Transcript

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

From Mark Hyman, MD · Episode page · Watch on YouTube

· 1 h 42 min · 21,314 words · 242 timestamped sections

This is the full, timestamped transcript of "You Can Prevent Alzheimer’s: The New Science of Brain Health", an episode of Mark Hyman, MD published November 5, 2025 (1 h 42 min, about 21,314 words). It mentions 19 people, works and ideas, including Statins, Function Health, APOE4, Cornell, Retain Your Brain.

What is discussed, and when

  1. – 10:00: Cornell, Harvard, Institute for Neurodeenerative Diseases, Retain Your Brain
  2. – 30:00: Function Health, Retain Your Brain
  3. – 40:00: Dr. Agson, Dr. Raggson, Function Health, Harvard
  4. – 50:00: Function Health, ind.org, Retain Your Brain, Statins
  5. – 1:10:00: MIND diet
  6. – 1:20:00: Alzheimer's Association International Conference, Cornell, Function Health, Statins
  7. – 1:40:00: Statins

Notable quotes from "You Can Prevent Alzheimer’s: The New Science of Brain Health"

  • And former director of the Alzheimer's prevention clinic at Wild Cornell Medical School. He now serves as the director of research at the Institute for Neurodeenerative Diseases.
    about Cornell · at
  • But you came from Cornell you're you're an academic, you're, 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.
    about Harvard · at
  • Break down some of the things that we're looking at now that are blood biomarkers. And at Function Health, we basically have a blood biomarker panel that helps identify that…
    about Function Health · at
  • Cardiovascular. literally just got an email from a friend of mine who's a doctor at Mass General who's a internist who's very well educated in the top of his field Harvard at…
    about Mass General · at
  • And that's like almost 20 years ago and I got my first calcium score 20 years ago. Thank you Dr. Agson. He was one of my old mentors. like I mean I got thrown into this because…
    about Dr. Agson · at
  • Right drug for the right person. And 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?
    about ind.org · at
  • Zia, a zettoi because he was an overabsorber of cholesterol, not a statin. He was afraid of statins. Okay he didn't need a statin anyway. and omega-3 fatty acids. His omega-3…
    about Statins · at
  • 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 you know if food…
    about MIND diet · at

Who and what is mentioned in this episode?

People

  • Richard Isacson — Person · 1 mention · first at
    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…
  • Dr. Agson — Person · 1 mention · first at
  • Dr. Raggson — Person · 1 mention · first at
    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 8990 and…

Companies & orgs

  • Function Health — Company · 5 mentions · first at
  • Cornell — Company · 3 mentions · first at
  • Harvard — Company · 2 mentions · first at
  • ind.org — Company · 2 mentions · first at
  • NIH — Company · 2 mentions
  • Wild Cornell Medical School — Company · 1 mention · first at
    Alzheimer's disease. He was the founder and former director of the Alzheimer's prevention clinic at Wild Cornell Medical School. He now serves as the director of research at the Institute for Neurodeenerative Diseases.
  • Institute for Neurodeenerative Diseases — Company · 1 mention · first at
    Cornell Medical School. He now serves as the director of research at the Institute for Neurodeenerative Diseases.
  • Mass General — Company · 1 mention · first at
  • Alzheimer's Association International Conference — Company · 1 mention · first at
    Study that we presented data that I can talk about because we presented this at the 2025 Alzheimer's Association International Conference in July 2025 and we showed that when…
  • Ezra — Company · 1 mention
  • Hyman Hive — Company · 1 mention

Concepts & topics

  • Statins — Concept · 6 mentions · first at
  • APOE4 — Concept · 4 mentions
  • Retain Your Brain — Concept · 3 mentions · first at
    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.
  • MIND diet — Concept · 1 mention · first at
  • B12 — Concept · 1 mention

