The Alarming Rise in Parkinson’s Disease with Dr. Ray Dorsey | The Empowering Neurologist EP. 167

We can slow the rate of progression by stopping exposure to certain pesticides and these dry cleaning chemicals or air pollution. And then I think most powerfully, we can create a world where these diseases are increasingly rare, not increasingly common.

Well, hello everyone. I'm Dr. David Perlmutter. Welcome again to The Empowering Neurologist. We are experiencing a virtual explosion in the number of new cases of Parkinson's disease. I know we talk quite a bit about Alzheimer's in the program, but all of a sudden Parkinson's is really becoming an issue. And as it turns out, there's very good data that relates risk for Parkinson's to some important modifiable issues like exposure to toxins, head trauma, for example. We know there's a genetic component, but it turns out that it's Probably not that significant. We also know, interestingly, that there is a contributor in terms of risk brought on by changes in the gut bacteria. Who knew? And today we're going to learn by looking at the book Ending Parkinson's Disease by Dr. Ray Dorsey. I hope that's in the frame. He's written a really terrific book, and looking forward to a very exciting interview. Let me tell you a little bit more about Dr. Dorsey. Dr. Ray Dorsey is the David M. Levy Professor of Neurology at the University of Rochester. He's working to identify and eliminate the root causes of Parkinson's disease, and his research on brain diseases and digital health has been published in leading academic journals and featured in multiple news outlets. In 2020, Ray and his colleagues wrote this book, Ending Parkinson's Disease, A book that provides a prescription for basically ending the world's fastest-growing brain disease. Ray previously directed the Movement Disorders Division and Neurology Telemedicine at Johns Hopkins and worked as a consultant for McKinsey and Company. In 2015, the White House recognized him as a Champion for Change for his work as it relates to Parkinson's. So, We're very delighted to have him on the program today. Let's get right to it. Hello, Dr. Dorsey, welcome to the program.

I'm delighted to be with you, David. Everyone calls me Ray.

Okay, uh, you can call me Ray. Um, terrific book. And, uh, you know, I'm reading this book in the context of what certainly we as neurologists, but I think even perhaps the general population, is, is recognizing. And that is suddenly, you know, it's well beyond Neil Diamond, Linda Ronstadt, and Michael J. Fox that We're seeing a really significant uptick in the number of cases of Parkinson's. I mean, it used to be sort of the forgotten stepchild. Everything was about Alzheimer's, and ratio was about 1 Parkinson's patient every 10 Alzheimer's. But suddenly we're seeing a big uptick. And, you know, I know we've got a lot to talk about, but maybe let's first start with why that's happening.

Yeah, so brain diseases are the leading source of disability in the world, and the fastest growing of these brain diseases is Parkinson's disease, even faster than Alzheimer's, as you mentioned. Over the last 25 years, the number of people with Parkinson's disease has more than doubled, and absent change, is poised to double again. And in our book, we argue that numerous environmental factors, 3 in particular— outdoor air pollution, certain pesticides, and a common dry cleaning chemical called trichloroethylene, all of which are mitochondrial toxicants— are fueling the rise of Parkinson's disease.

So they're all based on a mechanism, probably more, I would say, probably microbiome changes as well. But what you brought up is changes to function in the mitochondria, the energy producers of the cells that are also involved in turning on the pre-programmed cell death pathway, neuronal death pathway called apoptosis. So why would these particular cells In the pars compacta of the substantia nigra, the dopaminergic cells, why would they uniquely be at risk for these particular 3 events?

Yes, well, as you know, the brain is the gas-guzzling organ of the body, only accounts for 3% of body weight but 20% of energy demands. And the most— among the most energy-demanding cells are those in the substantia nigra, these nerve cells that produce the chemical called dopamine. These cells have a million or more different connections to different nerve cells. Many of them are not insulated; they're not covered with myelin, so they have even higher energy demands. If you stretch them out, they're four meters in length, which is you know double the height of even a tall person. And so I think those are the big reasons why these cells are particularly vulnerable or selectively vulnerable to mitochondrial toxic.

So the reason that we have mitochondrial toxins is because they kill things. For example, Paraquat was designed to kill weeds, ostensibly, and other things, I guess, marijuana plantations. But they did so by damaging actually the mitochondrial function in the bacteria that are supportive in the soil. And so it really, I think, goes a long way to supporting what you're talking about. And also, I think we get to this place back in the 1980s with the development of an illicit drug called MPTP that was, I think, a synthetic Demerol that was injected. It's a fascinating story. Maybe we could unpack that a little bit.

