You Can Prevent Alzheimer’s: The New Science of Brain Health

47 million Americans are going to get dementia if we don't do something about it.

People think of dementia and neurodegenerative disease as an older person's disease, and it's not.

We can detect changes in the brain decades before a person is going to develop dementia.

We spent $2 trillion over 400 studies, and 99% failed. So we're thinking about this wrong. Dr. Richard Isacson is a leading preventive neurologist, and he's dedicated to the prevention of Alzheimer's disease. He was the founder and former director of the Alzheimer's Prevention Clinic at Weill Cornell Medical School. He now serves as the director of research at the Institute for Neurodegenerative Diseases. He heads the NIH-funded Retain Your Brain program about retraining your brain and retaining your brain by doing specific practices that help you preserve your cognitive function. Take us down the sort of this framework of our current thinking and why it's flawed in the traditional neurological field, and how you've come to understand we need to take a different approach.

45% of cases of dementia may be preventable. When someone comes into your office, what are you looking at? What are you testing?

We do this all now digitally, and it's free. People can go right now and get an assessment and like learn about themselves and get automated brain health preventative care, preventive neurology care.

How do you approach diet with all this?

Women that have increased waist circumference are at a 39% higher risk of dementia.

Two more things I want to cover before we close out. What about pharmacologic interventions? Because drugs have a role, and also what about brain exercises?

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Hey, it's Dr. Heyman. I'm so excited to share this episode with you today. But before we dive in, I want to get your help. Please take a minute to hit that subscribe button. Whether you're watching here on YouTube or listening on your favorite podcast platform, it truly means the world to me and it helps my team and I bring you this podcast every single week. Plus, I don't want you to miss a thing. So, thanks so much for being part of this community, and I'm glad you're here.

Well, Richard, welcome back to the Dr. Heyman show. Uh, we had a few years ago a chance to do this uh over COVID. That was a long time ago, and you have been a man on a mission.

Things are very different now. It's only been 5 years, but man. And uh, there's a lot more to tell about this whole topic of neurodegenerative diseases, which is a crippling problem. It's the most expensive condition is Alzheimer's, uh, more than heart disease, cancer, diabetes, because of the long-term care and issues we have with it. The entire research enterprise pretty much failed to get an answer. There's a lot of sort of drugs that really don't work, and if they work, they're like, extend, you know, your nursing home free time by 3 months as a big win, and the drugs cost a fortune. And you know, we spent $2 trillion over 400 studies, and 99% failed. So we're thinking about this wrong. We're 100% thinking about this problem wrong. And so I want to sort of share a little bit about for you, what is sort of the current thinking that's flawed, and how should we be thinking about this from a both prevention and treatment perspective? Because no one is an Alzheimer's survivor, right? I mean, but there's cancer survivors, there's heart attack survivors, but we don't really hear about this. But there are, and I've certainly had them in my practice, and I know other doctors who are working in this field on the fringes are doing this. But you came from Cornell, you're, you're an academic, you're, you know, trained at Harvard in neurology. You've got the street creds, and you've come at the same thing that I came at decades ago.

Tomatoes getting thrown at us.

Yeah. I mean, we, you know, you're, what do they say? You know, the the pioneers always have arrows in their backs, right?

I'm still bloodied and bruised. So, so take us down your, you know, this sort of this framework of of our current thinking and why it's flawed in the in a traditional neurological field, and how you come to understand we need to take a different approach, and even a concept that isn't really well accepted, which is that you can actually prevent Alzheimer's.

So, you know, we we don't live in a healthcare system, we live in a sick care system. The medical system is is really positioned on treating disease. And what does disease mean? Well, disease means to most doctors a symptom, a problem, memory loss, dementia, treat then. But any chronic disease related to aging, heart disease, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, these are diseases that start decades silently in the body and brain. And that's when we need to do something. So I had this, you know, crazy idea. Oh, Alzheimer's prevention clinic, it can't start. You can't use Alzheimer's and prevention in the same sentence. That's that's cookie talk. And this is like over 15 years ago. And and what I wanted to do was not just treat people with cognitive decline and treat people with early dementia, but I wanted to see their family members and treat their family members. And in 2009, I got kind of kind of taken away in a in a hallway saying, "Is I know you got you got four family members with the disease. What What are you can we do anything to prevent like what what should I do?" It was a son of a patient of mine. And we we spent 45 minutes in the hallway discussing what what he and I could possibly do. And then next week, I saw his sister as a patient. And that was the first Alzheimer's prevention uh consult um in in the United States that that I did. And and that kind of changed everything to me. And and to me, we're thinking about things wrong. We're we're doing things all wrong. And people think of dementia and neurodegenerative disease as an older person's disease. And it's not.

We used to joke called Alzheimer's disease.

I get it, cuz we see people with dementia and they're older, right? But but these diseases start silently in people's 30s, 40s, and 50s and 60s and 70s, decades before symptoms. And there are 47 million Americans and hundreds of millions of people globally that have these pathologic features, these blood markers that you can now check, and these, you know, some cognitive assessments that you could do from the comfort of your own cell phone. We can detect changes in the brain decades before a person is going to develop dementia. So, let's go then. Let's do it then. Let's see the person then. But our our healthcare system is like so broken that like I can't see a person to try to prevent dementia or reduce risk for Alzheimer's or reduce risk for Lewy body disease or dementia because there's no billing codes for it. I can treat someone with a disease after you have a heart attack or a stroke or dementia, but we don't get paid for it because our again, I don't want to believe for this, but our whole healthcare system is broken. So, so to me, um, we just got to get ahead of things and the evidence, you know, the the totality of evidence is overwhelming that we can do something. And the last time we talked, I feel like I was doing cool stuff back then. And now it's just totally different. Like the objective markers, like the proof is in the pudding. Like we're able to do things today that are just like science fiction even 5, 10 or 15 years ago. So yeah, I'm excited about the progress, but um, you know, it's hard to keep pushing things forward.

It is, you know, and you talk about the 47 million Americans, forget globally, 47 million Americans are going to get dementia if we don't do something about it. And yet there is nobody pretty much besides you and a few others who are actually thinking this way. I did the math, and if we leave this unchecked, the bill for Americans over the next 30 years is going to be $18 trillion. That's basically the amount of our annual GDP one year. It's a huge amount of money, and what you're saying is that it's, it's really preventable.

Now I want to kind of hearken back to the flawed paradigm because in medicine we have this idea that you have a single disease Alzheimer's that's caused by a single pathway, amyloid deposition, which is this gunk that gunks up, in layman's terms, gunks up the brain and makes it not work. But it's really the body's band-aid where there's inflammation. And we've tried to find anti-amyloid drugs for decades, and we've spent $2 trillion, I like I said, 400 plus studies, and massive failure. Why has that failed, and and what's wrong with that thinking, and why should we look at a different framework that looks at each Alzheimer's patient differently? You you say, if you've seen one patient with Alzheimer's, you've seen one patient with Alzheimer's, right?

You took the words in the sentence right out of my mouth. Um, I'm a clinician, right? I'm a doctor. I see patients. I talk to patients. Patients are my petri dish. I don't study mice. I don't I don't do basic science stuff, you know, over my head. You're an old oldtime family doctor. I'm an oldtime neurologist, you know, carrying the bag in the old I'm calling myself old, too. So, it's a We're all We're all hippies. We're all deadheads in the room. So, you know, we're we're we're old in in a good sense of the word. But when you think about neurological disease and brain disease, and what I was taught in medical school was like Alzheimer's is like this protein called amyloid, and amyloid, like you said, is this the sticky protein that builds up in the brain of a person with Alzheimer's, and when you look at the brain of a person with Alzheimer's, there's amyloid in it, okay? But like, why are there up to a third of people that have amyloid in their brain but didn't have dementia?

Yeah. Yeah. Well, that's interesting. Well, how does that make sense? And then in the textbooks, I remember I remember the graph. The amyloid goes first, and then the tau protein, the other next protein, then brain inflammation and and neurodegeneration, brain cell death. And those were the that was it. That's how Alzheimer's works. But that's not how it works in the clinic. I'm a clinician. I look at the patients, you know, that model of amyloid, then brain inflammation, then neurodegeneration. Yeah, that happens. But in a recent study, journal of neurology, it was like a third of the time that was the trajectory. But all the textbooks say that's how it is. And the medical students are. So, so to me, there's buckets, and different people present different ways. And and the way that I view Alzheimer's, and also the way I view neurodegenerative disease as a whole, is it's very heterogeneous. There are so many different types and manifestations.

Even though this the end of the diagnosis is the same, each of these patients might have different causes and need different treatments.

Yeah. You can take different roads to Alzheimer's. You know, women, you know, for example, Mrs. Smith, she may be, you know, perimenopause. The estrogen is dropping. She may have a variant, a genetic variant called APOE, which we could talk about APOE4. And you have the APOE4 and the estrogen drops. Well, Mrs. Smith, she's going to need therapies A, B, and C. But Mr. Jones, he's totally different. You know, he doesn't have the gene. He's different. He has a a big belly. As a belly size gets larger, the memory center in the brain gets smaller. He needs a kind of more metabolic health and a different plan. He's going to need therapies X, Y, and Z.

The bigger your belly, the smaller your brain.

That's uh, small the memory center in the brain. Exactly. And there's lots of things we can do about it. So, you know, different people need different paths. And you know, our medical system is broken. I've said that a couple times, but you know, it one-size-fits-all is is not how this works. And we need to take a one-size-fits-all one approach. And

We call this N of one medicine. And the NIH has actually declared this as one of the most um important and actually um predictive forms of research and and they're funding some N of one research trials. But it it still hasn't kind of permeated the funding, really. It hasn't permeated the thinking at all.

No. And and you know

This is what you call it is precision neurology, precision prevention.

That's exactly it.

Right. Precision or personalized. It's it's not one size fits all.

Taking this individualized approach. It it, you know, people hear the term precision medicine. Ooh, that's that's fancy expensive tests. And no, actually, it's just like talking to the person and figuring out what road they may may be on.

And whether it's doing a genetic test or doing some blood markers, which, you know, the cost has come down, um, doing cognitive assessments. We do this all now digitally. We and it's and it's free. It's like people can go right now and get an assessment and like learn about themselves and get, you know, a way to like have automated brain health preventative care, preventive neurology care. And doctors just don't realize, and it's not doctor's fault. Like in medical school, I was taught one thing, and then the field's changed, and the field's changed so much in 5 years. So, so to me, you've seen one person, you've seen one person with with Alzheimer's. And what we've done recently is now not just studied people with at risk of Alzheimer's disease. My brother's a Parkinson's specialist. My brother's brother-in-law is a Parkinson's specialist. My brother's son is a Parkinson's specialist. So, I got the Parkinson's movement disorders thing covered on one side of the family. And and we bring everyone into the same research database or research cohort, which is a research group. We have something called the Bioan study, the the bio repository for Alzheimer's and neurodegenerative diseases. And when you start putting these people that have similarish diseases in the same group and look at the signatures, the biological signatures, they need to be studied together. How many times have I thought someone has like Alzheimer's, they have a different protein or a different pathology, or someone has a diagnosis of Parkinson's, it's well, wait a minute, it's something a little different. You have to study these things together. And there's so a lot of common mechanisms. It's inflammation, it's oxidative stress, it's mitochondrial dysfunction. These are universal things that happen. We talk about in functional medicine all the time that are fundamental to understand. And and the question is why? And and you've been asking why. It's not what we do in medicine. We say, okay, what disease you have? What drug do I give? Not why do you have this? And how are you different from everybody else who has this? And what do you need differently in terms of diagnostics and treatment that'll help you get better?

