The Science of Preventing (and Reversing) Dementia

You can engage in your own life plan to alter your risk. Welcome to the Doctor's Pharmacy.

I'm Dr. Mark Hyman, and that's Pharmacy with an F, F-A-R-M-A-C-Y, a place for conversations that matter. And today's conversation is going to matter many of you because it's about dementia, something we'd rather not have and talk about. But we have today with us an extraordinary guest, Dr. Marwan Sabbah, who I've gotten to know recently at Cleveland Clinic where I work, and he's considered one of the leading experts in Alzheimer's and dementia in the world. board-certified neurologist. He is now the Camille and Larry Ruvo Endowed Chair for Brain Health and the director of the Cleveland Clinic Ruvo Center for Brain Health in Las Vegas, where I'm going to go soon to share some of our thoughts in functional medicine and figure out how we can collaborate together. He's dedicated his career to finding a cure for Alzheimer's, something that people actually have tried but failed at, and we're going to talk about why that path may be different now going forward. And he's also interested in other age-related neurodegenerative diseases like Parkinson's and other kinds of dementias. Now, He's got quite a pedigree. He's graduated from the University of California, Berkeley, which explains his open mind. He's got a medical degree from the University of Arizona in Tucson. He received his residency training in neurology at Baylor College of Medicine in Texas and completed his fellowship in geriatric neurology and dementia at the University of California, San Diego School of Medicine, where he was an assistant professor. He's a leading investigator for many prominent national Alzheimer's prevention and treatment studies. He's a hardcore scientist. He's on the editorial board of the Journal of Alzheimer's Disease and BMC Neurology. Editor-in-Chief of Neurology and Therapy and has authored and co-authored more than 330 medical and scientific articles on Alzheimer's. That is a lot of papers. That's like, I don't know how many years I took, but it's a lot. You don't look that old. He's the author of the Alzheimer's Answer, Reduce youe Risk and Keep youp Brain Healthy and the Alzheimer's Prevention Cookbook, where he paired up with a celebrity chef to create a hundred recipes to boost your brain health. And his latest book, Fighting for My Life, How to Thrive in the Shadow of Alzheimer's is an extraordinary story of a woman who has the gene for Alzheimer's, who work with you to find a way to prevent it, which is an extraordinary story because most people don't think you can actually prevent it. So welcome to the Doctor's Pharmacy.

Dr. Hyman.

That was a long intro, but you.

Had a lot going on.

You should have been so busy, I wouldn't have had so much to say. So you grew up in Arizona, Tucson.

I did.

Had a family of doctors. I do. And you, at eight years old, knew you wanted to be a doctor, which is pretty amazing. And your dad encouraged you by giving you a copy of this anatomy textbook called Gray's Anatomy. He did it for your 14th birthday, which is crazy. And then eight years later, at 18, you started doing research in Alzheimer's when most people were thinking about what party they're going to. That's correct. So, how did you get inspired to go into medicine and this particular field, which is kind of depressing in a way, because there is nothing that we can do at this point, and hopefully that's changing.

Thankfully, I'm a perpetual optimist.

When they say optimists live longer, even if they're wrong-- Good.

Then I'm going to live a long time. But the reality is that when I was 18, I was afraid of getting old, very afraid of getting old. And I thought about the idea that Alzheimer's is the embodiment of everything sad and destructive about getting old. And so I decided at a very early age that I just gravitated to doing research around that. I was working in research labs in Berkeley and Karolinska Institute on the summer and to the point where I was able to say, this is something I wanted to dedicate my life to, my career to. I was a singular in my path to medical school. I wanted to do a brain, I wanted to be a neurologist. And that's it.

I've just been following that path ever since. Neurologist is a brave specialty in medicine. We have a joke we often say, which is for For neurology, the basic practice is diagnose and adios. That's what they said when I was in medical school. Meaning you can be great at diagnosing diseases, but there's not a lot of great therapies for things like Parkinson's and Alzheimer's and all these horrible diseases, but.

That'S changing, which is kind of exciting. So in one generation, in fact, when I graduated from medical school in 1991, that was the diagnose and adios was kind of the recurring theme, the refrain that I kept hearing. But in one generation, neurology has gone from a mainly diagnostic field to a mainly therapeutic field. We now have great treatments for stroke, we have great treatments for migraine headaches, we have great treatments for multiple sclerosis. These are drugs, diseases that people didn't have any hope for. So next on that list of things to take care of is Alzheimer's.

And it's important because six million people in this country either have pre-Alzheimer's or Alzheimer's and it's projected to be up to 15 million by 2060.

That's great.

And many people suffer from all kinds of brain dysfunction that is often occurring decades before they even get their first symptoms. And the cost is staggering. We think that heart disease and cancer are the most expensive diseases, but it's actually Alzheimer's. That's correct. And we spent billions and billions of dollars on hundreds and hundreds of studies and it really struck out, which is terrible. And often drug companies now are giving up and just saying, pulling the plug and said, We're not making any progress, we're gonna cut our research budget on this. And now you wrote a book called Fighting for your Life, which is actually a different story.

It is a different story.

About how to think about this disease and you actually present a path to preventing it. And you even talk in there and you hint about how to actually begin to start treating it in a new way. And there's some really interesting studies that have just been published looking at how we can use things like lifestyle, which seem like low tech interventions, not some fancy drug or surgery, to actually slow or even reverse some of this. So that's correct. How are these factors playing a role? What are the things that we can actually think about doing to help us prevent this disease and to maybe even start to think about how we treat it?

Right, so this is an area that has garnered great interest in the public consciousness. The idea is that we've been so focused on pharmacological interventions to treat the disease, when we now know that the disease starts 20 years before the first day of forgetfulness. So by the time somebody walks into my office with memory loss, they've had disease changes in their brains for two decades. And we understand that biologically now.