Yeah. So this really goes— Dr. Bill Langston was a neurologist at Santa Clara Valley Hospital in in Northern California when residents came to him and said, we have young people with Parkinson's, what looks like Parkinson's disease. And as you know, 30-year-olds with Parkinson's disease is really exceptionally rare. And that these individuals weren't developing Parkinson's symptoms over years but were developing it relatively acutely over days. And so he went and saw one of these patients, and then I think in the emergency room, And indeed, this person in their 30s had developed what looked— all the world looked like Parkinson's disease, but he was young and this had happened really acutely. And it turned out that in the book called The Case of the Frozen Addicts, they identified that a contaminant, MPTP, developed in a street form of heroin, was likely causing Parkinson's disease. Now, that MPTP also damages the energy-producing parts of cells, which is a near-universal finding in Parkinson's regardless of its environmental or one of the rare genetic causes. And MPTP has a very, very, very, very similar chemical structure to the weed killer paraquat, which is associated with 150% increased risk of Parkinson's disease. I don't think we can underestimate, like, the impact of this, is that finding an environmental cause for Parkinson's disease based on just close clinical observation, what an impact that has had. And I think we're here 40 years later saying that much of Parkinson's disease is likely man-made, just as the case of the frozen addicts was.

Well, you know, nobody really talks about this. We're seeing this explosive increase in incidence of Parkinson's, and people think, well, maybe that's just a genetic thing, but that's not how genetics work. We haven't suddenly seen a genetic mutation in the human population that's explaining this. Obviously, it's something environmental, it's something extrinsic. So then with this discovery that was made that this MPTP contaminant of the street drug induced almost instantaneous damage to the— which interestingly, these patients, to my understanding, were able to improve somewhat when they took standard pharmaceutical like Sinemet, L-DOPA. They actually had some improvements. So really, in many ways, mimicked The so-called idiopathic form of Parkinson's. So, so that said, thereafter MPTP was used in research, in animal research, to actually produce Parkinson's, wasn't it?

Yeah. So, uh, that was the basis for developing animal models of Parkinson's, was to give them an environmental toxicant to give mice and laboratory animals Parkinsonism for the benefit of, you know, trying to determine which new therapies might be beneficial and to better understand the underlying pathology of the disease.

Interestingly, I recall in neurology that there was a publication looking at 2 autopsies, actually brain postmortems, of a couple of these MPTP patients. And years later, they had passed away, and they looked at their substantia nigra, The area involved in dopamine production, uh, as it relates to Parkinson's. And interestingly, what they found was this, um, microglial proliferation, i.e., a continued inflammatory response in the area of the brain that had been damaged years ago. So it looks like it set up a, a damage that was perpetuating, that continued on long after the exposure.

Yeah. And we know that all these diseases in general take years to unfold. So, the relevant exposure could have been, in the case of regular Parkinson's disease, could have been when a person was a child, even potentially even a baby, even potentially in utero. Some of these pesticides and these dry cleaning chemicals can cross the placenta. And that triggers a response and a cascade of events that takes years or decades to unfold before people develop the classic tremor or slowness in movement.

Well, that's very interesting because it makes it very difficult to do the detective work then. And I think what you've done is you've demonstrated, you know, the risk from exposure retrospectively into ultimately higher risk for having Parkinson's today. So you've done a lot of work more recently, in fact, just published a paper, which is how you and I connected, on a chemical that's called TCE or trichloroethylene. So let's first talk about what it is, where and where, how we're exposed to it.