Yeah. And what are we going to do about it? Exactly. There was an old saying, neurologists don't treat disease. We admire it. Adios and diagnos. No, not not anymore.

That's right. That's that's an old neurology saying, adios and diagnose and adios. Meaning meaning you make the diagnosis and there's nothing you can do about it.

Yeah. And that's just that's just plain wrong. And you know, with with four family members with Alzheimer's disease and like and it's just seeing the suffering that's not okay. And I don't care if it's a if it's

You have four family members.

Yeah. Oh yeah. Oh yeah. And I've seen this. I mean, I I now have a new family member with some Parkinson's-like syndrome that I still can't understand, despite having like hundreds of blood tests that we're developing to try to figure it out. Like it and it it makes me sad, and and it just motivates me to just keep going. And there's so much confusion out there. But it's it's it's all about one thing. What road could a person be on? If it's evidence-based and safe, let's go do something about it. And we can't do can't be like tricked into thinking, oh, you have to do a randomized, controlled, double-blind study where everyone gets, you know, one group, they get one treatment, another group, they get a placebo. Like, no, different people need different treatments. So we've kind of turned the paradigm, the research paradigm um on its head, I believe, and we use that person as their own control. And just like you said, this N of one paradigm, we're following over 250 people over the last 5 years. And each person is getting their own different plan. And then what we do is we then group them together and we say, okay, the people that got the multimodal lifestyle interventions, specific vitamins and supplements, that's one group. Then you have, okay, well, some people take drugs and they have specific medical conditions, and those people get that. And then we have a group that has the anti-amyloid drugs that you mentioned. And then we map them all out together and we group them together, and that's real-world evidence to show look what's working, look what's not, and we're helping the individual people. And if we just put everyone on an anti-amyloid drug, or everyone on a, you know, one of the GLP-1 weight loss drugs, or just put everyone just on exercise, it ain't going to work. So um, that's the style of research we do, and the style of research we do isn't like funded well, and it's not like recognized the way it should be.

Well, I agree. I mean, I think what what what the challenge is, is that in each person, there are different causes, and you have to map them out. And if you give a person a drug or a supplement that they don't need, it's not going to do anything. So I always say, if you don't have vitamin D deficiency, giving vitamin D isn't going to do anything. If you don't have insulin resistance, giving a GLP-1 drug probably isn't going to do anything. So you've got to customize the treatments. One of the failures of medicine is, and is, you know, we have a a rule in functional medicine called the tack rule. We talked about last night at dinner. If you're standing on a tack, it takes a lot of acid to make it feel better. So if something's in your system that's bothering you, that's irritating you. You mentioned a case, for example, of some kind of herpes lesion on their lips, and a herpes virus, which is linked to Alzheimer's in some cases. So the end pathway is the same. It's inflammation. It's damage to the brain. It's amyloid deposition. That's just a reaction to various insults. The insults could be toxins. They could be allergens. It could be crappy diet. It could be too much sugar. It could be alcohol. It could be mold. They could be um other factors that they don't have that they need, like deficiencies of vitamin D or omega-3s, and various things that all play a role in keeping your brain healthy. And so if you don't actually map out what that particular person's individual issues are, then you're not going to customize the treatments and personalize it in a way. And and what you're doing is so radical because most physicians are focused and trained on diagnosing a disease and then finding that single pathway that explains the disease and that single drug that will fix the problem. And that worked for infections, sort of. I mean, with Louis Pasteur, we got the bacteria, we said, oh, there's this pneumococcal bacteria. Oh, that causes pneumococcal pneumonia, that single disease. Oh, it's treated with a single drug, penicillin. It it's a miracle. And yeah, it was a miracle. And even with infections like COVID, we saw the host matters. If you're an older person, or you have chronic disease, you're obese, you're more likely to die from COVID, even the same virus. So it's not just the virus, but what happens is in in that model, we basically treated all chronic diseases in the same way, which is a massive failure because chronic diseases are complicated and they have multiple causes, even if you have the same diagnosis. If you have, for example, diabetes, or heart disease, or cancer, or Alzheimer's, or Parkinson's, it may be different causes, even if you have the same diagnosis. And that's what you're that's what you're kind of coming up with. And and then you're having to do investigations to figure that out, and then you're doing diagnostics to help you map that out in terms of blood testing, and we call these new blood biomarkers for dementia, which is I want to talk about in a minute, and imaging, brain imaging, and then you start to treat these people individually, and you see remarkable changes, and lowering of these biomarkers of dementia, improvements in brain function, and improvements in their subjective function and their objective neurocognitive tests, which measure, you know, their brain function. And these are things that are real heresy. Cuz you talk to any neurologist, say, "But I've reversed the effects of Alzheimer's." They're going to just laugh in your face. The tools that we have are not tools that are radically expensive, are radically unobtainable. um, it's just having the wherewithal to try to do something about it. And you know, when we identify that a person is at high risk due to a gene or or otherwise um, and the person starts adopting changes, um, you know, we now have the tools to to truly, you know, in my opinion, definitively show that the things we tell people to do are getting people off the road to dementia. They may have amyloid in their blood, or they may have some cognitive glitches. um, they may have some symptoms that are still early, but they can go about all of their, you know, usual daily daily lives. And and to me, I don't care if it's a vitamin, a drug, or a supplement. If if there's evidence and it's safe, you're agnostic to the treatment. I don't care what the treatment is, right? Like, yes, I'd rather people, you know, food is medicine. I I couldn't couldn't couldn't say that enough times. And, you know, I and I wasn't trained that way. I was I was not trained in medical school. I didn't learn about that stuff. And in residency, I didn't learn about that stuff. But I don't care what it is. Just just just try it, and then just recheck markers, and whether the markers are blood markers, cognitive assessment markers, which again, it's easy to do now. um, or brain volume markers, and then some of the slides that I sent you, not yet fully published. And I mean, people's brains are growing. Like that's like that's heresy. That doesn't make sense. And I'll be honest, a decade ago or 20 years ago, I would say that's not true or BS. But but I see it. And when everything is going in the right way, when everything about his everything improves, you know, that's that's evidence for me.

Yeah, it's true. I mean, I think you're you're you're gathering data that is really solid. What I want to sort of dive into now is is this idea of, you know, this the sort of early intervention and assessment. We do it for a lot of things. Chol, we check cholesterol. Cholesterol is a risk factor for heart disease. It doesn't necessarily cause heart disease. There's other blood biomarkers we tested function that are also very big risk factors, like lipoprotein little A, which is genetic. So you can actually map a person's trajectory by knowing their biomarkers. We do the same thing for metabolic health. We can measure glucose or insulin or A1C and see the trajectory of it going up before they get diabetes. So this is there's a there's a proxy for this in medicine. But with dementia, we don't really do that. And what's really remarkable about your work is that you're you're not just doing neurocognitive assessments. You're not just measuring normal things like omega-3 fats or vitamin D or blood sugar, cholesterol, or blood pressure, which are all important, have to be managed if you're going to reduce risk. But you're you're finding that these particular blood biomarkers, these you're developing new tests that are from protein signatures expressed in people early, decades and decades before they even forget their keys for the first time. I'd love you to sort of break down some of the things that we're looking at now that are blood biomarkers. And at Function Health, we basically have a a blood biomarker panel that helps identify that risk, including APOE4 testing and APOE testing, which is a gene for risk for Alzheimer's, looking at PA27, which is another marker, AD4240, which is amyloid biomarkers, but you're going way deeper than that.

Yeah. So, you know, when it comes to blood testing for Alzheimer's, and by the way, 5 years ago, or whenever we last spoke on on the podcast, like never in a million years, whether it was two years, was 5 years ago, 10 years ago, 20 years, never in a million years did I would have ever pictured myself having a lab in Boca Raton, Florida, developing

There's a lot of Alzheimer's disease.

That's well, that's what they call it. And it should should be called something else.

Joke. Bruce Ames, who's a very famous scientist, said on epidemiology, which is population studies. He says if you did a a study of of population in Miami, everybody be born Hispanic and die Jewish.

I can I can say that that's true from the evidence I've seen. We had to create a lab. We had to go deep on the blood test. Like I I'm not a basic science guy. Like I I've never like centrifuging blood and and developing at-home testing using different devices and

Develop, you know, starting with a panel of say, a thousand, and now coming, we're we're down, hey, we're down to 150 tests, and we're getting it down. And and my goal and our goal, you know, at IND and and and elsewhere, we are trying to develop what will one day be termed the cholesterol test for the brain.

And, you know, if we're talking baseball analogies, we're still in the first inning, in my opinion, of a nine-inning, you know, baseball game where the tests we use now, I think are are are are good in certain ways, and I think can be helpful. For example, if a person has symptoms, and the doctor and the person with symptoms is wondering, are those symptoms from Alzheimer's disease? Then then yeah, there's this P-tau217 test. It's a very good test. It's not a perfect test, but it's a good test. But we're just just taking things with a very different lens. And we're looking at people ages 21 and up to understand what the signature of proteins should be, what is the normal values of these proteins. Because when you start doing a regular cholesterol test to prevent a heart attack or stroke, and you start doing those tests in people's say 60 or 70 and above, that's often times a lot of times too late. The cholesterol test for the brain. I envision a day where people are going to come to the office, and I hope that you know, our work will will help, you know, inform this. But people in their 20s and 30s and 40s and 50s and 60s and 70s and beyond, before they have symptoms, will get this panel of tests. And we're just starting to like I think the the we're in the black and white television phase. I think we're we're now in the color television phase where I can kind of see what the five to seven, maybe 10 markers will be, and we can track these tests, and we can do it in a way that we can um, you know, lower cost, improve increase access, and then give people digital tools to like help interpret it and give that person care. So what we what we believe is that we need to look earlier, and we need to look more deeply, and we need to look at other markers. And then the other problem is that some of these markers that may be positive, uh-oh, got a positive Alzheimer's blood test. What if the person had a virus that morning? What if the person got a blood draw in the afternoon rather than the morning? You know, these are things, and and what is a normal value for someone in their 20s or 30s versus someone in their 40s or 50s versus someone in their 60s or

What are the reference ranges?

Reference ranges. And and and, you know, most of the research that's been done are people with dementia, people aged 55 or 60 and above. And we need to start earlier. So the focus of our research is to to figure out what is this cholesterol test for the brain going to be. These and these tests, we're going to want to talk a little bit about them in detail. They're the way I think about them is they're they're kind of early warning signs. They're not necessarily the cause, but they're they're the things we can look at that are resulting from causes that drive those biomarkers to be abnormal.

