information specialists can provide answers in English or Spanish. You can reach them at 1-800-4PD-INFO. News and updates about future events and resources are available by joining our email list at the bottom of our website's homepage. If you want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts.

At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

John Duda, MD is the Director of the Parkinson's Disease Research, Education and Clinical Center (PADRECC) and Co-Director of the Center for Neurotrauma, Neurodegeneration and Restoration of the Cpl. Michael J. Crescenz VA Medical Center and a Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. For the past 19 years, he has worked with his colleagues in Philadelphia to provide state-of-the-art care for thousands of Veterans with PD and related disorders.

His research activities have included basic science investigations into the role of Lewy pathology in the pathophysiology of Parkinson’s disease and related disorders as well as investigations into the mechanisms involved in traumatic brain injury. He has also conducted clinical research in Parkinson’s disease with studies of deep brain stimulation therapy, transcranial magnetic stimulation, the benefits of a plant-based, whole food diet, and the use of olfaction as a biomarker of disease diagnosis and progression. He has received research grants from the Department of Veterans Affairs, NIH, the Michael J. Fox Foundation for Parkinson Research, and the Department of Defense. He has been recognized as a BLR&D Senior Clinical Research Scientist and authored more than 120 scientific publications including articles in JAMA, Science, Neuron, The New England Journal of Medicine and Neurology.

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow. While our bodies consist of our own human cells, they also contain and interact with a vast array of microorganisms. These microbes normally keep us healthy, maintaining a balance on our skin and within the various niches within us. A major repository of microbes is the human gut, from the stomach through the large intestine, which contains about 1,000 kinds of bacteria, along with fungi and other organisms. These microbes are essential for digestion, the production of vitamins, and immune regulation. Mounting evidence indicates that, in addition, they influence the nervous system, including the brain. They can also affect drug absorption, metabolism, and elimination from the body. For this second podcast on the microbiome and Parkinson's, I speak with Ai Huey Tan of the University of Malaya. She studies the relationship of the gut microbiome to Parkinson's and tells me about her work and that of other researchers. Before she describes how the microbiome affects the disease, she starts off by describing how the disease affects the gut.

Ai Huey Tan 1:56

As we all know, Parkinson's is more than just a movement problem. Patients with Parkinson's suffer from non-movement, or what we call non-motor problems, as well, and in this regard, problems related to the gut can be very common in patients with Parkinson's. And this can include drooling of saliva, difficulty in swallowing, bloatedness, constipation. Several studies have even shown that up to maybe about 70% of patients with Parkinson's can experience constipation in their disease course, and this can be due to reduced gut motility or dysfunction of the anal sphincter itself.

Dan Keller 2:37

We know there's feedback from the gut to the brain. We feel full when we eat. Sometimes we feel nauseous. So what kind of transmission is there, or cross-talk between the two?

Ai Huey Tan 2:49

Yes, you are right. The brain and the gut communicate through several pathways. One will be the neuronal pathway where the vagus nerve and the enteric nervous system are thought to play a major role; two, via hormonal or metabolic signaling; and three, via an immune pathway.

Dan Keller 3:09

There's been increasing interest about the gut microbiome. What do we mean by microbiome?

Ai Huey Tan 3:15

Microbiome refers to the microorganisms that live in a particular environment. Our body harbors a huge array of microorganisms, and we actually have 10 times more microbial cells in our bodies as compared to human cells, and the majority of these microorganisms live in our gut, especially in the large bowel. We also know that microbiomes from different parts of the body differ from one another, i.e., the microbiome composition in the oral cavity is very different from the microbiome composition in the large bowel itself.

Dan Keller 3:55

Does the microbiome change over the course of the disease, and which causes which? Is the microbiome affecting the disease? Or is the disease affecting what's in our gut?

