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The Dr. Hyman Show
Become an Alzheimer’s Survivor: Dr. Richard Isaacson’s Breakthrough Approach
01:45:27
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A
47 million Americans are going to get dementia if we don't do something about it.
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People think of dementia and neurodegenerative disease as an older person's disease and it's not.
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A
Wow.
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B
We can detect changes in the brain decades before a person is going to develop dementia.
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We spent $2 trillion over 400 studies and 99% failed. So we're thinking about this wrong.
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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 Weill Cornell Medical School. He now serves as the director of research at the Institute for Neurodegenerative Diseases.
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A
And he heads the NIH funded retain your brain program about retraining your brain.
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C
And retaining your brain by doing specific.
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Practices that help you preserve your cognitive function. Take us 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 we need to take a different approach.
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45% of cases of dementia may be preventable.
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A
When someone comes into your office, what are you looking at? What are you testing?
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We do this all now digitally and it's free. People can go right now and get an assessment and like learn about themselves and get automated brain health. Preventative care, preventive neurology care.
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How do you approach diet with all this?
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B
Women that have increased waist circumference are at a 39% higher risk of dementia.
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A
Two more things I want to cover before we close out. What about pharmacologic interventions? Because drugs have a role. And also what about brain exercises?
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C
As you know, I'm always talking about how central the gut is to living.
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A long, healthy life.
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C
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A
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.
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B
Things are very different now. It's only been five years and there's.
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A
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 sort 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 $2 trillion 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 in this field on the fringes are doing this. But you came from Cornel, you know, an academic. You're trained at Harvard in neurology. You've got the street creds, and you've come at the same thing that I came at decades ago.
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B
Tomatoes getting thrown at us.
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A
Yeah, I mean, you're. What do they say? You know, the pioneers always have arrows in their backs. Right.
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B
I'm still bloodied and bruised.
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A
So take us down your. 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 we need to take a different approach and even a concept that isn't really well accepted, which is that you can actually prevent Alzheimer's.
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B
So, you know, we don't live in a healthcare 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 Lewy bodies. These are diseases that start decades silently in the body and brain, and that's when we need to do something. So I had this crazy idea. Alzheimer's Prevention Clinic, it can't start. You can't use Alzheimer's and prevention in the same sentence. That's cookie talk. And this is 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. Can we do anything to prevent. Like, what should I do? As a son of a patient of mine, and we spent 45 minutes in the hallway discussing what he and I could possibly do. And then next week, I saw his sister as a patient. And that was the first Alzheimer's prevention 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.
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A
We used to joke and call it Alzheimer's disease.
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B
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 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 gonna 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 I can't see a person to try to prevent dementia or reduce risk for Alzheimer's or reduce risk for Lewy Body Disease or dementia because there's no billing codes for it. I can treat someone with a disease after you have a heart attack or a stroke or dementia we don't get paid for. Because again, I don't want to belabor this, but our whole healthcare system is broken. So to me, we just got to get ahead of things. And the evidence, the totality of evidence is overwhelming that we can do something. And the last time we talked, I feel like I was doing cool stuff back then. And now it's just totally different. The objective markers, the proof is in the pudding. We're able to do things today that are just science fiction, even 5, 10, or 15 years ago. So, yeah, I'm excited about the progress, but it's hard to keep pushing things forward.
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A
It is. And you talk about the 47 million Americans. Forget globally, 47 million Americans are going to get dementia if we don't do something about it. And yet there is nobody pretty much besides you and a few others who are actually thinking this way. I did the math. And if we leave this unchecked, the bill for Americans over the next 30 years is going to be 18 trillion. That's basically the amount of our annual GDP one year. It's a huge amount of money. And what you're saying is that it's really preventable. Now, I want to kind of hearken back to the flawed paradigm, because in medicine we have this idea that you have a single disease, Alzheimer's, that's caused by a single pathway, amyloid deposition, which is this gunk. Gunk suck 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 amyloid drugs for decades and we've spent $2 trillion, like I said, 400 plus studies and massive failure. Why has 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.
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C
Right.
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B
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 over my head. You're an old time family doctor. I'm an old time neurologist carrying the bag. I'm calling myself old, too. So we're all hippies, we're all deadheads in the room. So 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 amyloid, like you said, is the sticky protein that builds up in the brain of a person with Alzheimer's. And when you look at the brain of a person with Alzheimer's, there's amyloid in it. Okay, but 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. 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, then neurodegeneration. Yeah, that happens. But in a recent study, Journal of Neurology, it was like a third of the time. That was the trajectory. But all the textbooks say that's how it is. And the medical students. So to me, there's buckets and different people present different ways. And the way that I view Alzheimer' and also the way I view neurodegenerative disease as a whole is it's very heterogeneous. There are so many different types and manifestations.
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A
And even though the end symptomatology and the diagnosis is the same, each of these patients might have different causes and need different treatments.
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B
Yeah, you can take different roads to Alzheimer's. You know, women, you know, for example, Mrs. Smith, she may be, you know, perimenopause, the estrogen is dropping she may have a variant, a genetic variant called Apoe, which we could talk about Apoe 4. And you have the Apoe 4 and the estrogen drops. Will 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. As a belly size gets larger, the memory center in the brain gets smaller. He needs a kind of more metabolic health and a different plan. He's going to need therapies X, Y and Z.
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A
The bigger your belly, the smaller your brain.
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B
That's smaller 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.
- [12:11]
A
And we call this N of one medicine. And, and the NIH has actually declared this as one of the most important and actually predictive forms of research and they're funding some N of 1 research trials. But it still hasn't kind of permeated the funding really. It hasn't permeated the thinking at all.
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B
No. And you know, this is what you.
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A
Call it as precision neurology, precision prevention.
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B
That's exactly it, right?
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A
Precision or personalized, it's, it's not one's.
