The Dr. Hyman Show - Become an Alzheimer’s Survivor: Dr. Richard Isaacson’s Breakthrough Approach

Episode Date: November 5, 2025

Your brain doesn’t wait until old age to start changing. It’s being shaped right now by the choices you make every single day. On this episode of The Dr. Hyman Show, I’m joined by preventive neurologist Dr. Richard Isaacson—founder of RetainYourBrain, a free assessment platform empowering people to understand and improve their cognitive health. Dr. Isaacson was also recently featured in a CNN documentary highlighting his groundbreaking work on Alzheimer’s prevention. In our conversation, we dig into what the latest science reveals about cognitive longevity—how biomarkers, metabolism, nutrition, and sleep shape the brain’s long-term performance. Watch the full conversation on YouTube, or listen wherever you get your podcasts. We cover: • What early biomarkers can reveal about long-term brain health • How metabolism, blood sugar, and belly fat impact memory and focus • Why a personalized plan beats a one-size-fits-all approach to Alzheimer’s • Lifestyle changes that strengthen cognitive resilience starting now • The role of hormones, exercise, sleep, and supplements in prevention Resource mentioned: CNN Feature I believe we deserve to stay sharp, engaged, and fully ourselves as we age—this conversation shows what’s possible. View Show Notes From This Episode Get Free Weekly Health Tips from Dr. Hyman https://drhyman.com/pages/picks?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Sign Up for Dr. Hyman’s Weekly Longevity Journal https://drhyman.com/pages/longevity?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Join the 10-Day Detox to Reset Your Health https://drhyman.com/pages/10-day-detox Join the Hyman Hive for Expert Support and Real Results https://drhyman.com/pages/hyman-hive This episode is brought to you by Seed, Paleovalley, Function Health, BON CHARGE, Sunlighten and PerfectAmino. Visit seed.com/hyman and use code 20HYMAN for 20% off your first month of Seed's DS-01® Daily Synbiotic. Get nutrient-dense, whole foods. Head to paleovalley.com/hyman for 15% off your first purchase. Join today at FunctionHealth.com/Mark and use code HYMAN100 to get $100 toward your membership.Head to boncharge.com and use code DRMARK for 15% off your order. Head over to sunlighten.com and save up to $1400 or more this holiday season with code HYMAN. Go to bodyhealth.com and use code HYMAN20 for 20% off your first order.

47 million Americans are going to get dementia if we don't do something about it. People think of dementia in neurodegenerative 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 in 99% failed. So we're thinking about this wrong. Dr. Richard Isaacson 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 Neurodegenerative diseases. He heads the NIH-funded, retain your brain program about retraining your brain and retaining your brain by doing specific practices that help you preserve your cognitive function. Take this down this sort of this framework of our current thinking and why it's flawed in the traditional neurological field and how you come to understand when you take a different approach. Forty-five percent 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 digital. It's free. People can go right now and get an assessment and like learn about themselves

and get automated brain health preventative care, prevented 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? As you know, I'm always talking about how central the gut is to living a long healthy life. A high-quality probiotic is one of the most important things you can do for your gut, which is why I have been recommending Seeds DSO-1 daily symbiotic. I've reviewed hundreds of probiotics over the years,

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purchase and try them today. Well, Richard, welcome back to the Dr. Hyman show. We had a few years ago a chance to do this over COVID. That was a long time ago. And you have been a man on a mission. Things are very different now. It's only been five years, but, yeah, it's great. And there's a lot more to tell about this whole topic of neurodegenerative diseases, which is a crippling problem. It's the most expensive condition is Alzheimer's, more than heart disease, cancer, diabetes,

because of the long-term care and issues we have with it. The entire research enterprise pretty much failed to get an answer. There's a lot of drugs that really don't work. And if they work, they're like, extend, you know, your nursing free home time by three months as a big win and the drugs cost a fortune and you know we spent two trillion dollars over 400 studies and 99% failed so we're thinking about this wrong or 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, 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 this field on the fringes are doing this. But you came from Cornell. You're, you know, an academic. You're, you know, trained at Harvard in neurology. You've got the street CREs. And you've come at the same thing that I came at decades ago. Tomatoes getting thrown out as me. Yeah. I mean, you know, you're, you know, what do they say, you know, the pioneers always have arrows in their backs, right?

I'm still bloodied and bruised. So take this down, you know, this sort of this framework of our current thinking and why it's flawed in a traditional neurological field and how you come to understand when you 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 don't live in a health care system. We live in a sick care system. The medical system 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, 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 crazy idea, oh, Alzheimer's Prevention Clinic, you can't start. You can't use Alzheimer's and prevention in the same sentence. That's cookie talk. And

So like over 15 years ago, 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 taken away in a hallway saying, Isaacson, I know you got four family members with the disease. What do you, can we do anything to prevent? Like, what should I do as a son of a patient of mine? And we spend 45 minutes in the hallway discussing what he and I could possibly do. And then next week, I saw it. sister as a patient, and that was the first Alzheimer's prevention consult in the United States that I did, and that kind of changed everything to me. And to me, we're thinking about things

wrong. We're doing things all wrong, and people think of dementia and neurodegenerative disease as an older person's disease, and it's not. We used to joke called Alzheimer's disease. I get it because we see people with dementia and they're older, right? 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 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 louis body disease or dementia because there's no billing codes for it. I can treat someone with a disease after you have a heart attack or a stroke or dementia, but we don't get paid for it because, again, I don't want to belay for this, but our whole health care system is broken. So to me, we just got to get ahead of things. And the evidence, you know, the totality of evidence is overwhelming that we can do something.

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 five, 10, or 15 years ago. So, yeah, I'm excited about the progress, but, you know, it's hard to keep pushing things forward. It is, you know, and you talk about the 47 million Americans,

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

And what you're saying is that it's really preventable. Now, I want to kind of harken back to the flawed paradigm because in medicine, we have this idea that you have a single disease, Alzheimer's, that's caused by a single pathway amyloid deposition, which is this gunk, 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-aminoid drugs for decades, and we've spent $2 trillion, like I said, 400 plus studies and massive failure. Why is that failed? And what's wrong with that thinking? And why should we look at a different framework that looks at each Alzheimer's patient differently. You say if you've seen

one patient with Alzheimer's, you're seeing one patient with Alzheimer's, right? You took the words in the sentence right out of my mouth. 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 do basic science stuff, you know, over my head. You're an old-time family doctor. I'm an old-time neurologist, you know, carrying the bag. Who you're calling old? I'm calling myself old, too. So we're all hippies. We're all hippies. We're all deadheads in the room, so, you know, we're old in the good sense of the word. But when you think about neurological disease and brain disease, and what I was taught in medical school was like Alzheimer's is like this protein called amyloid. And the amyloid, like you said, is this sticky protein that builds up in the brain of a person with Alzheimer's.