Ai Huey Tan 4:05

We know that the gut microbiome evolves from infancy all the way through puberty, as we experience changes in our diet and also expansion in our gut mucosa, and the microbiome composition becomes fairly stable once we reach adulthood and remains stable for quite a number of decades, but it may experience changes again as we enter the aging process. Now, many studies on gut microbiome in Parkinson's disease are cross-sectional in nature. That means they only look at one time point. There is only one study that looked at several bacterial groups over a period of two years in Parkinson's disease. So we do not really have enough data to tell us whether the gut microbiome actually evolves through the disease course in Parkinson's disease. We also do not have enough data to say whether or not it is Parkinson's disease that affects the gut microbiome or vice versa. But my gut feeling about this is that it's probably bidirectional. They contribute to each other in a bidirectional way.

Dan Keller 5:15

The large intestine, the colon, has a much greater load or burden of microbes than the small intestine, but there is something called SIBO—Small Intestinal Bacterial Overgrowth. Is there significance to that?

Ai Huey Tan 5:30

Small intestinal bacterial overgrowth is an acquired condition where there is an increased amount of bacteria, or changes in the type of bacteria, in our small bowel. There are quite a number of risk factors for SIBO, which can include low stomach acid, reduced gut motility, recurrent use of antibiotics, and proton pump inhibitors. So patients with SIBO can experience bloating, belching, diarrhea, and constipation. In Parkinson's disease, SIBO has been associated with worse disease severity and longer "off" time and more episodes of delayed "on" time or dose failure, where there is no "on" time at all when the patients take their Parkinson's medication.

Dan Keller 6:18

Do you know if it's because of absorption, or is the small intestinal microbiome breaking down the drug?

Ai Huey Tan 6:25

We now have some evidence that SIBO may affect Parkinson's medication absorption in the small bowel.

Dan Keller 6:33

Let's move up the gastrointestinal tract to the stomach. We've heard a lot about Helicobacter pylori, H. pylori, and its causing stomach ulcers. But what is the significance of H. pylori and Parkinson's?

Ai Huey Tan 6:49

Well, there are quite a number of studies regarding H. pylori infection in people who have had Parkinson's disease. So the prevalence of H. pylori infection in Parkinson's ranges from about 32% to about 70% in all these various studies. H. pylori infection in Parkinson's has been associated with worse disease severity and, again, with worse motor response complications such as longer time for medications to take effect and also shorter "on" periods.

Dan Keller 7:24

Many people have H. pylori and they don't get stomach ulcers. Is there a reason to think of eliminating H. pylori in people with Parkinson's disease, even if they don't have stomach ulcers, because of its effect on the medication? Or is it really too early to say we should do something about it?

Ai Huey Tan 7:44

At the moment, we have a few studies looking at the effect of H. pylori eradication in Parkinson's disease. There is one well-conducted randomized controlled trial that looked at the effect of H. pylori eradication on motor response complications in Parkinson's disease. They were able to show that after eradication of H. pylori, patients improved in terms of their "on" time after taking the Parkinson's medication. And in their basic pharmacokinetic studies, they found that the bioavailability of levodopa actually improved by about 20% after H. pylori eradication. So there is some evidence that by eradicating H. pylori infection, especially in patients who have motor response complications, this may improve medication absorption and therefore improve the duration of action for these medications. But at the moment, there is a lack of well-conducted, randomized controlled trials in this field to make a standardized recommendation across the board. So hopefully we will see more high-quality trials in this field in the future.

Dan Keller 9:01

Are there any recommendations about diet in Parkinson's? Are there any types of foods that people should think of eating or think of avoiding?

Ai Huey Tan 9:10

Generally, a normal, healthy, balanced diet is recommended without any special restrictions.

Dan Keller 9:18

What about probiotics? A lot of people have been talking about them for a lot of things. Do any of these supplements have a proven effect in Parkinson's disease? Is it too early to make a recommendation? Can they even be harmful?