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B
Heist fits all taking this individualized approach. People hear the term precision medicine. Ooh, that's fancy, expensive tests. 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 the cost has come down doing cognitive assessments. We do this all now digitally. It's free. People can go right now and get an assessment and learn about themselves and get a way to have automated brain health, preventative care, preventive neurology care. And doctors just don't realize and it's not doctors fault. Like in medical school I was taught one thing and the fields change and the fields change so much in five years. So to me you've seen one person, you see one person with Alzheimer's. And what we've done recently is now not just studied people 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 something called the bioran Study, 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 has a diagnosis of Parkinson's. It's all, wait a minute, something a little different. You have to study these things together. And there's so much.
- [14:10]
A
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 the question is why? And you've been asking why? It's not what 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 that will help you get better? Yeah.
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B
And what are we going to do do about it? Exactly. There was an old saying. Neurologists don't treat disease. We admire it. Adios and diagnosis. No, not. Not anymore.
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A
That's, that's an old neurology saying. Adios and diagnose, diagnose and adios. Meaning. Meaning you make the diagnosis and there's nothing you can do about it.
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B
Yeah. And that's just, that's just plain wrong. And you know, with, with four family members with Alzheimer's disease and like, and just seeing the suffering, that's not okay. And I don't care if it's a. If it's.
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A
You have four family members.
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B
Yeah.
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A
Oh yeah.
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B
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. And it makes me sad and it just motivates me to just keep going. And there's so much confusion out there. But 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, we can't be tricked into thinking, oh, you have to do a randomized, controlled, double blind study where everyone gets one group, they get one treatment, another group, they get a placebo. No, different people need different treatments. 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 plans. 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 amyloid drugs that you mentioned. And then we map them all out together and we group them together. And that's real world evidence to show look what's working, look what's not, and we're helping the individual people. And if we just put everyone on an anti amyloid drug or everyone on a one of the GLP1 weight loss drugs or just put everyone just on exercise, it ain't gonna 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 recognized the way it should be.
- [16:41]
A
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 gonna do anything. So I always say, if you don't have vitamin D deficiency, giving vitamin D isn't gonna do anything. If you don't have insulin resistance, giving a GLP one isn't going to do anything. So you've got to customize the treatments. One of the failures of medicine is, you know, we have a rule in functional medicine called the tack grills. We talked about it last night at dinner. If you're standing on attack, it takes a lot of aspirin to make it feel better. So if something's in your system that's bothering you, that's irritating you, and you mentioned a case, for example, someone 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 damaged to the brain, it's amyloid deposition. That's just a reaction to Various insults. The insults could be toxins, they could be Alzheimer's, 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 gonna 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. 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 in terms of blood testing. And we 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 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, if I've reversed the effects of Alzheimer's, they're going to just laugh in your face.
- [19:41]
C
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- [20:48]
A
This week.
- [20:49]
C
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- [21:42]
B
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 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, 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, 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, you're.
- [22:39]
A
Agnostic to the treatment.
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B
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, 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 in residency. I didn't learn about that stuff. But I don't care what it is. Just, just, just try it. And then just recheck markers and whether the markers are blood markers, cognitive assessment markers, which, again, it's easy to do now, or brain volume markers, and some of the slides that I sent you, not yet fully published. And, and people's brains are growing. Like, that's, like that's heresy. That doesn't make sense. And I'll be honest, a decade ago or 20 years ago, I would say that's not true or BS, but I see it. And when everything is going in the right way, when everything about his, everything improves, that's evidence for me.
- [23:30]
A
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. Cholesterol. We check cholesterol. Cholesterol is a risk factor for heart disease. It doesn't necessarily cause heart disease. There's other blood biomarkers. We tested function that are also very big risk factors, like lipoprotein little A, which is genetics. So you can actually map person's trajectory by knowing their biomarkers. We do the same thing for metabolic health. We can measure glucose or insulin or A1C and see the trajectory of it going up before they get diabetes. So this is a. There's a proxy for this in medicine, but with dementia, we don't really do that. And what's really remarkable about your work is that you're 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 that these particular blood biomarkers, you're developing new tests that are from protein signatures expressed in people early decades and decades before they eat, 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 us identify that risk, including APOE 4 testing and APOE testing, which is a gene for risk for Alzheimer's. Looking at P Tau217, which is another marker, AD4240, which is amyloid biomarkers. But you're going way deeper than that.
- [25:03]
B
Yeah. So when it comes to blood testing for Alzheimer's, and by the way, five years ago or whenever we last spoke on the podcast, like, like never in a million years, whether it was two years, five years ago, 10 years ago, 20 years ago, never in a million years did I would have ever pictured myself having a lab in Boca Raton.
- [25:21]
A
Florida, developing, there's a lot of Alzheimer's disease.
- [25:26]
B
Well, that's what they call it and it should be called something else.
- [25:28]
A
Joke. Bruce Ames, who's a very famous scientist, said on epidemiology with his population studies, he says if you did a study of population in Miami, everybody be born Hispanic and die Jewish.
- [25:43]
B
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. I'm not a basic science guy. I never like centrifuging blood and developing at home, testing using different devices and starting with a panel of say 1,000. And now coming, hey, we're down to 150 tests and we're getting it down. And my goal and our goal at IND and elsewhere, we are trying to develop what will one day be termed the cholesterol test for the brain. And if we're talking baseball analogies, we're still in the first inning, in my opinion, of a nine inning 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 yeah, there's this P Tau 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 gonna come to the office, and I hope that our work will help 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 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 5 to 7, maybe 10 markers will be. And we can track these test, and we can do it in a way that we can lower cost, increase access, and then give people digital tools to 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 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 or 6?
- [28:18]
A
What are the reference ranges?
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B
What are the reference ranges? And 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 gonna be, and these tests.
- [28:36]
A
And we'll talk a little bit about them in detail. 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?
- [28:51]
B
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 talk to the patient. Looks like they have Alzheimer's. They don't have amyloid. Oh, I wonder. Well, I guess amyloid didn't cause Alzheimer's in that person. But by definition, you have to have amyloid to have Alzheimer's. Our instruction manuals are totally wrong.
- [29:22]
A
Rudy Tansey, who's a friend of both of ours, an amazing guy who's an.
- [29:24]
B
Alzheimer's researcher, we just said amazing guy in unison. So I hope he hears that. And he's a deadhead.
