The Parkinson’s Plan: How to Stop the World’s Fastest-Growing Brain Disease

I had the pleasure of speaking with Dr. Ray Dorsey, neurologist and co-author of The Parkinson’s Plan with Dr. Michael Okun. In our conversation, we dive into why Parkinson’s disease has become the world’s fastest-growing brain disorder — and, more importantly, how much of it can actually be prevented.

Dr. Dorsey shares eye-opening insights on how environmental toxins — from pesticides and dry-cleaning chemicals to air pollution — play a bigger role in Parkinson’s than most people realize. He also outlines 25 practical steps we can all take to reduce our risk and emphasizes the need to address the root causes of this disease.

This is an empowering discussion about how awareness, advocacy, and science can come together to build a future free from Parkinson’s disease.

🎧 Tune in now to listen and share with anyone who cares about brain health and prevention.

Transcript

00:33 **[Akshata]** Hi, everyone. I'm really excited today, to have with us Dr. Ray Dorsey. And Dr. Dorsey is the Director of Center for Brain and the Environment at the Atria Health and Research Institute. The center's mission is to identify the causes of brain diseases from autism to Alzheimer's, so we can prevent them. With his colleagues, he's written the book previously called Ending Parkinson's Disease, and now Dr. Dorsey has a new book with Dr. Michael Okun called The Parkinson's Plan which details a new part to preventing and treating Parkinson's. He's previously directed the center for Health and Technology at the University of Rochester, and he's chaired the International Huntington Study Group. He's led the Movement Disorder Division at Johns Hopkins, and consulted for McKinsey & Company. In 2015, the White House has recognized Ray as a champion for change for Parkinson's disease. And with that, I would like to welcome you to the show, Dr. Darcy.

01:37 **[Ray]** Thank you very much for having me Akshata. Everyone calls me Ray.

**[Akshata]** Welcome on the show, Ray. And congratulations to both you and Michael on your book being named as New York Times bestseller.

01:49 **[Ray]** Thank you very much, that's very kind of you.

**[Akshata]** That is really exciting, and if people don't have it, I would highly recommend, you know, bringing... getting this book. It talks a lot about, you know, all the things I think I, certainly found useful, and I'm hoping today we can dive in more into it. But before we start, as a neurologist, you know, I was hoping you could explain, you know, how do you diagnose someone with Parkinson's or has Parkinsonianism spectrum?

02:17 **[Ray]** So the classical, clinical, diagnosis of Parkinson's disease is based on having two of the following four key characteristics. One's a rest tremor, using your hands, usually asymmetric. Second and nearly universal is slowness of movement. Third is stiffness or rigidity. And fourth is difficulties with balance or walking. We now know that these classical motor features of the disease are just a small part of the disease, which affects large portions of the body and many, many systems. In the body, and actually the origins of Parkinson's disease actually might not begin in the brain, but might actually begin in the gut, or in the nose.

03:06 **[Akshata]** Yeah, and how are the I guess there have been subtypes which are is that right? Like, are there subtypes that are classified as, like, Parkinsonianism, or it's mostly the symptoms that is referred to as?

03:17 **[Ray]** So, Parkinsonism is the umbrella term, just like dementia is an umbrella term, and the most common cause of dementia is Alzheimer's disease, but there are other causes of dementia, vascular dementia, Lewy Body dementia, and the like. Parkinsonism is the umbrella term for anyone who has two of those four characteristics. Parkinson's disease is the most common expression is 60-70%, but some people have it for the side effect of medications, like antipsychotics can have Parkinsonism. And then there are a wide range of other Parkinsonian disorders, progressive supranuclear palsy, multiple systems atrophy, dementia with Lewy bodies. That are, more disabling, less responsive to treatment, and generally have a worse prognosis.

03:52 **[Akshata]** I see. Thank you for clarifying that. And in your new book, you Parkinson's plan, you mentioned that Parkinson's is considered world's fastest growing brain disorder. That's that's a pretty bold claim, and I'm just curious, like, why are we seeing this rapid rise in the number of people diagnosed?

04:32 **[Ray]** The Global Burden of Disease Study estimated that 6 million people have the disease. So how do you go from a disease that Dr. Parkinson said had not been classified in the medical literature. And affecting 6 people in his case, series, to one affecting 6 million. Well, genetics don't change in that short period of time, and aging alone is insufficient to explain the rise. Even adjusted for age, Parkinson's disease has grown by about, I think, 60% since 1990. And we have some clues to what's causing the disease. There's been a great study called PD Generation, funded, led by the Parkinson's Foundation, which looked at which offered individuals in the United States and other countries around the world free genetic testing and genetic counseling, and they found that the first 8,000 individuals they looked at, that only 12.5% carry a genetic cause or genetic risk factor for the disease. Said another way, the overwhelming majority of individuals with Parkinson's in the United States, 87% of Americans with Parkinson's have no known genetic cause or genetic risk factor. 87% have no known genetic cause or genetic risk factor. the answer to what's causing the disease lies not within us, but outside of us, externally in our environment. Yeah. And I'll stop there.

05:56 **[Akshata]** Yeah, no, and you've highlighted those some of those environmental factors, like pollution and pesticides, are big contributors, and I guess, seems to have tipped the scale of not genetics as such, but more the environmental factors, and in your book, you've beautifully both of you have, you know, written about what is the evidence for it, and yeah, I would love to hear a little bit about, you know, some of the strongest, like, you know, environmental factors that have contributed to these.