Yes. To me, the the word is biomarker. It's a biomarker. It's a marker of a biological condition or a disease. Amyloid to me does not cause Alzheimer's disease. I've just never felt that way. Why are there people without amyloid that have a clinical meaning like

You know, talk to the patient, looks like they have Alzheimer's, they don't have amyloid. Oh, I wonder why. I guess amyloid didn't cause Alzheimer's in that person. But by definition, you have to have amyloid to have Alzheimer's. Like our our instruction manuals are like totally wrong. Rudy Tanzi, who's a friend of ours, is an amazing guy who's an Alzheimer's researcher.

We just said amazing guy like in unison. So I hope he and he's a deadhead. So like

He's a cool dude. And uh, he discovered Nobel Prize quality science on the very unique early Alzheimer's genes through lucid dreaming. If that tells you anything about the guy um, he, you know, he said that there are patients who have brains full of amyloid but die old cognitively intact, meaning normal. And he said, what's unique about these people, and I love to hear your perspective, is that they have certain genetic variations in their immune system that don't mount an inflammatory response. So as far as I understand the literature, Alzheimer's, the the end result is the end result of an inflammatory process in the brain. And there are many things that can cause inflammation, from infections to toxins to diet to pre-diabetes or diabetes to a mold to, you know, Lyme disease. I mean, Christopherson had quote dementia and Alzheimer's, but he had Lyme disease, and he got treated with antibiotics, and his dementia went away. So I think we we have to think more about what what the underlying pathology is, which is inflammation, and then why is there inflammation, and then hunt down the sources and the causes of inflammation and remove those, and that will lower, I might believe, lower these blood biomarkers that are around. Even a few years ago, they they weren't really available. These things like p-tau217 or amyloid biomarkers like A A um AB4240, other PAs like 181, 231, neurofilament light chain, which is more for brain damage or something called glial fibrillary acidic protein or GFAP, and beta-synuclein, which you're actually developing the test for. So there's all these novel biomarkers that are going to be available clinically, probably in the not too distant future, where you can go get a blood test and you can say, gee, you know, where are my levels? You know, it's like, is my blood sugar high? Is my cholesterol high? Is my blood pressure high? And those are risk factors, and then these that tell you that you need to do something. And the question is, how do you figure out what to do in each individual? If you're treating everybody as an N of one, or as a precision medicine or personalized medicine, what's the actual clinical workup? What are you looking for? And then how do you identify the targets? And what are you doing for those targets that you find?

The way that I do it in my um in our research program in clinical practice um, what I would call it, the ABCD and E of Alzheimer's and neurodegenerative disease prevention. Okay, ABCD and E. And then when someone can't access a doctor or can't get into a research trial, we have, you know, five sites in the US and United States and Canada. And if you can't access one of those sites, and if you can't see a preventive neurologist, then we do it through software. And I'll explain how that is. And we got funded by the National Institutes of Health. We conducted a very, very large, almost a thousand-person NIH-funded randomized control trial that showed that free software online. You go into the website retainyoubrain.com. It's all free.

Retainyourbrain.com.

Retainyourbrain.com. If there is anyone out there with a brain that wants to like

Wait, I have a brain. I think.

You I think you do. You you definitely have a brain. It's it's uh, you you have a very robust brain. It's functioning. Check mark. Uh, neurologist approved. I'm going to give the cliff notes version um in the ABCs and Es. But if there's anyone out there like we've just spent six years developing, and this was before AI was cool. We just developed, we put my brain and you know, a virtual neurologist in your pocket, and retainyoubrain.com. It's available by web, tablet, cell phone, whatever. It's all free, and you can get access to this type of education and and and, you know, does a risk assessment. You can do cognitive games, if you like games, whatever. And then the software will tell you what to do.

This is mostly based on your history. You're not necessarily doing blood work or

Baby steps. Yeah. In time, in time. But but right now, it's it's all it's all accessible, and there's, you know, no cost. And and, you know, doing the blood test would just add another layer of that. That's amazing. But right now, clinically, that's what we do, and from a research perspective, we do use the blood test for sure. So, so the Retain Your Brain, which is what we all want to do, is retainyourbrain.com is a platform that you've developed that basically is downloaded that your thinking into a a system that allows you to assess people, identify their individual issues, then make specific personalized recommendations that they can implement even without a whole bunch of diagnostics. And it's free. So, everybody should go check that out and do it. And if you have a family history of any of these neurodegenerative diseases, or you're worried about getting it,

Get on it.

And it's free. Now, what I'm talking about is when someone comes into your office, or you're part of this 250% research study, how deep do you go? What are you looking at? What are you testing?

Oh, we go really deep.

Yeah. Tell us what you're Because I think this is important because people don't know what to look for.

And I think there may be many physicians listening to this podcast.

Hopefully, there's some philanthropists who have family members with these diseases who are going to listen to this and go, "Wait a minute. This is a place where I can make a huge impact that is being neglected by the outdated medical research establishment uh and the antiquated thinking about a reductionist model of disease and the fear of doing too many things at once in a patient. It's like, you know, I think that's that's the joke is like, you you have to treat everything, right? If you have uh low vitamin D, or low omega-3s, or you have pre-diabetes, or you have heavy metals, or you have mold, or whatever you're fighting, or you have high cholesterol, you got to treat all those things. You can't just treat one thing. But that's what we do in traditional medicine. The A B C D and E of Alzheimer's and neurodegenerative disease risk factor risk reduction prevention management is a paradigm that we published on at Nature Mental Health, January 2024, was the last time we kind of updated the paradigm, and it's all again, doctors out there listening, any healthcare providers, you can read the paper. But the A is simple, it's anthropometrics. So what does A stand for? Anthropometrics is body composition, body fat.

Muscle mass. I also kind of throw bone density in there. Bone density, grip strength, also an important proxy for

Why is that important?

As you go through this, I'm going to kind of have you go through and explain why each one's

Important for sure. And and by the way, I'm going to talk about things and people are going to be like, wait, what? What is this guy? He's a neurologist. Why isn't he talking about neurology about belly fat?

Yeah. So, so I believe, and and, you know, you wrote a paper on this, I think back in 2007, about how like our brain disease is really like body, and I'm paraphrasing. I don't remember what the title was.

Is it a disease of the brain or a body disorder that affects the brain?

So I believe Alzheimer's, and and I mean this is going to sound like heresy, but I believe neurodegenerative disease many times, or most times, those are big statements, are medical conditions that have secondary negative effects on the brain. So just like when a person has diabetes, the sign of end-organ damage is kidney failure, or tingling and numbness in the toes, or something called macular degeneration where people lose vision, you know, because of diabetes. I believe medical conditions, the neck and below, things affect the brain when they

That's a heresy because most neurologists stop looking at anything below the neck.

Yeah. And and I'm like a I'm an old-time family doctor. Like I'm an inter, you know, I I I feel like I practice one-third internal medicine, one-third uh preventive cardiology, and one-third, you know, preventive neurology, which is a field that, you know, just barely exists. So So what I'm going to talk about now is going to be very medical. So I'm glad I'm with you because you can you can

I can translate if you translate. Exactly. So So A, anthropometrics. Uh, again, it's a fancy uh, long term, and I I couldn't use B because body composition is is the next letter, but everyone needs to know their numbers. Belly fat, uh, especially as the belly size gets larger, the memory center in the brain gets smaller. Women that have increased waist circumference, okay, visceral fat, meaning fat around their their body organs. Women are at a 39% higher risk of dementia. Wow. That have fat around their visceral organs and belly fat. And you know what happens to women during the perimenopause transition? It gets really, really, really hard to lose belly fat. And there are things that we can do to to change that. So, so we track all these things, and we use belly fat, muscle mass. You know, people lose 1% of muscle mass per year. I mean, like like people like muscle mass is not easy to build, and and doctors don't focus on. Like, why are people talking about weight? Like, stop talking about weight.

Body composition.

Talk about body comp. Everyone needs to know these scales. Okay, they're a couple hundred, but you know, everyone needs to know their body fat. We want to lose fat, we want to gain muscle. We want to put on muscle, we want to lose body fat. A lot of people take these, you know, weight loss drugs. Okay, they have some really interesting features. They're maybe too high a dose. We'll talk about the GLP-1 drugs.

The GLP-1 drugs.

But we shouldn't be tracking weight. I don't want to hear about someone's weight. I want to hear about body fat, body condition, and and muscle, and muscle, and bone density, which is really critical. So the A, all of these things and anthropometrics are brain markers. So we track those. The B.

So measuring your belly fat is a brain marker, is what you're saying?

100%. Yeah. Muscle mass, um, you know, and and and belly fat, absolutely critical risk factors to to prevent cognitive decline, dementia, even Lewy body dementia, Parkinson's. These are all metabolic factors that actually do influence these diseases.

They're all connected.

They're all connected.

So what's B? B is blood-based biomarkers. And what do I mean by blood-based biomarkers? I don't just mean the brain markers. I mean, um, cholesterol markers, I mean inflammatory markers, markers of inflammation, um, nutritional markers, metabolic markers, um, and then a bunch of hormones.

Metabolic markers, meaning like looking at blood sugar, insulin. So fasting blood sugar, um, fasting insulin, um, you know, there's a lot of us may have heard of something called a hemoglobin A1C or glycosylated hemoglobin or HbA1C, and you know, people say, oh, above 5.7 is pre-diabetes, and 6.5 or whatever is is diabetes. Metabolism, memory. If you want to have memory decline, don't mind your metabolic risk factors. Like metabolism and memory is so critical. And

Well, because they they even call Alzheimer's type three diabetes, right? It's Alzheimer's diabetes of the brain.

Yep. And there's a lot of a lot of overlap with with the with the with the pathophysiology, which is a big word for, you know, potentially why these diseases happen, and and metabolic health. Um, you know, if you want to fast forward cognitive decline, we don't want to do that. You know, high cholesterol, high blood sugar, high blood pressure. These are all things that can, you know, fast forward uh cognitive decline. And also, cholesterol is really complicated. I'm not sure how much time we have to get dive into this, but like, there's good cholesterol, there's bad cholesterol, like HDL, that's the good stuff, right? Well, maybe not. It's a little confusing. There's there's a lot of confusing stuff with with cholesterol. And and

It is. And and it's unfortunately, Richard, most doctors, even cardiologists, don't fully assess cardiovascular. Literally just got an email from a friend of mine who's a doctor at Mass General, who's an internist, who's very well educated in the top of his field, Harvard at Harvard.

His wife did Function Health and found she had a lipoprotein A of 500.

Which is a and no one's ever checked.

Which she said, no one's ever he was like, her doctor wouldn't check it, I wouldn't have checked it. And now we did a full cardiac workup, we can actually manage her risk and look differently at her health. And at Function Health, we do these very deep biomarkers for cardiovascular that are far just beyond a regular cholesterol panel. ApoB, which never gets checked, lipoprotein A, particle size. We look at function of HDL. You said HDL is not all the same. Some good, the good isn't just all good, and the bad isn't all just bad. It's a it's kind of a false false framework. And so we're able to get the nuances of what's happening. And we look at insulin, which again, is never tested. So a lot of things you're talking about are things that now people can access for a very low cost.