So you're seeing now a whole- and.

You can see that on imaging scans. We can see that on whole imaging scans. So we're now seeing now a big push to move the calculus beyond the time of symptoms to much earlier and try to find people and identify people at risk. Along the way, but most of that research has been focused on drug interventions to prevent, to prevent, delay or forestall the onset of symptoms. But along the way, of course, if I'm gonna, if I'm in my 70s and I know my disease started in my 50s or 40s, we can change beyond drugs. We can change to say lifestyle interventions have benefits and there's now a whole new area of research. Exercise has really emerged as one of the areas that has grown. with real biological evidence that it can prevent and improve brain function and brain health. And beyond that, we're seeing now people are looking at things like diet and supplements and other ways to manage the disease. And so I think this is an area that's just relatively new, but very exciting. Yeah, I mean, there was a recent.

Study called the Finger Study. The Finger Study is one of the.

Ones that we're going to talk about.

Which I talk about in the book. Yeah, I know. And this study was done in Europe and it was a very large study where they did an intervention with diet and exercise and stress and cog-stressing.

And cognitive stress.

Yeah, addressing cardiovascular risk factors. And tell us about the study. What did they find?

Yeah, so this study is done at the Karolinska Institute, the geriatrician, her name is Mia Kivimaki-Pelto, a really, really sharp, very thoughtful physician scientist. And she said we're going to create a multimodal intervention, including diet, managing health conditions, improving exercise, improving all their parameters. And one group was randomized to the intervention and one group was randomized to just kind of passive intervention. And in an objective way, followed for over two years, with aggressive intervention, the treated group did much, much better over the two years. Not only did they not get a decline, they actually got better.

Wow.

And so, and these are people not young, they were sort of starting in their late 60s into their 70s. So these aren't people in the middle of life, they're kind of in the senior, running into the senior age, and they actually got better. And this has been published in the journal Lancet, so it's a very respected.

You know, peer reviewed scientific journal. Well, this is really remarkable. I just want to pause here because what you just said is pretty radical. Now, like I said, we spent billions of dollars on hundreds of studies, and none of them show this. We can't slow or reverse it. Now you're saying just by eating better, exercising, optimizing your health, we literally can slow and even start to reverse the disease.

That is correct. In fact, the US is taking the finger study and in 2019-2020 there will be the US version of it called the Pointer Study. Which is being rolled out in about six sites in the United States this year.

And the government has to pay for it because there's no drug involved.

The government, well, this is to be very clear, the point of study so far as I know is being funded by the Alzheimer's Association. I don't know if there will be federal dollars behind it, but the fundamental issue is- But it's not a drug company. It is not a drug company. But the fundamental issue is we want to answer an important question. Do these things objectively work? The signal, the way the evidence suggests the answer is yes. And so having more evidence, because I have to tell you, you and I are both physicians.

Part of our day job is taking.

Care of people with disease.

Right.

So here we are saying, let's step back from that. Let's say instead of treating disease, let's treat health. Yeah. And did you take the course in.

Medical school called Creating Health?

I did not. I did not take that course. We didn't learn that. We did not. But the advantage of that is that it's not prescriptive. Then you can give health recommendations that come up from consensus panels and then it can have effect change at a larger level. This is actually easier to roll out if we can prove there's a signal than it is by just writing a prescription.

It's unbelievable. Yeah, I think what you said is really remarkable that we need to focus on how do we create health rather than just treat disease or symptoms or pathways or some pathology. And that's essentially what functional medicine is. It's asking the question, how do you create a healthy human being? What are the factors that knock you off that path? And what are the things that actually help create health. And those studies, the finger study, the pointer study, are looking at those factors. And there are more, right?

There are more. And I think that's the exciting thing is that I think, you know, I have to tell you, I've been involved in all these clinical trials. Every time there's a failure, it breaks everybody's heart. Yeah. There is no ego involved. It's not like, haha, I told you so. Because I will say to you whether the drugs work or not, I'm going to clinic tomorrow or the next day, and I still got to look at these people in the eye and say, you know, something good is coming. We just kind of hope that it's coming soon. And so I say this to you because if I can see a path forward, whether it's a drug, a device, a lifestyle intervention, any way forward to help my patients either prevent, postpone, or delay.

Well, let's talk about the disease a little more in a medical way, because The understanding was, from my training, was that the brain seemed to be disconnected from the rest of the body. We learned about this barrier called the blood-brain barrier, where nothing except some nutrients got in.

That's correct.

It was like this thing that disconnected our head from the rest of us. Turns out that our body is one system and that our brains are connected to everything else that's happening in our gut microbiome. in infections, what we eat, everything is actually influencing our brain function. So can you share a little bit about how this understanding has changed the way we think about the brain and how some of these factors that are driving inflammation are actually causing this disease? Because it's a disease of brain inflammation.

It is. So the conventional wisdom that we're trying to look at is that inflammation is a response to an injury. or is it the injury itself? At the end of the day, you know, a lot of people think that there's an amyloid triggered event and then the inflammatory events occur because of the production of the amyloid.

And amyloid is sticky gooey stuff that gums up your brain.

That is correct. And importantly, but we, you know, we used to think, as you said, there was, you know, north of the neck and south of the neck, right? And that everything in the Alzheimer's was north of the neck and nothing South of the neck was related to it. When in fact now we know that things like gut microbiome can alter your immune system and having a healthy microbiome can keep you healthy and by the innate and you can boost your innate immunity which might reduce inflammation across the body including the brain.

Yeah, and exercise helps reduce inflammation.