Ai Huey Tan 9:30

We have a recent well-conducted randomized controlled study looking at the use of probiotics in treating constipation in Parkinson's disease, and the researchers were able to show that probiotics, in combination with prebiotic fiber, were effective in improving constipation and without any significant adverse events. So probiotics can be considered for patients with Parkinson's disease who are experiencing constipation. There is still a lack of studies on probiotics in Parkinson's disease. It is hoped that in the future, with further advancement in scientific knowledge, doctors will be able to prescribe certain specific dietary interventions or specific supplements based on the understanding of the diet and also the microbiome in Parkinson's disease.

Dan Keller 10:24

It sounds like this is a whole wide-open area for research. People have looked at the drugs, people have looked at motor symptoms, non-motor symptoms, but the microbiome and the gut seems to be just a new field entirely.

Ai Huey Tan 10:37

Yes, and this is a very exciting field, and we can see there are more and more studies being produced in this field over the past three to four years. And hopefully in the future, we will be able to understand better the bidirectional connection between the brain and the gut and the gut microbiome. And hopefully we can use some of this knowledge to potentially help identify, perhaps a biomarker for Parkinson's disease, and also probably to consider whether we can modulate the gut microbiome effectively in Parkinson's disease to change the disease course or to treat certain aspects of the disease. And we hope that this research will ultimately benefit our patients with Parkinson's in the future.

Dan Keller 11:29

Excellent. Thank you. To find out more about the microbiome, the gut-brain connection, and how gut bacteria may be linked to Parkinson's symptoms, search our PD library for fact sheets, articles, and more at parkinson.org/library. There's also an expert briefing on nutrition and PD at parkinson.org/eb led by Dr. John Duda of the University of Pennsylvania, who discusses the possibility that sound nutritional choices may provide disease-modifying effects. And in Episode 68 of this substantial matter series, Dr. Ali Keshavarzian expands on the importance of our microbiomes in health and disease, with a particular focus on Parkinson's. Also for a general overview of research on the human microbiome, take a look at the National Institutes of Health's Integrative Human Microbiome Project at hmpdacc.org. As always, our PD information specialists can answer questions and provide information in English or Spanish about this topic or anything else having to do with Parkinson's. You can reach them at 1-800-4PD-INFO. If you have questions or want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life. Today, to that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

Dr. Tan Ai Huey is a Senior Lecturer and Consultant Neurologist at the University of Malaya Medical Centre, Malaysia. She completed her specialty training in Neurology at the University of Malaya, Malaysia. Her main areas of research are in Parkinson's Disease and Movement Disorders, with a particular interest in exploring the role of gut infections and neuro-inflammation in Parkinson's Disease, and the characterization of rare/"orphan" diseases. She has numerous peer-reviewed journal publications and book chapters and has been awarded the Best Neuroscience Publication Award (UM Faculty of Medicine), and the International Scholarship Award from the American Academy of Neurology.

Dr. Tan has served as a Council Member of the Malaysian Movement Disorder Council since 2013 and was Co-Author of the National Consensus Guidelines for the treatment of Parkinson's disease. Currently, she is the Honorary Secretary of the Malaysian Society of Neurosciences (MSN), the professional body that represents Malaysian clinicians and scientists in the neurology/neuroscience field. At the international level, she serves on several committees in the International Parkinson’s and Movement Disorder Society (MDS) including the MDS Education Committee, which oversees the planning of movement disorder education programs around the world.

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow. Many factors may influence the development of Parkinson's disease and its progression: one's genetics, the environment, and even the microorganisms inhabiting a person's body, known as the microbiome. A major part of that is what is in the gut—the bacteria, fungi, and viruses in the intestines—and in most cases, living peacefully and beneficially within us. It does not only function locally in the gut in terms of digestion and nutrition, but it influences other parts of the body. Researchers studying various conditions in the brain have found influences of the gut microbiome there as well. Unfortunately, at times, it may essentially malfunction and contribute to disease. Dr. Ali Keshavarzian of Rush University studies the relationship between the gut microbiome and inflammation, including when this occurs in Parkinson's disease. We spoke at a Parkinson's and movement disorders conference in Hong Kong, where he told me about how the microbiome may influence the development of PD and how it may be manipulated to potentially help manage the disease. You're a gastroenterologist. We're here at the Parkinson's disease and movement disorders meeting. What's the connection?