And when you look at the brain of a person with Alzheimer's, there's amyloid in it. Okay. But like, why are there up to a third of people that have amyloid in their brain but didn't have dementia? Well, that's interesting. Well, how does that make sense? And then in the textbooks, I remember, I remember the graph, then the amyloid goes first, and then the tau protein, the other next protein, then brain inflammation and neurodegeneration, 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 amyloid, then tau, then brain inflammation, the neurodemeanor. degeneration. Yeah, that happens. But in a recent study, journal Neurology, it was like a third of the time. That was the trajectory. But all the textbooks say that's how it is. And medical students are that. So to me, there's buckets and different people present different ways and the way that I view Alzheimer's. And also the way I view neurodegenerative disease as a whole is it's very heterogeneous. There are so many different types and manifestations. Even though the end symptomatology in the diagnosis, This is the same. Each of these patients might have different causes and need different treatment.

Yeah, you can take different roads to Alzheimer's. You know, women, you know, for example, Mrs. Smith, she may be, you know, parimenopause. The estrogen is dropping. She may have a variant, genetic variant called APOE, which we could talk about, APOE 4. And you have the APOE 4 and the estrogen drops. Well, Mrs. Smith, she's going to need therapies, A, B, and C. Mr. Jones, he's totally different. You know, he doesn't have the gene. He's different. He has a big belly, has a belly size that's 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 C. The bigger your belly, the smaller your brain. That's small in the memory center of 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, one size fits all is not how this works. And we need to take a one-size-fits-one approach. And we call this N of one medicine. And the NIH has actually declared this is one of the most

important and actually predictive forms of research. And they're funding some N of one research trials, but it still hasn't kind of permeated the funding, really. It hasn't permeated the thinking at all. No, and you know, this is what you call it as precision neurology, precision prevention. That's exactly, right? Precision or personalized.

It's not one-size-fits-all. Taking this individualized approach, it, you know, people hear the term precision medicine. Ooh, that's fancy, expensive tests. And no, actually, it's just like talking to the person and figuring out what road they may be on. And whether it's doing a genetic test or doing some blood markers, which, you know, the cost has come down, doing cognitive assessments. We do this all now digitally. 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. medical school, I was taught one thing, and then the field's changed, and the fields changed so much in five years. So to me, you've seen one person, you've seen one person with Alzheimer's. And what we've done recently is now not just studied people with, at risk of Alzheimer's disease, my brother's a Parkinson's specialist, my brother's brother-in-law is a Parkinson's specialist, my brother's son is a Parkinson's specialist. So I got the Parkinson's movement disorders

thing covered on one side of the family. And we bring everyone into the same research database, or research cohort, which is a research group. We have kind of called a BioRAN study, the the biorepository for Alzheimer's and neurodegenerative diseases. And when you start putting these people that have similar-ish 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-ish? They have a different protein or a different pathology. Or someone is a diagnosis of Parkinson's, it's, oh, wait a minute, something a little different.

You have to study these things together. And there's 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 then the question is why.

And you've been asking why? It's not all we do in medicine. We say, okay, what disease do 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? It'll help you get better.

Yeah. And what are we going to do about it exactly? There was an old saying, a neurologist don't treat disease. We admire it. Adios and diagnose. No, not. Not anymore.

That's that old neurology saying, adios and diagnose and adios, meaning you make the diagnosis and there's nothing you can do about it. Yeah, and that's just plain wrong. And, you know, with four family members with Alzheimer's disease and, like, and 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 have a 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 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 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 and other group they get a placebo like no different people need different treatment. So we've kind of turned the paradigm, the research paradigm, 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 five years. And each person's 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, the 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-amoloid 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-amoloid drug or everyone on a, you know, one of the GLP one, the weight loss drugs or just put everyone just on exercise, it ain't going to work. So 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 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 GOP1 drug probably isn't going to do anything. So you've got to customize the treatments. One of the failures is, you know, we have a rule in functional medicine called the TACRills. We talked about a night at dinner. If you're standing on attack, it takes a lot of aspirin make it feel better.

So something's in your system that's bothering you, this irritating. And you mentioned a case, for example, some had a 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 amy deposition. That's just a reaction to various insults. The insults could be toxins. They could be allergens. They could be crappy diet. It could be too much sugar. It could be alcohol. It could be mold. It could be 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 be able to customize the treatments and personalize it in a way. And what you're doing is so radical because most physicians are focused and trained on diagnosing a disease and then finding that single pathway that explains the disease and that single drug that will fix the problem. And that worked for infections, sort of. I mean, with Louis Pasteur, we got the bacteria. We said, oh, there's this pneumococcal bacteria. Oh, that causes pneumococcal pneumonia, that single disease. Oh, it's treated with a single drug. Penicillin. It'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 COVID, even the same virus. So it's not just the virus. But what happens is 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 kind of coming up with. And then you're having to do investigations to figure that out.

and then you're doing diagnostics to help you map that out into the blood testing and you call these new blood biomarkers for dementia which is i want to talk about a minute and imaging brain imaging and then you start to treat these people individually and you see remarkable changes in lowering of these biomarkers of a 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 because you talk to any neurologist, but I've reversed the effects of Alzheimer's. They're going to just laugh in your face. I always stress the importance of breathing to my patients, and not just for survival. November

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I'm waking up feeling more mobile and less stiff and ready to go. If you're dealing with chronic pain, back issues, or just want to support faster recovery and longevity, I can't recommend this enough. Go to bondcharge.com and use code DRMark for 15% off. That's B-O-N-C-H-A-R-G-E.com, code DR-Mark. The tools that we have are not tools that are radically expensive, are radically unobtainable. 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 otherwise and the person starts adopting changes, you know, we now have the tools to truly, you know, in my opinion, definitively show that the things we tell people to do are getting people off the road to dementia. They may have amyloid in their blood or they may have some cognitive glitches.

they may have some symptoms that are still early, but they can go about all of their, you know, usual daily lives. And to me, I don't care if it's a vitamin, a drug, or a supplement. If there's evidence and it's safe, I don't care what the treatment is, right? Like, yes, I'd rather people, you know, food is medicine. I couldn't, couldn't say that enough times. And, you know, 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. 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, 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 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 I see it. And when everything is going in the right way, when everything about his everything improves, you know, that's evidence for me.

Yeah, it's true. I mean, I think you're gathering data that is really solid. What I want to sort of dive into now is this idea of, you know, this sort of early intervention and assessment. We do it for a lot of things. We check cholesterol.

Chlestral 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 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 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 finding these particular blood biomarkers. 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 blood biomarker panel that helps identify that risk, including APOE4 chesting and APOE testing, which is a gene for risk for Alzheimer's, looking at PETA2-17, which is another marker, AD40, 240, which is amyloid biomarkers, but you're going way deeper than that.