And BDNF. So the exercise, I have to tell you, I hated running. But I've taken up running. because of BDNF. So what is that? That's brain-derived neurotrophic factor because of... It's like miracle grow for the brain. Miracle grow for the brain and the funny part about it is almost neuroscientists are runners. They don't do anything but run. They have to have something to it. It's the fastest way to raise your BDNF levels.

Which is basically this growth factor that connects your brain cells together. So it calls neuroplasticity which increases connections and helps neurogenesis which is the development of new brain cells. That is correct.

So we never thought that was possible. We never thought it was possible. They said once you're born with your neurons, you're gonna get it, but we.

Now know that the brain's making neurons throughout their life. Yeah, I mean, I read a study where they studied terminal cancer patients and they gave them this dye that only goes to dividing brain cells and they.

Found even at the point of death they're making new brain cells. That's correct. We did a, when I was in Sun City, Arizona at the Banner Sun Health Research Institute, we had a brain and body donation program and we had scientists that could take brains of patients who just expired and culture out, bring out the stem cells that were still left alive in dead brain.

That's unbelievable.

So, pretty cool stuff.

So, these things like diet and exercise and optimizing your gut microbiome and stress reduction, they all in a sense work by regulating this inflammatory process.

That's correct. That is correct. The inflammation, of course, is the unifying common pathway that we can manage. And, you know, at the end of.

The day, that's what we want to do as researchers. The studies taking Advil never really worked.

They tried it. Well, COX inhibitors have not worked. So then the questions are scientifically, is it that pathway of inflammation? People are now looking at different pathways of inflammation. Now looking at TNF-alpha, which is tumor necrosis alpha, they're looking at the fact that TNF-alpha might trigger enzymes related to Alzheimer's called base. So we think that there's a link that Inflammation is not just a broad category, but there are specific segments that seem to work and others that we've tried, like you said. We tried anti-inflammatories for years to treat or prevent Alzheimer's. It didn't work worth a darn.

Right. Well, that sort of goes back to the thinking in functional medicine, which is what's causing it in the first place. So if you're standing on a tack, it takes a lot of aspirin to make it feel better. Pull the tack out. So it's not necessarily the best logic, but it's something that we have to sort of begin to wonder about. I'm talking to one of your colleagues, Rudy Tanzi from Harvard, who said to me that they've done studies of patients who had brains full of this amyloid, but they had the gene somehow that didn't let them create inflammation and they weren't cognitively intact.

They didn't have dementia. Right, and that's the amazing thing is that you can go to your grave with a brain full of amyloid and not develop dementia. And we want to study those people because there's something protecting them against the development of symptoms. And of course, they may have just less inflammation, as you commented. Rudy Tanzi would be the guy to figure that out.

Yeah, and he talked about the microbiome of the brain. I don't think they're still trying to figure it out, but they're finding microbes in the brain.

Right.

We thought it was sterile up there, but turns out it may not be.

It may not be. And there's a new one that you probably have just hearing about. There's a company out of the Bay Area that found there's oral bacteria called P. Gingivalis, which creates a protein called gingipain, which may be a neurotoxin and neuro trigger of neuroinflammation. And so, they're looking at a drugs to stop that. Maybe brushing your teeth, flossing, getting them.

Clean is a good idea. Not just good for the heart, it's good for the brain as well. That's right.

I mean, people probably know that, but.

One of the biggest triggers for heart disease is gum disease, right? That's correct. So, let's talk about the genetics here for a minute. Okay. So, you know, most people think you get your genes, they're fixed. your, your fate is sealed. There's nothing you can do. Right. It's not actually how genes work. Now, you can modify these genes expression, which ones get turned on and off and how they work. And I, I remember had this patient years ago, was 90 year old woman. She was a dentist. She had ApoE double four, meaning she had two of the worst genes you could have that are triggers or maybe predisposing to Alzheimer's. And she was 90 years old. She was still working, and she was completely cognitively intact. and she was a health nut her whole life. She ate a perfect diet, she exercised, she never smoked, she never drank, she took her vitamins. I mean, it was remarkable to see that. That's impressive. And this is what you talk about in this book with this woman, Jamie, she came to you because she had a family history of Alzheimer's and you checked her genes and she had that dreaded APOE4 gene, which many people are afraid to test because they feel like it's just a, why bother? So you talk about why bother. Tell us why bother. So.

I'll answer the why bother in a second, but Jamie is like your dentist patient. She's a 4-4. She found, her story of course, she found out her genetic risk by accident. Now you and I know that if you are two copies of the APOA4 gene, your lifetime risk is 91% that you're going to develop it. It's almost a matter of when, not if. And the problem is that fortunately there's only 2% of the population that are double copy, 20% of the population is a single copy of the APOE4. But people are now finding out because there's commercial genetic testing by accident.

23 and me.

23 and me, right? And then they go to Dr. Google. It's me and my friend Dr. Google. And they're like, well, what does this mean? And they go and they-- and so the Jamie's of the world are finding out day in and day out by accident, and they're trying to figure out what does this all mean? So the story is, on her half, is how she found out by accident and how it affected her. My half of the book is, is it a good idea to be tested? What are the consequences of being tested? What does it mean? And so that's what my half of the book is. It's a nice convergence of two storylines that help people to become informed because this is happening every day of the week.

It's happening anyway, but what your book, Fighting for My Life, suggests is that by knowing that it can motivate people to take control of their life and their lifestyle and address the modifiable risk factors.

That is exactly right. And I want everybody who reads the book to be like your dentist patient, right?

Yeah, she was.

I have to say to you, I had one other.

Not sure I would go to her at 90 years old to clean my teeth.

Sure, but she got to 90.

She was, right? And working, still working.

And I've seen only one other elderly person get to late 80s, 90s, a 4-4 who was unaffected. In my career, I've almost said that if you have that genetic profile, it's almost a foregone conclusion you're going to get Alzheimer's dementia eventually. But there was one exception to that. So we want everybody to be the.