Dr. Ali Keshavarzian 2:08

Yeah, it's the question I get asked very frequently. The reason is that for the last decade, we have been studying the impact of gut-derived inflammation and, in particular, intestinal microbiota in Parkinson's disease in collaboration with the movement disorder division at Rush University.

Dan Keller 2:38

Now you're doing basic science studies. So what does that imply? You're not looking at people directly, but you're using animal systems? Or how are you studying the microbiome?

Dr. Ali Keshavarzian 2:48

No, we are doing it both. Our first study was in patients with Parkinson's disease, and that was followed by animal study as well as basic science cellular studies to better understand how the microbiome impacts Parkinson's disease.

Dan Keller 3:06

Can you give me some examples of what you found—how it does impact Parkinson's?

Dr. Ali Keshavarzian 3:12

Before that, let me explain why even we thought about the microbiome. In fact, in the last 30 years, my research has been concentrated on a better understanding of the impact of environmental factors, and specifically factors associated with Western lifestyle in chronic diseases. Initially it was gastrointestinal diseases, and in the last 20 years in non-gastrointestinal diseases that are chronic, and experimental studies suggest that inflammation is a major factor for either initiation of a disease or progression of the disease, and Parkinson's disease is one of those potential disorders. And the reason is that there is now compelling evidence, both experimentally as well as in humans, that loss of brain cells in Parkinson's disease is a consequence of inflammation in the brain, so-called neuro-inflammation. And the question was, what is that source of inflammation? And we reasoned an intestinal microbiota is a reasonable candidate for a trigger of that inflammation, because we carry 10 kilograms of bacteria in our intestine. In fact, we are more bacteria than human. We initially thought 10 bacteria compared to one human cell. That is probably exaggerated, but at least two bacteria to human cells; we have 100 bacterial genes compared to one human gene. And more importantly, those bacteria are highly diverse and capable of producing inflammation when they are put in a position to be mischievous, and the many factors associated with Western lifestyle are those that make intestinal microbiota to become so-called pro-inflammatory. And Parkinson's disease, like many chronic diseases—whether it is obesity, diabetes, just to name a few—is more common in Western societies and became more common in developing countries when they adopted a Western lifestyle.

Dan Keller 5:57

How does the microbiome in the gut interact with the brain? Is it releasing factors that circulate? Is there transmission through nerves, back and forth? What's going on for the cross-talk?

Dr. Ali Keshavarzian 6:11

We don't know for a fact, but all of the above: that it can lead to inflammation in the intestinal wall, affecting the nerve cells in the gut. By the way, we have more than 10 millions of nerve cells in the gut. In fact, it is said that the gut is a small brain, and therefore there's plenty of nerve cells in the gut. And when they get inflamed, they have direct communications with the nerves in the brain, but that is one potential. But I believe that the effect is more systemic, that so-called abnormal intestinal microbiota can do two things or three things. One is impact the intestinal lining, so-called intestinal barrier, and disrupt the barrier, make it more leaky and make it more possible for bacterial products to penetrate into the intestinal wall and systemic circulation, and those products can eventually reach the brain and cause inflammation in the brain. The other part is that those bacterial products, because of the intestinal leak, get access to the nerve cells within the intestinal wall, and that inflammation either, again, by producing factors into the systemic circulation to reach the brain, or directly through the brain and cause nerve inflammation, leading to loss of nerve cells in genetically susceptible individuals, leading to Parkinson's disease, or at least result in progression of Parkinson's disease.

Dan Keller 8:07

It sounds like what you're finding now is really what leads to Parkinson's disease, what leads to progression, things like that. Does it have any implication yet for treatment or prevention of progression?