So TCE is a really, really simple molecule. So most of your listeners know that water has 3 atoms, H2O, 2 hydrogens and 1 oxygen. Trichloroethylene has 6 atoms. So it's really simple, 2 carbons in black, 1 hydrogen in white, and then 3 chlorines in green, hence its name trichloroethylene or TCE. A very closely related chemical is perchloroethylene, widely used in dry cleaning. It just has one additional chlorine atom, and this has 4 chlorine atoms. TC was developed in 1864, first commercially used in the 1920s, and been used to do everything from dry cleaning clothes, as we mentioned, to degreasing metal, which is one of its principal uses, to even decaffeinating coffee. In the 1970s, 2 pounds per American were produced. It was found in carpet cleaners. It was found in typewriter correction fluid. It was found in gun cleaners, wide variety of commercial products. It's still permitted. Use is still permitted in the United States, even though it's known to cause cancer. So it's a carcinogen according to the World Health Organization, according to the Environmental Protection Agency. It's known to cause cancer, especially leukemia in kids, liver, kidney, non-Hodgkin's lymphoma, prostate cancer, multiple myeloma, and likely many others. And research done by Dr. Sam Goldman and Dr. Caroline Tanner 10 years ago indicated that this chemical is associated with a 500% increased risk of Parkinson's disease.

Well, it really harkens back to our earlier conversation that, um, the gun may not be smoking any longer, that, you know, these could be exposures that we've had decades ago that have damaged that area in the brain. And finally, you get— I mean, I— there's a, uh, there's apparently a threshold below which you begin to have symptoms of damage to those cells. You have to lose a certain number of those dopaminergic cells in order to begin to manifest Parkinson's. But maybe it's just that initial damage coupled with the normal loss of aging might be why then, uh, things begin to manifest. But yet, uh, clearly, I, I think— when did James Parkinson write his book? I think it was in, uh, early 1800s, if I'm correct.

Yeah, 1817. And when he described it, he described 6 individuals with the disease. 200 years later, the Global Burden of Disease study estimated that 6 million people had Parkinson's disease. So you go from a disease of— a rare disease, a disease that he said had not been classified in the medical literature, to one that's affecting over 6 million, uh, people worldwide in the span of just 200 years.

I'm tempted to turn around right now because somewhere on my, uh, and somewhere on my shelf I have a copy of the original book, which is really quite interesting. You know, in those days, the observation and the documentation was just so elegant. And, you know, when you see what people were able to describe and how things have changed today, of course, now with ChatGPT, that'll probably change once again. But that said, let's get back to the trichloroethylene story. I mean, I think most people are going to say, yeah, it's something in dry cleaning fluid, so I don't dry clean my clothes anymore. But despite that, we're still exposed, aren't we?

Yeah. So most of your listeners will know about the Marine base Camp Lejeune, where lots of Marines were exposed to this dry cleaning chemical. which got into the groundwater. And so Marines from 1953 to 1987 were drinking water at the Marine base while they're being trained that had levels up to 3,000 times which are that which are safe. Um, a study done by—

Whatever that means.

Yeah. Yes.

What level of an, uh, um, unnatural chemical is safe? But anyway, sorry to interrupt.

Exactly. And, um, a study just came out 2 weeks ago, but again, the same individuals who looked found a 500% increased risk associated with The TCE looked at Marines who served at Camp Lejeune and then compared that to Marines who served at Camp Pendleton on the West Coast, which was much less contaminated. They found that the Marines who served at Camp Lejeune had a 70% increased risk of developing Parkinson's disease, a 70% increased risk of developing Parkinson's disease. And this is among healthy individuals. So these Marines, obviously among the best and brightest of us, Were on average 20 years old when they were at Camp Lejeune and were there for only 2 years. So although the level of exposure was likely very high, they were young, they were healthy, and they had a limited duration of exposure, only 2 years. And this was all environmental exposure. This was not individuals using this as degreasing the tanks or anything like this. This is likely principally from drinking contaminated water or inhaling this volatile chemical in their barracks or their home.

So what does that tell us we should be doing right now? I mean, you know, as you described in your book, what, what is the call to action for me and you?

Yeah, so, uh, it's time to ban the chemical. Uh, for 100 years it's been causing cancer, and for 4 generations it's likely been contributing to the rise of Parkinson's disease. Western European nations have banned it. The EPA says that TCE and the closely related chemical perchloroethylene Both pose, quote, an unreasonable risk to human health. If chemicals pose an unreasonable risk to human health, it's time to ban them. We have safer alternatives. Companies even advertise safer alternatives. Few of us would step into a car or none of us would fly an airplane from the 1920s. Why are we using chemicals from the 1920s that we know cause cancer and are likely causing or contributing to the rise of Parkinson's?

So you're stepping out, I think, a little bit from mainstream. Mainstream medicine doesn't usually involve itself in castigating things like a particular chemical. How are your colleagues responding to what you're doing?