Exception, not the rule. Now, one of the things we haven't really talked about yet is the role of sugar in the brain. And many people may remember Ronald Reagan's favorite food was jelly beans. And he got Alzheimer's. Now, maybe there's a correlation. But it turns out that diabetics have four times the risk of getting dementia. That is correct. we sometimes talk about Alzheimer's as type 3 diabetes.

Yes, this is Susan Del Monte from the University of Rhode Island.

Brown, yeah. Yeah, brown, yes. And the truth is that we all have control over whether or not we get diabetes. This is almost 100% preventable and reversible.

Disease by changing our diet. Right. And you know that insulin resistance, of course, is the hallmark of type 2 diabetes and that we can see insulin resistance in the brain and that's what the type 3 diabetes, even if you're not having insulin resistance in the rest of your body. And we think that, of course, and I I strongly believe, like you, that that's a modifiable risk factor. We can alter that. We can alter it, of course, the epigenome, which we're going to talk about, I hope we're going to talk about epigenetics. But the diet and reducing the sugar intake and the diabetes risk is something we can alter and have a positive effect on. So we all learned, I mean, I.

Learned in medical school that your brain uses 25% of your glucose and it needs sugar to run.

Yes, it does. And the PET scans, show that you need sugar to make your brain light up. So the rule of thumb on a PET scan is you want your south of the neck, you want to be dark, north of the neck you want.

To be bright on sugar PET.

Because if it's dark below, you got cancer. If it's bright below, you got cancer. If it's dark, that's why you put it in the brain, you want it to be nice and bright.

You want that brain to light up because it can consume much of the sugar metabolism is in the brain. But you also say in your book, in patients who have Alzheimer's, that people are exploring the role of ketogenic diets, which means no sugar and lots of fat and the brain running on ketones instead of glucose.

And the issue that people are trying to decide is can you bypass insulin pathway mechanism? So if you're relying on insulin and pathways related to insulin to nourish your brain and you have insulin resistance, either you can pharmacologically improve that or you can dietarily improve that.

I mean, you know, I remember this patient I had at the Ultra Wellness Center in my practice in Lenox, and she came in to about 78 and she started having what we call MCI or mild cognitive impairment, and she had a whole bunch of things wrong with her. Her thyroid was bad. She had gut issues. She had low vitamin B12. She had heavy metals and mercury, but she was able to fix a lot of these things and do a lot better for many years. And then she started to decline, and I'm like, well, let's try a ketogenic diet. and we got someone to work with her and cook for her. And it was like the lights went on again. It was pretty dramatic. And I think, you know, there's some preliminary studies that are showing that.

And, and, you know, people have been looking at. So the ketogenic diet all starts with the whole coconut oil conversation, which is coconut oil is controversial by itself. But the story behind ketogenic diets is that we do understand there's insulin resistance. The NIH actually funded a study looking at the ketogenic diets. So I think the science is there. It's just a matter of being able to prove it and more importantly to adhere to it. Ketogenic diets, not easy. Not easy. It's not new to neurology. We've been using ketogenic diet to treat childhood epilepsy for 30 plus years. So it's new to Alzheimer's but it's not new to brain disease. It's been used to treat other brain diseases for a long, long time. But fundamentally it's really hard diet to stick to.

Yeah, we're finding more and more people are doing it. It's one of the hottest diet trends out there. If you look at all the best-selling books, it's not mine, it's the keto books. And we're seeing much more interest and we're running keto programs at Cleveland Clinic. They're our most popular programs, which is pretty amazing.

So, people seem to be willing to try it. I know you had Dan Pompa on a few weeks ago and Dan and I have- David Pompa. He and I have had an internet debate about this. and I will say to you that I think it's more nuanced. I think that ketogenic diets that are insulin sparing make more sense in the symptomatic phase of the disease. And I have to tell you, I look at Alzheimer's disease in a dichotomous way. There's the pre-symptomatic and then there's the symptomatic. Symptomatic disease means mild cognitive impairment and dementia. and I think there is some logic to a ketogenic diet in the dementia phase.

I agree. I think an ounce of prevention is worth a pound of cure as Benjamin Franklin said.

Correct. I think that the ketogenic diet is a pound of cure. It's a pound of cure, but I would not necessarily advocate for it in the pre-symptomatic phase. I'm more advocating for the Mediterranean diet.

In the pre-symptomatic phase. And that's the beauty of your book, is you talk about how to create resilience, and health, so you don't need the pound to cure.

Correct.

Because the whole person's life isn't to be restricted and restricted, it's to actually be more resilient, healthy, so you actually are resistant to these diseases. That's correct. So it's actually exactly the right idea. So let's just dial back a little bit to the genetics. You kind of mentioned epigenetics, but I don't know what that is. I want you to explain it. And it sort of speaks to the modifiable ways that we can alter our genes to improve our health outcomes. So tell us about this.

So this is an area of great controversy and frankly, I'm not sure we have a clear answer for this. The idea that people said in your remarks is that what your genetic profile that you're born with, it's like your fate in life, right? And people are starting to challenge that idea. And really think about it, can I take a genetic risk for Alzheimer's and and create a life program that offsets that genetic risk. So if I'm genetically prone to getting Alzheimer's, can I create an intervention program that would buffer or mitigate or offset that risk? And that's the questions about it.

And we- Like precision health or precision.

Health is a great example of that. And that's a really critical point because if that's true in Alzheimer's, we could try that across the board, right? In diabetes, heart disease, cancer, All those disease states could respond in a, maybe not in the same paradigm, but in a similar paradigm to alter those risks as well. And I'm not sure we've answered that question to the greatest answer that we could have, but we're still working on it. I think there's people that would say that's possible. So epigenetics is a fairly new field. It's very exciting. And the idea is that we can say that to things like diet, exercise, lifestyle, stress, sleep, lack of sleep, that you're turning genes on and off. And that we want to, in many cases, turn genes off, but in some cases we want to turn genes on, and that would alter our health.