Yeah, so, you know, when it comes to blood testing for Alzheimer's, and by the way, five years ago, whenever we spoke on the podcast, like never in a million years, whether it was two years, five years ago, 10 years ago, 20 years, never in a million years did I,

would have ever pictured myself having a lab in Bocarem Well, there's a lot of Alzheimer's disease. That's what they call it, and it should be called something else. Joe Bruce Ames, who's a very famous scientist said on epidemiology, which is population studies. He says, if you did a study of population in Miami, everybody would be born Hispanic and die Jewish. 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'm not a basic science guy. Like, I never, like centrifuging blood and developing at-home testing using different devices and developing, starting with a panel of, say, 1,000 and now coming, we're down, hey, we're down to 150 tests and we're getting it down. And in my goal and our goal at, you know, at I&D and elsewhere, we are trying to develop what will one day be termed the cholesterol test for the brain. And, you know, if we're talking baseball analogies, we're still in the first inning, in my

opinion of a nine-inning, you know, baseball game, where the tests we use now, I think, are 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 Ptow 217 test is a very good test. It's not a perfect test, but it's a good test. But we're 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 oftentimes, 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 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 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 you know lower cost improve increase access yeah and then give people digital tools to like help interpret it and give that

person care. So 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 what is a normal value for someone in their 20s or 30s versus someone in their 40s or 50s versus someone in their 60s. Like what are the reference ranges? The reference ranges.

And, you know, most of the research that's been done are people with dementia, people age 55 or 60 and above, and we need to start earlier. So the focus of our research is to figure out what is this cholesterol test for the brain going to be. 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 kind of early warning signs. They're not necessarily the cause, but they're the things we can look at that are, resulting from causes that drive those biomarkers to be abnormal.

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

They don't have amyloid. Oh, I wonder, whoa, I guess amyloid didn't cause Alzheimer's in that person. but by definition, you have to have amyloid to have Alzheimer's. Like, our instruction manuals are, like, totally wrong. I mean, Rudy Tansy, who's a friend of Orthoward, is an amazing guy who's an Alzheimer's researcher. We just said amazing guy, like, in unison, so I hope he hears that. And he's a deadhead, so like.

He's a cool dude, and he discovered Nobel Prize quality science on the very unique early Alzheimer's genes through lucid dreaming, if that tells you anything about the guy. He, you know, he said that there are patients who have brains, full of amyloid, but die old, cognitively intact, meaning normal. And he said, what's unique about these people and a little here 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 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 toxins to diet to pre-diabetes or diabetes to a mold to you know lime disease i mean chris christopherson had quote dementia Alzheimer's but trotny had Lyme disease and you got treated with antibiotics and it's dementia went away so i think we we have to think more about what what the unlike pathology is which is inflammation and then why is their inflammation and then hunt down the sources and the cause inflammation and remove those and that will lower i might believe lower these blood biomarkers that are around even a few years ago they weren't really available

these things like P-Tow 217 or amyloid biomarkers like AB-2-40, other P-tows like 181, 231, neurofilm and light chain, which is more for brain damage or something called glial fibularia acidic protein or G-FAP, and beta synuclein, which you're actually developing the test for. So there's all these novel biomarkers that are going to be available clinically, and 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? 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 1 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, in our research performance, and clinical practice, what I would call it, the A, B, C, D, and E of Alzheimer's and neurodegenerative disease prevention, okay, A, B, C, D, 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 U.S. 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 large, almost

a thousand-person NIH-funded, randomized controlled trial that showed that free software online, you go into the website, retainyourbrain.com. It's all free. Retainyourbrain.com. Retain your brain.com. If there is anyone out there with a brain that wants to like...

Wait, I have a brain, I think. I think you do. You definitely have a brain. It's a very robust brain. It's functioning. Checkmark, neurologist approved. I'm going to give the Cliff Notes version in the ABCs, these and these,

but if there's anyone out there, like, we've just spent six years developing, And this was before AI was cool. We just developed, we put my brain, you know, a virtual neurologist in your pocket, and retain your brain.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, 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. It's mostly based on your history. You're not necessarily doing blood work or baby steps, yeah, in time, in time. But right now, it's all, it's all. and there's, you know, no cost. And, you know, doing the blood test would just add another layer 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 the retain your brain, which is what we all want to do, is retain our brain. Dot com is a platform that you develop that basically has downloaded the your thinking into 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 neurogenital diseases or your word

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 when 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 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 the joke. It's like you have to treat everything, right? If you have low vitamin D or low omega-3s or you have pre-diabetes or have head. metal or you have mold or whatever you're finding or you have high cholesterol. You've got to treat all those things. You can't just treat one thing, but that's what we do in traditional medicine. The ABC, D&E of Alzheimer's and neurodegenerative disease risk factor risk reduction prevention management is a paradigm that we published on it. Nature Mental Health, January 2024 was the last time we kind of updated the paradigm. And it's all, again, doctors out there

listening. Any health care providers, you can read the paper. But the A, is simple. It's anthropometrics. So what does A stand for? Antipometrics is body composition, body fat, muscle mass. I also kind of throw bone density in there. Yeah. Bone density, grip strength, also an important proxy. And why is that important? Well, as you go through, so I'm going to kind of have you go through and expect why it's important. And by the way, I'm going to talk about things. And people are going to be like, wait, what is this guy? He's a neurologist. Why isn't talking about? Why is you talking about belly fat? Yeah. So I believe. And, you know, you wrote a paper on this, I think back in 2007 about how, like, our brain disease is really, like,

Body disease, and I'm paraphrase. I don't remember what the title was. Is it a disease of the brain or a body disorder that affects the brain? So I believe Alzheimer's and, I mean, this is going to sound like heresy, but I believe neurodegenerative disease many times or most times, those are big statements, are medical conditions that have secondary negative effects on the brain. So just like when a person has diabetes, the sign of end organ damage is kidney failure or tingling and numbness in the toes or something called macular generation where people lose

vision, you know, because of diabetes. I believe medical conditions, the neck and below things affect the brain. That's a heresy because most neurologists stop looking at anything below the neck. Yeah. And I'm like, I'm an old-time family doctor. Like I'm an intro, you know, I feel like I practice one-third internal medicine, one-third preventive cardiology and one-third, you know, preventive neurology, which is a field that, you know, just barely exists. So what I'm going to talk about now was going to be very medical. So, and I'm glad I'm with you because you can. I can translate it.

So, so A, anthropometrics, again, it's a fancy long term. And I couldn't use B because body composition is the next letter. But everyone needs to know their numbers, belly fat, especially as a belly size gets larger, the memory center and the brain gets smaller. Women that have increased waist circumference, okay, visceral fat, meaning fat around 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 paramedopause transition? It gets really, really, really hard to lose belly fat. And there are things that we can do to change that. 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, muscle mass is not easy to build. And doctors don't focus on, like, why are people talking about

weight like stop talking about weight body composition talk about body company everyone needs to these scales okay there are a couple hundred dollars but you know everyone needs to 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 uh you know weight loss drugs okay they have some really interesting features they made too high a dose we'll talk about like the glp1 drugs yeah 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 composition and and muscle and muscle and bone density which is really critical so The A, all of these things in 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, you know, and belly fat, absolutely critical risk factors to prevent cognitive decline, dementia, in louis body, dementia, Parkinson's. These are all metabolic factors that actually do influence these diseases.