I think, you know, we're both taught in medicine, both taught as neurologists, you know, we go from disease to treatment, but rarely do we think about going from disease to cause. And when you, uh—

Story of my life. There you go.

And so when you go from these— when you go to disease to cause, you get a couple great bonuses. One, you can find treatments. So you and I both remember that, uh, ulcers, stomach ulcers, we used to thought were due to stress, and we would tell people to, you know, stop working. Meanwhile, the ulcers got worse. Or have a vagotomy. Or have a vagotomy. And all of a sudden, we found out it was due to a bacteria, and we can— we cure ulcers by giving people antibiotics. Same thing happened with hepatitis C. Same thing happened with a wide range of things. So if we identify what the cause is, we can cure it. We can slow the rate of progression by stopping exposure to certain pesticides and these dry cleaning chemicals or air pollution. And then I think most powerfully, we can create a world where these diseases are increasingly rare, not increasingly common. And think about what a great gift would be to give future generations, one where Parkinson's disease is extraordinarily rare. Just like we live in a world where polio is extraordinarily rare. We live in a world where drinking and driving is socially unacceptable. We live in a world today where HIV is not only treatable, but preventable, and rates of HIV in the United States are decreasing, things that we would never have considered, and just in our lifetimes.

You were mentioning ulcers, and forgive me for digressing, but a thought came to mind after you mentioned the work of Dr. Barry Marshall and H. pylori. That in the day, my day, prior to that discovery, we would do a surgical procedure called vagotomy pyloroplasty. But part of that procedure for ulcers was to cut the vagus nerve with the now retrospectively misguided understanding that it was hyperactivity of the vagus nerve that may somehow be contributing to ulcers. But that said, interestingly, back to our discussion of Parkinson's, it was demonstrated subsequently, and actually much more recently retrospectively, Yeah. That individuals who had their vagus nerve cut had a very significant reduction in risk for developing Parkinson's. And it's a little bit tangential to our topic today, but how interesting it is because the supposition was that this— the precursors, or actually fully formed protein called alpha-synuclein, may come from the gut and travel up this vagus nerve, getting its way into the brain, Alpha-synuclein being one of the markers, hallmarks of Parkinson's in the brain. And therefore, when you cut the highway and this protein couldn't make its way to the brain, that might explain the reduction in risk of Parkinson's. So it seems that there certainly is a developing interest in the role of things gut-related as it relates to Parkinson's.

Yes. So if we said classically Parkinson's is tremor and slowness of movement, difficulties with walking, but The earliest features of Parkinson's don't have anything to do with movement. They have to do with loss of smell and constipation, both of which are found in over 80% of individuals. Both are found years, if not decades, before people develop these classical tremors, for example. I think that's telling us where the disease begins. So these chemicals are either inhaled— pesticides, for example, trichloroethylene is often inhaled— or they're ingested. So TC contaminated the drinking water at Camp Lejeune. Pesticides can get into drinking water, especially well water. And it could be that these toxicants are causing misfolding of this protein alpha-synuclein, which can be found in early individuals in the gut. And as you suggest, there's the vagus nerve, the highway, as you, as you indicated, runs from the gut all the way up to the lower part of the brain, the brainstem. And that misfolded protein can spread from nerve cell to nerve cell. And may explain why constipation is an early feature of the disease. And then as it spreads up to the part of the brain that's responsible for movement, the substantia nigra, you get the classical tremor and then spreads to the other parts of the brain that are implicated in memory and then can cause in the late stages of Parkinson's disease dementia, for example.

Is it fair to say that— I don't mean to put— well, I guess I do mean to put you on the spot. That's what an interview is. That by and large, mainstream medicine/neurology is really focused as it relates to Parkinson's on symptom management. Fair to say?

Yeah, I, I would just say that, you know, everyone's looking for cures. And, uh, your book, uh, so, uh, as I indicated before, I was reading Grain Brain as I was flying in today. Can I read from your introduction? Like, the opening quote of your book, I think, uh, tells it all. Uh, you quote, um, from a Chinese, Chinese text from the 2nd century BC,

the Neijing: Prevention is the ultimate principle of wisdom. Yes. After it is manifested, is like digging a well when one feels thirsty. Or forging weapons when the war has already begun. Is that the quote?