Dr. Ali Keshavarzian 8:21

Quite honestly, we don't know for a fact whether it leads to Parkinson's disease or progression of Parkinson's disease. At least in animal study, in a genetically susceptible mouse, it can, in fact, lead to Parkinson's disease. What we have found first in humans: in patients with Parkinson's disease, they have abnormal microbiota, so-called pro-inflammatory. And also we find in the same group of patients, they have disruption of the intestinal barrier, the leaky gut, and also evidence that those pro-inflammatory factors derived from the bacteria reach the circulation in patients with Parkinson's disease. Also there was association between those leaked factors and progression of a disease—more severe disease, higher level of those pro-inflammatory factors. And then we followed those human studies in animal models, and we showed that in animal models of Parkinson's disease, indeed, the same phenomenon happens, and factors such as stress and the type of food worsen that abnormal bacteria, intestinal leak, and inflammation in the brain and loss of nerve cells, very similar to patients with Parkinson's disease. Therefore, that provided opportunity to find a novel means to at least modify disease progression in those that they already have Parkinson's disease. And more exciting: that even prevent or delay the onset of Parkinson's disease in those at risk of Parkinson's disease, and that can be done by so-called microbiota-directed intervention. There are now primarily experimental, but also human studies outside Parkinson's disease, that we are able to change the composition and function of intestinal bacteria through diet, through supplements. And we have also data that when we took the stool of patients with Parkinson's disease and demonstrated that they have that abnormal bacteria and they have abnormal bacterial products, predominantly less amount of so-called anti-inflammatory products, short-chain fatty acids. When we incubated the stool with a series of supplements—prebiotics—we were able to change the composition of the bacteria to so-called less inflammatory bacteria, and we were able to increase the production of those putative anti-inflammatory products, such as short-chain fatty acids. It remains to be seen whether the use of those supplements or change of diet could also lead to this similar beneficial effect on bacteria—that is the first step. And secondly, whether that beneficial change will lead to improvement of symptoms of patients with Parkinson's.

Dan Keller 11:56

Anything important to add or words for people with Parkinson's today?

Dr. Ali Keshavarzian 12:02

We feel that the work we have done and others—in fact, now there are 13 studies from all over the world, from different parts of the United States (ours was obviously Chicago), in Europe (both northern, eastern, southern, and western Europe), as well as Asia—that patients with Parkinson's disease have abnormal bacteria. Whether it is a cause or consequence of Parkinson's remains to be seen, and therefore it is opening up a new avenue to add treatments such as diet or supplements to see whether we will benefit patients with Parkinson's disease. It remains to be seen through high-quality clinical trials, but in the meantime, that is what I suggest to my patients that come to see me. I'm a gastroenterologist, but because of my work, I have a large number of patients with Parkinson's disease, many of them with GI symptoms, that come to see me. And I tell them that there is no direct study in patients that change of microbiota will impact, but I provide dietary and what I call sleep circadian hygiene to improve their intestinal macro-environment and their microbiota. These are what I call common-sense recommendations: to try to avoid what is known as junk food, to try to be as organic as possible. Have food such as fresh food and vegetables, and have so-called Mediterranean diet with berries and legumes, and try to eat most of their food during sunlight to improve that circadian rhythm—that is breakfast and lunch—and try to have a regulated sleep-wake pattern. These are the factors, and we and others have shown that clearly improve microbiota in other diseases such as obesity or cardiovascular disease. Those common-sense dietary advice have shown to be beneficial; the hope is that that will also be beneficial in Parkinson's disease. But I'm eagerly waiting the opportunity to do clinical trials in Parkinson's patients to see whether those gut-directed interventions benefit the disease course.