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

Metabolic markers, meaning like looking at blood sugar, insulin. So fasting blood sugar, fasting insulin. You know, there's a lot of us may have heard of something called a hemoglobin A1C or glycosylated hemoglobin or HBA1C. and, you know, people say, oh, above 5.7 is pre-diabetes and 6.5 or whatever is 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. Well, because they even call Alzheimer's Type 3 diabetes, right? Alzheimer's diabetes of the brain.

Yep, and there's a lot of overlap with the pathophysiology, which is a big word for, you know, potentially why these disease happen. And metabolic health, 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 cognitive decline. And also, cholesterol is really complicated. I'm not sure how much time we have to dive into this. But like there's good cholesterol, there's bad cholesterol, like HGL. That's the good stuff, right? Well, maybe not. It's a little confusing. There's a lot of confusing stuff with cholesterol. And it is. And it's unfortunately, Richard, most, doctors, even cardiologists, don't fully assess cardiovascular. I literally just got an email from a friend of mine who's a doctor at Mass General, was an internist who's very well educated on the top of his field, Harvard at Harvard. His wife did function health and found she had a lipoprotein A of 500, which is a...

And no one's ever checked it. She said no one's ever... He was like, her doctor wouldn't check it. I wouldn't have checked it. And now we did a full cardiac workup. We can actually manage her risk and look differently at her health. And at function health, we do these very deep biomarkers for cardiovascularists that are far just beyond a regular cholesterol panel gluten, APOB, which never gets checked, hyperprotein A,

particle size. We look at function of HDL. You said HDL's not all the same. Some good is, the good isn't just all good and the bad isn't all just bad. It's kind of a false framework. And so we're able to look at 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 got my first calcium score 20 years ago. Thank you, Dr. Agateson. He was one of my old mentors. I mean, I got thrown into this because I had mentors and people that thought differently, thought in a contrarian way. You know, Dr. Agateson, for example, the calcium score, I think he invented that in like, I don't know, 89, 90. And it became part of the guidelines, the physician, you know, consensus guidelines in 2018 it took 30 years to make you know the guidelines that like you know

okay if you have high cholesterol maybe we should look at the heart to see if there's you know plaque and you know because by the way you can have like just the way you can have amyloid but no Alzheimer's you you're going to have extremely abnormal cholesterol and it's clean arteries and I have patients like that and I'm like wow your LPA is high your apope is higher your particle number's high your particle size is small I mean it's a whistle yeah clean is a whistle and and that's the thing like And this is precision medicine and personalized care. So anyway, we look at all these markers and we look at APOB, we look at LP L-P-L-A, we look at L-D-O, we look at particle size.

I mean, if you have to choose one, like I choose APOB as a good proxy, we always check LP little A. We look at markers of absorper, like, is someone, you know, if someone has high cholesterol, instead of just throwing them on a drug that, you know, in the grand scheme of things may work for 70 or 80% of the population, what if you're in that 20 or 30% where you're not the right person. And I think you and I, whatever, we may be, like I have a different version of my cholesterol's not high.

It's just borderline, but I'm an over-absorber 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 stop. A statin drug, that's not the right drug for me. Generic drug calls it a Zetamib. It's a plant sterile inhibitor. That's the right drug for me because I've had that checks in 2007. And right now I'm able to control it without a drug.

But if I need a drug one day, that's the one I would. It's basically also called Zeta, but it's interesting because, you know, I have genetics, and I've done my cardiovascular genetics, and I have a very strong family history of heart disease, and I'm a hyper-absorber. And when I actually started taking this drug, it was like a drop like a stone. Because you had the right drug for you based on the original. It's not that cholesterol is eating from eggs. It's the cholesterol that's produced by your liver and bile, it'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, what is it? Like, how do I get these tests? Like, it will be available, all this stuff, and some of this is available now. All this is what we talked about just now is all available through function health for $499, and there's add-ons

for cardiovascular alcohol. You all start going deeper on blood bomb markers. I want to stay on the B way, because you are looking at additional things that in addition to we offer as add-ons like a function, but P-Tau and amyloid and APOE and neurofilament, light chain, other things, but you're going even deeper into these, the stuff we're doing, like, you know,

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 there'll be you know at least two years before you know 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 it 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. And you need to track everything. And you've got to figure out

which drug is the right drug for the right person. And, you know, we're working on this through I&D.org, which is our nonprofit. That's the Institute for Neurneurneumdum diseases, right? 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 tests and we're trying to like, you know, figure this stuff out. And, 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, but there is so much nuance and so much confusion. And, you know, my worry is that someone may get a test and then it's positive, but it's not really positive because of a variety of reasons. So, like,

the take home 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 that is the type of stuff that's not, you know, wouldn't say it's available yet. It's coming soon. But to me, when a person does not have symptoms of cognitive decline and wants to understand their risk, I believe that the current tests available are good, but we need more. We need more higher fidelity. I believe that if our work keeps moving at the rate it's going within a year or less, maybe a year and a half, we're just going to be able to ramp up that fidelity to make these blood tests more 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 GLP1 drug because their doctors said they were overweight and they had a little diabetes and they want to well then we're going to track these markers and we can then show is there a ground truth is there you know and using that person as they're in 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 I&D.org, I'm allslabs.org is one of the arms that we're investing a lot of money to try to figure this out and develop these blood tests. 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 put that in his data? Yeah, I mean, in time, we're, you know, for people without symptoms for the panel that we want to deploy, I feel that we're not there just yet. But that's the future. But you could, I mean, you could have them check their blood pressure. You could have them do a body composition. And they do that. And they have them check their cholesterol or their insulin or the type of B or the heavy metals

or the vitamin D or whatever. You can add all that data into retrain your brain now? Can you do that? Well, so, yes. So, for example, 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 for. 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.

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 one percent of the population has two copies of E4. And honestly, one of the key drivers of why we created this 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, they got tested through 23 in me. It's like, oh, shoot, I don't want to know. I don't want to test it. And doctor said, we 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 that our research for the last, you know, 15 years have studied to show maybe effective. And then the 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. It's more personalized. It's more personalized, yeah, to help manage risk factors for Alzheimer's disease.

So, I'm sorry short, there's a bunch of blood tests that are available now that you're already measuring that are easily accessible through your doctor or, well, they might not order, but function health for $409.00 and things like your blood sugar, insulin, you know, cholesterol, particle size, LPA, APOB, all the nutrients, omega-3s, all that, we could get that now. But there's another layer that you're doing, that you're developing your lab that are new biomarkers that are specific for, neurogenital 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 that. It's a whole bunch of things you do. Exactly.