And the accessibility is critical. And, you know, in 2007 was the first time that I ever had these markers checked in me, and that's like almost 20 years ago. And I I got my first calcium score 20 years ago. Thank you, Dr. Agason. He was one of my old mentors. Um, like, I mean, I I got thrown into this because I had mentors and people that thought differently, thought in a contrarian way. You know, Dr. Raggson, for example, the calcium score, I think he invented that in like, I don't know, '89, '90, and it became part of the guidelines, the physician, you know, consensus guidelines in 2018. It took 30 years to make, you know, the guidelines that like, you know, okay, if you have high cholesterol, maybe we should look at the heart to see if there's, you know, plaque. And, you know

Because by the way, you can have like, just the way you can have amyloid but no Alzheimer's, you can have extremely abnormal cholesterol and clean arteries. And I have patients like that, and they're like, wow.

Your LP(a) is high, your ApoB is high, your your particle number is high, your particle size is small.

Clean as a whistle.

Yeah, clean as a whistle.

And and that's the thing, like, and and this is precision medicine and personalized care. So So anyway, we look at all these markers, and we look at Apo, we look at LP little A, we look at H, we look at LDL, we look at particle size. I mean, if you have to choose one, like I choose Apo as a good proxy. We always check LP little A. Um, we look at markers of absorb, like is is someone, you know, if someone has high cholesterol, instead of just throwing them on a drug that you know, um, you know, in the grand scheme of things, may work for 70 or 80% of the population. What if you're in that 20 or 30% where you're not the right person? And I think you and I, whatever we may be, I I have a different version of of my cholesterol is not high, it's just borderline, but I'm an overabsorber of the cholesterol that I eat in my food in my stomach. I don't overproduce cholesterol.

So I don't need a drug that would like a statin drug. That's not the right drug for me. Generic drug calls it a zetami. It's a plant sterile inhibitor. That's the right drug for me because I've had that check since 2007. And right now I'm able to control it without a drug. But if I need a drug one day, that that's the one I would choose.

It's basically also called zedia. It it it's interesting because you know you know I have genetics and I've done my cardiovascular genetics and I I'm have a very strong family history of heart disease and I'm a hyperabsorber and when I actually started taking this drug it was like I dropped like a like a stone cuz you had the right drug for you basically.

It's not it's not the cholesterol is eating from eggs. It's the cholesterol that's produced by your liver and bile. that's excreted in your bile that gets reabsorbed that you kind of have to manage.

For people that are listening, you may say, "Oh my god, what is it? Like, how do I get these tests?" Like, it will be available. All this stuff and some of this is available.

All this what we talked about just now is all available through function health for $499 and there's add-ons for cardiovascular. You also are going deeper on blood barkers. I want to stay on the B with you because because you are looking at additional things that in addition we offer as add-ons like at function but PTA and amaloid and APOE and uh neuroplimate light chain other things but you're going even deeper into these the stuff we're doing like you know we're we're developing blood tests like that that's our goal and some of these tests are like not anywhere on the market yet and they'll be you know at least two years before you know I I believe that we have a potential test that like if someone is worried about taking a statin for example and they want to know, are they the person that probably shouldn't take a statin because it may or may not hurt X, Y, or Z? We're working on a blood test to figure that out. Like, by the way, I can't believe I'm saying this. Like, this is not me. I'm not like that guy. I'm a clinical guy, but I had to do this.

Because no one else is going to do it. And for some patients with dementia, taking a satin might be a bad thing.

Yeah. Certain genetics and you need to track everything. And you got to figure out which drug is the right drug for the right person. And you know, we're we're working on this through ind.org, which is our nonprofit on.

That's the institute for neuren neuron degenerative diseases, right? Yeah. But ind.org and people can learn about all this stuff and we have so much education, you know, all for free online. And we're trying to develop these these tests and we're trying to like, you know, figure this stuff out. And um, you know, when it comes to brain markers, I think again the markers that are out now are good and I'm glad they're here. Um, but there is so much nuance and so much confusion. And you know, my worry is is that someone may get a test and then it's it's positive, but it's not really positive because of a variety of reasons. So like the takehome here is what we're doing is we're doing like for example ratios where we divide this by divide this. We take this marker, that marker, and that marker and we put it in a formula and and that is the type of stuff that's not, you know, I wouldn't say it's available yet. It's coming soon. Um but to me when a person does not have symptoms of cognitive decline and wants to understand their risk um I believe that the current tests available are good but we need more we need more higher fidelity. I believe that we're if our work keeps moving at the rate it's going within a year or less, maybe a year and a half, um we're just going to be able to ramp up that fidelity to make these blood tests more um accurate, more accessible, more meaningful, and it can help guide us to say when that person changes their exercise routine or changes their diet or starts on a GLP-1 drug because their doctor said they were overweight and they had a little diabetes and they want well then we're going to track these markers and we can then show is there a ground truth is there you know in in using that person as their end of one control can treating risk factors for cognitive decline actually impact in a positive way brain biomarkers of disease and we're getting really close so between ind.org um allslabs.org or is one of the arms that we're investing a lot of money to try to figure this out and and and develop these blood tests and and then honestly once you have access to the testing and you have access.

Will you be able to include your lab tests in that if you pull if you put that in as data? Yeah, I mean in time I I we're you know for people without symptoms for the panel that we want to deploy. Um I feel that we're not there just yet but that's that's the future. But you could even you could have them check their blood pressure. You could have them do a body composition. Have them check their cholesterol or their insulin or the heavy metals or the vitamin D or whatever. You can add all that data in to retain your brain. Now, can you do that?

Well, so yes. So, for example, the one of the key things about retain your brain is there's, you know, there's tens of millions of people out there that have a gene called APOE 4. So having one, you know, 25% of the population, 25% of the people listening today has one or more copies of a gene called APOE uh for the four variant. You get one from mom, one from dad, a two, three or four. You and I have both been tested for this. We know lots of people that have been tested. About 1% of the population has two copies of E4. And honestly, one of the key drivers of why we created this um free, you know, automated software is because when someone has an APOE4 variant, they're scared, right? and they can type in what their genes what they got tested through 23 you find that it's like oh shoot I don't want to know I don't want to test it and doctors say well don't test it because there's nothing you can do about it so don't don't make sure you don't test it and that's wrong.

That's entirely wrong because you know if you have an APOE4 variant I'm going to tell you to do all these different things and if you don't have an APOE4 I'm going to tell you to do different things and if you have two copies of the APOE4 variant which is again 1% of the population doesn't mean you're going to get Alzheimer's but you may be at higher risk so I'm going to tell you to do these things that our research for the last you know 15 years has have studied to show may be effective. And then this software, you type in that you have the ApoE4 variant and it's going to tell you, you know, what you can do to reduce your risk.

So, it's it's more personaliz. It's more personalized. Yeah. To help manage risk factors for Alzheimer's disease. Long story short, there's a bunch of blood tests that are available now that you're already measuring that are easily accessible through through your doctor or by the way might not order, but the function health for $49 and things like your blood sugar, insulin, you know, cholesterol, particle size, LPA, AOB, yep. All the nutrients, omega-3s, all that. We we we could get that now. But there's another layer that you're doing that you're developing in your lab that are new biomarkers that are specific for uh neurogen diseases that we can measure and then are lowered or changed or improved by doing various interventions that are specific to that person.

Yep. So, it's not like there's one thing you do to fix all all that. It's a whole bunch of things you do.

Exactly. and and we while we are just starting to scratch the surface and we're in the first inning of a nine inning baseball game, the fidelity and the accuracy, I'm telling you in 2026 and 2027, these are going to be amazing years because my belief, my hypothesis right now is that you, Mark, are going to need these five tests to track over time. Me, I'm different. I'm going to need these four tests. And a woman, especially during the permenopause transition, two out of three brains affected by Alzheimer's, these are women's brains. and we got to do something about that. A woman may need six different blood tests that we follow and we track and then they make a change or they take hormone replacement therapy or they do something and then those six markers improve and then we know we're on the right track. So I think we are within maybe 18 months away or less from having this this road map clear.

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And we could go a lot more into the blood markers because I think I think there's ones that we're even not looking like tick infections like mold exposure and I I've only talked about kind of some of the traditional ones, but like the these inflammatory markers that we're looking at and the immune you mentioned Dr. Tany earlier. I mean, a third of our markers are focused on the immune system and inflammation. Like, and we're I'm a neurologist, right? We're supposed to be talking about brain proteins. No, we look at inflammatory markers. We look at cascades. We look at interlucans. We look at CCLs. We look at TNF alpha. We look at so many things. And then if someone.

Inter those are all blood tests for inflammation. Exactly. Yeah. In our in our multimodal panel, you know, we have this guy who he has psoriasis and it's mild psoriasis. Okay. It's mild psoriasis. He can deal with it. He doesn't want to take a drug or change his diet or do whatever because it doesn't bother him. It's fine. Yeah. Well, this guy also has an APOE4 variant. Okay. And this guy's 49 years old.

You're like, oh, there's inflammation on this person. So, wait a minute. I look at the panel and I say, but but call him Bob. Bob. Um, hey bud. You got an AOE4. You got a interlucan 17A, which is a inflammatory marker that's elevated in people with psoriasis. And bud, your uh amaloids uh higher than it should be for a 49year-old. No towel. Okay, check mark. Okay, nothing nothing too worrisome, but the train's going to go off the tracks if you don't do something. And then you change your diet. This guy also had high cholesterol. He wasn't treating. Started Zia, a zettoi because he was an overabsorber of cholesterol, not not a statin. He was afraid of statins. Okay, he didn't need a statin anyway. Uh and omega-3 fatty acids. His omega-3 fatty acids were in the toilet. And he's like, "Oh, I don't really like fish." like then take the caps and sardines sardines are alboc tuna is high in mercury but like you know wild salmon at least once a week but wild salmon has all sorts of stuff in it too um so you take certain supplements that are high quality and everything improved the interlucans came down the in his inflammation came down his psoriasis gets better the amaloid comes like everything about his everything improves through some mild changes that were personalized for him right and and that's that's the.

We could talk about blood biomark with you is heresy. I was literally talking to one of the key funders of Alzheimer's research in the world and he looked at me straight in the eye. He said there's no way and proof that you can lower these biomarkers of Alzheimer's. It's not been done. It's never been done. You can't engrow brain. You can't lower these biomarkers. We're going to try to find a drug that's going to fix it. And I'm just thinking to myself, no, actually, I've seen these things change. You've seen these things change. And that's what's so exciting because you can now start to intervene with multiple different approaches and actually start to change those biomarkers that are risk factors for or indicators of damage that's happening at a subclinical preymptomatic level, but it's still happening. It's like it's like like the Bogaloosa Heart study where they looked at fatty streaks in the arteries of teenagers who were eating crappy diets in Louisiana. They were were a prelude to heart disease that they were going to get in their 30s and 40s, but we could see it in their teens.

In May of 2024, there was a CNN documentary that came out and Dr. Sanjay Gupta came down, you know, Sanjay and you know, he actually joined joined my research study and it's been really great to get to know him better through that, even though I've known him for a long time. Um, and this guy named Simon was profiled in this documentary. And documentaries are interesting because, you know, they they send a film crew and you get they get to know people and they see people for years and they get to know them. And and if that guy that doesn't believe that the stuff that I'm doing and our team is doing is possible, he thinks it's it's it's heresy. He thinks it's not real. Well, Simon was followed for years. And we have his brain on the same MRI, the same magnet, the same software. We have it in 2022. We have an image in 2024. And we have an image in 2025. And Simon is an APE4. He's got two little kids. Okay? He's in his early 50s now mid-50s. Got.