Yeah, and it's so possible. I mean, food is one of the most important and prevalent things that we are connected to every day that alter our gene expression. And this is one of the fundamental ideas of functional medicine. So you eat broccoli, it tastes good. but it also upregulates genes that increase glutathione, which helps you detoxify and helps.

The liver work better.

And you have green tea catechins, but those upregulate genes that increase your ability to get rid of heavy metals. So, there's incredible research on these components in food that have these biological effects on our genes. And I think it's one of the fundamental tenets of functional medicine, which is that your genes interact with your environment to create who you are. That's correct. And when you say environment, I mean food, exercise, stress, relationships, connection, love, meaning, everything. All those things are things that we have control over. Right. People think that you go to the doctor, they're gonna fix you. But the truth is 80% of your health is determined by what you do, not what the doctor does.

That is correct. That's correct.

We have an amazing opportunity and that's just such a great message that you have in your book, Fighting for my life because you talk about this woman who otherwise would be in a way facing a death sentence who has a plan, a hope, a roadmap to slow, prevent and maybe never get the disease.

And I hope that we'll have this conversation 10 years from now and say she's still fine.

Yeah. Now, this is super exciting and there are other things that are sort of being looked at and one of the things that has been linked to brain injury is neurotoxins. Neurotoxins, you mentioned from your mouth, but we're exposed to all sorts of things, whether it's pesticides or heavy metals vaccines, viruses, we know for example in Parkinson's that it's pretty well accepted that environmental toxins like pesticides increase the risk significantly. And farming is probably one of the worst occupations in terms of your risk of death. You're seven times more likely to die if you're a farmer because of some of these use of pesticides. So how do these things play a role in Alzheimer's? There's been mixed research. What is your take on the idea that things like mercury, environmental toxins may play a role.

Yes, so that's been looked at and the associations are very clear in Parkinson's. There's no question about that. The associations with heavy metals and pesticides, we do know that some heavy metals impair cognition, maybe an impaired development.

You know, like lead in kids, we know that, right?

But they don't necessarily have been strongly, they have not necessarily been strongly associated with the development of Alzheimer's, but it's.

Still being looked at. But in a sense, it's all these things that are sort of coming together to create this stress on the brain, right?

Well, there's so many things that stress the brain, right? So I also talk about not just the risk factor for developing Alzheimer's, but I talk about the cognitive killers, right? Sleep deprivation is a cognitive killer. Mood disorders, depression is clearly a cognitive killer. And substance abuse are cognitive killers. Alcohol. Alcohol, yeah. So, the reason I say this to you is that, and we're talking about alcohol. The J curve, we need to talk.

About the J curve in alcohol.

All right, so you can have wine tonight, but not too much. That's exactly right, that's the J curve. So, the reason I say this to you is that a lot of things can help your brain function, a lot.

Of things can make your brain function worse.

Yeah, and I like to call them dementogens.

Dementogens, I never used that. Yeah, that's a good one.

Dementogens, because there's a lot of them.

It's our inflammatory diet. Right, our diet is a cognitive killer. processed food, lack of fiber, things that don't help our microbiome be healthy. Right. You know, like you said, lack of sleep, stress, fascinating research on, you know, improving immune function in the brain just through meditation.

Right. You know, and, you know, I started meditating this year, 2019, first time I ever started.

Unbelievable. That's so good. You know, when you start to look at the data, it's like, okay, it's pretty compelling.

Right.

It's, it's, it's a very hopeful message. So you talk about things like BDNF and yoga. helping with, I mean, yoga helping with BDNF and meditation. So, those are really things that people can do. It's not just a hopeless thing.

And that's the thing I want people to take away from this is that you can engage in your own life plan to alter your risk. Don't wait. You know, if people should start, they can change their diet today. They can start exercising today. They can do yoga starting today. They don't need to wait. And I, you know, I emphasize over and over again that By the time somebody walks in my office, it's been going on in their brain for a while. So, now is today is the day, not later, not Christmas, not New Year's of next year. Today is the day you alter your diet.

Yeah, so you've changed your diet. You started running, you started meditating. I did.

And I was eating pretty healthy to begin with, but I said there's more that I can do.

Yeah, and as one of the world's leading experts on Alzheimer's, you're reading all the science. Yeah. And you're going, holy crap, I better.

Get started on this. Oh, yeah. Even if I don't have the ApoE3/3.

I do not have it.

I'm an ApoE3/3, I found out.

Out. But I'm a 2-3 which.

Oh, you're gonna live forever. I know.

And you will not get Alzheimer's. The two is the longevity gene. These are the people who can smoke and drink and eat whatever they want and live forever. That's correct. And the ones with the double four, they gotta, you know, basically monastic. That's true. So it's really true. Now, one of the studies that came out a few years ago was called the mind study about the Mediterranean diet. And you mentioned that. briefly. First of all, no one knows what a Mediterranean diet is, but there are certain characteristics of that diet that I really want you to talk about that really help the brain.

So, the Mediterranean diet is a convergence of fish, whole grains, legumes, olive oil, extra virgin olive oil, antioxidant spices, and a little bit of red wine, a little bit.

Tequila. Tequila.

Tequila, you know, tequila is kind of selling themselves as helping your microbiome. So, we'll see.

Oh, really?