Dan Keller 14:34

Very good. Thank you. You can find much more about the gut-brain connection, and specifically how it relates to PD, by going to parkinson.org/blog where you will find several articles on gut bacteria linked to PD symptoms, nutrition, and the PD gut-brain connection. You can also find an expert briefing on nutrition and PD at parkinson.org/eb by Dr. John Duda of the University of Pennsylvania, in which he discusses how the gut microbiome may be involved in PD and explores the possibility that sound nutritional choices may provide disease-modifying effects. Along that line, Professor Bas Bloem talks about how diet can help improve some of the symptoms of Parkinson's and optimize the effects of medication. In podcast episode four in this series, as always, our PD Information Specialists can answer questions and provide information in English or Spanish about this topic or anything else having to do with Parkinson's. They can help you find dietitians in your area or other resources having to do with diet and nutrition. You can reach them at 1-800-4PD-INFO. If you have questions or want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life. Today, to that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

Ali Keshavarzian, MD, FRCP, FACP, MACG, AGAF the Josephine M. Dyrenforth Chair of Gastroenterology, Professor of Medicine and the Graduate College, Director of the Division of Digestive Diseases and Nutrition (1999) and Director of the Institute for Advanced Study of the Gut, Chronobiology and Inflammation (2017) at Rush University Medical Center in Chicago, Illinois has been a practicing gastroenterologist with a specialty in managing patients with inflammatory bowel disease for over 30 years.

As a clinician scientist, he has been studying the impact of environmental factors [stress, alcohol, sleep and circadian disruption] on intestinal barrier function host/microbe interaction that promote intestinal and systemic [gut-derived] inflammation leading to initiation and/or progression of inflammatory disorders including IBD, IBS, food allergy, metabolic syndrome, alcoholic cirrhosis, NASH and Parkinson’s disease. He has contributed to over 350 published articles [h-index of 77] and book chapters. His works have been supported by multiple NIH, DoD, NASA and USDA grants. He was one of the first investigators to report the key role of oxygen free radicals in tissue injury in inflammatory bowel disease and one of the first investigators to begin to focus on the role of intestinal microbiota in health and disease in alcoholism, IBD, cancer, HIV and Parkinson. He is one of the early investigators to examine the effects of circadian and sleep disruption on GI tract and to report the negative impact of sleep and circadian disruption in IBD.

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.

John Eric Duda, MD
Professor of Neurology at the Veteran's Administration Medical Center
Director, Parkinson's Disease Research, Education and Clinical Center of the Michael J. Crescenz VA Medical Center, University of Pennsylvania
Co-Director, Center for Neurotrauma, Neurodegeneration and Restoration of the Michael J. Crescenz VA Medical Center, University of Pennsylvania

James F. Morley, MD, PhD
Assistant Professor of Neurology at the Veteran's Administration Medical Center Staff Neurologist, Philadelphia VA Medical Center
Associate Director, University of Pennsylvania/PADRECC Movement Disorders Fellowship Program. Co-director, Parkinson's Disease Research, Education and Clinical Center, Crescenz VA Medical Center

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need.

Part of that support is sharing resources and practices with people with PD that can enhance their lives. One of these practices is Tai Chi Chuan, or just Tai Chi, a distinctive Chinese form of exercise that aims to balance the forces of yin and yang to bring good health and balance in our lives. As a practical matter, for people with PD, tai chi can be helpful at various stages of the disease. The slow, gentle body movements present little risk for injury, generally done in a standing or somewhat squat position. Some classes for people with PD teach it in a seated position. Studies have shown many benefits of tai chi, including increased flexibility, body awareness, balance, posture, breath control, stress reduction, and quality of life.

While many people in Western countries practice Tai Chi, I asked Dr. Pei-Fang Tang of National Taiwan University about its uptake in Eastern versus Western societies. Do you think that people with Parkinson's, or just people with any condition in Taiwan, are more likely than Western patients to explore conventional Chinese exercises like tai chi?

Dr. Pei-Fang Tang 1:56

Yes, I think so, because there are two reasons. We may have more resources; we may have more tai chi instructors there and available courses there, so people are more likely to explore Tai Chi Chuan as their exercise choices. And the other thing is that because of the influence of Chinese culture, so we are more inclined to, for example, take Chinese medicine or be engaged in Chinese-style exercises, and Tai Chi Chuan is one of them.

Dan Keller 2:29

What do the parts of Tai Chi Chuan mean?