- [29:29]
A
So 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 said that there are patients who have brains full of amyloid but die old, cognitively intact, meaning normal. And he said, what's unique about these people, and I'd love to hear a perspective, is that they have certain genetic variations in their immune system that don't mount an inflammatory response. So as far as I understand the literature, Alzheimer's, the, the end result is the end result of an inflammatory process in the brain. And there are many things that can cause inflammation, from infections to toxins to diet, to pre diabetes or diabetes to mold, to, you know, Lyme disease. I mean, Chris Christopherson had, quote, dementia and Alzheimer's, but he had Lyme disease and he got treated with antibiotics and his dementia went away. So, so I think we have to think more about what the underlying pathology is, which is inflammation and then why is there inflammation? And then hunt down the sources and the cause of inflammation and remove those. And that will lower, I might believe, lower. These blood biomarkers that are around even a few years ago, they weren't really available. These things like P Tau217 or amyloid biomarkers like AB4240, other P Taus like 181, 231 neurofilament light chain, which is more for brain damage, or something called glutathione allele fibrillary acidic protein, or G, 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, is my blood pressure high? And those are risk factors. And then these that tell you that you need to do something. And the question is, how do you figure out out what to do in each individual? If you're treating Everybody as an NM1 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?
- [31:41]
B
The way that I do it in our research program 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. And when someone can't access a doctor or can't get into a research trial, we have five sites in the US and United States and Canada. And if you can't access one of those sites and if you can't see a preventive neurologist, then we do it through software. And I'll explain how that is. And we got funded by the National Institutes of Health. We conducted a very large, almost 1000 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 retainyourbrain.com if there is anyone out there with a brain, brain that wants to like, wait, I have a brain? I think you, I think you do. You definitely have a brain. It's, it's, you have a very robust brain. It's functioning. Check mark. Neurologist approved. I'm going to give the cliff notes version in the ABCs and E's, but if there's anyone out there, like we 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 retainyourbrain.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 does a risk assessment. It can do cognitive games, feel like games, whatever. And then the software will tell you what to do.
- [33:03]
A
This is mostly based on your history. You're not necessarily doing blood work or baby steps.
- [33:08]
B
Yeah, in time, in time. But right now it's all accessible and there's no cost. And 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.
- [33:22]
A
So the retain your brain, which is what we all want to do is retain our brain, is a platform that you develop that basically has downloaded 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 neurodegenerative diseases or you're worried about getting it, get on it and it's free.
- [33:50]
B
Next.
- [33:51]
A
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?
- [33:59]
B
Oh, we go really deep.
- [34:00]
A
Yeah, tell us what you're. Because I think this is important because people don't know what to look for. And I think there may be many physicians listening to this podcast. Hopefully there's some philanthropists who have family members with these diseases who are going to listen to this and go, wait a minute, this is a place where I can make a huge impact that is being neglected by the outdated medical research establishment and the antiquated thinking about a reductionist model disease and the fear of doing too many things at once in a patient. It's like, you know, I think that's, that's the joke is like you have to treat everything right. If you have low vitamin D or low omega 3s or you have pre diabetes or you have heavy metals or you have mold or whatever you're 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.
- [34:49]
B
Medicine, the A, B, C, D and E of Alzheimer's and neurodegenerative disease. Risk factor, risk reduction, prevention, management is a paradigm that we published on at nature mental health. January 2024 was the last time we kind of updated the paradigm and it's all again, doctors out there listening, any healthcare providers just you can read the paper. But the A is simple. It's anthropometrics. So what does A stand for? Anthropometrics is body composition, body fat, muscle mass. I also kind of throw bone density in there because bone density, grip, streng, I think also an important proxy for.
- [35:22]
A
And why is that important? Well, as you go through this, I'm going to kind of have you go through and explain why it's important.
- [35:27]
B
Sure. 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 he talking about.
- [35:32]
A
Why is he talking about belly fat?
- [35:34]
B
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. And I'm paraphrasing, I don't remember what.
- [35:43]
A
The title was, but it's a disease of the brain or a body disorder that affects the brain.
- [35:47]
B
So I believe Alzheimer's, and 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, sign of end organ damage is kidney failure or tingling and numbness in the toes or something called macular degeneration where people lose vision because of diabetes. I believe medical conditions, the neck and below things affect the brain.
- [36:21]
A
When I talk about that's a heresy because most neurologists stop looking at anything below the neck. Yeah.
- [36:25]
B
And I'm like, I'm an old time family doctor. Like I'm an internal. I feel like I practice one third internal medicine, one third preventive cardiology, and one third preventive neurology, which is a field that just barely exists. So what I'm going to talk about now is going to be very medical and I'm glad I'm with you because.
- [36:43]
A
You can, I can translate if you can.
- [36:45]
B
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 belly size gets larger, the memory center in the brain gets smaller. Women that have increased waist circumference, okay. Visceral fat, meaning fat around their body organs. Women are at a 39% higher risk of dementia.
- [37:11]
C
Wow.
- [37:12]
B
That have fat around their visceral organs and belly fat. And you know what happens to women during the perimenopause transition? It gets really, really, really hard to lose belly fat. And there are things that we can do change that. So we track all these things and we use belly fat, muscle mass. People lose 1% of muscle mass per year. I mean, muscle mass is not easy to build. And doctors don't focus on. Why are people talking about weight. Stop talking about weight.
- [37:40]
A
Body composition.
- [37:40]
B
Talk about body composition. Everyone needs to know these scales, okay? They're a couple hundred dollars. But everyone needs to know their body fat. We want to lose fat. We want to gain muscle muscle. We want to put on muscle. We want to lose body fat. A lot of people take these weight loss drugs. Okay. They have some really interesting features. They're maybe 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 condition, 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.
- [38:15]
A
So measuring your belly fat is a brain marker is what you're saying, 100%?
- [38:18]
B
Yeah, yeah. Muscle mass, you know, and. And. And belly fat. Absolutely. Critical risk factors to. To prevent cognitive decline, dementia, even Lewy body dementia, Parkinson's. These are all metabolic factors that actually do influence these diseases.
- [38:32]
A
They're all connected.