And 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 27, these are going to be amazing years because my belief, my hypothesis right now is that you, you 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 perimenopause 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

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I think there's ones that we're even not looking. Oh, so many. metals, like tick infections, like mold exposure. And I've only talked about some of the traditional ones, but like these inflammatory markers that we're looking at and the immune, you mentioned Dr. Tanzi 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 interleukins. We look at CCLs. We look at TNF alpha. We look at so many things.

And then if someone, oh, interleukes. Those are all blood tests. for inflammation. Exactly, yeah. 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. I'm like, so wait a minute, and I look at the panel, and I say, but call him Bob. Bob, Hey, bud, you got an 8-O-E-4. You got a interleukin-17A,

which is an inflammatory marker that's elevated in people with psoriasis. And bud, your amyloids higher than it should be for a 49-year-old. No tau, okay, check mark. Okay, 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 zetamide because he was an over-absorber of cholesterol, not. a statin. He was afraid of statins. Okay, he didn't need a statin anyway. And omega-3 fatty acids. There's omega-3 fatty acids were in the toilet. And he's like, oh, I don't really like fish. I'm like, then take the cats. Carrion and sardines. And sardines are albuquerque and tunas high

in mercury, but like in a wild salmon, at least once a week, but wild salmon has all sorts of stuff in it too. So you take certain supplements that are high quality and everything improved. The interleukins came down. His inflammation came down. His psoriasis gets better. The amyloid comes to, like, everything about is everything improves through some mild changes that were personalized for him, right? And that's the key. We could talk about blood biomarkers. I mean, what you're saying just to be honest 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, 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 grow brain. You can't. 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, pre-symptomatic level. But it's still happening. It's like the Bogalosa heart study where they looked at fatty streaks and the arteries of teenagers who were eating crappy diets to Louisiana,

they 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 he officially joined my research study, and it's been really great to get to know him better through that. You know, I've known him for a long time.

And this guy named Simon was profiled in this documentary. And documentaries were interesting because, you know, they send a film crew, and they get to know people, and they get to know people, and they get to know them. 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 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 8.Bu44. He's got two little kids. Okay. He's in his early 50s, now in mid-50s. got it. And that's 8.O.E4 is the high risk. He believes he's got, 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 should call Simon right now. We're going to link

to the documentary in the show notes. Everybody, we're going to link to all your studies, all your research, all your websites. It's all there. It's all there. It's all there. Now, you've seen the scientific slides because I sent them to you, but the brain volumes grew. And then a year later, his brain grew again. His amyloid and tau, the first at the, the documentary stage, is amyloid improved His amyloid, actually normalized, his tau was still a little bit there. It's gone. Amaloid and tau 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 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.

not the only one. I mean, there's others like Del Bredeson and others who's been on the podcast who's shown that you can increase the size of the hippocampus, the memory center of the brain. You can increase the brain itself and reduce the atrophy. And that leads to changes in cognitive function and improvement in outcomes. We have a saying that we say it a lot, promise not to over promise. And we're cautious. And we want to like undersell 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 in awe. It's a miracle. It's a miracle. 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 story is there. 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 let me finish on the ABCD and E first real quick. The C is cognitive testing. And again, like, 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, we try to make cognitive activities. We call them cognitive activities. We call them cognitive activities. We call them cognitive activities. We call them, you know, worrisome. But we do track your brain.com. You join. You get to know yourself. You can, you know, assess or whatever word you want to use with these cognitive, we call them, you know, activities because they seem less, you know, worrisome. But we do track cognitive function. in our ABCD-N-E model. D is DNA. We do look at some genetics, especially the APO-E-4 variant,

which is super, super, super-important to personalize care, not to deduct or deduce, sorry, if you're going to get Alzheimer's, but it does help personalize care. And the E, in the ABCD-N-E is emotional and social support and health and, you know, stress management,

staying socially engaged, having a meaningful life, mindfulness-based stress reduction is something that we, you know, advocate for, you know, learning new things. The E is something we really, really, really take seriously. And we have to focus on the biological, the cognitive, and the psychosocial

in order to get people off the road to neurodegenerative disease. And you're talking about these social connections and relationships and having meaning and purpose and connection and belonging. 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 and 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 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- So get hearing aids if you can't hear this. Yeah, and if 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 audiologist and see a doctor,

obviously, if you can, 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 for years like we're a hearing aid you'll be more engaged it it may help prevent dementia um you know that's that's that's that's not a pill um that's not a dietary change 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 is a what is a cock what are the cocktail of therapies and what's the what's the what besides the things we

already talked about you know that are so 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 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, I'm sorry to say, but it's not like one

or two things can do this because Alzheimer's and neurodegenerative disease, 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 actually had improvements in cognition, like, again, heresy. That hadn't been shown like that.

So this is symptomatic early dimension. Symptomatic? Well, so both. We had two groups. We had the early treatment. group and the prevention group. And I think 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 percent in order to have an impact on their cognitive function. Benjamin Franklin, right? Yeah. Announce the prevention is where the powder cure. 100, 100 percent agree with that. But the people before they had symptoms, whether they followed greater than 60 percent or less than 60

percent of the recommendations, they still had cognitive optimization, 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 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. 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. But the, the two kind of categories that I put it on are in are, I would say, non-pharmacologic and then pharmacologic. And in the non-pharmacological bucket, you know, for example, actually.

There's non-drug. Yeah, non-drugs. So non-drug. 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, exercise on a regular basis is by far the number one thing a person can do to reduce their risk of cognitive decline. If you put mice on a treadmill, their amyloid can go down. And most people don't realize, like people say, oh, there's these new anti-ameloid drugs. I want an anti-ameloid drugs. That'll fix me, right? Well, they're expensive. They have side effects. There's a whole thing. And 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 amyloid in their blood and in their brain tomorrow, they should start on an exercise program that's approved by their physician and targets the thing that they need to target. And there's major papers published that in JAMA, like just walking prevents Alzheimer's. Yeah, I mean, anything is better than nothing. And, you know, someone who's sedentary, I'd rather they walk. I think walking is physical activity and physical activity is better than nothing. But to me, physical exercise, especially when we get past a certain age, We need to be mindful and we need to be intentional about how we do this.

So if a person is going to say, well, I'm going to go walk three times a week and I'm going to prevent Alzheimer's, well, not if you have excess belly fat and not if you're undermuscled. 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 example, if someone needs to lose belly fat, you know, walking slowly is probably not going to be enough. You need to get into a higher, you know, what we call zone two or steady state cardio or the heart rate goes to 60 to 65 percent of, of, you know, the person's maximum. The best way to kind of approximate that is 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 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 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. 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. But that's a way to do it. And for people that are fit and their doctors say, okay, doing fasted walking, fast walking with a weighted vest early in the mornings before they've had any, maybe black coffee.

But if you don't have any carbohydrates in the system, you may be able to burn fast. fat even more efficiently, but again, some people, you know, shouldn't start like that. But the belly fat, you know, you're not going to fix it by doing crunches 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. Incredibly. 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, 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 someone is trying to lose body fat they should be doing zone two 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 because there's a there's the mind diet which is Mediterranean and you know like the way I think

about it 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 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 malcon 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 methylation issues and high homocysteine, she had low omega-3 fats, I mean, just the list went on and on. And we fixed everything, and her cognitive function dramatically improved.