That's a4 is the high-risisk. He's got so and he's been totally public and he's obviously been in the documentary. If someone out there is listening to this and doesn't think this is possible, like I I should call Simon right now.

We'll we're going to link to the documentary in the show notes. We're going to link to all your studies, all your research, all your websites. It's all there. It's all there. Like this is there's now you've seen the scientific slides cuz I sent them to you. But the brain volumes grew and then a year later his brain grew again. His amaloid and tow at the first at the the documentary stage his amaloid improved and his his amaloid actually was normalized. His tow was still a little bit there. It's gone. Everything amaloid and tow are gone. His symptoms are improved. Even though he still is doing great and he had some subjective symptoms, his brain grew twice. This is all real.

So just just for everybody listening, this doesn't happen, right? Brains don't grow. They just atrophy as you age. That's orthodoxy. And what you're challenging is a paradigm is so stuck. But you're seeing objective evidence. And you're not the only one. I mean, there's others like Dale Bredesen and others who's been on the podcast who shown that you can increase the size of the hippocampus, the memory center of the brain. you can increase the the brain itself and and reduce the atrophy and and that leads to changes in cognitive function and improvement in outcomes. We have a saying uh that we say it a lot, promise not to overpromise and we're we're cautious um and we want to like underell just to be extra safe because we need to like really prove that this works. But my gosh, I mean when you see it once you're like wow. When you see it twice, you're like wow. And now I've seen it so many times I'm still like, "Wow."

Right? Because I'm I'm in awe. It's a mirror because compared to what we were trained in in medical school, it just doesn't happen. But I'm still I try to be conservative about it because if I get too excited about it, people won't believe it. But the story after story after.

Take us through some of the kinds of ways and the things that you're finding and the treatments that you're doing that are part of the cocktail of things that are available. Sure. So, so let me finish on the ABCD and E first real real quick. The C is cognitive testing and and again like um uh cog a lot of people don't want to do cognitive testing. A lot of people in our research don't want to do it. If someone you know wants to you know you know we try to make uh cognitive uh activities we call them cognitive activities at retainyoubrain.com. You you join you get to know yourself you can you know track or you know assess or whatever word you want to use with these cognitive we call them you know uh activities because they seem less um you know worrisome but we do track cognitive function um in in our ABCD and E model. Uh D is DNA. We do look at um some genetics, especially the APOE4 variant, which is super super super important to personalized care. Not to deduct or deduce, sorry, if you're going to get Alzheimer's, but it does help personalized care. And the E in the ABCD and E is um emotional and social uh support and health and and and you know stress um management um staying socially engaged um having a meaningful life mindfulness based stress reduction is something that we you know advocate for um you know learning new things um the E is something we really really really take um seriously and um we have to focus on the biological the cognitive and the psychosocial in order to get people off the road to neurodeenerative disease.

And you're talking about these social connections and relationships and having meaning and purpose and connection and belonging and and and it even speaks to, you know, how things like hearing loss or visual loss will actually cause people to withdraw from these social connections which actually accelerates dementia. Yeah. 45% of cases of dementia may be preventable if that person does everything right. And 45% to me is a very conservative number. I think that number is going to be, you know, from a, you know, evidence-based way in the next big study to come out, it's going to be 50% or 60% or whatever magic number it's going to be. But the the majority of cases, in my opinion, of dementia may be preventable if that person does everything right and we get ahead of things before symptoms. And in that 45% the Lancet 2024 paper, 8% of cases of dementia are attributable to the modifiable risk factor of hearing loss.

8%. And now whether you have get hearing aids if you can't hear this and you're age 50 and above or whatever word whatever age you want to use get a hearing screen. You don't have to I mean you should you know go to an aiologist and see a doctor obviously if you can but but you could do this on your headphones now. You could do it on a computer. You can get a hearing screen and people that have hearing challenges. You know my mom I fought with my mom about this like for for for years. Like wear a hearing aid. You'll be more engaged. It it it may help prevent dementia. um you know that's a that's that's not a pill um that's not a dietary change it it's just have a hearing vision loss um there's so many things that we can do to to screen and intervene. So, so again going back to like what what are the things that you're actually specifically using and how do you kind of customize the treatments and what are the what is a what are the cocktail of therapies and what are the what's the what besides the things we've already talked about you know that are sort of easy to measure what are the kind of things that we should be testing for and looking for and what are the kind of interventions that seem to be promising.

So um you know in our in our 2019 paper where we showed um really back then like for the first time that through multimodal meaning multiple therapies at once that we personalize or the title of the paper was individualized clinical management of people at risk for Alzheimer's uh disease something like that when you individualize treatments on average back in our 2019 paper people got 21 different interventions. So, if there's someone out there listening that wants a magic pill or wants to do one thing or two things, um, I'm sorry to say, but it's it's not like one or two things can do this because Alzheimer's and neurogenerative diseases, they're they're complicated, right? Any chronic disease of aging, right? Diabetes, can you take a magic pill to prevent or cure diabetes? No. Can you eat a magic blueberry? I love blueberries. I think blueberries are great, right? Well, you can't eat a magic blueberry and prevent or cure diabetes or Alzheimer's or whatever. The people that did the best were people that followed greater than 60% of the recommendations. So if we gave 21 on average, if you followed greater than 60%, people did better. People with mild cognitive impairment, the earliest symptomatic phase of Alzheimer's uh actually had improvements in cognition like again heresy that hadn't been shown like that.

So this is symptomatic early dementia. Symptomatic. Well, so both we had two groups. We had the the early treatment group and the prevention group. And I think the the the takehome for people listening is that there are so many things you can do. I'm going to go through those in a second. On average, we gave 21 different things. Ooh, that sounds like a lot. The people that had early cognitive symptoms needed to follow greater than 60% in order to have an impact on their cognitive function.

Benjamin Franklin, right, announcer preventions were the pound of cure. 100 100% agree with that. But the people before they had symptoms, whether they followed greater than 60% or less than 60% of the recommendations, they still had cognitive optimization. and their cognition improved at 18 months in our 2019 study. So the earlier you are, the less you have to do to move the needle. The later you are, the more you have to do to move the needle. So, so that was our 2019 paper and I think that was, you know, really critical. What are those 21 things on average? Well, those are average. Um, in our whole universe of things, we've probably recommended right around 50 different things across all of the, you know, thousand plus people that we've seen. Um but the the two kind of categories that I put it on are in are I would say non-farmacologic and then pharmacologic and in the non-farmacological bucket um you know for example there's non drugs.

Yeah non-drugs so non-drug and and you know in the pharmacological bucket I mean I guess you could I don't know where to put the vitamins and supplements because those are like really important and critical but like wherever you want to put those um exercise on a regular basis is by far the number one thing a person can do to reduce their risk of cogn negative decline. Um, you know, if you put mice on a treadmill, um, their amaloid can go down and and most people don't realize like the people say, "Oh, there's these new anti-amaloid drugs. I want an anti-amaloid drug. That'll fix me, right?" Well, they're expensive. They have side effects. There's a whole thing. And I I do believe in them in the right person at the right dose for the right duration of time. But if someone out there today wants to reduce the amaloid in their blood and in their brain tomorrow, they should start on an exercise program that's approved by their physician. and and and targets the thing that need they need to target.

And there's major papers published within JAMMA, like just walking prevents Alzheimer. Yeah. I mean, anything is better than nothing. And and you know, someone who's sedentary, I'd rather they walk. I think walking is physical activity and physical activity is better than nothing. But to me, physical exercise, especially when we get past a certain age, we need to be mindful and we need to be intentional about how we do this. So if a person is going to say, "Well, I'm going to go walk three times a week and I'm going to prevent Alzheimer's." Well, not if you have excess belly fat and not if you're under muscled. So, someone that wants to use exercise as a primary lever to pull needs to figure out, well, what are they trying to do? So, for for example, if someone needs to lose belly fat, you know, um, walking slowly is probably not going to be enough. You need to get into a higher, you know, what we call zone 2 or steady state cardio where the the heart rate goes to 60 to 65% of of, you know, the person's maximum. The best way to kind of approximate that is if someone wants to get into fat burning mode is where they can still have a conversation with someone, but the person that they're talking to can hear that they're a little bit short of breath. They they can hear that they're exercising, but they can still carry on a conversation. To me, that's in the zone two. And you need to get I would say at least 40, 45, 60 minutes of of that. and walking alone may not be able to do it, but fast walking sometimes with a weighted vest or up and down hills like that, that could be a way to get um in Austin there are a lot of hills, so in Austin it may be very easy to get into zone 2 to get into the fat burning mode. Um but that's a way to do it. And for people that um are are fit and their doctors say okay um doing fasted um walking fast walking with a weighted vest early in the mornings before they've uh you know had any uh maybe maybe black coffee. But if you don't have any carbohydrates in the system you may be able to burn fat even more efficiently. But again some people um you know shouldn't start like that.

But the belly fat you know you're not going to fix it by doing crunches or or ab exercises. It's basically sugar and starch that are driving it. And if you cut out sugar and starch, which is driving metabolic disease, which is a big part of Alzheimer's, you're going to fix it quickly in incredibly. And and I think, you know, if you're trying to just lose body fat, but not realizing that if a person has a lot of muscle, they're more metabolically active and they can break down sugar, break down whatever, you need to build muscle mass. People should be doing strength training at least twice a week, you know, depending on their individual situation. If someone is trying to lose body fat, they should be doing zone 2, you know, fast walking with a weighted vest, you know, three times a week for 45 to 60 minutes. So, exercise is not just like, you know, going for a walk is better than sitting on the couch, but being intentional about your physical activity and physical exercise routine is what it takes to really have an impact on brain health.

So, exercise is one of the interventions. Diet, let's talk about nutrition because there's a there's the mind diet, which is Mediterranean. And you know like the way I think about it is is is you know if food is medicine what's the drug? What's the dose? What's the duration? Right? And I think yes the mind diet which is a sort of a modified Mediterranean diet lots of omega-3 fats and anti-inflammatory foods. Great. But it there's there's different levels that you can push on the gas pedal to get more effect. I had a patient once who had MCI mugg impairment. She had a whole bunch of problems. the 21 things and we fixed all her thyroid was off. She has heavy metals. She was pre-diabetic. She had u methylation issues and high homocyine. She had low omega-3 fats. I mean just the list went on and on and we fixed everything and her cogn function dramatically improved. And then after like 3 or four years, she started noticing a little bit of a dwindling. And I said, "Geez, why don't we try a ketogenic diet?" Because I've been reading about ketogenic diets and changing the metabolism of the brain by cutting out all sugar and starch and carbohydrates pretty much and eating 75% fat and we did it and like the lights came back on and I was like, "Holy cow." So again, how do you approach diet uh with with all this?