- [38:33]
B
They're all connected.
- [38:34]
A
So what's B?
- [38:35]
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.
- [38:53]
A
Metabolic markers, meaning, like looking at blood sugar, insulin.
- [38:56]
B
So fasting blood sugar, fasting insulin. A lot of us may have heard of something called a hemoglobin A1c or glycosylated hemoglobin or HbA1c. And people say, oh, above 5.7 is prediabetes 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.
- [39:22]
A
And because they even call Alzheimer's type 3 diabetes. Right, Alzheimer, diabetes of the brain.
- [39:27]
B
Yep. And there's a lot of overlap with the pathophysiology, which is a big word for potentially why these disease happen. And metabolic health, 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 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 hdl. That's the good stuff, right? Well, maybe not. It's a little confusing. There's a lot of confusing stuff with cholesterol.
- [40:02]
A
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, who's 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.
- [40:24]
B
And no one's ever checked.
- [40:25]
A
Which she said, no one's ever. He's 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 our health and at function health. We do these very deep biomarkers for cardiovascular risk that are far just beyond a regular cholesterol panel, including apob, which never gets checked. Lipoprotein A, particle size. We look at function of hdl. You said HDL is not all the same. 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 get the nuances of what's happening. And we look at insulin, which, again, is never tested. So a lot of things you're talking about are things that now people can access for a very low cost, and.
- [41:02]
B
The accessibility is critical. And 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. Agatson, who 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. Dr. Agatson, 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 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.
- [41:42]
A
You can have, like, just the way you can have amyloid but no Alzheimer's, you're gonna have extremely abnormal cholesterol and clean arteries. And I have patients like that. I'm like, wow. Yeah, your LPA is high, Your APOB is higher. Your particle number is high. Your particle size is small.
- [41:56]
B
Clean as a whistle.
- [41:57]
A
Yeah, clean as a whistle.
- [41:58]
B
And. And that's the thing, like in. This is precision medicine and personalized care. So anyway, we look at all these markers, and we look at apob, we look at lp, we look at ldl, 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, we look at markers of absorption. Is someone, you know, if someone has high cholesterol instead of just throwing them on a drug that you know, you know in the grand scheme of things may work for 70 or 80% of the population. What if you're in that 20 or 30% where you're not the right person? And I think you and I, whatever we may be, I 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 like statin, right? A statin drug. That's not the right drug for me. Generic drug, calls it Ezetimibe. It's a plant sterol inhibitor. That's the right drug for me. Cause I've had that checked since 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 choose.
- [42:58]
A
It's basically also called Zetiaback. But it's interesting because I have genetics and I've done my cardiovascular genetics and 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 I dropped like a stone.
- [43:18]
B
Because you had the right drug for you.
- [43:19]
A
Basically it's not the cholesterol I was eating from eggs, it's the cholesterol that's produced by your liver and bile. It's excreted in your bile that gets reabsorbed, formed that you kind of have to manage.
- [43:30]
B
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.
- [43:36]
A
All this, what we talked about just now is all available through function health for $499. And there's ADD ons for cardiovascular health. You all start going deeper on blood biomarkers. I want to stay on the B because you are looking at additional things that in addition 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.
- [43:56]
B
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, by the way, I can't believe I'm saying this. Like, this is 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.
- [44:30]
A
And for some patients with dementia, taking a statin might be a bad thing.
- [44:33]
B
Yeah, certain genetics. And you need to track everything, and you got to figure out which drug is the right drug for the right person. And we're working on this through Ind.org, which is our nonprofit.
- [44:43]
A
That's the Institute for Neurodegenerative Diseases.
- [44:46]
C
Right?
- [44:46]
B
Yeah. But ind.org and people can learn about all this stuff. And we have so much education, all for free online. And we're trying to develop these tests and we're trying to figure this stuff out. 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, 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, I 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 doctor 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, in using that person as their n of one control, can treating risk factors for cognitive decline actually impact in a positive way brain biomarkers of disease? And we're getting really close. So between ind.org, 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.
- [46:42]
A
To it and will you be able to include your lab tests in that if you put that in as data?
- [46:46]
B
Yeah, I mean, in time for people without symptoms, for the panel that we want to deploy, I feel that we're not there just yet, but that's, that's the future.
- [46:56]
A
But you could, I mean, you could have them check their blood pressure, you could have them do a body composition.
- [47:01]
B
And they do that.
- [47:01]
A
Check their cholesterol or their insulin and they type that all in or they, the heavy metals or the vitamin D or whatever, you can add all that data in to retrain your brain. Now can you do that?
- [47:09]
B
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 APOE4. 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 variants, you get one from mom, one from dad, a two, three or four. You and I have both been tested for this. We know lots of people that have been tested. About 1% of the population has two copies of E4. And honestly, one of the key drivers of why we created this free automated software is because when someone has an Apoe 4 variant, they're scared, right? And they can type in what their genes they got tested through 23 and million.
- [47:48]
A
Yeah, you find that it's like, oh, shoot, I don't want to know, I don't want to test it. And doctors say, well, don't test it because there's nothing you can do about it. So don't make sure you don't test it. And that's wrong.
- [47:56]
B
That's entirely wrong. Because if you have an Apoe 4 variant, I'm gonna tell you to do all these different things. And if you don't have an APOE 4 I'm gonna tell you to do different things. And if you have two copies of the Apoe 4 variant, which is again 1% of the population, doesn't mean you're gonna get Alzheimer's, but you may be at higher risk. So I'm gonna tell you to do these things that our research for the last 15 years have studied to show may be effective. And then this software you type in that you have the Apoe 4 variant and it's gonna tell you what you can do to reduce your risk.
- [48:23]
A
So it's more personal.
- [48:24]
B
It's more personalized, yeah. To help manage risk factors for Alzheimer's disease.
- [48:27]
A
So long story short, there's a bunch 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 $490 and things like your blood sugar, insulin, cholesterol, particle size, LPA, APOB, all the nutrients, omega 3s, all that, we can get that now. But there's another layer that you're doing that you're developing in your lab that are new biomarkers that are specific for neurogenic diseases that we can measure and then are low or changed or improved by doing various interventions that are specific to that person.