And then after like three or four years, she started noticing a little bit of the 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 with all this? Yeah.

Well, so nutrition and dietary patterns versus single or multiple nutrients. Like 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 to me, different diets, you know, we're not in the realm yet where precision nutrition is like easy off the shelf straightforward, but different people, I believe, need to follow different dietary patterns. And I, and I too, back in, I think, 2007 was the first time that I put someone on a ketogenic diet

and saw something that I just did not think was possible. But then I've had other people where I put on ketogenic diets and, like, things kind of went the wrong way. And to me, you know, 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 where we could put into a computer and the computer will spit out exactly what the person could eat. 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 APO-E-4 gene, like we have to have enough

omega-3 brain-healthy fats, otherwise people will have cognitive decline in the synapses. Because a lot of your brain is made up of DHA, which is 60% as far as I remember, which is And DHA and EPA are the two most brain healthy fats, and DHA is especially important for people with one or more copies of the APOE4 variant. So brain healthy fats, that's Pufa's polyunsaturated fat. Then you have mono-unsaturated fats. Mono-insaturated 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, of the olive oil out there is corrupt. Exactly. So, you know, getting quality olive oil, like literally taking a shot of it, one or two shots a day, or pouring it on everything. You know, I have olive oil moustache in different parts of the house and just pour it on whatever I can get it in because I need. And if it burns the mouth, yep, that's exactly the proxy has a taste to it. So avocados, olive oil, fatty fish, brain healthy fats are like so critical. 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 goat milk way, which was a first for me. So I appreciate it, which is really nutritious and actually tasted really good. So, you know, green leafy vegetables, high antioxidants. People should be eating mostly plant-based. I would call plant rich. Yeah, plant rich, yeah, plant rich. And, you know, there's totally different.

Because plant base is vegan. Yeah, oh, no, no. 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, yeah, I don't know the exact terminology. But, you know, and then, like, meat is all not created equal. 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 otherwise, they need to get protein levels, whether it's through way protein, through goat or weight protein through regular milk from cows. I think each person needs their own individual kind of 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 mouth this morning. I travel with dark cocoa powder, which is completely ridiculous, but I never leave home

without my dark cocoa powder. And yeah, 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. Again, it has to be like pure and not have the heavy metals in it and things like that. But dark cocoa powder can help with insulin regulation, blood pressure control, and has shown to be beneficial for brain health too. So Richard Isaac starts this morning with a mocha.

I do. 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 Montanahal 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 brain health. Exactly. Yeah. We don't want people to do it too much at home because then they practice and the doctor see the doctor and they memorize a test. But I don't disagree. Yeah, for sure. There are definitely ways to track track. So fatty foods, omega-free fats, monocytes, berries, leafy greens. You know, nuts and seeds, you know, balancing the omega-6 with omega-3s. There's so much nuance with nutrition, but I think that's it. Also, the elf diet. What's that? Oh, my, did.

Eating moss in the Arctic Circle. I just stuck. Dr. Mark Hyman on a diet. 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 Ulf diet, eat less food. Oh, eat less food. Yeah, yeah. Like Michael Paul, they eat food, not too much, mostly plants, right?

Yeah, so just less. Like, people just eat so much in excess. Like, it's crazy. And, you know, there was a study out of Mayo that showed that people that ate, like, I think of the cutoff was, like, 2,100 calories a day, less than 2,100 or more have, you know, delayed cognitive decline. And, and again, this is, like, imprecise. So the Okinawa principle, right?

Hari-hachi-boo, which is eat pay percentful. Exactly. Hari-ha-chipu. That's exactly it. So the take-home here is, though, if you're trying to gain muscle, well, you better eat sufficient protein and calories because you need both carbs and protein to build muscle and you don't want to, like, just starve yourself, and there's good carbs and bad carbs and know the difference. 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 not if a person's not active. you know so so anyway uh yeah nutrition is you know tricky um you know vitamins we we talked about um you know mega three fatty acids but vitamin d especially people with one or more copies of the apoey four 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 an example 60 percent of the people in miami even with sun exposure are deficient in vitamin d so we check vitamin d and we have to be

naked between 10 and 2 in the afternoon for 20 minutes. And if you're not, you're not going to get out vitamin D. If you're if you're if you're if you're if you're if you're 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 12 to 15 minutes between the hours of 11 and one to try to split the difference. I don't want to, you know, it's it's hard to know for sure. But, you know, we, we check vitamin D 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 size fits. everyone. The Vitacog study, which is published over a decade ago, showed that when people

had a marker in their blood called homocysteine, if homocysteine is high, the people that took B complex vitamins, B12 folic acid and a tiny little bit of B6, those people not only did they have slightly improved memory function on cognitive testing, but those people actually also had slower shrinkage of the memory, sorry, of the total shrinkage of the total brain size. So for me, it was a paper published A number of years ago in Jammer, in the New England Journal, I read where if your homocysteen was over 14, the year 50% more likely to get Alzheimer's or dementia. And that's, again, something we test that function health and also methamelotic acid, which is a marker B12 function.

And I remember a patient who came to me who was, you know, a very successful businesswoman, was on multiple boards. She was in her early 80s, and she's like, I got diagnosed with MCI, mild cognitive 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 homocysteine and high methamlonic acid, which is a marker of B12, which are probably better than measuring folate and B12 in the blood.

Probably had a double MTHFR mutation. And she did. She had the genetics that made her having trouble with her metabolic pathways. 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 to get acid blockers. They don't get, I mean, that made me crazy.

I mean, there's the third most leading prescribed drugs after statins and psychiatric drugs is the acid-blocking drugs, which are now over-the-counter. And they're dangerous to take long-term, fine, short-term, but long-term. And so I said, I found this, and I gave her B-12 shots, and I gave her high dose of methyl folate and some B-6, some of these methylating nutrients, and completely cured her MCI. Now, it's not that everybody with MCI or pre-dimension 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's, well, I'm going for a trek in Bhutan. She's 85, and I want to know what I should be doing and 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, I think, you know, curcum and the active ingraten curry, I think in certain people,

especially with elevated amyloid levels in the blood, you know, we usually, we sometimes use this. And I think in terms of like the big picture, those are like the one size fits many ones. But I mean, the list just, I mean, list is really long. So, I mean, there's definitely other things people can do. But the take home here is, you know, we check it in the blood.