Oh yeah. But I will say to you that that's kind of the Mediterranean diet. And the reason I have to tell you is that of all the places that they looked at the Mediterranean diet, they looked at it in New York City. Down in Little Italy or what? Columbia University. At Columbia University, they did something called the North Manhattan Aging Project and the Y-CAP study, Washington Heights study, and basically showed that people who had adhered to the Mediterranean diet, 2,200 people who adhered to the Mediterranean Mediterranean diet had lower risk of progression from mild cognitive impairment to dementia, had lower risk of developing mild cognitive impairment, and were stable, more stable over time. And of course, the question is, what of that element is it? And other people ask, is it an epi-phenomenon because the people live in the Mediterranean, but it's not because we studied in New York City. So I think that it is a diet that's easy to have and.

Delicious.

Delicious. But I also want you to know that there was a paper published, I think in 2019, just a few weeks ago, comparing the dash, the mind, and exercise, and the combination, and showed that the combination worked best, but exercise beat diet for brain health.

That's good. I'm glad I worked out today. Yeah, it's pretty mild. So there's a number of medication trials that are going on. There are preventive medication trials. like the A4 study, tomorrow's study, the early trial. Share with us what that research is, because it seems kind of a new approach rather than waiting until you get it.

So the idea is that we can find people, identify people who are at risk, either through their genetics or through their imaging. You take a scan of their brain and say they already have Alzheimer's changes or other risk factors and say, okay, on the basis of some risk profile, we know these people are very highly likely to get Alzheimer's. and then you try an intervention, whether it's a drug. So the A4 study is trying an IV infusion of a drug that's trying to clear out the amyloid before you develop it in your brain. And so that's going on. We think that's going to be a common platform to do this. You know, you saw the Columbia South America, who are very highly risk for developing Alzheimer's, we're trying treatments on them. That's the Alzheimer's Prevention Initiative. There's the Generation Study looking at 44s, people like Jamie, and see if you can do a prevention. on people who are genetically predisposed. What kind of drugs? Either, I'm not involved in that study. I think they were going to do a vaccine and a base inhibitor, beta-amylase cleaving enzyme inhibitor.

So there's a lot of different approaches being tried. Well, it seems to me that the most logical approach would be, you know, sort of reminds me of an article that I read in a medical journal years ago was, Diet and exercise double the effect of statin drugs. You know, I'm like, well, okay, maybe Combining the kinds of things we've been just talking about, creating a better foundation of health will allow these drugs to maybe work better.

Yes, exactly.

But the problem is we don't study in that way. We just study the drug and we let people eat whatever they want and do whatever they want.

And the funny part when you're talking about stans is that people think, you know, I'm on a statin, that's good.

I can eat whatever I want. They want it to sell.

They think it's a pass. behave. Yeah.

In the UK, I think they wanted to sell them at McDonald's over the counter.

Are you serious? Yeah. Oh, my goodness. I'm serious. So that's the, that brings up the very important point, is that people have to understand you just can't go to Costco and buy the whole row of supplements and have a terrible life and think that just because I'm taking the supplements that it, absolutely. You have to buy, you have to drink the Kool-Aid. You have exercise, you have to eat right, you have to sleep, you have to reduce your stress, you have to take the supplements, you got to do it all. You can't just say one thing like it's taking a statin. Cures everything else and you can just.

Be bad, you know, have bad behavior otherwise. Yeah, it's so true. So combining the drug research with these kind of finger pointer kind of studies seems like a logical way to do things. Absolutely. It's some of the things we've been talking about, collaborating on at Cleveland Clinic, which is really exciting. I'm really excited. bring together functional medicine and the systems thinking and lifestyle issues with sort of the rigorous science that you do. It's just, I'm so excited about it.

I am really excited about it too.

Yeah, it's great. And you also been thinking about creating a preventive clinic for summers.

Correct. There's not many out there, right? There are not. And we've been in discussions with very important people in the universe who really.

Want to see a prevention clinic.

Not in America, but in the whole universe? Well, my universe, who are really vested and invested and seeing prevention clinics move forward. I know it's kind of out of the box thinking, but I think this is the time to have those kinds of out of the box ideas.

Yeah, I think it is important because what we've been doing doesn't work. It doesn't work. It's like what Einstein said, you can't solve the problems with the same level of thinking that created them or that we use that aren't fixing them.

But this is a paradigm shift. As we started earlier in our conversation, we're going to go from treating disease to treating health. This is like, this is the gospel for me.

I know it is. This is exactly what I spent my last 25 years in medicine doing, which is thinking about how do you create a healthy human? What are the impediments to health? How do you get rid of them? And what are the ingredients for health? And how do you provide them? And it's really a very simple notion. I mean, it's, you know, one of our mentors, Sid Baker, was one of the, I think one of the greatest thinkers in medicine ever, was a Yale professor. He said, you know, just ask two simple questions when you see a patient. What is it in their life that is disturbing their health? Like what is it that doesn't agree with them? Right. Is it their diet, lack of exercise, stress, a toxin, microbes, allergen? And what are those things that the organism, the human needs to thrive? Their particular unique needs. Because some people might need, you know, 400 micrograms of folate that you can buy over the counter. Some people might need five milligrams of methylfolate, a special kind because they have this unique gene. So it's really about finding the unique needs, optimizing what each person needs, and creating the opportunity for the body to heal. Yes. You know?

And that's where I think precision medicine is going to come on board, is that we are not all the same. Yeah. And that we can now, with using molecular diagnostics, determine the differences between you. You're right, you might respond to folate, I might respond to methylfolate, because our genetics are different.

Right, and so this is really it's precision medicine, but it's also precision health.

It is precision health.

Something that has to sort of upend medical education, upend medical practice. It's not what we're trained to do, but it really is how we're going.

To solve this epidemic of chronic disease. And I have to say to you, there's one statistic that's thrown out in my world often, which is that up to a third of dementia is preventable. I hope that's true.