Exactly. And so, what a greater— I mean, who wants to be cured of prostate cancer? Who wants to be cured of breast cancer? I just assume never get prostate cancer. I just assume never get prostate cancer or breast cancer. And we can prevent Parkinson's disease. We can probably prevent other brain diseases too. And we've seen that. We've seen like stroke, you know, rates of stroke have declined in the United States because of efforts aimed at preventing the disease from ever happening. And we can do exactly the same thing for Parkinson's. Parkinson's, to a large extent, is preventable. To a large extent, Parkinson's disease is a preventable disease. The sooner we recognize that, the sooner we act on that, the sooner we prevent millions of people in the United States and around the world from ever developing this disease. And we can do that not just for now, but for generations to come.

I'm almost speechless. It's hard to make me speechless, but, um, it— there are not a lot of us out there, uh, and to hear you, uh, project what you just projected in terms of keeping people healthy in the first place so that they don't need these treatment protocols is, uh, really close to my heart because really what we've been doing for such a long time and It's great to know that there are people like you out there that are looking at these things and asking why. You know, in my practice, after 10 years of mainstream neurology, I finally said, why are all these people coming in in the first place? What's causing their headaches? Could it be food-related? Why is there such a relationship between diabetes and Alzheimer's risk? You know, what's this exposure? Why, you know, with respect to toxins and Parkinson's, what can we do about it? When I realized that, interestingly, the same chemicals used to create Parkinson's in the laboratory animal were being sold on Amazon to be used on our vegetable gardens, Maneb and Mancozeb, that are used to create Parkinson's in laboratory animals, I thought that was a little challenging. And so it's great that you're out there. What do you see has developed since your book was published that you wish maybe you would have had the opportunity to include?

Well, I think my colleagues, even my co-authors in the book, I think were a little skeptical of some of the directions I was pushing us. And all this, by the way, is based on a great neurologist, Dr. Caroline Tanner, at who's now at the University of California, San Francisco, who's detailed the environmental risk factors for Parkinson's disease for over a generation. And all I've done is just read her work and agree. Um, I, I think there's nothing wrong with that.

There's nothing— because now you're out doing what you're doing. You've written this book, you're on podcasts, and you're spreading her word. It's great. I mean, I, I know what that's like.

And, uh, I think we know way, way more about trichloroethylene. I'll give you a story that was a vignette from our recent paper. Brian Grant, the former NBA basketball player who has Parkinson's disease and has a foundation, a great foundation called the Brian Grant Foundation. He was, uh, when he was 3 years old, his father was a Marine. His father was stationed at Camp Lejeune at the peak of the contamination of TCE and other chemicals at the Marine base. He almost certainly was drinking, uh, the contaminated drinking water. He, while he, in his last year in the NBA, developed a tremor and was subsequently diagnosed with Parkinson's disease. His father dies of esophageal cancer, which is linked to TCE. His younger brother nearly dies from a respiratory illness that was likely associated with TCE. So we found in this individual, Brian Grant, one of the most prominent individuals with Parkinson's, a champion for the disease for millions of people across the country and around the world, Early childhood exposure at age 3 as a young boy based on a Marine base getting contaminated water and paying a really high price for it by getting Parkinson's disease 30 years later. The study that came out 2 weeks ago suggesting that Marines who served there, and again, adults who served there, are at 74% increased risk. I think we just know much more. The evidence from laboratory studies showing that feeding TC to mice and rats produces the clinical pathological features of Parkinson's disease. This is all really hopeful that we're identifying what might be one of the principal causes of Parkinson's disease, especially in suburban and urban areas. And these contaminated sites are everywhere. There are 3 dry cleaning sites that are contaminated with it near, within 5 minutes of where I live in suburban Rochester, New York. I'm hanging out in New York City today, and it turns out, you know, many of the high-rises in New York City have a dry cleaner on the ground floor. And so these dry cleaners are obviously dry cleaning clothes, many of them, And they can find in the apartments above that dry cleaner, these chemicals, these dry cleaning chemicals, perchloroethylene, especially in the indoor air of apartments above dry cleaners. And people are breathing this in, not even knowing it. And you can even go to supermarkets that are near dry cleaners. And because TCE and perchloroethylene dissolve in fat, and as you indicate in one of your books, I think the brain's the fattiest organ in the body, they find that per chloroethylene in the butter, in the margarine, in the cheese in those supermarkets. So it was getting into the butter, cheese, and margarine of supermarkets that are near dry cleaners. What's it doing to people when we are inhaling it in our apartments, our schools, our workplaces, or our homes? And what does this mean for, for both for cancer and for Parkinson's disease? And I think the only thing you conclude is very concerning answers.