Dr. Pei-Fang Tang 2:33

Let me explain what Tai Chi means first. "Tai" means big, huge, and "Ji" means endless. So Tai Chi together means the endless, formless state of the universe, and that's the basic principle of the universe. Also, Tai Chi is based on ancient Chinese philosophy, Taoism, and it's believed that there are several principles. For example, there are yin and yang aspects of everything in the universe, and then yin and yang interchange and interact dynamically. And so in Tai Chi Chuan, we believe that there are yin and yang components you can practice.

Tai Chi Chuan is actually martial arts based on Tai Chi philosophy. So when the movements are going out or going upward, they indicate the yang aspect, meaning the fullness of the movement. And the movement coming down or coming toward ourselves is the yin aspect, meaning emptiness. And it's believed that the balance between yin and yang, the coexistence of yin and yang, helps balance our life and also helps us have good health and longevity.

When we practice tai chi, it is believed that it can bring balance in our health and our life. And so in terms of breathing, when we practice tai chi, inhalation also indicates yang, and then exhalation indicates yin, so that helps us learn the switching between yin and yang. So the breathing component of tai chi also helps us to stay focused and concentrated, and helps us become more relaxed. So practicing tai chi is like practicing the Taoism philosophy with mind and body.

Dan Keller 4:41

How often do people do tai chi? Is this a regular thing or occasional?

Dr. Pei-Fang Tang 4:45

For people who choose tai chi as their exercise, they may do it twice or three times as a group a week. And for people who are really into tai chi exercise, they may practice every day as a daily routine. And you often see older people in the park—they practice tai chi every day because they are very into it.

Dan Keller 5:12

If people do tai chi and they have Parkinson's, how does this help them in their daily life?

Dr. Pei-Fang Tang 5:21

There is evidence showing that—actually, two recent articles show that tai chi helps them have better balance, especially dynamic balance, so they can move further without falling. And also they have less, for instance, after the training, after about three months' training or six months' training, also they can feel more relaxed, and the movement speed can be faster, and so on.

Dan Keller 5:52

Are general tai chi classes for the public safe for people with Parkinson's?

Dr. Pei-Fang Tang 5:58

I would say that it's safe for people at the de novo stage, that's the very beginning stage, and stage one of Hoehn and Yahr—stage one patients with Parkinson's, because their symptoms are not so obvious yet, and so that's safe. But for people at stage two of Hoehn and Yahr, they may need to find courses specially designed for patients with movement disorders or Parkinson's.

Dan Keller 6:26

Is it only their body that's affected, or is there any effect in cognition, mood, things like that?

Dr. Pei-Fang Tang 6:34

Yes, there's more and more evidence that Parkinson's affects the mood and the cognitive performance, and tai chi helps with the mood also, and helps with cognitive function also.

Dan Keller 6:48

Can people begin at any time, or is this something that you should start young?

Dr. Pei-Fang Tang 6:54

Actually, it's never too late. And in our society, and also in a lot of studies, Tai Chi Chuan was given to older people—older people after 65, the age of 65—and they can still learn Tai Chi, Tai Chi Chuan. So I think it's never too late.

Dan Keller 7:16

How much instruction is required? Is it set kinds of movements and exercises?

Dr. Pei-Fang Tang 7:22

Yes, there are simple forms, like eight forms, that's the simplest one I saw. And I usually, in my research, I usually use the 24-form Yang-style Tai Chi Chuan. And I give our participants 12 weeks, three months, to learn 24 forms, and they learn two to three new forms each week. And the course is like three times a week, so in those three sections they learn two to three forms. And then by week 10, they probably already learn all 24 forms, and they can practice all 24 forms in sequence without the instructor's instructions. So I think that's how it operates, usually in my studies, and usually in communities it's taught this way also.

Dan Keller 8:17

I've heard that it's good for people with Parkinson's to learn new things, keep their minds stimulated. It sounds like learning 24 forms is a good way, at least for those 12 weeks, to keep learning, keep picking up stuff. Is it possible to do it from books or online instruction, or does it really need to be done in person?