Yeah. Well, so you know, nutrition and and dietary patterns versus single or multiple nutrients. Like this is a this is a long topic and you and I both have written books about this and we could talk about this probably for an hour, but um to me um different diets, you know, we're not in the realm yet where precision nutrition is like um easy offtheshelf straightforward, but different people um I believe need to follow different dietary patterns. And I too back in I think 2007 was the first time that I put someone on a ketogenic diet um and and saw something that I just did not think was possible. Um but then I've had other people where I put on ketogenic diets and like things kind of went the wrong way. And and to me um you know it we're not we're going to get there very soon where one day we'll have you know whether it's a blood test or a genetic test or something um where we could put into a computer and the computer will spit out exactly what the person could eat. until until we get to that time, I think you think about the big bucket. So, the Mediterranean style diet, fatty fish, brain healthy fats, omega-3 fatty acids, especially people with one or more copies of the APOE4 gene, um like we have to have enough omega-3 brain healthy fats, otherwise people will have cognitive decline and the synaps.

Because a lot of your brain is made up of DHA, which is 60% as far as I remember, which is. And and DHA and EPA are the two most brain healthy fats. DHA is especially important for people with one or more copies of the APOE4 variant. So brainhealthy fats, um that's PUFA, polyunsaturated fat. Then you have monounsaturated fats, monounsaturated fats. Like if you want to drink olive oil like an ounce or two a day and your doctor says, "Okay, that's like anti-tow protein." Like that is good for.

But it's got to be good olive oil. It's got to be bitter and burn the back of your tongue otherwise it doesn't have the polyphenols. Exactly. And 60% one study I read of the alcohol of the uh of the olive oil out there is corrupt. Exactly. So you know getting quality olive oil um like literally taking a shot of it one or two shots a day or pouring it on everything. Um you know I have olive oil stashed in different parts of the house and just pour it on pour it on whatever I can get it in cuz I I need and if it burns the mouth. Yep. That's exactly the the proxy has a taste to it. So um avocados, olive oil, fatty fish, brain healthy fats are like so critical. um green leafy vegetables. So, you know, berries, you know, half a cup of strawberries or blueberries two to three times a week. Nurses health study published over a decade ago showed you could delay cognitive decline just by eating berries on a regular basis by two years just from one intervention.

That's why I gave you a berry shake this morning. You did. It was good with with goat milk, which was a first for me. So, I I appreciate it, which is uh really nutritious and and actually tasted really good. Um so, you know, green leafy vegetables, high antioxidants. Um, people should be eating mostly plant-based. Um, you know.

I would call plant rich. Yeah, plant rich. Yeah, plant rich. Plant rich. And, you know, there's totally different. Cuz plant-based is vegan. That might be problematic for people who want to build muscle. Mostly plant rich. Okay. Yeah, that's a better and I wouldn't maybe maybe Yeah, I don't know the exact terminology, but you know, and then like meat is all not created equal. Like like red meat, grass-fed beef is totally different than other beef that isn't, you know, whatever. So, I think people need to eat, you know, where they feel comfortable with, whether ethically or or otherwise. They need to get protein levels, whether it's through whey protein, through goat or or whey protein through regular milk from cows. I think each person needs their own individual kind of um thing, and some people may be more sensitive to one thing versus the other. And there's lots of different.

And I saw you putting like cocoa polyphenols in your coffee this morning. I travel I travel with dark cocoa powder, which is completely ridiculous, but I never leave home without my dark cocoa powder. Um and yeah, I have I have coffee in the morning with dark cocoa powder because to me actually caffeinated coffee I think is brain healthy and has been shown to have better brain outcomes. Dark cocoa powder um again has to be like pure and not have the heavy metals in it and things like that. But um dark cocoa powder can help with insulin regulation, blood pressure control and has shown to be beneficial for for brain health too.

So Richard starts his morning with a mocha. I do a mocha for your a mocha for your memory in the morning. And it's funny because Mocha is actually one of the names for a test we use, the Montal Cognitive Assessment Test, which is actually something you can actually do at home. It's something you download on the internet and it's a pretty good way of tracking your your brain health.

Exactly. Yeah. We don't want people to do it too much at home because then they practice and the doctors see the doctor and they memorize a test. But I I don't disagree. Yeah. For Yeah, for sure. There are definitely ways to to track check track. So fatty fatty foods like omega-3 fats, monocy fats, berries, leafy greens, you know, nut nuts and seeds, antioxidants, nuts and balancing the omega-6 with omega-3s. Um there there's so much um nuance with nutrition, but I think that's it. Um also the elf diet.

What's that? Oh my. Eating moss in the art. I I just Dr. Mark Heyman on a dietary pattern that he's never heard of. Wow. This is this is a great day. I'm never going to forget this day. The elf diet. Eat less food. Oh, eat less food. Yeah. Yeah. Like Michael Paul eat food not too much, mostly plants, right? Yeah. So just less like people just eat so much in excess. Like it's it's crazy. And you know there was a study out of Mayo that showed that people that ate like I think the cut off was like 2100 calories a day less than 2100 or more um have you know delayed cognitive decline. And and again this is like imprecise. So the okanawa principle right harachibu which is eaten full percent. Exactly. Harihachibu. That's exactly it. So, the takehome here is though, if you're trying to gain muscle, well, you better eat sufficient protein and and and calories because you need both carbs and protein to build muscle and you don't want to like just, you know, starve yourself. And there's good carbs and bad carbs and know the difference. Um, that's really key.

Berries and leafy greens are carbs, right? Exactly. Yeah. And, you know, some whole grains in moderation, I think, are okay, but but not if a person's not active, you know. So, so anyway, uh, yeah, nutrition's, you know, tricky. um you know vitamins we we talked about um you know omega-3 fatty acids but vitamin D especially people with one or more copies of the APOE4 variant um we check vitamin D and just like you mentioned earlier we don't just tell everyone to take vitamin D but I think the statistic in Miami as a as an example 60% of the people in Miami even with sun exposure are deficient in vitamin D so we check vitamin D and.

Well, you have to be naked between 10 and 2 in the in the morning 2 in the afternoon for 20 minutes and if you're not you're not going to get enough vitamin D if If you're if you're a lifeguard, you will, but otherwise, forget it. Exactly. People wear sunscreen now. People are indoors. And yeah, you know, I usually tell people you need 15 minutes of of 12 to 15 minutes between the hours of 11 and 1 to try to split the difference. I don't want to, you know, it's it's it's hard to know for sure, but um you know, we we check vitamin D and and and supplement if needed. Um we also talk a lot about B complex vitamins and B complex vitamins again are not something that's one sizefits everyone. Um the Vitito study which was published over a decade ago showed that when people had a marker in their blood called homocyine homoyine is high the people that took B complex vitamins B12 folic acid and a tiny little bit of B6 those people not only um did they um have slightly improved memory function on cognitive testing but those people actually also had slower shrinkage of the memory of of the of the of the total brain size. So I think there was a paper published a number of years ago jammer New England journal I read where if your homoysteine was over 14 you're 50% more likely to get Alzheimer's or dementia and that's again something we test at function health and also methylonic acid which is a marker of B12 function and I I remember a patient who came to me who was you know very successful business woman was on multiple boards she was in her early 80s and she's like I got diagnosed with MCI mild cogn impairment early dementia and she was pretty upset and I'm like well I don't know let's see what we find and she had extremely high homocyine and high methylonic acid which is a marker of B12 which are better probably better than measuring folate and B12 in the blood.

Probably had a double MTHFR. She did she had the genetics that made her having trouble with her metabolic pathway yeah and she was older and probably not absorbing B12 which is common as you get older you get less stomach acid and so on and so forth there are people taking acid blockers they don't get I mean that's what that made me crazy I mean there's the third most leading um prescribed drugs after statins and psychiatric drugs is the acid blocking drugs which are now over the counter and they they're they're dangerous to take long term fine short term but long term and so I I I said I found this and I gave her uh B12 shots and I gave her high dose of methylolate and some B6 some of these methylating nutrients and completely cured her MCI. Now it's not that everybody with MCI or predment has that problem. It's just that she had that problem. And then a number of years later, probably five years later, I got a call from her and I thought, "Oh, she's probably going downhill and I'm a little worried about her and I saw her on my schedule." And I'm like, "What's going on?" She says, "Well, I'm going for a trek in Bhutan. She's 85 and I want to know what I should be doing to prepare and take and blah blah blah." I'm like, "Okay, great.

Amazing. Yeah. What else supplements? What other supplements? Vitamin D, fish oil, the B vitamins.

Yeah. I mean, turmeric um I think um you know, kurcumin, the active ingredient curry. Um I think in certain people especially with um elevated um amaloid levels um in the blood you know we usually we we sometimes use this and I think in terms of like the, big picture those are like the one size fits many ones but I mean the list just I mean the list is really long so I mean there's there's definitely other things people can do. Um but but the takehome here is um you know um we check it in the blood, we do the history and then we personalize the plant for them. So I think nutrition is is really nutrition and exercise are like critical critical levers. Um and you know in our research study that we uh presented data um that I can talk about because we presented this at the uh 2025 Alzheimer's Association International Conference in July 2025 and we showed that when you looked at and I'll talk about different interventions in a moment but if you look at multimodal lifestyle intervention that included exercise, nutrition, vitamins, supplements, you know, uh sleep, sleep modification, stress management, uh keeping the brain engaged, learning something new. Yep. Seeing a doctor on a regular basis to make sure their blood pressure, cholesterol, uh you know, blood sugar is all modified and in in in an optimal range for specifically for them. when you when you put all those together but no um drugs if you look at the the groupings of of the the categories of the people we followed. So intensive lifestyle intervention.

Intensive lifestyle intervention of all the interventions that we tried moved the needle the most. More than any of these billion dollar amaloid drug studies. in in our in our study that we've and this hasn't been fully published but I can talk about it because we present an abstract form there are people that for example took GLP-1 drugs and GLP-1 drugs are tricky because you know I believe that too high a dose if you're not eating right and doing the right thing you can you know lose muscle and have all the things lower dose you know I'm more of like the micro dose crew when it comes to GLP1 ones, GLP-1s, positive effect on biomarkers, you know, in my opinion based on the our results, you know, impressive results when used in the right person at the right dose for the right duration of time. Well, they improve metabolic health, which and there's many roads to Rome to do that, right? If you radically improve your diet, I mean, I mean, before GP1s were on the market, I was reversing diabetes, getting people to lose 200 lb, 100 lb, 150 lbs. You you can do it. It just it just and I think my guess is that they would do a head-to-head comparison of GLOP ones and the same diet that you would eat if you were on GLP1 ones, there would be no difference in any of the biology. That's my feeling.

So, while multimodal treatments, you know, I would say worked the best, the other categories that worked exceptionally well, that meaning exceptionally well to me means statistically significant improvements in a variety of pathologic proteins that are associated with neurodeenerative disease. So.

So you're testing, not guessing. We test everything. Let me try these 20 things and let's cross our fingers and maybe do a like a a sort of semi semi-ubjective objective test which is a bunch of questions. You're actually looking at blood test show changes. Try one thing, we repeat it. We don't try 10 things. Well, for multimodal interventions, we try a group and then if we're going to try a drug, we're going to recheck the 150 biomarker proteins. We check the proteins on different machines in duplicates. Every blood test we do, we run twice. This is not normal. This is not cost-effective. we do it anyway because we care about quality, not about anything else. Um, but and and and we just try to do things as as as rigorous as as humanly possible. Um, and what we show is that when we do these tests, we call these NF1 studies, we'll try a GLP1 and we'll check, we'll try hormone replacement therapy, like hormone replacement therapy, bioididentical hormones for women during the parameopause trans transition in the right woman at the right dose. the the women in our in our little hormone replacement therapy group, uh, believe it or not, the age ranges from 42 to 67. We have multiple women that have actually started.