I would love to prove that. Yeah, I would maybe be even more optimistic than that. I think when we put all the pieces together, you talked about this idea of a multimodal study that was the finger study, which is in a way not something well accepted in medicine. We look at the randomized clinical trial, which is one drug for one disease with one outcome. And it's great for studying drugs, but the truth is you can't just say, oh, I'm just going to test diet, but I'm not going to care about people's exercise or sleep or stress.

That's correct.

You have to deal with all of those things.

You have to deal with all of that. And I think that's why I started with the physician scientist. She's very thoughtful, very highly respected. And that's the key here is that the science was done rigorously. I think people inject their biases and they don't really kind of take an objective approach. So that's why the rigor of the science matters a lot.

So important, yeah. And it's a tough thing to struggle with because the way the NIH is set up, the National Institute of Health, the way research is organized, it's not around studying systems and complexity. And the truth is the brain is infinitely complex. It's influenced by complex factors. It's not going to be a simple one drug fix. That's correct. I mean, and we're just, we've been just running down the wrong rabbit hole. Exactly right. And, and, and this is a huge message of hope. It is. And, and in the book, and I, I want to sort of, I want to broach this subject because it's a little bit scary for people think, oh, I'm forgetting things or I have Alzheimer's in my family. I think my brain isn't as good as it used to be, but I'm not going to go to the doctor because what are they going to tell me? I have Alzheimer's, then I'm just going to be depressed and miserable and I'm just going to wait and they don't go in. But you talk about ways in which you can assess people early and how important it is to assess people early and what diagnostic things they should do. So can you go through some of the diagnostics that are available today that help people to become empowered to change the course of their health?

So I have to tell you early assessment and diagnosis is paramount. People, as you said, they kind of avoid delay going to the doctor when in fact we know that we believe very strongly that early interventions, even something like a finger study, could postpone or delay the onset of or progression of symptoms.

Or reverse it.

Or reverse it. So that's why it's so paramount. The fundamental issue is that people and I have to say that I think the public, well informed, would be interested. You know, people, we did this with a generation ago. You have chest pain, you may be having a heart attack. The public campaigns worked, right?

Yeah.

And then 25 years later, it was stroke, you know, brain health or what was it, brain death, I forget what the saying was about the stroke, know the signs of stroke and then you can get in, so-- Treatment, and then.

You get treatment like clot dissolving drugs.

Time is brain, I remember that's what it was. The reason I say this to you is that if we inform the public to be aware and mindful of what symptoms look like, then we have to inform the medical system, particularly primary care physicians, to be comfortable to assess, screen, diagnose, and manage dementia. And that's, I think, those are small issues but they're large issues because I think a lot of doctors don't feel comfortable with that. And it's one of the things we need to do is educate physicians as much as we need to educate It's not that hard.

We can get into, I want to get into more of the sophisticated diagnostics. But, I mean, I just did a screening in my office the other day with a patient called the Mocha Test, which is, you know, I love the Mocha. Yeah, which is a Montreal Cognitive Assessment Tool where you have one sheet of paper with a bunch of questions and some drawings. Takes five, 10 minutes. Correct. And it's pretty good.

It is very good. It's pretty good.

It's not like a four-hour neurocognitive test, but it's pretty good.

It's pretty accurate. And it's something that can be done.

By a family doctor, by a nurse.

By you know, a medical assistant. My medical assistant does it before I.

Walk in the door every time I see a patient. Right, and then you can do that pretty easily as a primary care doctor. That's why you're here in New York to train primary care doctors on how to do these early assessments. That is correct. So once they've done that, then what? Then the MOCA comes up and their score is low.

What do you have available to start to look at for these patients to treat? Well, what we were trying to see now is a sea change in our approach. Historically, the way we've approached Diagnostic is what we call a diagnosis of exclusion, right? We do an MRI of their brain. They don't have a stroke, they don't have a brain tumor, they don't have water on the brain. We check their thyroid, we check their B12, they're normal. So they don't have these other conditions. By default, they must have Alzheimer's dementia or Alzheimer's disease. The problem with that is that that turns out to be grossly inaccurate. Best case scenario, that's only right 70% of the time. So one out of three and between one out of three and one out of four times, we're just flat wrong. Even the experts, like me, were wrong three out of 10 times. So the reason I say this is that we're seeing now a transformative process in the medical field going on. We're seeing the idea that we're going to go from a diagnosis of exclusion, like I just told you, to a diagnosis of inclusion, spinal fluid, genetic markers.

PET scans, A PET scan is a brain imaging study looking at blood flow.

Blood flow, but now we can actually image amyloid itself. You can see the plaque. We can now see the plaques in themselves. It's very expensive, not covered by Medicare.

But we can- 10 grand a pop?

It's about six. Oh, six. That's a bargain. But I will say to you, but it allows us to be precise. We are not guessing anymore. We can make a diagnosis with greater than 93% accuracy. without the guessing element. So, the reason that's important.

You can measure the volume of the memory center in the brain, which is called the hippocampus. That shrinks as you get older. That is correct.

I had mine done.

I was like 90%.

Then you're in good shape.

Because you're 2-3, APOE 2-3.

You're going to live forever and you're going to think my wife is going to be happy about that. That's good, that's good. So, I will say to you that there's clear evidence that we can measure these things and not be guessing anymore. And that allows confidence. What you don't know, or you may know, what's very exciting, the newest development in my field, is that we're seeing now the possibility of a peripheral diagnosis, a blood test to diagnose Alzheimer's disease.

What would that be?

Like a PSA or like a hemoglobin test.

What are they looking at?

They can now measure tau and amyloid in plasma.

In the blood.

In the blood. And this is brand new stuff. We are probably only two years away from a blood test or some people are even looking at saliva, spit in a tube and you can tell if they have amyloid in the saliva. So, there is, we're a couple years away from making a diagnosis with something simple like a blood test or a saliva test.