06:27 **[Ray]** Yeah, so the three major environmental factors we highlight in the book, and we think three that are probably most prevalent in the United States, and probably around the world, but there are likely others, are certain pesticides, dry cleaning chemicals, including a chemical called trichloroethylene. And air pollution, outdoor air pollution. Let me grab my So the studies that have linked pesticides, spanned 40 years. In 1987, Dr. Andre Barbeau looked at the prevalence of Parkinson's disease in rural parts of Canada, and he found that there was a near-perfect correlation between pesticide use in rural parts of Canada and prevalence of Parkinson's disease. The higher the pesticide use, the higher, the prevalence of Parkinson's disease, the correlation coefficient was .967.

**[Akshata]** Oh, wow. That's hard to argue.

**[Ray]** Yeah. It's hard to argue and hard to replicate. And that same study's been shown in France by my colleague, Dr. Alexis Albaz, and his colleagues have shown that, again, a very high correlation between use of pesticides in vineyards and in the cantons, and vineyards in cantons of France, and the prevalence of Parkinson's disease. I think the same study's been done in Israel. And in a lab, you've exposed laboratory animals to Paraquat, you expose them to Chlorpyrifos, you expose them to Rotenone, you reproduce the features of Parkinson's disease. In some places, you even get the animals to tremor or to shake. And in lab, these also damage the dopamine-producing nerve cells, which we know are lost in Parkinson's. So you have a wide range of evidence from epidemiological studies conducted around the world by different investigators over the last 40 years. You have laboratory studies looking at laboratory animals from researchers around the world, and you have cell studies looking at their effects. You know, taken together, they provide a pretty compelling case for example, that pesticides are certain pesticides are causing Parkinson's disease.

08:31 **[Akshata]** Yeah, and I guess it's been, yeah, interesting from, like, you know, from my perspective of having studied this in lab, like, the models used have been pesticides, like, a long time ago, and this kind of certainly, you know, makes you be cautious as you're doing with these lab studies, or, like, you know, even people have taken 20 to 30 years to even develop the symptoms, so it's not overnight, it's been happening, slowly.

08:59 **[Ray]** Yeah, and so two things. One, you know, you put a laboratory animal in an animal in the lab, and you let it age, it does not spontaneously develop Parkinson's disease. An animal placed in the lab, left to its own devices, does not spontaneously develop Parkinson's disease. It will only develop Parkinson's disease if you manipulate its genes, or as you indicate, expose it to toxic chemicals. Second is, as we highlight in the book, and as the journal Science wrote, the great Tim Greenemeyer, a neurologist and neuroscientist who linked a naturally occurring pesticide, who showed that a naturally occurring pesticide called Rotenone causes Parkinson's in rats in 2000, he himself recently disclosed that he had developed Parkinson's disease. Perhaps due to insufficient protection of himself from the same chemical that he was studying.

09:57 **[Akshata]** Yeah, yeah, I think that while alpha-synuclein is the protein that's affected, it certainly is, I guess, induced, the pathology seems to be induced with these other environmental toxins. Yeah, and I guess I know that you've laid out nicely about the prevention plan in your book, which the plan being prevent, learn, amplify, and navigate. And I would love for us to dive into each of these elements, and if we could, you know, start with prevent, and you've spoken a little bit about TC, PC, and Paraquat, but what are, like, some of the food, water, and environmental toxins, that could influence?

10:39 **[Ray]** Yeah, so We talked about pesticides, which are sprayed on farms and can be found in foods, and our water is a common contaminant, is a chemical called trichloroethylene, or TCE. like many neurologists, I was really unfamiliar with this until my colleague, Dr. Caroline Tanner, introduced it to me when we wrote our first book. And trichloroethylene's a really simple molecule, so it's a whopping 6 atoms, so water's 3 atoms, trichloroethylene's 6, 2 carbons in black, 1 hydrogen atom in white on this model, and 3 chlorine atoms in blue. It's got a cousin called protochloroethylene, or tetrachlorethylene, which just has a fourth chlorine atom instead of hydrogen, and the chemicals that have been used in dry cleaning still are. Perchloroethylene's the most commonly used dry cleaning chemical in the U.S, to my knowledge. And, in twin studies, trichlorethylene's associated with a 500% increased risk of Parkinson's disease. The marine-based Camp Lejeune in North Carolina in the U.S. has been contaminated with that chemical, and Dr. Tanner and her colleague, Dr. Sam Goldman and others have demonstrated that Marines exposed to this toxic chemical in the water at this marine base when they were 20, 34 years later, had a 70% increased risk of developing Parkinson's compared to Marines who served at a less contaminated base. In the lab, TCE reproduces the features. And then TCE, like radon, can evaporate, so if you are if TCE is in the groundwater or soil underneath your home, school, or workplace, it can evaporate, and you can be breathing in your indoor air and never know it, and we give you studies of that in the book. And then outdoor air pollution just today, a major article in Science by Dr. Ted Dawson and his colleagues at Johns Hopkins were used to study, and you probably even knew Dr. Dawson, showed that, in both epidemiological studies and in the laboratory, particulate matter increases the risk of Parkinson's disease.

12:41 **[Akshata]** Yeah, that's yeah, it is a little scary to think of how many everyday tasks that we do, have the, you know, the risk of being exposed, and I think that in you lay out, like, your, I guess, Parkinson's 25 as, like, a way of kind of really trying to understand, like, what could we do, and what could we avoid, and I'm wondering if you could highlight some of these, especially something like dry cleaning, right? Like, I think that we all need that, like, how do we go about preventing and learning about it.