We do the history and then we personalize a plant for them. So I think nutrition is really, nutrition and exercise are like critical, critical levers. And, you know, in our research study that we presented data that I can talk about because we presented this. at the 2025 Altimers 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. Sleep, sleep, stress management, keeping the brain engaged, learning something new, seeing a doctor on a regular basis to make sure their blood pressure, cholesterol, you know, blood sugar is all modified

and in an optimal range specifically for them. When you put all those together, but no drugs, if you look at the groupings of 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 amyloid drug studies. In our study that we've, and this has been fully published, but I can talk about it because we present an abstract form, there are people that, for example, took GLP1 drugs. And GLP1 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 microdose crew when it comes to GLP1's. GLP1's positive effect on biomarkers, you know, in my opinion, based on 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 roam to do that, right? If you radically improve your diet. I mean, I mean, before GLP-1s were on the market, I was reversing diabetes, getting people to lose 200 pounds, 100 pounds, 150 pounds. You can do it. It's just, and I think my guess is that they would do a head-to-head comparison of GLP-1s and the same diet that you would eat if you were on GLP-1s. There would be no difference in any of the biology. That's my funny. So while multimodal treatments, you know, I would say work 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 neurodegenerate disease.

So you're testing, not guessing. We test everything. You're like, hey, let me try these 20 things, and let's cross our fingers and maybe do a, like, a sort of semi, semi-subjective, objective test, which is a bunch of questions. We try something. You're actually looking at blood tests that 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.

But, and we just try to do things as rigorous as humanly possible. And what we show is that when we do these tests, we call these N of one studies, we'll try a GLP1 and we'll check, we'll try hormone replacement therapy. Like hormone replacement therapy, bioidentical hormones for women during the paramedopause transition, in the right woman, at the right dose, the women in our little hormone replacement therapy group, 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 in our team. We've had, I'll just say what I feel like I should say, amazing success with using hormone replacement therapy. And when that rapid drop of estrogen comes in a genetically

susceptible woman. You know, we did this whole women's brain imaging study at Cornell and spent, you know, millions and millions of dollars on this. Women that had, you know, hormone replacement therapy on board had better brain volumes and less amyloid. But it had never really been proven in a study that you could use H hormone replacement therapy. And then there's this, that women's health study that used like synthetic hormones in horse urine derived, whatever, like when you use a bioidentical patch and you use progesterone, and we talk to the GYN and we talk to the doctor's, hormone replacement therapy during the paramedal post-transition has helped improve brain biomarkers associated with Alzheimer's and neurogenital disease risk. It's been striking. So

this is more than just what it's 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 and improve the blood biomarkers that are associated with neurodegenerative disease. That's a 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. What end early? I want to start both. Both. Both. I see, yes, start early. Does that mean every woman should be on porn replacement therapy? Like what are the implications here? Yeah, this is, these are really, you know, and by the way, why hasn't this been better studied? Why are we the only group to my knowledge? Because we have misogynistic. in research infrastructure. Like, it's, it's just so, it's demoralizing. It's just so wrong that women are taught that, like,

oh, you're having night sweats. Oh, oh, you don't feel good. Oh, you're having brain fog. Oh, okay. Sorry, you know, we'll see you back in six months. Perimenopause is a neurological disease. Like, you're just going to have a woman suffer. These are 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 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 the right duration in collaboration with the multidisciplinary team, when we start seeing the estrogen drop, even if the symptoms are very mild, you get the

estrogen back up, the tau starts coming down, even though the tau wasn't elevated to a degree where we're like, uh-oh, sky is falling, but the tau is higher than it should be in that woman who's 47 years old. And this whole concept of like, you know, uh, it's normal. Well, no, optimal is where we want a brain protein. Normal, uh, 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 paramedopause transition, to me, is one of the most impactful tools that we can use to reduce the risk of cognitive decline dimension, Alzheimer's disease, and women. And I think, you know, it's tricky. I think there's risks and benefits with every one of these decisions.

But, you know, I've just seen too many women suffer, and it's just not fair. So if they're symptomatic, or if you do evaluations that you have a higher risk, based on your Alzheimer's risk score, which you've developed, then maybe it's a good idea. But even if you're not symptomatic. Well, I think if you're symptomatic, it's 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, 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? Ptal 217 changes and these other markers change too. How has this never been done before? So we have women, we have like, Val, thank you. Thank you. I'm not going to say their code numbers 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 petal be at what depending on what day the blood was drawn, we need to correct for what the tau level should be

based on where the estrogen and progesterone is. 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, we've seen women in their early 40s, like 42 is the earliest we've started, where we've seen the estrogen going down and we've seen the amyloid going up well maybe they're a little symptomatic

but it's not really bothering them but we're going to start on low-dose hormone replacement therapy if everyone is in agreement and guess what she feels better her cholesterol comes down that's interesting her amyloids 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 you 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 to me it's if symptomatic like please talk to your doctor and if your doctor says tough it out like go to another doctor if you're pre-symptomatic um follow it closely i think women pre-menopause should should probably get checked every six to 12 months for these brain biomarkers and hormones 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 are emerging are abnormal, then it's better to get out 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 woman is actually lives in Austin. One woman is in California. I mean, I know these cases, like, you know, the back of my mind, like, you just start

and you see everything improve. This is honestly, Richard, why we co-founded function, 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 very low cost, we've dramatically reduced the cost. You can get all these biomarkers, including APOE4 and some of these brain biomarkers, and then you can kind of start to decide what to do and take control of your own health. I want to ask you about guys because two-thirds are women, but then one-third is guys. Do guys benefit from hormone replacement therapy in terms of testosterone?

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

And then what else is going on? Like what other hormones? Because sometimes when people use testosterone, they're also doing like. five other things. 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 and, 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, you want a physiological level because then your estrogen levels will go because you convert testosterone and estrogen, then you start having libido issues and other issues that are, it's like, it's, it has to be done right. Exactly. 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 productivity 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 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 benzos or Valium or that category of Xanax, Ativan, 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 of minutes, huh? Yeah. So, you know, everyone out there 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 the 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. Like objective blood test. Every, I mean, objective cardiovascular tests. I wear all these trackers. We track everything in all of our patients.

I mean, the only, this is like crazy, but the only thing that changed in an otherwise optimized person, if you get sleep right, the amyloid can come down, the cognition can improve. Sleep is so critical. 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 in, like, 7-11, that's how I remember it, like 7-11. Seven hours and 11 minutes, the people that slept more than that did better cognitively, the sleep that did less. Seven hours and 48 minutes last night. Great, I take it.

That's good. And, you know, obviously, you know, it depends on the sleep quality. Yeah. Deep sleep is restorative sleep. That's when the trash gets taken out. The amyloid gets, you know, taken out in the garbage. You know, REM sleep is when short-term memories are consolidated or really formed into long-term memories. So there's sleep quality and their sleep quantity.

And the number one way to get more sleep quality is to sleep longer to have more REM and more deep sleep. Like that's a cheat code. You know, to me, you know, actually retainyourbrain.com is the, actually, I'm in a routine right now. What retain your brain does is gives a person suggestions. And as I'm holding my coffee, I don't know what time, and it's 11 or 12, 12 in the afternoon, I am not allowed to drink coffee after 11 p.m. based on my time's up.