When you pick up your dry cleaning, how long does it outgas these chemicals?

So it's, um, so I now use a dry cleaner that does not use these chemicals. Um, it's these chemicals, if you put the dry cleaning in your car, your car will, will soon fill up with these gases and you'll be inhaling these chemicals while you're bringing your dry cleaning back from the dry cleaners. You put it in your house, it'll do exactly the same thing. If you have a kid and you bring a kid in with— a kid's having an ice cream cone, licking his ice cream cone, he goes in the dry cleaner with you. When he's going out, leaving that dry cleaner, he's got perchloroethylene in his ice cream cone. So—

What is wrong with this picture?

We're paying a really high price for dry cleaning.

Yeah. Wow. So the, the notion of dry cleaning though, it's not actually dry. I mean, you're soaking your clothes or they're being treated with this chemical that's actually a liquid, correct?

Yeah, so it's a liquid. It rarely evaporates, and hence its use in dry cleaning, and it doesn't shrink clothes. So we're doing all this because water shrinks clothes, and so we used to use flammable liquids for dry cleaning like kerosene. That has its limitations. So then we started using trichloroethylene and then perchloroethylene, which aren't flammable, but they— TC is known to cause cancer. Perchloroethylene is a probable carcinogen. And they're both associated with a 500%, roughly 500% risk of Parkinson's disease. The price is way, way, way too high. Yeah. If we ban these chemicals, we're going to prevent people from ever getting cancer. We're going to prevent kids from ever getting cancer. We're going to prevent adults from ever getting cancer.

What are you doing to help move that ball down the field in terms of getting raising awareness that these things need to be banned? Where do we stand in Washington, for example, on these offers?

So two states, New York and Minnesota, have banned trichloroethylene. A couple states are trying to ban perchloroethylene. I think California may have done so. The EPA reached its conclusion about these chemicals posing unreasonable risk to human health. The hope is that they will follow on with that. Conclusion and lead to regulation and ideally banning of these chemicals. We visited— I visited dozens of Superfund sites throughout the entire United States that are contaminated with these chemicals. And these Superfund sites are in neighborhoods. There's no— I thought, I thought I'd go see people with hazmat suits and, you know, security guards and fences and skull and crossbones signs. There was nothing of that nature. There's no indication to the public at all if they live next to a Superfund site. You could be living next to one in Silicon Valley, you could be living next to one in New Jersey, you could be living next to one in Wilbur, Massachusetts, and not even know that you are right next to a site that's off-gassing TCE and PCE into people's homes, schools, and workplaces. This is happening in Newport Beach, California right now. There are homes on top of an aerospace facility And they find these chemicals in the playroom of children in multimillion-dollar homes in Newport Beach. If that's happening in Newport Beach, California, in multimillion-dollar homes, think about where else that's occurring.

You know, now that you paint the picture, then understanding why this incredible increase in Parkinson's incidence, you know, there's no question here. There's no doubting it in terms of this connection. So how has your personal life been changed by these discoveries?

Uh, well, you know, I used to think the, the air we breathe, the water we drink, and the food we eat is safe. Uh, I no longer, uh, think that at all. Mm-hmm. Um, so, um, I buy organic wherever possible. I wash all my fruits and vegetables, even the organic ones, with, uh, water and a pesticide wash, which is essentially just soap. Uh, I put a carbon filter, uh, on my water. Um, my kids bought— my parents live in Southern California. My kids bought, uh, them air filters for their homes, uh, because, you know, air pollution Air pollution's a big issue. And as you know, air pollution's linked to cognitive decline and Alzheimer's disease. So there are lots of things that I do individually to decrease my risk. I've upped my exercise level. As you know, vigorous exercise can decrease your risk of developing Parkinson's disease and likely a wide range of other conditions. I always wear a helmet when I bicycle. I was doing that—

We'll get to that in a moment.