13:11 **[Ray]** Yeah, so in the book, we give you 25 recommendations that individuals can take in their everyday life. Many of them are free, almost all of them are low cost. That you can do take to reduce your risk of ever getting Parkinson's. Parkinson's is preventable. We give you 25 actions you as an individual can take to reduce your risk. Parkinson's is preventable. And then, if you already have the disease, like, about 12 million people around the world have the disease, these actions might slow the rate of progression of the disease. And so, this is, for dry cleaning. Number 13 of the 25 recommendations is to dry clean cautiously. Dry clean clothes release dangerous chemicals like trichlorethylene and perchloroethylene into your car or home. To limit exposure, first consider minimizing your dry cleaning. Second, find a dry cleaner that does not use PCE, also called PERC. So you can just find a green dry cleaner and ask them if they use PERC. If they don't if they use PERC, avoid them. If they don't use PERC, you're in better shape. Third, if you dry If your dry cleaner does use PCE, air out your clothes before taking them inside the home. Take off the plastic bag and let the clothes breathe so you don't have to breathe in the chemicals.

14:28 **[Akshata]** So these dry-cleaning chemicals are not yet on the list that are banned, I guess, by the U.S. government, essentially.

14:35 **[Ray]** So, in 2024, the EPA actually banned trichloroethylene, perchloroethylene, and it looks like the current administration's gonna let that ban stand. If it does, it calls for a phase-out in the use of these chemicals in most applications over the next decade.

14:53 **[Akshata]** Yeah, yeah, and it appears that, like, some of the countries that have been manufacturing them have been cautious about it and have banned them years ago. And then this, like, slower ban that's coming here in the US.

15:07 **[Ray]** Yes, and so, like, some countries, as you indicate, have banned it, like many in Europe, and there are some indications, for example, that the instance number of new cases of Parkinson's may be plateauing in Europe, and maybe even falling in countries like the Netherlands and Germany, which have taken actions to ban these chemicals, ban the most toxic pesticides, ban TCE, and clean up their air, and we can see early signs of the fall of Parkinson's disease in certain countries in Western Europe.

15:08**[Akshata]** That is, yeah, that's hopeful, I would say. Say the least. Yeah, yeah. And are these chemicals, like, if they are in water, like, I guess just curious, like, is this something that can be eliminated through filtration systems, or, you know, would people need to relocate, I guess, like, if that's the case?

16:03 **[Ray]** So, well, I'll read you, I think, number I'll review another, of the Parkinson's 25, on water. And so it says, number 9 is use a water filter. A simple carbon filter widely available in supermarkets can reduce exposures to pesticides, trichlorathlene, and other chemicals that may be in your water. These carbon filters can be installed for the whole house at the point of entry, or at the point of use, such as faucets or even a water pitcher. So again, there are lots of things you can do to reduce your risk. We even have a water filter in our home. We used to have one, on our faucet in the kitchen, and now we have basically a tank of water that we just have the water go through a carbon filter to reduce exposure, even when we have city water. If you get your water from a well, huge issue in the United States, 1 in 8 Americans get their water from a well. Or around the world, lots of people get their water from a well. Definitely get a carbon filter, and if you can, test your water, and test it not just for pests, for bacteria, which is often tested in the U.S, but test it for these pesticides if you live in rural areas. Or if you have water in an area if you have well water in an area that had industrial plants, tested for trichloroethylene and perchloroethylene. There are companies like Simple Labs and others that offer testing. They're not making any endorsements of any companies, but there are testing companies out there.

17:29 **[Akshata]** Yeah, yeah, no, and those are things that are doable, that I guess people can can certainly try to, you know, on an everyday basis, implement some of those. Which is super helpful. I yeah, I guess I also wanted to understand your, like, you know, as your journey of, like, recognizing this need of writing a book, right, about this, saying that, yes, Parkinson's is preventable, and this is something we can actually take a bold move, take a bold initiative, and start spreading the word. Like, I guess, how have, you reached out, and I know that there have been many players, but I guess, in terms of as a clinician, how else is this being incorporated? You know, for patients who come in for diagnosis? Is there any kind of correlation that can be done? And of course, like, sometimes some of these things have happened years ago, and but I think there's empirical evidence sometimes suggesting, and that something is building the case. I'm just curious, like, is there a way of incorporating that in your clinical notes, or, like, you know, even from a clinical trial perspective? Like, how how neurologists think about it.