- [49:02]
B
Yep.
- [49:03]
A
So it's not like there's one thing you do to fix all that, It's a whole bunch of things you do.
- [49:07]
B
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 2027, these are going to be amazing years. Because my belief, my hypothesis right now is that you, Mark, are going to need these five tests to track over time. Me, I'm different. I'm going to need these four tests. And a woman, especially during the 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 markers improve and then we know we're on the right track. So I think we are within maybe 18 months away or less from having this roadmap clear.
- [49:59]
C
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- [50:06]
A
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C
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- [51:45]
A
And we can go a lot more into the butter because I think, I think there's ones that we're even not looking. Oh, so many metals, like tick infections, like mold exposure.
- [51:53]
B
And I, I've only talked about kind of some of the traditional ones, but like these inflammatory markers that we're looking at and the immune. You mentioned Dr. Tansey 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, interleukin.
- [52:19]
A
Those are all blood tests for inflammation.
- [52:20]
B
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 Apoe 4 variant. Okay? And this guy's 49 years old.
- [52:40]
A
And you're like, oh, there's inflammation on this person.
- [52:43]
B
So wait a minute. And I look at the panel and I say, but call him Bob. Bob. Hey, bud, you got an APOE 4. You got a Interleukin 17A, which is an inflammatory marker that's elevated in people with psoriasis. And bud, your amyloid's higher than it should be for a 49 year old. No towel. Okay. Check mark. Okay. Nothing too worrisome, but the train's gonna 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 zetia, ezetimibe because he was an over absorber of cholesterol. Not, not a statin. He was afraid of statins. Okay. He didn't need a statin anyway. And omega 3 fatty acids. His omega 3 fatty acids were in the toilet. And he's like, oh, I don't really like fish. I'm like, then take the capsule.
- [53:29]
A
Sardines.
- [53:29]
B
Sardines or albacore. Tuna's high in mercury, but like in a wild salmon, 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 down. Everything about his everything improves through some mild changes that were personalized for him. Right? And that's the key. We could talk about blood biomarkers.
- [53:58]
A
What you're saying 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 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 Bogaloosa Heart Study where they looked at fatty streaks in the arteries of teenagers who were eating crappy diets in Louisiana. They were a prelude to heart disease that they were gonna get in their 30s and 40s, but we could see it in their teens.
- [54:54]
B
In May of 2024, there was a CNN documentary that came out and Dr. Sanjay Gupta came down. You know Sanjay, and you know, he actually joined my research study and it's been really great to get to know him better through that. I've known him for a long time. And this guy named Simon was profiled in this documentary. And documentaries are interesting because, you know, they send a film crew and you get, they get to know people and they see people for years and they get to know them. And 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 brother 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 Apoe 4 4. He's got two little kids, okay? He's in his early 50s now, mid-50s.
- [55:43]
A
That's Apoe 4 is the high risk.
- [55:44]
B
Apoe 4. He's got me. 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.
- [55:53]
A
Well, 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.
- [55:59]
B
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. At the first, at the documentary stage, his amyloid improved and his amyloid actually normalized. His tau was still a little bit there. It's gone. Amyloid and tau are gone. His symptoms are improved. Even though he still is doing great. And he had some subjective symptoms, symptoms. His Brain grew twice. This is all real.
- [56:27]
A
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 that's so stuck, but you're seeing objective evidence. And you're not the only one. I mean, there's others like Dale Bredesen and others who's been on the podcast who've 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.
- [57:01]
B
We have a saying that we say it a lot, promise not to over promise, and we're cautious and we want to undersell just to be extra safe because we need to 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, times, I'm still like, wow, right? Because I'm in awe.
- [57:23]
A
It's a miracle because compared to what we were trained in, in medical school, it just doesn't happen.
- [57:27]
B
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, I get excited.
- [57:34]
A
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.
- [57:42]
B
Sure. So, actually, 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 wants to. We try to make cognitive activities. We call them cognitive activities. At retainyourbrain.com, you join, you get to know yourself. You can track or assess or whatever word you want to use with these cognitive. We call them activities because they seem less worrisome. But we do track cognitive function in our ABCD and E model. D is DNA. We do look at some genetics, especially the Apoe 4 variant, which is super, super, super, super important to personalized care. Not to deduct or deduce. Sorry if you're going to get Alzheimer's, but it does help personalized care. And the E in the A, B, C, D and E is emotional and social support and health and stress management. Staying socially Engaged, having a meaningful life. Mindfulness based stress reduction is something that we advocate for learning new things, 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.
- [59:00]
A
And you're talking about these social connections and relationships and having meaning and purpose and connection and belonging. And it even speaks to how things like hearing loss or visual loss will actually cause people to withdraw from these social connections, which actually accelerates dementia.
- [59:15]
B
Yeah, 45% of cases of dementia may be pre, if that person does everything right. And 45% to me is a very conservative number. I think that number is going to be from a 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 demographics dementia are attributable to the modifiable risk factor of hearing loss. 8%. And now whether you have to get.
- [59:51]
A
Hearing aids if you can't hear this.
- [59:52]
B
Yeah. And 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 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. My mom, I fought with my mom about this for years, is like, wear a hearing aid, you'll be more engaged. It may help prevent dementia. You know, that's, that's, that's not a pill, that's not a dietary change. It's just have a hearing vision loss. There's so many things that we can do to screen and intervene on.
- [60:29]
A
So again, going back to like, what, what are the things that you're actually specifically using and how do you kind of customize the treatments? And what are the, what is a cock? What is a cocktail of therapy? And besides the things we've already talked about 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?
- [60:50]
B
So in our 2019 paper where we showed really back then for the first time, that through multimodal meaning Multiple therapies at once that we personalized. Or the title of the paper was Individualized Clinical management of people at risk for Alzheimer's Disease. Something like that. 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 diseases, they're complicated any chronic disease of aging, 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.
- [62:01]
A
So this is symptomatic early dementia, Symptomatic, not.
- [62:04]
B
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% in order to have an impact on their cognitive function.