Full transcript with timestamps

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

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

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 Wild Cornell Medical School. He now serves as the director of research at the Institute for Neurodeenerative 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? 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 co that was a long time ago and you have been a man on a mission

things, are, [clears throat], 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 neurodeenerative 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 fail 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 free home 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 health care 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 Louis 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 neurodeenerative 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 Louisibody 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 left 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 amaloid deposition which is this gunk that gunks up in layman's term 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-amaloid 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 al 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 dead heads in the room., So,, you, know,, we're, we're we're old in 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 amaloid and amaloid 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 amaloid in it okay but like why are there up to a third of people that have amaloid 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 amaloid goes first and then the tow protein, the other next protein, then brain inflammation and and neurodeeneration, brain cell death. And those were the that was it. That's how Alzheimer's work. But that's not how it works in the clinic. I'm a clinician. I look at the patients, you know, that model of amaloid, then brain

inflammation, then neurodeeneration. 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 way ways. And and the way that I view Alzheimer's and also the way I view neurodeenerative disease as a whole is it's very heterogeneous. There are so many different types and manifestations. And

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, permenopause. 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 oneizefits-all is is not how this works. And we need to take a one-izefits-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 sizefits-all.

Taking, this, individualized, approach., It it you know he people hear the term precision medicine. Ooh, that's that's fancy expensive tests and 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 specialist. My brother's son is a Parkinson 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 neurodeenerative 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, a 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 diagn 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-amaloid 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-amaloid drug or everyone on a you know one of the GLP1 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 attack, 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 mention 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 amaloid 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 Pastor we got the bacteria we said oh there's this numaccoal bacteria. Oh that causes numaccoal pneumonia that single disease. Oh it's treated with a single drug penicellin. 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 if co 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 amaloid 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 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. Chole, 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 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 amaloid 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 of a nine- ining 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 PAL 217 test is 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. Amaloid to me does not cause Alzheimer's disease. I've just never felt that way. Why are there people without amalloid that have a clinical meaning like

you, know, talk, to, the, patient, looks, like they have Alzheimer's they don't have amaloid oh I wonder why I guess amaloid didn't cause Alzheimer's in that person but by definition you have to have amaloid to have Alzheimer's like our our instruction manuals are like totally wrong Rudy Tany 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 dead head so like

he's, a, cool, dude, and, uh, he, discovered, a 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 amaloid 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 ptow 217 or amaloid biomarkers like a a um AB 4240 other PAS like 181 231 neuropilament light chain which is more for brain damage or something called gle al fibrillary acidic protein or GFAP and beta sinuclean 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 AB CD and E of Alzheimer's and neurodeenerative 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 cliffotes version um in the ABCs and Ess. But if there's anyone out there like we've just spent six years developing and this was before AI was cool. Uh 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

ba, baby, steps., Yeah., In, time, in, time. But but right now it's 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 retain ourbrain.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 neurogen 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 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 neurogenerative disease risk factor risk

reduction prevention management is a paradigm that we published on at Nature Mental Health. uh 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, is, a, disease, of, the, brain, or, a body disorder that affects the brain? So I believe Alzheimer's and and and I mean this is going to sound like heresy but I believe neurodeenerative 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, I'm, like, a, I'm, an oldtime family doctor. Like I'm an inter, you know, I I I I feel like I practice a one-/3 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 permenopause 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 GLP1 drugs

the, GLP1, 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 Louisbody 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, bloodbased, 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 glycosillated hemoglobin or HBA1C and you know people say oh above 5.7 is pre-diabetes and 6.5 or whatever is is diabetes. M 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 diabetes of the brain.

Yep., And, there's, a, lot, of, a, lot, of overlap with with the with with the with the pathophysiology, which is a big word for, you know, potentially why these disease 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 a 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, AF, of 500

which, is, a, and, no, one's, ever, checked which, she, said, no, one's, ever, he, was, like I 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 and at function health we do these very deep biomarkers for cardiovascular that are far just beyond a regular cholesterol panel APO B which never gets checked protein A uh 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 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. Agson. 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 8990 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 amaloid 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, PA, is, high,, your, APOB, is, high, your your particle number is high, your particle size is small, like