18:39 **[Ray]** Yeah, so what do neurologists do perhaps better than other physicians, or at least more oriented towards, is we figure out why people have diseases, you know, and we do this for good reason. We try to figure out why people have a stroke so we can prevent the stroke, if they had a stroke because they have plaque in their carotid artery, we can take the plaque out. If they have stroke because they have an abnormal heart rhythm, we can correct the underlying heart rhythm. If someone has a seizure, we figure out why they have a seizure. If they have a headache, we figure out, do they have a headache because they have migraine versus a brain tumor? Those are treated entirely differently and have entirely different guidance for preventing and treating the disease. And once you have a cause, you can treat it, slow it down, prevent it, and even possibly cure it. If you want to cure Parkinson's, a prerequisite to getting a medical cure is knowing what its cause is. And so I actually spend a lot of time now, with new patients trying to figure out why they have Parkinson's disease. One, I'm a curious guy. Two, I think it enhances our understanding and a lot of the stories in the book are from people who share their stories, and people who are trying to identify their cause. You can't say for certain that it necessarily is, but you can certainly get a lot of clues. And it really informs prognosis, so if someone got exposed to trichlorethylene, for example, this chemical's known to cause cancer. The EPA says it's carcinogenic by all routes of exposure, and it's linked to prostate cancer, multiple myeloma, non-Hodgkin's lymphoma, renal cell carcinoma, the like. So you might counsel them about exposure to, the chemical, about exposure to the chemical, which can cause cancer. Other thing, more importantly, is making sure they're not having ongoing exposure. If a smoker comes in with lung cancer, your first thing you're going to tell them to do is stop smoking, but if a farmer comes in with Parkinson's, are we telling them to stop getting exposed to pesticides? If a dry cleaner comes in with Parkinson's, are we asking if they're still working in dry cleaning? Do they still have these chemicals in their home? Are they still spraying pesticides on their yard? I mean, the list goes on and on. So there are lots of, like, very, very, very, very pragmatic things that we could be telling people with Parkinson's to do that could possibly slow their rate of progression. We know that people with Parkinson's disease have a wide range in terms of their rates of progression. It may be that some of that is due to some individuals that have ongoing exposure to these toxicants, which could be enhancing or exacerbating the rate of progression, where some people are no longer getting exposed and may be have a greater chance of having a slower rate of progression.

21:14 **[Akshata]** Yeah, yeah, and I like that in the book, you guys mentioned about how, you know, if you have lung cancer, like, I guess the genetics component of it is much smaller, you know, while people think, like, oh, it may be genetically related, and I think it's the same same is true for neurological diseases, and you still need to you know, you stop smoking, and you now take it seriously, there's enough evidence built for it. So it seems like you need to make a case for this to really say that, yeah, you need to stop exposure to these environmental toxins. And, and continue that. Yeah. Now, I think that, in terms of one of the things why people also are interested, like, you know, I'm personally also interested, like, how does I guess if it's the same environment, why it may potentially affect different people in different ways. And that's something obviously very hard to understand, but I'm just curious what your hypothesis is, like, you know, what why that may be happening in a family. Yeah. Yeah.

22:11 **[Ray]** So, not all smokers get lung cancer. In fact, only a minority of smokers, a small minority, only 10-20% of smokers get lung cancer. Not everyone exposed to asbestos gets mesothelioma. Not everyone exposed to benzene gets cancer, and not every farmer's gonna get Parkinson's, and not every Marine exposed to trichloroethane's gonna get Parkinson's disease. In the book, we highlight three possible explanations, which probably all play a role. One is exposure, the dose, duration, route, and timing. So, children, young babies, may be especially susceptible to Parkinson's disease, or to the effects of these toxins. The seeds of Parkinson's are likely planted early. We saw that in the Camp Lejeune study, where the individuals were on average 20. So some of them were teenagers when they were exposed, so teenagers exposed to these toxins developing Parkinson's 3 decades later, 4 decades later, the seeds of Parkinson's may be planted early. Second is interactions with the gene. So, for example, the most common genetic risk factor for Parkinson's are mutations in a gene called GBA. Those individuals who carry that may be more susceptible to the effects of pesticides, as suggested from a recent study by Dr. Caroline Tanner and Ethan Brown at UCSF. There are in addition to interactions with genes, there's interactions with, the environment. So we know that the effects of head trauma and pesticides are amplified when they co-occur. And then there's probably chance, so we're probably misfolding proteins like alpha-synuclein or beta-amyloid all the time, or at large at a great high frequency, and most of the time it's cleared or controlled, but some of the time it becomes uncontrolled, probably like mutations leading to cancer. We are clearing most of the mutations, but sometimes it gets out of control. Chance may play a role. So we talked about exposures, interactions. The third are modifiers, age, perhaps sex, comorbidities, stress, other infections, other things could be, modifying the role as well.

24:17 **[Akshata]** And I'm curious if, in addition to this, has there been any correlation for different ethnicities? And I know there have been, like, you know, fewer, I guess, countries in which the data has been collected. It's not, like, you know, as vastly collected in all countries, so I'm curious if there is any correlation, or it's more lack of data, because

24:29 **[Ray]** I think I think the exposures vary by geography, and by group. So if you're in rural parts of the United States, or you're in Sub-Saharan Africa, or I would be worried about pesticides. And again, Sub-Saharan Africa, if you're a farmer, if you're living near an agricultural thing. If you're in India, if you're in China, you might worry a lot about pesticides in India, you might worry a lot about pesticides and air pollution. If you're in China, which has half the market for trichloroethylene, you might worry about trichloroethylene, you might worry about in urban areas, about air pollution, in rural areas, about pesticides. Other parts of the world in the North Atlantic have had high levels of exposure to PCBs. So, polychlorinated biphenyls, widely used in the electronics industry, so I think it varies by region. I think most of the differences are due to sociology more than biology, and even more than genetics. Likely.

25:36 **[Akshata]** Yeah, no, that's that's helpful to create that awareness that it's not gonna be one thing that's gonna potentially affect, you know, one population. There might be as all these diseases are complex, but I guess, like, at least what is there in your ecosystem that you could potentially pay attention to and alter. And what are the, I guess, current standard of care for Parkinson's? And, also would love to hear more about what can those people now, you know, what are some of the interventions from a lifestyle perspective, in addition to those 25, like, you know, would help.