But I think there are lots of things that individuals like I can do and you can do, and lots of things that others can do. But the real solution to many of these things are societal. We don't need to live in a world where pesticides are used indiscriminately. We don't need to use pesticides on our lawn all the time. I have lots of dandelions in our house. We, we don't need to be exposing golfers to, or people who live near golf courses, to toxic levels. Of pesticides. We should be able— and the wealthiest nation in the world should be able to have clean water and provide that for all of its citizens. And have that— we should be able to breathe our air in our homes without concern that we live near a dry cleaning site or an industrial site or a military site that's contaminated with these chemicals. And so that people in Long Island or Woburn, Massachusetts, or Toms River, New Jersey, need not be concerned about the air that they're breathing in their own community.

I should be frowning, but I'm actually smiling. I'm smiling because you're out there getting the word out. I could frown because it's clearly an S-show. We'll leave it at that. It's a scary proposition, and it doesn't look like there's any change in the direction that the ship is sailing right now, and we're paying the price. And the problem is, as you mentioned earlier, is There's no direct chronological connection that's easy for people. You know, if you bend over and pick something up, the next day your back hurts. Oh, obviously I shouldn't have picked that up. But here we are decades out, and it's very, very challenging to make that connection. But God, you've done an incredible job in raising our awareness. One of the things that I liked, I'm going to just tell you, you have these recommendations here about reduce your A risk at work. Ban paraquat and trichloroethylene. Drink clean water. I haven't heard that before on this program. Breathe fresh air. Avoid activities with high risk of concussion. We should talk about that in just a moment. But you said enjoy your coffee, and you made a friend when you, when you did that. I'm all in. So is, is there a mechanism that you're aware of, or what do you think? I mean, the data would show that it's, it's, uh, protective.

So, caffeine has been associated with a decreased risk of Parkinson's disease, and it may protect the dopaminergic neurons. So, that's one thought. Other thought is that it turns out Parkinson's disease, it may be easier to give up habits because there's less of a reward mechanism. So, for example, it turns out that people with Parkinson's disease have a little bit easier time giving up smoking, for example. So, it's still unclear. There are people who are far better educated on the effects of caffeine in the brain, probably you, than me to speak more about that.

Well, you know, as it relates to coffee, if I may, people immediately go to the caffeine part of that discussion. And, you know, there are more than 200 bioactive components found in caffeine. Importantly, one called chlorogenic acid that really is quite protective as it relates to mitochondrial function. And as you indicated earlier, this is we call it an acquired mitochondriopathy, complex 1 dysfunction, which I think was the reason we saw the coenzyme Q10 work originally. But you did mention something just now that I thought was kind of interesting, that they can— Parkinson's patients are able— Yeah, yeah, something else interesting as well. They don't stay on things as readily. They're able to give up smoking. And yet, interestingly, well, maybe we'll get to the— there's a certain drug used for Parkinson's that makes people a bit Makes their decision-making very challenging. But let's talk about smoking for just a moment because there is some literature that suggests that cigarette smoking is somehow protective against Parkinson's. It's a tough one to talk about, but it is, you know, it is in peer-reviewed literature. So what's going on with that?

So there have been a number of studies that have associated a decreased risk of Parkinson's among smokers. Since writing the book, I'm moved by my colleague Jeff Bronstein at UCLA, who thinks this might be a case of reverse causation, where smoking doesn't decrease your risk of Parkinson's disease, but Parkinson's disease decreases your risk of smoking.

You

mentioned it. So, as we indicated early on, this disease plays out for years, and by the time you're diagnosed, 60% of those dopamine-producing nerve cells have died off by the time you're diagnosed with Parkinson's disease. You can imagine when 20% of them have died off, it may be you have less of a reward mechanism, and therefore it may be easier to give up smoking. And there's evidence that that's the case for people with Parkinson's disease. So, it may be that subclinical, before people make the diagnosis, that it's easier for people who are going to go on to develop Parkinson's disease for them to give up smoking. Therefore, by the time that they're diagnosed, Non-smokers tend to be more commonly diagnosed with the disease than smokers are.

Well, it's interesting because you're talking about decision-making and being able to modify one's behavior, different in Parkinson's in comparison to the non-Parkinson's patient. And yet, interestingly, there are a number of patients who are taking a particular drug that activates this dopaminergic pathway, pramipexole, Mirapex, who actually have been shown to have a real high risk for developing addiction to gambling. So, I mean, I think the whole notion of this chemistry is that, you know, there are a lot of nuances to it when we go manipulating dopaminergic pathways in the brain with various medications, or how it's changed in the Parkinson's patient that relate to behavior.