On hormone replacement therapy with approval and agreement by the gyn and the primary care doctor and our and our team. Um, we've had, uh, I'll just say what I feel like I should say, amazing success with using hormone replacement therapy. And, and when that rapid drop of estrogen comes in a genetically susceptible woman, you know, we did this whole women's uh, brain imaging study at at Cornell and spent, you know, millions and millions of dollars on this.

Women that had, you know, hormone replacement therapy on board had better brain volumes and less amyloid. But it had never really been proven in a in a study that you could use H hormone replacement therapy. Um and then there was this that women's health study that used like synthetic hormones and horse urine derived whatever like when you use a bioidentical patch and you use progesterone and we talked to the gyn and we talked to the doctors hormone replacement therapy during the perimenopausal transition has helped improve brain biomarkers associated with Alzheimer's and neurodegenerative disease risk. It's been striking.

So, so this is more than just what has been done before, which is population-based studies, which can't really directly look at cause and effect. You're actually looking at blood biomarkers that change that improve the the blood biomarkers that are associated with neurodegenerative disease. That's a big deal. And the other thing I want to just say is that the consensus most of that I've heard is that it's it's important to start right away after your menopausal transition. But what I hear you saying is that you can actually start it later.

>> Well, and early. I I want to start both time. Yes. Start early. Does that mean every woman should be on hormone replacement therapy? Like what what are the implications here?

>> Yeah, this is these are these are really it, you know. And by the way, why hasn't this been better studied? Why are we the only group to my knowledge like

>> We have misogynistic research infrastructure.

>> Like it's it's just so it's demoralizing. It's just so wrong that women are taught that like, oh, you're having night sweats. Oh, oh, you don't feel good. Oh, you're having brain fog. Oh, okay. Sorry. You know, we'll see you back in six months. Perimenopause is a neurological disease. Like, you're just going to have a woman suffer. These are these are symptoms that are treated. Oh, go change the temperature in your room and maybe you'll sweat less or maybe change your sheets, get better sheets, like like no, this is a medical condition.

Like really? Or get like, you know, the cooling thing like, okay, or a weighted like, fine, okay, treat the problem. And what we've shown is that, you know, through ridiculous amounts of time, effort, money spent, and research, which needs to be quadrupled or or probably increased even much more than that, we've shown that when we use hormone replacement therapy in the right woman at the right dose, at the right duration, in collaboration with the multidisciplinary team, when we start seeing the estrogen drop, even if the symptoms are very mild, you get the estrogen back up, the tau starts coming down. Now, even though the tau wasn't elevated to a degree where we're like, uh-oh, sky is falling, but the tau is higher than it should be in that woman who's 47 years old. And this whole concept of like, you know, uh, it's normal. Well, no. Optimal is where we want a brain protein. Normal, uh, a little borderline, a little high, like, no. In order to have the most benefit, we need to make these incremental changes. And hormone replacement therapy during the perimenopausal transition to me is one of the most impactful tools that we can use to reduce the risk of cognitive decline, dementia, Alzheimer's disease in women. And and I think, you know, it's tricky. I think there's risks and benefits with every one of these decisions, but um, you know, I've just seen too many women suffer and it's just not fair. So, they're symptomatic or if you if you do evaluations and you have a higher risk based on your Alzheimer's risk score, which you developed, then maybe it's a good idea. But even even if you're not symptomatic.

>> Well, I think if you're symptomatic, it's it's like how like how could you not? I think it's like, you know, it's unethical not to try to figure out how to. In our cohort, we track estrogen, estradiol levels, and other hormone levels. Um, you know, I mean, women 21 and above. We also, this is crazy, but like, you know, this hasn't been done before to my knowledge. We do multiple blood draws through the menstrual cycle to try to figure out like as estrogen and progesterone change during the cycle. Guess what? Tau 217 changes and these other markers change too. How has this never been done before? So we have women, we have like, thank you. Thank you. I'm not going to say their their code numbers in in our research study. They get six blood draws on day one, on day three, on day seven. Like we get six blood draws during the menstrual cycle. We're just trying to figure out like what should the PTA be at? What depending on what day the blood was drawn, we need to correct for what the tau level should be based on where the estrogen and progesterone is. Like these are things that just haven't been figured out yet. And these are the types of questions we're asking and these are the types of things that need to be figured out. And when you take this approach, precision, personalized, individualized approach, um, we've seen women in their early 40s, like 42 is the earliest we've started, where we've seen the estrogen going down and we've seen the amyloid going up. Well, maybe they're a little symptomatic, but it's not really bothering them, but we're going to start on low-dose hormone replacement therapy if everyone is in agreement. And guess what? She feels better. Her cholesterol comes down. That's interesting. Her amyloid is improving even though it wasn't abnormal. And this is really the key. Like we have to personalize these therapies and we have to, you know, we also just monitor for a change. We've been monitoring these women for so long. We see the change and then you intervene. And so, so to me, it's if symptomatic, like please talk to your doctor and and if your doctor says tough it out, like go to another doctor. If you're presymptomatic, um, follow it closely. I think women pre-menopause should should probably get checked every six to 12 months for these brain biomarkers and hormones.

>> So essentially what you're saying is if you're symptomatic, don't suffer. And if you're not symptomatic and you have a lot of risk factors and some of these blood biomarkers that were that are emerging are abnormal, then it's better to get on early even if you're not symptomatic. I believe that specifically in people that are at the high, women that are in the highest risk category, which are APOE4 positive, especially women with two copies of the APOE4 variant. Some of the most striking improvements actually, one one woman is actually lives in Austin, one woman is in California. I mean, I know these cases like, you know, the back of my my my my mind, like you just start and you see everything improve. This this is honestly, Richard, why we co-founded Function and and I don't mean to kind of oversell it here, but these tests are not things that your doctor likes to order or often will order. And for a very low cost, we've dramatically reduced the cost. You can get all these biomarkers including APOE4 and some of these brain biomarkers and then you can kind of start to decide what to do and and take control of your own health.

>> I want to ask you about guys because two-thirds are women, but then one-third is guys. Do guys benefit from hormone replacement therapy in terms of testosterone?

>> Great question. And I I think um the literature has been um I would say the literature has been um not conclusive is is how I would answer this question. It doesn't mean it helps or hurts. It's just the lit the the evidence has not been sufficient for I would say the vast majority of the times that I've looked into the data. Um I would say more recently um, you know, I would say it's more likely than not, but not a certainty that using um hormone replacement in men um specifically testosterone in the right man at the right dose for the right duration. Whole different discussion and and like which types and how many times a week and what version and is it the cream or is it inject? Like there's a lot of confusion here, a lot of confusion.

>> And then what else is going on? Like what other hormones? Because sometimes when people use testosterone, they're also doing like five other things.

>> Um, what I would say is if hormone replacement is used judiciously in men and the person is putting in the work, exercising and trying to build muscle mass in addition to taking, you know, lower end. I mean, some of these testosterone levels I see are just like really, really high and like a lot of these.

>> A lot of the doctors I've spoken to who specialize in this like are not bothered by this in any way, shape or form. And I'm just like, just.

>> No, you want a physiological level because then your estrogen levels will go up because you convert testosterone to estrogen. Then you start having sex, you know, libido issues and other issues that are it's like it's a it has to be done right.

>> Exactly. So, so, so with all of these caveats, I would say at this moment today, I don't have a definitive answer, but I would say it is more likely than not that when testosterone replacement therapy is used cautiously and judiciously, there is a beneficial brain effect. I'm talking very carefully and generically because is it truly Alzheimer's protective, vascular protective, cognitive health protective for a reason other than like maybe age-related cognitive decline? I don't fully understand the pathological um protectivity of testosterone, but there's something that is protective cognitively. I'm just not sure if it's strictly Alzheimer's pathology.

>> Well, it's kind of the motivation hormone, right? And when people drop off in motivation, they withdraw from life. They stop doing the things they want. They might not want to exercise as much. It's kind of like a a dirty cascade. Okay. So, we've got we've got nutrition, we've got exercise, we've got certain supplements can be helpful. We've got hormone therapy. You know, you didn't really say a lot about sleep, but I think that's another pillar and correcting sleep disturbances and also sleep apnea, but also even being careful of sleep drugs, the benzo or Valium or that category, Xanax, Adavan, those those drugs are commonly used and they do have impairment functions in the brain.

>> So, you have to be careful with sleep.

>> Yeah. Sleep. I mean, we could spend probably a whole podcast just on sleep.

>> Give me a couple minutes on sleep.

>> Yeah. So, so, you know, everyone out there um has to make a plan for sleep. You know, you could be burning the candle at both ends, pushing, pushing, pushing, sleeping five, six hours a night. If you're exercising, doing everything right from an exercise and nutrition perspective, but not getting adequate sleep, you will not have adequate brain health. It's not going to happen. So, everyone out there needs to prioritize and make a plan for sleep. I have people where the only thing they changed after I've read them the riot act was their sleep patterns. The only thing they've changed and the impact on their brain biomarkers.

>> Objective blood test.

>> Every I mean, objective cardiovascular test. I wear all these trackers. We track everything in all of our patients. I mean, the only this is this is like crazy, but the only thing that changed in in an otherwise optimized person if you get sleep right, the amyloid can come down, the cognition can improve. Sleep is so critical. Um, you know, it's not just about, you know, getting what's the magic? You know, in our study, we did a study on this. We tried to figure out like what's the optimal sleep and like 7-11, that's how I remember it, like 7 hours and 11 minutes. The people that slept more than that did better cognitively. People that did less, but

>> 7 hours and 48 minutes last night.

>> Great. I'll take that. That's that's good. And, you know, obviously, you know, it depends on the sleep quality. Deep sleep is restorative sleep. That's when the trash gets taken out. The amyloid gets, you know, taken out in the garbage. Um, you know, REM sleep is when short-term memories are consolidated or really formed into long-term memories. So their sleep quality and their sleep quantity. And the number one way to get more sleep quality is to sleep longer, to have more REM and more deep sleep. Like that's a cheat code. Um, you know, to me, you know, actually retainyourbrain.com is the the actually I'm I'm in a routine right now. What retainyourbrain does is gives a person um suggestions and uh as I'm holding my coffee, I don't know what time it's 11 or 12 in the afternoon. Um, I am not allowed to drink coffee after 11:00 p.m. based on my um based on what time's up. You know, because um, you know, caffeine lasts for five, six hours, the half-life. So, if I'm drinking coffee at two or three or four o'clock in the afternoon, I still have caffeine in my system as I'm going to bed. So, so, so to me, um, you know, taking a making a plan for sleep, you know, sleeping in a dark room, like if there's a little bit of like light coming in from the window, just

>> Earplugs and eye shades.

>> Yeah, exactly. Um, weighted blankets. Some people really like those. Like, um, you know, cooling temperature like

>> I like cold rooms and heavy blankets.