26:10 **[Ray]** So to give you 25, those are the best that we got on lifestyle. They're probably some that we understated or miss, and people let us know, so next time we'll have the Parkinson's 30 or 35. the care is really, really, really, really, really difficult in the United States. I get emails all the time today, someone in, you know, in a moderately-sized city with, I think said there's one Parkinson's specialist for the whole area, and trying to find Parkinson's specialist. In the United States, only 9% of people with Parkinson's disease see a Parkinson's specialist like Michael or me, or one of our outstanding colleagues. 40% don't see a neurologist of any kind, and those that don't have, according to research from Dr. Willis, Allison Willis at Penn, are more likely to fracture their hip, be placed in a skilled nursing facility, and to die prematurely. So it's a huge issue. Michael has a whole chapter on putting the patient at the center of the universe and calling for services to be put around them. There's a lot of work that needs to be done to that. We need to expand the number of centers of excellence. We need to increase training for clinicians at all levels, with, for to care for people with Parkinson's disease. But we're never gonna get out of this, by without addressing the root causes of the disease. If we don't go upstream, as Michael likes to say, if we go upstream and find out what the root causes of the disease are, we're never going to be able to do this. You know, it wasn't that long ago, even when I was in medical school, like, we were doctors were doing liver transplants all the time for hepatitis C, and we didn't hepatitis C before was called hepatitis C, it was called non-Hep A, non-Hep B. They didn't know what it was. They figured out what caused it, that led to treatments and then surgeries. And then I came up with a pill, and now we don't hepatitis C is curable with a pill. There aren't liver transplants being done for it. So we don't need to worry about more transplant centers or training transplant surgeons, or working about better immunosuppressive treatments, or, you know, any of the thousands of things due, or the surgical risk of transmission of hepatitis C to the surgeons and nurses who are in the operating room, and operating theater, and harvesting livers. I mean, all these things are just gone, and we can just make Parkinson's largely disappear. Instead of being one of the fastest growing diseases, it can be one of the fastest falling diseases, and we can just make a world largely free of Parkinson's disease, just like we live in a world largely free of polio, where smallpox, and a whole litany of diseases no longer affect mankind or humankind.

28:48 **[Akshata]** Yeah, and I think that analogy of having the Parkinson's universe with the patient as the sun and the center, and I guess all the different parts of the universe, that's beautiful, and I think it is helpful to have the patient-centric view, and it is also, I guess, the statistics around, like, in the US, which is obviously a very developed country, where, you know, we are still, like, trying to figure out, okay, who are who is the right doctor, like, you know, what other I guess, whether it's a nutritionist or, you know, physiotherapist who needs to help aid. I think in that care plan, what do you who are the people you think, like, you know, from a caregiving perspective need to be included. And, and this is worldwide.

29:30 **[Ray]** Yeah, I think we underestimate the toll this takes on caregivers, and I, I, I've underestimated it, and probably still do. One person, told me for our first book, this is no way to spend your golden years. And said, like, the first thing that happens after someone's diagnosed with Parkinson's disease is the phone stops ringing. And that's in the U.S. Other places, the stigma is huge. Our colleague Amatola Thomas, working really hard to reduce stigma for Parkinson's disease around the world, especially in Africa. I think caregivers play a bear a huge burden. I'll tell you a vignette. So I was caring for a person with Parkinson's disease. I did telemedicine, or I still do telemedicine for years. I was caring for them for 10 years, maybe more, and every time his wife came in, and he was a former firefighter, and he was, you know, a lumbering guy, and, you know, didn't talk very much, and the wife always did it. Petite woman, he's a big guy, she's petite. And then, after 10 plus years of caring for him, he's well into his 80s, one day, his wife's not there. And, I didn't have the heart to ask what it was, but I found out that his wife had died, and you know, we think a lot about the patient, but we sometimes forget that there are that disease affects more than just the individual. It's not just the spouse, necessarily. It can be the spouse, children, friends, family. And we know that caregiving is associated with worse health outcomes, including increased risk of death, depression, and the like. So, we have lots of reasons to try to reduce the burden of Parkinson's disease, not just for those with the disease, but their whole circle around them is affected.

31:31 **[Akshata]** Absolutely, yeah, and I certainly see this in my own household, like, you know, with my mom being the primary caregiver, and we have, you know, of course, physiotherapists, doctors, people who could help out, but the burden does feel real, and it can certainly take a toll. And we had Larry and Rebecca Gifford interview, and yeah, it was really helpful to hear Rebecca's perspective on caregiving, you know, and what can be done to kind of manage that kind of stress. Which unknowingly creeps up, sometimes very knowingly creeps up, and, especially, I think that, you know, I want to touch a little bit about this thing about stigma, and, you know, as we talk about also the amplifying part, right? Like, how can we, like, I guess, what is the stigma around, and how can people, like, you know, myself or others really help in making the stigma go away, because it's not something anyone can control, and it's just there.