Time's up, you know, because, you know, caffeine lasts for five, six hours, the half-life. So if I'm drinking coffee at two or three or four o'clock in the afternoon, I still have caffeine in my system as I'm going to bed. So to me, 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. Your plugs in eye shades. Yeah, exactly. Weighted blankets. Some people really like those. like cooling temperature. 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. The other thing is... In fact, I'm re-installing 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 the 70.

I'm like, that's not good enough. Yep, I agree. You know, my other routine that I got, 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 well what does that mean every night at 930 p.m. my alarm goes off as a reminder that says power down your electronics so at 930 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 there's my grateful dead bear 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 we're and his his band called the the wolf brothers i was waiting online to get into the show someone miracleed me with that so too many inside jokes yeah sorry yeah old old dead head 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 forward's cognitive decline. Okay, two more things I want to occur before we close out. Got sleep, got nutrition, exercise, we got supplements, we've got hormones. And you mentioned there are like 50 different choices. So there's a lot of things. And people can look at your research, we can only tell your papers, all the media on you, people can learn more.

There are, you know, two other pieces. One is what about pharmacologists? interventions because drugs have a role and kind of one of the one of the star players here and and and um and also like what about brain exercises like brain games learning language so those are two things we to talk about but i think they're key pieces 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 anything like that um i'm equal opportunity if it's a drug a vitamin a supple 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 intervention. So I'm not pro-work on anything. I'm pro-evidence and I'm pro-safety. That's all I am. 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 years and years and years to publish. The general categories of drugs that worked the best. Well, we talked about hormone replacement therapy and we talked about GLP-1s and those drugs, drug categories worked honestly,

amazingly well. Like, it's just, I was floored by it. There are 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, cholesterol treatments and those are two statins as a category and I'll explain the nuance there and then isetamib or zedia which is a plant sterile inhibitor and we've broken out groups into statin use versus zetia use that's the brand name but it's all generic now and then the other categories were I think this was in the paper SSRIs selective serotonum reuptake inhibitors and then the final category is anti-amilid drugs so these are drugs that we've studied and these are things that we've studied in our cohort. You're also talking about GLP-1s, too, are part of this.

Oh, yeah, yeah, GLP-1s and hormone replacement therapy are definite check marks. And I would say in our study, multimodal interventions work the best. GLP-1s 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, 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 spend billion dollars researching and have shown very incremental benefit.

Yeah. They're not like zero, but they're... Yeah, and they may be additive to an overall package of interviews. True, true. And in the right person at the right dose, azetamide, the plant sterile inhibitor, 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 Sanupy, Alpha synuclion is a pathologic protein that builds up in the brain of a person with Parkinson's disease and Louis body dementia. Like, we are working on these blood tests. Like, this is crazy. Never in a jillion years, like what I've ever, regardless of my family, my brother's son,

my brother's brother's brother-in-law, like we see these drops in alpha-sinuclion protein using some of these things. These are Parkinson-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 and the right duration,

you know, your mileage may vary, work. And it's improving what I believe to be brain health risk and brain health outcomes. Staten. Let's talk about statins. The people that start on statins in our cohort are not your typical, you know, Crestor, resuvastatin 20 milligrams. Like the amount of people I see on high-dose statins,

it like just blows my mind. 85% of the cholesterol lowering effect of resuvastatin or crustor, comes at five milligrams of the dose. So you get 80% of the benefit at the lowest dose. Yep. And no one knows this. 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 5% or 10% 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 as having healthy mitochondria.

Yeah. And, you know, the side of it. 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 you're an overproducer of statin genetically or biologically. So lower dose statins do show brain positive effects in our research.

But you guys are throwing out 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 me have myopathy or muscle damage. If I take a statin, I have that gene, I tested it. So, stats are not good for me. And they also cause mitochondrial damage. And if you do the test that helps you personalize or pre-precision approaches,

you're going to get a better effect with less side effects. And there's a friend of my David Faganbaum 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 Zetamide or Zeti, it works for Alzheimer's, but it 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, you know, these are, again, these are. Am I catching on? You are. You're catching on. 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 Louie Body and Parkinson's, but I want to be really conservative, not fully published yet, like we're just, we're just learning. S.SRI, selective serotonomy uptake inhibitors. Prozac. Yeah. 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 S. Cetalopram or Lexapro, it's all generic now, S. Cetalopram, 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 amyloids so in our little group you know we have a group of preventive neurologist preventive cardiologist 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 s etatalopram. 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 usually go high. And by the way, we're not treating, you know, I'm not a psychiatrist. I, we're, you know, mild depression versus major depression. 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 esotalopram or lexipro 5 milligrams, I would say, on average. And in our cohort, it's a small, small group, but we also saw, some, but not, I would say, slam dunk robust effects from low-dose etatalopram, low-dose lexoprop. So this is really important. I just want to step back, because we kind of have to wrap up.

But I think that, you know, 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. Isaacson, is that for the first time in history, we're actually able to do preventive neurology around neurodegenerative diseases 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 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 pre-symptomatic stage of Alzheimer's that are measurable by these blood blood margars, that is going to cost us $18 trillion over the next 30 years. This is revolutionary. And if anybody's listening who cares about this issue, who wants to help, and again, I have no affiliation with you other than being your friend and having a bond over the grateful dead, following your work for years, this is where the money needs to go.

This is where the philanthropic dollars need to go. This is where NIH funding needs to go. If you're listening, J. Badacharya, 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 Ultramine Solution 15 years ago, or more than 15 years ago now. And I think we're at this transitional moment in history where for the first time, 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,

you lose you. You lose your family members. It's a catastrophic disease. And everybody's terrified of getting it. And nobody should be afraid of doing the diagnostic test to figure it out. And now at Ezra, which is a company we bought with function, we actually can do brain imaging. And we can do quantitative brain imaging, which is a more advanced service we offer.

But we can actually start to track these things over time. And so you can begin to do these things. You can go to retainyourbrain.com and start to kind of get ahead of the game. So, Richard, I just want to say, thank you for what you've done. Thank you for the insights for the aha. moment you had in the hallway with that guy with the bishop with the manager. We never know how we get doing what we're doing. But I hope that you were continues. I hope that you get it funded not to 10 or 20 million dollars, but we need a billion dollars. We've spent so

many billions of dollars and wasted them. This is an area that needs real serious funding because what you're seeing is real. It's not quackery. It's not heresy. Well, it kind of is heresy, but it's actually valid scientifically. And we need to get behind it. So thank you for everything you've done. Thank you for what you're doing. You're leading the pack for the rest of us. And I just appreciate everything you are and everything you're doing. So thanks for being on the podcast. Thanks so much, Snyderheim. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to

the Dr. Hyman show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health, where I am chief medical officer. This podcast represents my opinions and my guest's opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical

professional professional professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at Ultra WellnessCenter.com, and request to become a patient. It's important to have someone in your corner who is a trained, licensed health care practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public, so I'd like to express gratitude to sponsors that made today's podcast possible.

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