>> Cold rooms and heavy blankets. Yes, you heard it here first. I mean, these are like really easy things that people can do. Um, the other thing is,

>> In fact, I'm reinstalling my air conditioning while you're here because it's an older house and it needs updating and it wasn't cooling down. When I put it at 65, it was only getting to 70. I'm like, that's not good enough.

>> Yeah, I I agree. Um, you know, my other routine that I got uh the the brain healthy habit that the software recommended because, you know, I typed in the thing like what are my issues and it said sleep is my issue. So, it's been telling me to help, you know, make my sleep better. And put electronics to bed was the brain healthy habit that was recommended to me. What does that mean? Every night at 9:30 p.m. my alarm goes off as a reminder that says power down your electronics. So at 9:30 I try to wrap up and by 10 I try to put, you know, like our biology wasn't meant to have two cell phones like like this, you know, at all times with the light and whatever else. And there's my there's my there's my Grateful Dead Bear. Got the Got the Bobby and the Wolf Brothers show a couple years ago. For those who don't know what he's talking about, it's Grateful Dead and Bob Weir and his his band called the the Wolf Brothers.

>> I was waiting online to get into the show. Someone miracled me with that.

>> So,

>> Too many inside jokes.

>> Yeah. Sorry. Yeah. Old old dead jokes. Um, but but like why are we on our cell phones right before bed? Like that causes rumination. If you want to fast forward brain aging, worry. Worry about everything. Like that will make rumination or worry is the number one thing that basically fast forwards um cognitive decline.

>> Two more things I want to cover before we close out. Got sleep, got nutrition, exercise, we got supplements, we've got hormones. Um, and you mentioned there are like 50 different choices. So there's a lot of things and people can look at your research. We're going to link to all your papers, all the media on you. People can learn more. There are um, you know, two other pieces. One is is what about um pharmacologic interventions because drugs have a role and kind of one of the one of the star players here.

>> And and um and also like what about brain exercises like brain gains, learning new language. So those are two things we need to talk about, but I think they're key pieces of of keeping and retaining your brain.

>> I'm equal opportunity. I got I got no skin in this game. I take no, you know, funding from pharmaceutical companies, any any anything like that. Um, I'm equal opportunity. If it's a drug, a vitamin, a supplement, and it's relatively safe, and I would be willing to take it myself or give it to a family member, it is on my list of potential interventions. So, I'm I'm not pro-drug on anything. I'm pro-evidence and I'm pro-safety. That's all I am. Um, in our research study that we presented in July 2025 at the International Alzheimer's Conference, paper is getting ready to be published, not going to be published yet. It's going to take these papers, take, you know, years and years and years to publish. The general categories of of of drugs that um worked the best. Well, we talked about hormone replacement therapy and we talked about GLP1s and those drugs, uh, drug categories worked um, honestly um, amazingly well. Like it's just it's just I I was I was floored by it. There are uh three other drug categories that people have heard of, many people are probably taking, and then there's one drug category that is more specific for Alzheimer's. So the next four categories that I can talk about briefly are um cholesterol treatments, and those are two um um statins as a category, and I'll explain the nuance there, and then um Ezetimibe or Zetia, which is a plant sterol inhibitor, and we've broken out groups into statin use versus Zetia use. That's the the brand name, but it's all generic now. And then the other categories were um, I think this was in the paper, SSRIs, selective serotonin reuptake inhibitors, um, um, and then the final category was anti-amyloid drugs. So these are drugs that we've studied and these are things that we've studied in our cohort.

>> But you're also talking about GLP1s too, are part of this.

>> Oh yeah. Yeah. Oh, GLP. Yeah. GLP1s and hormone replacement therapy are definite check, check marks. And I would say in our in our study, multimodal interventions work the best. GLP1s and hormone replacement therapy, I would say work the next best. And then there's these four other categories which we studied and across a variety of biomarkers, but maybe not as like not home run, grand slam. Um, there were statistically significant improvements across select blood biomarkers.

>> So, basically what you're saying is the basics work better than these fancy drugs that we spent billions of dollars researching and have shown very incremental benefits.

>> Yeah. They're not like zero, but they're and they may be additive to an overall package of interest. True. And in the right person at the right dose um, Ezetimibe, the plant sterol inhibitor. I I never in a million years would I have like ever said that I would be saying something like this. But, you know, we're developing these blood tests and, you know, we talked a lot about Alzheimer's today, but alpha-synuclein. Alpha-synuclein is the pathologic protein that that builds up in the brain of a person with Parkinson's disease and Lewy body dementia. Like we are working on these blood tests. Like this is crazy. Never in a jillion years like would I have ever, regardless of my my family, my brother, my brother's son, my brother's brother-in-law, like like we see these drops in alpha-synuclein protein using some of these things.

>> And these are related related things. So I don't fully know what this means yet. But what I would say is the cholesterol drugs in the right person at the right dose in the right duration. Um, you know, your mileage may vary. Um, work and it's improving what I believe to be brain health risk and brain health outcomes. Statins. Let's talk about statins. The people that start on statins in our cohort are not your typical um, you know, Crestor, rosuvastatin 20 milligrams. Like the amount of people I see on high-dose statins, it like just blows my mind. 85% of the cholesterol-lowering effect of rosuvastatin or Crestor comes at 5 milligrams of the dose.

>> So you get 80% of the benefit at the lowest dose.

>> Yep. And no one knows this. And like and I think that's correct. I mean, that's what I've read and that's what I've been taught. But like if the majority of the effect comes at low dose, like why do we keep like to get an extra five or 10 percent benefit when you like keep pushing and pushing and pushing these doses that are just like really high? To me.

>> And those cause mitochondrial injury, and that is important in keeping your brain healthy is having healthy mitochondria.

>> Yeah. And and, you know, the the side effects go up and across, you know, a variety of ways. In our cohort, lower dose statins in the right person that are biologically attuned to respond to statins, meaning when we do the blood test, it says you should take a statin because it's you're an overproducer of statin genetically or biologically. So lower dose statins um do show brain positive effects in our research. But

>> You guys are throwing at everybody. You're doing tests that say, oh, you're somebody who produces more cholesterol, so you and I don't. So statins wouldn't be good. And even I have the gene that makes it me have myopathy or muscle damage if I take a statin. I have that gene. I tested it. So statins are not good for me. And they also cause mitochondrial damage. And if you do the test that's helps you personalize or precision approaches, you're going to get a better effect with less side effects. And and there there's a there's a friend of mine, David Fagenbaum, who created a company called Every Cure, which is about using drugs that have mechanism of action for diseases for which they were not developed. Right? So, what you're talking about is a Zetia or Zetia. It works for Alzheimer's, but it's was a cholesterol drug, but it has an effect that maybe we don't even understand why, but it's working on some pathway that's independent of just the cholesterol lowering because it's not just about lowering cholesterol because you could actually lower cholesterol just as much with another drug, but not see the same benefit.

>> Exactly. And and and, you know, these are um again, these are am I catching on?

>> You are. You're catching on. You got you've been to this rodeo before. So, so anyway, I would say cholesterol drugs when used in the right person at the right dose for the right duration of time are protective against dementia and Alzheimer's pathology and maybe even Lewy body and Parkinson's. But I want to be really conservative, not fully published yet, like we're we're just we're just learning.

>> SSRIs, selective serotonin reuptake inhibitors, and again, yeah, um, so in our cohort.

>> Does that category of drugs?

>> Actually, we have zero people in our cohort on Prozac. The only people in our cohort that are on SSRIs, I think this is because escitalopram or Lexapro, it's all generic now, escitalopram has been shown of all the SSRIs in a study that came out in Neurology like a few years ago to have the best um, uh, you know, lowering or attenuation effects on amyloid. So in our little group, you know, we have a group of preventive neurologists, preventive cardiologists, preventive medicine specialists, internal medicine doctors, um, that treat the patients in their own individual clinics and whatever. And then they're in our research study and we track the biomarkers. We all have gotten the memo that escitalopram, I'm going to sound like a broken record, at a pretty low dose. You know, we have a guy now on five milligrams. I almost never go, I mean, I don't I don't usually go high. And by the way, we're not treating um, you know, you know, I'm not a psy, I'm not a psychiatrist. We're, we're, you know, mild depression versus major dep, those things, I'm not going to get into the nuance. But the majority of people in our cohort that are on SSRIs are on escitalopram or Lexapro, five milligrams, I would say on average. And in our cohort um, it's a small, small group um, but we also saw some, but not I would say slam dunk, robust effects um, from low-dose escitalopram, low-dose Lexapro.

>> So this is really important. I just want to step back. So we kind of have to wrap up, but I think I think that you for those of you listening who have a family history or who are suffering from memory loss or are concerned about getting it, you know, what you're saying, Richard, Dr. Isacson, is that for the first time in history, we're actually able to do preventive neurology around neurodegenerative diseases and and that you can actually slow or even reverse the changes that happen that are measurable by new and innovative blood biomarkers that you're developing and that are ones that are already developed and are available. And you're seeing change in brain structure, growing brains, and the function of brains, improvement in cognition, and you're not using the old paradigm of a single drug for a single disease, using over 50 different things that you pick from depending on how you want to personalize the treatment. That if you see one person with Alzheimer's, you've seen one person with Alzheimer's. And that this field is changing radically in such a way that will actually be able to help us avert this catastrophe of 47 million people who are in the presymptomatic stage of Alzheimer's that are measurable by these blood markers that is going to cost us $18 trillion over the next 30 years. This is revolutionary. And if anybody's listening who cares about this issue, who wants to help, and again, I have no affiliation with you other than being your friend and having a bond over the Grateful Dead, following your work for years.

>> This is where the money needs to go. This is where the philanthropic dollars need to go. This is where NIH funding needs to go. So if you're listening, J. Bacharia, this this is the future because it's what I have seen over 30 years in the practice of functional medicine from a very amateur scientific perspective. I'm not a researcher, although I've done some research studies. It's what I wrote about in my book, The Ultra Mind Solution, 15 years ago or more than 15 years ago now. And I think I think we're at this this transitional moment in history where for the first time we're we're getting a handle on this horrific condition. You know, yeah, you get a heart attack, okay? You have chest pain, you get a bypass, you get a new heart transplant, you're still you. When you get Alzheimer's, it you lose you, you lose your family members. It's a catastrophic disease. And no, and everybody's terrified of getting it. And nobody should be afraid of doing the diagnostic test to figure it out. And now at Ezra, which is a company we bought with Function, we actually can do brain imaging and we can do quantitative brain imaging, which is a more advanced service we offer. But we can actually start to track these things over time. And so you can begin to do these things. You can go to retainyourbrain.com and start to kind of get ahead of the game. So Richard, I just want to say thank you for what you've done. Thank you for the insights, for the aha moment you had in the hallway with that guy with a patient with dementia. We never know how we get doing what we're doing, but I hope that your work continues. I hope that you get it funded not to 10 or $20 million, but we need a billion dollars. We've spent so many billions of dollars and wasted them. This is an area that needs real serious funding because what you're seeing is real. It's not quackery. It's not heresy. Well, it kind of is heresy, but it's actually valid scientifically and and we need to get behind it. So, thank you for everything you've done. Thank you for what you're doing. You're uh leading the pack for the rest of us and uh I just appreciate everything you are and everything you're doing. So, thanks for being on the podcast.

>> That's much better.

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