32:26 **[Ray]** So, one, we gotta applaud the people who reduce stigma. People who have the disease and service that having Parkinson's stinks, and being the face of someone with being the face of a disease is burdensome. So we have to thank Michael J. Fox, we need to thank Davis Finney, we need to thank the basketball player Brian Grant, we need to thank the PD Avengers, we need to thank all these individuals who reduce the burden. And then people need to make their voices heard. People need to join the PD Avengers. People need to join the PD Avengers. So the PD Avengers is a global grassroots organization founded by three individuals with Parkinson's disease, led by these three individuals, and his goal is to make the lives of people with Parkinson's disease better, and to help us get rid of Parkinson's disease forever. And if you haven't joined the PD Avengers, you should join it. Whether you have Parkinson's disease or don't, I'm a member. It's free to do so. You go to PDAvengers.com, PDAvengers.com. It takes 30 seconds to sign up. It's free to do so. They have over 8,000 members from 100 countries. They need to have 10,000 or 100,000 members. If we have 100,000 PD Avengers, we reduce the stigma of Parkinson's disease, we improve the care for people affected by the disease. We find out its root causes, we slow the rate of progression for those 12 million with it, and we prevent Parkinson's disease for generations to come. I can't think of a better way, a better service we can do in the neurologist or a neuroscientist than to create a world without the diseases that we study.

33:55 **[Akshata]** Yeah, absolutely agree, and yeah, I would also plug in, like, you know, I am a PD Avenger, and I also urge everybody to join. It's a really easy way, and it's nice that they kind of send you resources, and especially for families that are looking for resources, it's something easy enough to sign up and learn more about it. And I I also think that the engagement of neurologists like yourself with with these, you know, groups that are, you know, patient-led advocacy groups, you know, or, like, even, whether it's clinicians, but also academic groups, as well as patient families and caregivers. I think coming together of all of these different groups have been I think, has been a game changer, and it seems like science used to not always be done this way, so I'm curious over the time, like, how you've seen has there been these shifts? And of course, Michael J. Fox Foundation has been really amazing at bringing some of these resources and initiatives, but would love to hear your perspective of how you think it's moved a needle on engagement.

35:05 **[Ray]** Well, I don't think we're doing enough, and I think Michael and I, as we alluded to in the introduction, I think we're failing to serve the Parkinson's community. Parkinson's, as you said at the outset, is one of the world's fastest growing brain diseases, and that's occurring on our watch. And so, our colleagues answered the bell for HIV, our colleagues answered the bell for hepatitis C, our colleagues answered the bell for COVID-19. Michael and I have not yet answered the bell for Parkinson disease, and so we view that as a personal failure, professional failure on our part, personal professional failure on our part, and we take it personally. And so that's why we spent 2 years working on this plan and this book. We give it a lot of thought. I think you I always say when I read somebody's book, I'm getting the best of them, and I think you got the best of Ray Dorsey and Michael Okun in our professional capacities from 2023 to 2024, when we wrote the book over 2 years. And we give you very we give you strong evidence for what's likely causing Parkinson's. We give you a rationale for learning why the disease happens in the first place, so we can cure it. If you want to cure, you've got to figure out why it's caused what its causes are. We call for the amplification of the voices, as you indicate, and then Michael outlines in chapters 8 and 9 of the book, the new frontiers for treatments. And then we give you, in Chapter 10, a plan for preventing for preventing and treating this disease, and we give you 20 specific action items that individuals can take, that communities can take, get rid of pesticides in your kids' schools and playgrounds. Get rid of pesticides on your kids' schools and playgrounds. Your kids don't mind weeds, and they don't need nerve toxins. Get rid of pesticides on your kids' playgrounds and schools. And what we can do as society, banning the most toxic chemicals, measuring more accurately the incidence of Parkinson's so we can see if we're making progress, increase funding for Parkinson's research and devote 10 times as much to preventing the disease as we currently do. Almost all the money's trying to treat the disease, and we don't even bother to find the cause. There's a little bit of arrogance in that. We need to take some humility, take a step back, figure out what the causes are, then systematically test therapies to address the root causes of the disease, and then we make levodopa available 100% of people with Parkinson's disease. We've done that for HIV. 90 almost 90% of people with HIV have access to high highly active antiretroviral antiretroviral treatment. Levodopa costs less than a dollar a day, costs less than a dollar a day in the United States, yet large, numerous countries around the world have no access to the medication, which is a game changer for people with the disease.

37:51 **[Akshata]** Yeah, yeah, I think that having medication access and, of course, like, the prevention plan that you mentioned, that would be that would be huge. And I think in terms of some of the things that can be done at more at a grassroot level, you know, with policy changes, and I'm curious, like, what are the policy changes that you think are most urgently needed? Like, some of these pesticide ones are already in place, is that correct? 

38:16 **[Ray]** Well, I mean, we still have Paraquat in the United States. China and over 50 countries have banned Paraquat. The EPA says one sip can kill, one sip can kill. Wow. Paraquat is still sprayed on corn, on fields of corn, soybeans, grapes and cotton throughout the United States, and according to the U.S. Geological Survey, sprayed in increasing amounts. We need to ban Paraquat. If we ban Paraquat, we prevent the seeds of Parkinson's from being planted, not just for farmers, but for people who simply live or work near where Paraquat is sprayed. Dr. Beata Ritz and Kimberly Paul at UCLA show that individuals who work or live near where Paraquat is sprayed, not the farmers themselves, have a doubling the risk of Parkinson's disease. Dr. Brittany Krasinowski and colleagues showed that the incidence of Parkinson's disease among individuals who lived within one mile of a golf course in Rochester, Minnesota, was 126% higher than people who lived 6 or more miles away. We can reduce the amount of pesticides we use on golf courses, we can spray less frequently, we can use less toxic pesticides on golf courses, and we can stop spraying pesticides on kids' playgrounds and schools. If we do that, we will stop withering brains of children at young ages, we'll stop withering brains of adults with, like, getting ALS, and we'll stop withering the brains of seniors who are getting Parkinson's disease and Alzheimer's disease in increasing numbers.