- [62:25]
A
Benjamin Franklin, right, announced the prevention is worth the pound of cure.
- [62:29]
B
100% agree with that. But the people before they had symptoms, whether they followed greater than 60% or less than 60% of the recommendations, they still 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 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. The thousand plus people that we've seen. But 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, for example, extra.
- [63:20]
C
There's non drug.
- [63:21]
B
Yeah, non drugs. So non drugs. 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. You know, 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 amyloid drugs. I want an anti amyloid drug 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.
- [64:11]
A
And there's major papers published within jama like just walking prevents Alzheimer's.
- [64:15]
B
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 under muscled. So someone that wants to use exercise as a primary lever to pull needs to figure out, well, what are they trying to do? So for example, if someone needs to lose belly fat, walking slowly is probably not going to be enough. You need to get into a higher, what we call zone two or steady state cardio, where the heart rate goes to 60 to 65% of the person's maximum. The best way to kind of approximate that is if someone wants to get into fat burning mode is where they can still have a conversation with someone, but the person that they're talking to can hear that they're a little bit short of breath, they can hear that they're exercising, but they can still carry on a conversation. To me, that's in the zone too. 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 two to get into the fat burning mode. But that's the 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 fat even more efficiently. But again, some people shouldn't start like that.
- [65:59]
A
But the belly fat, 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.
- [66:14]
B
Incredibly. And I think 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 active and they can break down whatever you need to build muscle mass. People should be doing strength training at least twice a week depending on their individual situation. If someone is trying to lose body fat, they should be doing zone two fast walking with a weighted vest three times a week for 45 to 60 minutes. So exercise is not just like 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, impact on brain health.
- [66:52]
A
So exercise is one of the interventions diet. Let's talk about nutrition because there's a, there's the mind diet which is Mediterranean. And you know, like the way I think about it is, is, 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.
- [67:14]
C
Great.
- [67:15]
A
But it, there's, there's different levels that you can push on the gas pedal to get more effect. I had a patient once who, who had MCI monocog impairment. She had a whole bunch of problems, the 21 things. And we fixed all her thyroid was off, she had 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 diet 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 the lights came back on and I was like, holy cow. So again, how do you approach diet with all this?
- [68:04]
B
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, we're not in the realm yet where precision nutrition is easy, off the shelf, straightforward. But different people, I believe, need to follow different dietary patterns. And I too, back In, I think 2007 was the first time that I put someone on a ketogenic diet 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 things kind of went the wrong way. And to me, you know, 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, until we get to that time. I think you think about the big bucket. So the Mediterranean style diet, fatty fish, brain healthy fats, omega 3 fatty acids, especially people with one or more copies of the APOE4 gene. Like we have to have enough omega 3 brain healthy fats fats, otherwise people will have cognitive decline and the synapses.
- [69:16]
A
Because a lot of your brain is made up of DHA, which is 60% as far as I remember, which is.
- [69:21]
B
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 APOE 4 variant. So brain healthy fats, that's PUFAs, polyunsaturated fat, then you have monounsaturated fats, Monounsaturated fats. Like if you want to drink olive oil like an ounce or two a day and your doctor says, okay, that's like anti tau protein, like that is.
- [69:44]
A
Good for, but it's gotta be good olive oil, it's gotta be bitter and burn the back of your tongue. Otherwise it doesn't have the polyphenols.
- [69:50]
B
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 stash in different parts of the house and just pour it on, pour it on, whatever I can get it in because I need it. And if it burns the mouth. Yep. That's exactly the proxy as a taste to it. So avocados, olive oil, fatty fish brain healthy fats are like so critical. Green leafy vegetables. So berries. 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.
- [70:33]
A
That's why I gave you a berry shake this morning.
- [70:35]
B
You did. It was good with goat milk whey, which was a first for me. 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. You know, I would call it plant rich. Yeah, plant rich. Yeah, plant rich. Plant rich. And you know, there's totally different.
- [70:56]
A
Because plant based is vegan.
- [70:57]
B
Yeah.
- [70:57]
A
That might be problematic for people who want to build muscle.
- [70:59]
B
Mostly plant rich. Okay, yeah, that's a better. And I wouldn't.
- [71:01]
A
Maybe, maybe.
- [71:02]
B
Yeah, I don't know the exact terminology, but you know, and then like meat is all not created equal. Like, like red meat. Grass fed beef is totally different than other beef that isn't, you know, whatever. So I think people need to eat, you know, where they feel comfortable with, whether ethically or otherwise. They need to get protein levels, whether it's through whey protein through goat or. Or whey protein through regular milk from cows. I think each person needs their own individual kind of thing. And some people may be more sensitive to one thing versus the other and there's lots of different.
- [71:30]
A
And I saw you putting like cocoa polyphenols in your.
- [71:32]
B
Oh yeah, I travel. I travel with dark cocoa powder, which is completely ridicul. 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 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.
- [71:58]
A
So Richard Isaac starts this morning with a mocha.
- [72:00]
B
I do a mocha for your memory in the morning.
- [72:03]
A
And as funny as mocha is actually one of the names for a test we use the Montreal Cognitive Assessment Test, which is actually something you can actually do at home. It's something you download on the Internet and it's a pretty good way of tracking your. Your brain health.
- [72:18]
B
Exactly. Yeah. We don't want people to do it too much at home. Cause then they practice and the doctors see the doctor and they memorize the test. But I, I don't disagree. Yeah, yeah, for sure. There are definitely ways to, to track. Track.
- [72:26]
A
So fatty, fatty foods, omega 3 fats, monetize fats, berries, leafy greens, you know.
- [72:32]
B
Nut, nuts and seeds, antioxidants, nuts and seeds. You know, balancing the Omega 6 with Omega 3s, I'm. There's so much nuance with nutrition, but I think that's it. Also the ELF diet.
- [72:41]
A
What's that?
- [72:42]
B
Oh my.
- [72:43]
A
Eating moss in the Arctic Circle.
- [72:45]
B
I just stung Dr. Mark Hyman on a dietary pattern that he's never heard of. Well, this is a great day. I'm never ever going to forget this day. The ELF diet. Eat less food.