And how early can that pick it up? Because the amyloid scans, the PET scans.

Can pick it up 20 or 30 years before. Yeah, we're not sure how early that go, how far back that goes. But, and I will say to you that I don't think that's going to be an inherent diagnostic. What I think it will be screening measure. So let's say you have a little bit of memory issue, you go to the doctor, you get a blood test, it's abnormal, then that would warrant more investigations.

They would not say, aha, you're fine.

But it's not like a mammogram that.

You do before you have cancer. You could. We're still making that determination. It's very exciting. And you also look at other factors too. Correct. So there's a lot of stuff in the book about how to map out your risk and to not be afraid of going to see a doctor. That's great. Encourage people to go get help because.

There'S so much that we can do.

That is exactly. we didn't even know we could do even just a few years ago.

That is exactly right.

So, this is really a great message of hope. You quote Desmond Tutu in your book who is a South African cleric and Nobel Peace Prize winner. He said, Hope is being able to see that there is light despite all the darkness. So, that sums up your message, it is pretty good.

It is.

Are there any last things you want to share with people about this condition and what they should know?

I am just grateful to be on your show. I am grateful that we talked about the book. I do want to say to your audience that you should go and engage in your health and try to alter your risk starting today. Don't wait.

Don't wait. And should we get tested for genetics? Is that something people should do?

So that's very controversial, as you know. And the American Academy of Neurology and other bodies would not recommend testing of people who do not have symptoms. And yet commercial testing now can be done without genetic counseling. so it's controversial. I would tell people not to get tested. And the reason that we would tell people not to get tested is because of a law called the GINA Act, the Genetic Information Nondiscrimination Act, which says you cannot lose your ability to get health care insurance on the basis of your genetics, but they exempted long-term care insurance. I have to tell you a funny story. On my 48th birthday, I bought long-term care insurance. I better do that. I'm 59. I was gonna say I'm 53. And the lady comes to her home and she's like, you,'re awfully young to be getting long-term care insurance. I said, lady, if you do what I do for a living, you'll be getting long-term care insurance too. So my point is that, you know, people need to be careful when they manage their genetics. If they're curious.

So, again, long-term health insurance first, then test.

That's exactly right. So, if they're curious, you need to be careful on how you manage your own genetics.

And I just want to loop back on something we didn't actually get a chance to talk about, which is that there is no such thing as just dementia. There are many dementias.

Saying dementia is like saying cancer. If I say cancer, you say what kind? If I say dementia, you should say what kind. Dementia just means a memory or cognitive decline severe enough to cause a functional impairment. So all Alzheimer's is dementia. but not all dementia is Alzheimer's. Parkinson's Lewy body dementia, which is what Robin Williams had, and I understand Ted Turner has been now diagnosed with Lewy body dementia, strokes vascular dementia, and a variety of other conditions. I will tell you Lewy body dementia is much, much more common than most people think. There's a million cases of it in the United States. But it's a disease that nobody's heard.

Of, but it's very common. It's true. I've treated patients with it, and I just want to share a story of this patient who was actually a very well-known person who was in her early 80s and started having motor, instead of a mixture like Parkinson's and Alzheimer's in a way. And she was having trouble walking, she was having trouble running her business. She was quite dysfunctional in her life. And we identified all these factors that were fixable. She had terrible gut issues her whole life. She was constipated, took enemas, laxatives. She had terrible irritable bowel. she ate, she had diabetes and no one had even diagnosed. Blood sugar A1C was like nine, I think, eight or nine. And she, she had significant B vitamin issues, B12 and folate and a few other little things. And we just mixed all those little things. And it was amazing what happened to this woman. And I, listen, I'm not a neurologist. I don't see all these patients like you do, but. I just follow basic principles. It's like follow the laws of nature. How to get people healthy and cross your fingers. That's what I do. And within a month, she was significantly better. Within a year, she was walking out of a wheelchair. She was going up and down the stairs. She actually wrote a book. And recorded an album. Functioning better than she ever has. And all her numbers got better. Yeah, well, maybe you can help me.

I would love to write that book with you. That's awesome.

Yeah, and I've seen these one-off stories, but what they tell me is that by applying these principles of creating health, that we can really modify these diseases in real ways.

I have to tell you, Alzheimer's so dominates the bandwidth that people don't even think about other conditions. What if we could alter many of these dementias, not just Alzheimer's?

Well, there's a great paper that was in JAMA years ago, it was called Shifting Thinking and Dementia. and it says that we combine categorical misclassification with etiologic imprecision. And in English, that means we categorize people according to symptoms, not according to causes. So, I don't know if you've seen that, but I'll share with you. It's a fascinating paper because we're really good at naming diseases and categorizing things according to the symptoms, but not according to the actual cause. And functional medicine is much more interested in the cause. And so that's that's when I go, what are those common causes of disease? Inflammation, it's mitochondrial issues, it's gut issues, it's hormonal regulation, it's toxins, and we just work on that stuff, nutrition. And it's really exciting. So, I can't tell you how excited I am that you now are leading Cleveland Clinic's Alzheimer's Dementia Program that you have this incredibly open mind. As Gretch and Mark said, keep your.

Mind open, but now it's open that your brains fall out.

I think that is, That is a cool thing.

I'm gonna use that. You can.

So I think you're one of those guys.

Thank you.

Still critical and rigorous in the science, but still open to ideas that could really change the world. So thank you for being on the Doctor's Pharmacy. Thank you very much. And you've been listening to Doctor's Pharmacy. If you love this podcast, please share with your friends and family on your social media. Leave a comment. We'd love to hear from you. And we'll see you next time on the Doctor's Pharmacy.

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