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 u 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

and, 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 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 Oh, 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 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 uh 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 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, take-home, 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 have 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 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 sorry of the of the of the total shrinkage 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 we, sometimes, use, this, and I think in terms of like the 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, a, 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 amaloid. 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 bio identical patch and you use progesterone

and we talked to the gyn and we talked to the doctors hormone replacement therapy during the parametransition has helped improve brain biomarkers associated with Alzheimer's and neurogenerative 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 neurogen 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,, end, early., I, I, want, to, start, both time. Yes. Start early. Does that mean every woman should be on porn 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 6 months. P menopause 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 multi-disiplinary team, when we start seeing the estrogen drop, even if the symptoms are very mild you get the estrogen back up, the towel starts coming Now, even though the towel wasn't elevated to a degree where we're like, uh-oh, sky is falling, but the towel 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 parmenopause 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? Pile 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 towel 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 amaloid going up.

Well, maybe they're a little symptomatic, but it's not really bothering them, but we're going to start on lowdose hormone replacement therapy if everyone is in agreement. And guess what? She feels better. Her cholesterol comes down. That's interesting. Her amaloid 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 preymptomatic um, follow it closely. I think women pre-menopause should should probably get checked every 6 to 12 months for these brain biomarkers and hormones. Um

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 I you just start and you see everything improve. This this is honestly Richard why we co-ounded 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 bioarkers including, AP4, 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 twothirds 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 um

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, cuz 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's 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 optim optimized person if you get sleep right the amaloid 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-Eleven that's how I remember it like 7-Eleven 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'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 amaloid 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 sweet sleep um 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 retainyoubrain.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 5 6 hours the halfife. So, if I'm drinking coffee at 2 or 3 or 4:00 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

ear, plugs, 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 recommend 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 Dad 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 that 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 work 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 isetto or zedia which is a plant sterile inhibitor and we've broken out groups into statin use versus zedia 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 SSRI selective serotonin reuptake inhibitors um um and then the final category was anti amaloid 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, GL, Yeah., GL, 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 billion 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 aetto the plant sterile inhibitor. I 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 senuclean alphasuclean is the pathologic protein that that builds up in the brain of a person with Parkinson's disease and louisibody dementia like we are working on these blood test 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 alphasuclean 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 rua statin 20 milligrams. Like the amount of people I see on highdose statins, it like just blows my mind. 85% of the cholesterol-lowering effect of ruaatin or crusttor comes at 5 milligs 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 come 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, 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 over producer 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 Fagenbomb 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 zettoite or zedia. 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 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 Louisibody and Parkinson's. But I want to be really conservative, not fully published yet, like we're we're just we're just learning.

SSRI,, 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 esatalopram or lexapro it's all generic now esatalopramg 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 amaloid. 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 acetatalopram, 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 esatalopram or lexopro 5 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 lowd dose esatalopram lowd do 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 neurodeenerative 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 murders 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 dad 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 retainyoubrain.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 a 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. If, you, love, that, last, video,, you're going to love the next one. Check it out here.

Questions about this episode

What is discussed in "You Can Prevent Alzheimer’s: The New Science of Brain Health"?

In order: 0:00 Cornell, Harvard, Institute for Neurodeenerative Diseases, Retain Your Brain; 20:00 Function Health, Retain Your Brain; 30:00 Dr. Agson, Dr. Raggson, Function Health, Harvard; 40:00 Function Health, ind.org, Retain Your Brain, Statins; 1:00:00 MIND diet; 1:10:00 Alzheimer's Association International Conference, Cornell, Function Health, Statins; 1:30:00 Statins.

What is mentioned in this Mark Hyman, MD episode?

19 people, works and ideas are mentioned, including Statins, Function Health, APOE4, Cornell, Retain Your Brain, Harvard. Each one on this page links to its own page with every episode that mentions it.

How long is "You Can Prevent Alzheimer’s: The New Science of Brain Health"?

The episode runs 1 h 42 min; the transcript is about 21,314 words in 242 timestamped sections.

More from Mark Hyman, MD

About this transcript: the episode's spoken words as captioned on YouTube, split into timestamped sections. Reclip.Me locates every person, work and idea in the text, keeps the time it is first named, and quotes the words around it verbatim. Last updated January 24, 2026.