- [72:57]
A
Oh, eat less food.
- [72:57]
B
Yeah, yeah.
- [72:58]
A
Like Michael Pollan, eat food. Not too much, mostly plants, right?
- [73:02]
B
Yeah. So just less. Like people just eat so much in excess. Like it's, it's crazy. And you know, there was a study at of Mayo that showed that people that ate like, I think the cutoff was like 2100 calories a day, less than 2100 or more, have delayed cognitive decline. And again, this is like imprecise.
- [73:19]
A
So the Okinawa principle, Right. Hari hachi bu, which is eat percent full.
- [73:23]
B
Exactly. Harihachi boo. 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 just starve yourself. And there's good carbs and bad carbs and know the difference. That's really key.
- [73:41]
A
Berries and leafy greens are carbs, right?
- [73:43]
B
Exactly. Yeah. And some whole grains in moderation I think are okay, but not if a person's not active. So anyway, yeah, nutrition's tricky. Vitamins, we Talked about omega 3 fatty acids, but vitamin D, especially people with one or more copies of the APOE 4 variant, 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% of the people in Miami, even with sun exposure, are deficient in vitamin D. So we check vitamin D. Well, you have to be.
- [74:16]
A
Naked between 10 and 2 in the morning, 2 in the afternoon for 20 minutes. And if you're not, you're not going to get enough vitamin D. If you're a lifeguard, you will, but otherwise, forget it.
- [74:24]
B
Exactly. People wear sunscreen now. People are indoors. And yeah, I usually tell people you need 15 minutes, 12 to 15 minutes between the hours of 11 and 1 to try to split the difference. I don't want to. It's hard to know for sure. But, you know, we check vitamin D and supplement if needed. 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 was 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.
- [75:11]
A
So it was a paper published a number of years ago in Jamar New England Journal I read, where if your homocysteine was over 14, you're 50% more likely to get Alzheimer's or dementia. And that's again something we test at Function Health. And also methylmalonic acid, which is a marker of B12 function. And I remember a patient who came to me who was a very successful businesswoman, was on multiple boards, she was in her early 80s and she's like, I got. Got diagnosed with MCI, mild cog 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 methylmalonic acid, which is a marker of B12, which are probably better than measuring folate and B12 in the blood.
- [75:50]
B
Probably had a double MTHFR mutation.
- [75:51]
A
She did. She had the genetics that made her having trouble with her semi 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 that get acid blockers. They don't get, I mean that's what, that may drive 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, they're, they're dangerous to take long term, fine, short term, but long term. And so I, I, I, I said I found this and I gave her B12 shots and I gave her high dose of methylfolate and some B6, some of these methylating nutrients and completely cured her MCI. Now it's not that everybody with MCI or pre dementia 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 in my schedule and I'm like, what's going on? She says, well, I'm going for a trek in Bhutan. She's 85 and I want to know what I should be doing to prepare and take and blah blah, blah, like okay, great, Amazing.
- [76:55]
B
Yeah. What else?
- [76:55]
A
Supplements. What other supplements? Vitamin D, fish oil, the B vitam.
- [76:59]
B
Yeah, I mean turmeric, I think, you know, curcumin, the active ingredient, 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 the 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 the plant for them. So I think nutrition is really, nutrition, exercise are like critical, critical levers. And in our research study that we presented data that I can talk about because we presented this at the 2025 Alzheimer's Association International Conference in July 2025. And we showed that when 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, sleep, stress management, keeping the brain engaged, learning social connection, Y a doctor on a regular basis to make sure their blood pressure, cholesterol, blood sugar is all modified 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.
- [78:27]
A
Any of these billion dollars dollar amyloid.
- [78:29]
B
Drug studies in our study that we've, and this hasn't been fully published, but I can talk about it because we present an abstract form. There are people that for example, took GLP1 drugs. And GLP1 drugs are tricky because I believe that too high a dose, if you're not eating right and doing the right thing, you can lose muscle and have all the things lower dose. I'm more of like the microdose crew when it comes to GLP1s. GLP1s positive effect on biomarkers. In my, 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.
- [79:01]
A
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 GLP1s were on the market, I was reversing diabetes, getting people to lose £200, £100, £150. You can do it. And I think my guess is if they were to do a head to head comparison of GLP1s and the same diet that you would eat if you were on GLP1s, there would be no difference in any of the biology. That's my first.
- [79:25]
B
So, so while multimodal treatments, you know, obviously 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 neurodegenerative disease.
- [79:41]
A
So, so you're testing, not guessing.
- [79:43]
B
We test everything.
- [79:43]
A
Here, let me try these 20 things and let's cross our fingers and maybe do a, like a, a sort of semi, semi subjective objective test, which is a bunch of questions. You're actually looking at blood tests. We would show changes.
- [79:55]
B
Try one thing, we repeat it. We don 10 things that 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. And we just try to do things as rigorous as humanly possible. And what we should show is that when we do these tests, call these NF1 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 perimenopause 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 and, and 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. We did this whole women's brain imaging study at Cornell and spent millions and millions of dollars on this. Women that had 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 hormone replacement therapy. And then there was that women's health study that used synthetic hormones and 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 doctors. Hormone replacement therapy during the perimenopost transition has helped improve brain biomarkers associated with Alzheimer's and neurodegenerative disease risk. It's been striking.
- [81:48]
A
So this is more than just what has been done before, which is population based studies which can't really directly look at cause and effect. You're actually looking at blood biomarkers that change, that improve the blood biomarkers that are associated with neurodegenerative disease. That's a big deal. And the other thing I wanted to say is that the consensus most that I've heard is that 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.
- [82:15]
B
Well, end early. I want to start both.
- [82:19]
A
Does that mean every woman should be on hormone replacement therapy? Like what, what are the implications here?
- [82:24]
B
Yeah, this is, these are, these are really, you know, and by the way, why hasn't this been better studied? Why are we the only group?
- [82:31]
A
To my knowledge, like, because we have misogynistic research infrastructure.