Yeah, so every medication has its side effects, and as you indicate, People with Parkinson's lose dopamine in the brain. And so one class of drugs is an artificial dopamine, a synthetic dopamine, and pramipexole or Ropinirole are 2 of those. And those have both been linked with a really high risk of developing something called impulse control disorders, which is compulsive gambling, compulsive sexual behavior, compulsive eating, and compulsive shopping. And these things can be really disruptive and to people's lives. One, many people don't admit that, you know, they don't come to their doctor saying, I'm watching too much porn, doctor, can you help me out? Or I'm spending too much money or losing too much money in the casino. Unless doctors tell them when they prescribe these medicines, which I rarely do, I rarely prescribe this class of medications, is that these are associated with them and then systematically assess for people for the risk of doing it. You know, I've seen priests who've been prescribed these medicines, and you can imagine the kinds of things that they things that are disrupting their lives. And people have lost a large portion of their life savings. People have had their marriages ruined. People have gained huge amounts of weight. In general, people with Parkinson's disease tend to lose weight. So that's at least one thing you can often observe is people gaining weight, and that's a red flag. So these medicines, if you're taking these medicines and you're experiencing these things, go to your doctor and tell them that you're experiencing these things, because the treatment's relatively easy in most cases, which is reducing or eliminating the medication. And there are other medications that are associated with much less risk of developing these side effects.

I want to cover before we close just the notion of, and you mentioned wearing head protection, the notion of pugilistic Parkinson's or how repeated head trauma might predispose a person to this situation.

Yeah, so our co-author on the book, Dr. Michael Okun, was one of the neurologists who cared for the great late Muhammad Ali, and he wrote a piece in JAMA Neurology recently in which he indicated that he thought repeated head trauma was a contributing factor to his Parkinson's disease, all done with the permission of Mr. Ali's family. Family. And so we know that significant head trauma increases your risk of Parkinson's disease, and repeated head trauma increases it even further. I think it's pretty clear that brain head trauma, not surprisingly, is not good for a wide range of brain diseases, Probably even worse for ALS, is probably worse for chronic traumatic encephalopathy, worse for dementia. So we should be thinking about some of the activities that we engage in seeking to minimize the risk of head trauma because there are a wide range of brain diseases that, again, don't have their onset immediately after, like a concussion, those symptoms, but will have— put you at higher risk for developing a neurodegenerative condition later in life or later in your child's

So the message then is headgear at all times. Biking, you know, look, look how it's taken off in snow skiing.

Yeah, and, you know, think about all the lives we're saving, the death and disability that we're preventing by doing this. It's almost like seat belts. And I think there are certain activities that may be inherently really too risky. I think, I think most people are reaching that conclusion about round tackle football. for young children. And I think there are ways that we can make the sports that we love, including soccer, including football, all much safer, all associated with a lower risk of developing significant head trauma, and allow athletes as well as us non-athletes, non-professional athletes, to live longer and, more importantly, healthier lives.

What I read into that is at 68, I shouldn't be learning paragliding, and I probably am going to. Anyway, great, great to spend time with you. This is a wonderful, wonderful book, and, uh, we'll put your contact information, of course, in, uh, in the blog that accompanies the podcast. Thank you so much for spending time with us today, and really enjoyed meeting you. This has been awesome.

Thank you very much, David. It's great to be speaking with a neurologist who's as passionate about preventing disease and brain diseases as, as I am. And I can't think of a better gift for neurologists than to create a world where brain diseases are increasingly rare and don't even affect people so they can live long, healthy lives and be free of concerns about things that are robbing them of their minds and their independence.

It's— I'm telling you, it's breathtaking for me to hear that coming from a fellow neurologist. It makes the world worth living. Thank you very much. We'll talk soon.

Thank you.

Bye for now.

Bye-bye.

So Dr. Dorsey explains to us, uh, very interesting information that relates to why we're seeing this sudden and significant uptick in the number of cases of Parkinson's disease. And, you know, interestingly, there's a delay here that these exposures to the various things he talks about may have happened years, decades before. So it's really all about cleaning up our act. And living a life that exposes us less to these potentially very toxic chemicals. Hope you enjoyed the program today. I sure did. Thanks for joining us. I'm Dr. David Perlmutter. Bye for now.