Dr. Pei-Fang Tang 8:39

Personally, I would like it to be done in person. That's because Tai Chi Chuan is not difficult, but it requires some body coordination. Because people do it differently, if you do it online—well, when we do it in person, the instructor can give you feedback about your movement immediately, and they may guide you more in detail. So if you do it online, if the instructor cannot provide online feedback to your movement, then it's difficult to know whether you perform it correctly or not.

Tai chi is called a low- to moderate-intensity exercise, and it doesn't cause too many injuries. But if you perform it in an incorrect way, it can cause, for example, knee pain, because it's performed in a semi-squat position. So I think for beginners, it's better to have instructors to teach you, teach you in person. And for people who have more experience, they may try online courses.

Dan Keller 9:48

In your research, what outcomes do you measure?

Dr. Pei-Fang Tang 9:52

We measure motor functions, cognitive function, and brain activations.

Dan Keller 9:59

Quality of life?

Dr. Pei-Fang Tang 10:01

Yes, quality of life as well. Yes.

Dan Keller 10:05

I guess it also promotes social interaction if you're taking classes and getting together.

Dr. Pei-Fang Tang 10:11

Oh, yes, because we use the group format of the practicing, so people get to know each other and they encourage each other, so their social interaction becomes better also.

Dan Keller 10:23

A little peer pressure to show up every time.

Dr. Pei-Fang Tang 10:25

Yeah, good adherence. Actually, it's amazing that I have three arms in my research. It means three groups: tai chi, aerobic, and the stretching group. And the tai chi and aerobic group, the adherence is almost 100%.

Dan Keller 10:46

Is there anything interesting or important to add?

Dr. Pei-Fang Tang 10:49

Well, I think learning tai chi needs some patience and perseverance. And at the beginning, you may find it difficult to chain the movements one after the other or to remember the sequence, and it does take time. But just be patient and relax, and enjoy the learning journey, and I think practice can make perfect.

Dan Keller 11:14

Very good. Thanks a lot. Bye.

To find out more about Tai Chi, search "Tai Chi" in our PD library by visiting parkinson.org/library, where you'll find fact sheets and additional resources on exercise, posture, and stress management for Parkinson's disease. Another excellent resource is MedlinePlus from the US National Library of Medicine at medlineplus.gov. Just search on "Tai Chi" for an extensive list of validated links. You can also call our helpline to see if there are Tai Chi classes in your area, some of them modified to meet the needs of people with PD.

While people in the early stages of PD are generally as strong and physically fit as healthy people of the same age, it's always good to check with a physical therapist trained to work with people with PD to see if a specific exercise or class is right for you. For more PD-tailored fitness videos that feature a different focus every week, from balance to coordination and more, be sure to tune into our Fitness Fridays series, part of our PD Health at Home virtual program. You can visit parkinson.org/pdhealth to view previously aired at-home workouts today.

If you have any questions about the topics discussed today, or if you want to leave feedback on this podcast, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe, rate, and review the series on Apple Podcasts, or wherever you get your podcasts.

At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new podcast every other week, and as always, our PD information specialists are available on the helpline to answer your questions about tai chi, exercise in general, or anything else having to do with Parkinson's. Call them toll-free at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

Professor Tang earned her BS degree in physical therapy from National Taiwan University, MS degree in physical therapy from University of North Carolina at Chapel Hill, and PhD degree in Exercise and Movement Science from University of Oregon. Her research interests focus on the influences of aging processes and neurologic disorders, especially stroke and degenerative ones, on the cognitive control, neuromuscular control, and brain mechanisms of motor control and motor learning. She also is interested in studying the efficacy and neural mechanisms of different forms of exercise interventions in the promotion of cognitive and motor functions, as well as neuroplasticity, and in the prevention of dementia and disability in middle-aged and older adults and in people with neurologic disorders. The primary research tools her lab uses are movement analysis, biomechanics, and neuroimaging techniques.