39:46 **[Akshata]** Yeah, yeah, no, that's right. And I hope that some of these policy changes are happening, and we need more voices by signing up for things like PD Avengers to amplify it. In terms of I think that it's true for probably not just Parkinson's, but other diseases as well, but, things like exercise and social engagement, how big of a role do you think that is? Especially social engagement, I'm curious.

40:12 **[Ray]** So if you get diagnosed with Parkinson's disease, first ask why, so you can stop ongoing exposure, follow the Parkinson's 25. Second, exercise at least an hour a day if you can. I tell people if I had Parkinson's disease, I'd exercise 2 hours a day. The more you exercise, the more you leave growth release growth factors that likely protect the remaining nerve cells. And then, staying socially engaged and connected, so you don't want to become isolated. If the phone stops ringing, start calling some people. If you know someone with Parkinson's disease, reach out to them. Their, diseases are tough. When someone gets diagnosed with a disease, what happens, whether it's you or a family member, is the world stops. We need to Take some actions to stop to address people who are in need. And, reduce the burden for everyone. So if you know someone with Parkinson's disease, call them up, tell them about our book, of who Michael and I are devoting the vast majority of our proceeds from the Parkinson's planned efforts to prevent and treat the disease. So let people know about the book. We really wrote it for people who for the 1.2 million Americans who have the disease, the 12 million people around the world who have it, but also for the 330 million Americans who don't have the disease, and the 8 billion people around the world who don't have the disease, what can you do to prevent yourself from ever having this terrible disease.

41:28 **[Akshata]** Yeah, absolutely. And I think that the use of, as you said, like, knowing the root cause, I guess I want to bring it back to what is my expertise, which is studying this in the lab and really understanding, like, so do you think that, you know, the chapter that we're talking about, the next frontier, right, like, in terms of therapies, but also models to test these. Like, should it be some of these pesticides? What, like, you know, should it be some of these environmental toxins, then, in terms of models? Or just curious what your thoughts are.

41:57 **[Ray]** Well, there are people who know way, way, way, way, way, way more about the lab than I do, but it certainly seems reasonable if you can figure out what the causes of the disease are, you can create those models in the lab, and then you can screen compounds against them. What a nice thing to be able to do. We do that for cancer. When you can figure out what causes cancer, you can expose the animal to carcinogens and test therapies against it, and we've done that for viruses and the like. So there's lots of ways to go about this, but there are basic scientists. Dr. Green and Meyer and others will be better versed than I.

42:31 **[Akshata]** And what I know that there's, of course, DBS, deep brain stimulation, and dopamine, but are there other therapies that you're excited about personally?

42:41 **[Ray]** So, Michael, in the book, highlights what are the most financing treatments in the near term, less than 5 years, and I think levodopa pumps, these subcutaneous pumps, full disclosure, I've done some consulting for companies doing it, are promising. We need to make better pumps, we need to have second and third and fourth generations, just like we do for pacemakers. Adaptive DBS, Michael's one of the world's experts.

43:06 **[Akshata]** Sorry, just for our listeners, like, would the goal then be to just have a continual supply of the job instead of an off period, and yeah.

43:12 **[Ray]** Yeah, so, I mean, like, we do this for diabetes. In the old days, right, you had to check your finger stick, and then you gave yourself insulin based on that finger stick, and now it's a closed loop, you can just measure your continuous glucose monitors. Insulin can be dosed based on your glucose level, and it can be done without you thinking about it. Shouldn't we have the ability to infuse the levodopa that's perhaps close the loop, not based on your finger stick of glucose, but based on your speed of walking, or your amount of walking. And so you're walking really slow, maybe it increases it, or if your tremor is increasing, maybe it increases the amount and close the loop so we can measure it. This is not shouldn't we should be, like, moving along on this. And then Michael highlights, you know, treatments in the midterm, you know, are there immune therapies that can be done to prevent the spread of the misfolded alpha-synuclein from nerve cell to nerve cell? And what's out there in the long term, like nanotechnologies that can remove misfolded alpha-synuclein or go into the brain and deliver treatments there?

44:11 **[Akshata]** Yeah, no. Definitely, there's a lot of new directions, and we are hoping that both with prevention, but also learning more about what else can be done, we could all join in in this journey of a prevention plan for Parkinson's. And, you know, for families like mine, and also others, as you said, like, of course, advocacy is one, and are there a lot like, I guess, in your experience, like, is there good community support in most areas in the U.S, you think, or it's something which needs to be you know, grown.

44:42 **[Ray]** If you look at my inbox, it's not good anywhere.

44:46 **[Akshata]** That's good to know, because I think that there is a there is an illusion based on sometimes social media, maybe, that, oh, there is, like, a lot already going on, but, the local community itself, and I can certainly also speak for India, like, where my parents are, they're based in Mumbai. Like, there are some, but they're very isolated, and they are hard to get to. Especially for those who have Parkinson's, and who need to reach there.

45:05 **[Ray]** And there are some shining lights, and, like, our great friend Boss Bloom has created, Parkinson Net in the Netherlands, which provides comprehensive care for people in the Netherlands. But the Shining Lights, Michael's Okun's Center at the University of Florida, these are the exceptions and not the rule, and we have lots of work to be done to make these, care models more accessible to everyone.

45:33 **[Akshata]** Yeah, and before we do our quick rapid fire, I guess I wanted to also just ask you, like, if you have a message for anyone who's newly diagnosed or has been, you know, suffering from Parkinson's, whether it's patient or family.

45:51 **[Ray]** Well, we give you some ideas for slowing the rate of progression, and that's what you can do. I think this disease is a lot better if we say that we're going to be the last generation to bear it. I have a colleague in the Huntington's disease world who's a neuroscientist, and he carries the gene that's responsible for Hunting's disease. Hunting's disease is due to a single genetic mutation. And he did pre-implement pre-implantation genetic diagnosis for his kids, and he doesn't really have many siblings and the like. And so he says that Huntington's disease is gonna die in his family with him. He'll be the last member of his family to veil Huntington's disease. That's a very powerful message. I think if you have Parkinson's disease, unlike your children's neurologist, I want our generation to be the last generation to bear the burden of Parkinson's disease. I don't want, you know, you Akshata, I don't want your grandchildren, I don't want your parents' grandchildren to have Parkinson's disease anymore. I want our generation to be the last to bear the burdens of disease, and we want to give future generations where Parkinson's is increasingly rare instead of increasingly common. And where, people live lives free of this terrible, debilitating disease.

47:03 **[Akshata]** Yeah, I would say amen to that, and yeah, everybody needs to read that book to get a sense of what are some of the ways that you can adopt, you know, the Parkinson's plan. And before I let you go, I want to do a quick rapid-fire of what book has book or movie has recently inspired you.

47:21 **[Ray]** Well, so we wrote the first book because of a great book called How to Survive a Plague by David France, which describes the act the response of New Yorkers. I'm sitting in New York, like, the late Larry Kramer, I'm forgetting the names. David France was one of them, Peter Staley, who changed the course of HIV, and they adopted a motto of silence equals death. And I think for Parkinson's disease, silence doesn't equal death, but silence equals suffering. And if you remember, the courageous actions of these individuals who were being blamed for their own illness, they changed the course of HIV. And because they changed the course of HIV, you don't have HIV, I don't have HIV, millions of us don't have HIV because they changed the course of it. And, we can do the same thing for Parkinson's disease. If they can change the course of HIV when there was no federal response, when doctors refused to care for them, when hospitals refused to admit them, when they were blamed for their own disease, we can certainly change the course of Parkinson's disease. We just need to have the creativity and the will to do so.

48:31 **[Akshata]** Yep. What's one thing that brings you joy every day?

48:37 **[Ray]** Well, uh, we have children, and they bring a lot of joy and have a wonderful wife, so those things bring me a lot of joy.

48:44 **[Akshata]** Yeah? And a mantra or phrase you live by.

48:50 **[Ray]** I don't know if I have one, I mean, I think there are a lot. Uh, I think resistance, I think progress one definition of progress is meeting resistance. So, when you're encountering resistance, and I think we're encountering some resistance, that's a sign of progress.

49:09 **[Akshata]** Yeah.

49:10 **[Ray]** And we're trying to really break through with this idea that the vast majority of Parkinson's disease is preventable, and this isn't Ray Dorsey's idea, this isn't Michael Okun's idea, this, if you want to go to someone, this Dr. Caroline Tanner, an outstanding Parkinson's specialist and an epidemiologist who, for 40 years, quietly, diligently, has been telling us through studies of twins, through studies of pesticides, through studies of TCE, that the principal causes of Parkinson's disease are in our environment, and as such, are preventable.

49:38 **[Akshata]** Yeah? Thank you so much, Dr. Darcy. It's been a pleasure having you, and yeah, I think for all our listeners, this was super helpful to actually have a practical guide of what we could do.

49:49 **[Ray]** Thank you very much, Akshata, and best to your family.

49:50 **[Akshata]** Thank you very much. Thank you.

 49:53 **[Akshata]** Hope you found this episode helpful just as I did. I want to share with you 10 of the Parkinson's 25 actions that was shared in this book to lower risk for Parkinson's.

Number 1. Wash your produce. Even if it's organic, to remove any pesticide remnants.

Number two, diet. Mediterranean diet, which is high in fruits and vegetables, is found to be effective for Parkinson's patients.

Third, avoid or at least manage diabetes as it is a factor that can lead to faster progression rate of Parkinson's.

Number 4. Have a cup of caffeinated coffee. As there are studies showing decreased risk of Parkinson's With a cup of coffee every day.

Number 5. Use a water filter at home. A simple carbon filter would suffice to reduce pesticide exposure in your water.

Number 6. Use an air purifier to lower indoor air pollution.

Number 7. Roll up windows in traffic to avoid bringing toxic fumes inside your car and home.

Number 8, Garden with Care. Plants like mums can produce their own pesticides. And be careful with the type of weed killers you use while gardening.

Number 9, Exercise. It is the number one thing that can lower your risk of developing Parkinson's. And also helps in slowing of Parkinson's.

Number 10. Last but not the least, sleep. Sleep is important for brain function, and it helps clear toxic buildup of toxins in the brain.

I hope these are easy and helpful ways of incorporating how you could lower your risk of Parkinson's.

If you've enjoyed this episode, please subscribe, share, and leave a comment.

Thank you, and keep listening!