- [82:35]
B
Like, it's, it's just so, it's demoralizing, it's just so wrong that women are taught that like, oh, you're having night sweats. Oh, oh, you don't feel good. Oh, you're having brain fog. Oh, okay, sorry. You know, we'll see you back in 6, 6 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. No, this is a medical condition. Like, really? Or the cooling thing. Okay. Or a weighted fine. Okay. Treat the problem. And what we've shown is that through ridiculous amounts of time, effort, money spent, and research, which needs to be quadrupled or probably increased, even much more than that, we've shown that when we use hormone replacement therapy in the right woman at the right dose, at the right duration, in collaboration with a multidisciplinary team, when we start seeing the estrogen drop, even if the symptoms are very mild, you get the estrogen back up, the TAO starts coming down. Even though the TAO wasn't elevated to a degree where we're like, oh, sky is falling. But the TAO is higher than it should be in that woman who's 47 years old. And this whole concept of, like, you know, it's normal. Well, no. Optimal is where we want a brain protein. Normal, A little borderline, a little high. Like, no. In order to have the most benefit, we need to make these incremental changes. And hormone replacement therapy during the perimenopause transition, to me, is one of the most impactful tools that we can use to reduce the risk of cognitive decline, dementia, and Alzheimer's disease in women. And I think it's tricky. I think there's risks and benefits with every one of these decisions, but I've just seen too many women suffer, and it's just not fair.
- [84:29]
A
So if they're symptomatic or if you do evaluations and 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.
- [84:38]
B
Well, I think if you're symptomatic, it's like, how could you not? I think it's like, it's unethical not to try to figure out how to. In our cohort, we track estradiol levels and other hormone levels. I mean, women 21 and above, we also. This is crazy, but this hasn't been done before. To my knowledge. We do multiple blood draws through the menstrual cycle to try to figure out, as estrogen and progesterone change during the cycle, guess what? P tau217 changes, and these other markers change, too. How has this never been done before? So we have women. We have, like, thank you. Thank you. I'm not going to say their Code numbers. In our research study, they get six blood draws on day one, on day three, on day seven, we get six blood draws during the menstrual cycle. We're just trying to figure out what should the P tau be 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 both bothering them. But we're going to start on low dose hormone replacement therapy if everyone is in agreement. And guess what, she feels better. Her cholesterol comes down. That's interesting. Her amyloid's improving even though it wasn't abnormal. And this is really the key. We have to personalize these therapies and we have to 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 it's 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, follow it closely. I think women perimenopause should probably get checked every six to 12 months for these brain biomarkers and hormones.
- [86:52]
A
So essentially what you're saying is if you're symptomatic, don't suffer and if you're not symptomatic and you have a lot of risk factors and some of these blood biomarkers that were emerging are abnormal, then it's better to get on early even if you're not symptomatic.
- [87:06]
B
I believe that specifically in people that are at the highest, 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 actually lives in Austin, one woman is in California. I mean I know these cases like the back of my mind. You just start and you see everything improve.
- [87:30]
A
This is honestly Richard, why we cope 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 a very low cost, we've dramatically reduced the cost. You can get all these biomarkers, including ApoE4 and some of these brain biomarkers, and then you can kind of start to decide what to do and 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?
- [87:58]
B
Great question. I think the literature, 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, 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. Whole different discussion. And which types and how many times a week and what version and is it the cream or is it inject? There's a lot of confusion here. A lot of confusion. And then what else is going on? What other hormones? Because sometimes when people use testosterone, they're also doing five other things. What I would say is if hormone replacement is used judiciously mostly in men and the person is putting in the work, exercising and trying to build muscle mass in addition to taking, you know, lower end, I mean some of these testosterone levels I see are just like really, really high. And like a lot of these, a lot of the doctors I've spoken to who specialize in this, like are not bothered by this in any way, shape or form. And I'm just like just now you.
- [89:14]
A
Want a physiological level because then your estrogen levels will go up because you convert testosterone, estrogen, then you start having sex, you know, libido issues and other issues that are, it's like, it's a, it's, it has to be done.
- [89:25]
B
Right, exactly. So, so, so with all of these caveats, I would say at this moment today, I don't have a definitive answer, but I would say it is more likely than not that when testosterone replacement therapy is used cautiously and judiciously, there is a beneficial brain effect. I'm talking very carefully and generically because is it truly Alzheimer's protective vascular protection. Protective cognitive health protective for a reason other than like maybe age related cognitive decline. I don't fully understand the pathological protectivity of testosterone but there's something that is protective cognitively. I'm just not sure if it's strictly Alzheimer's pathology.
- [90:08]
A
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 want to exercise as much. It's kind of like a dirty cascade. Okay, so, so we've got, we've got nutrition, we've got exercise, we've got certain supplements that 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, those drugs are commonly used and they do have impairment functions in the brain. So you have to be careful with sleep.
- [90:46]
B
Yeah, sleep. I mean, we could spend probably a whole podcast just on sleep.
- [90:49]
A
Give me a couple minutes on sleep.
- [90:51]
B
Yeah. So everyone out there has to make a plan for sleep. You could be burning the candle at both ends, pushing, pushing, pushing, sleeping five, six hours a night. If you're exercising, doing everything right from an exercise and nutrition perspective, but not getting adequate sleep, you will not have adequate brain health. It's not going to happen. So everyone out there needs to prioritize and make a plan for sleep. I have people where the only thing they changed after I've read them the riot act was that there's sleep patterns. The only thing they've changed and the impact on their brain biomarkers, 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. It's not just about getting what's the magic. In our study, we did a study on this, tried to figure out like, what's the optimal sleep and like 7, 11, that's how I remember it. Like 7 11, 7 hours and 11 minutes. The people that slept more than that did better cognitively. The sleep that did less.
- [91:57]
A
But 7 hours and 48 minutes last night.
- [91:59]
B
Great, I'll take it. That's good. And obviously it depends on the sleep quality. Deep sleep is restorative sleep. That's when the trash gets taken out, the amyloid gets taken out in the garbage. REM sleep is when short term memories are Consolidated or really formed into long term memories. So their sleep quality and their sleep quantity and the number one way to get more sleep quality is to sleep longer, to have more REM and more deep sleep. Like that's a cheat code, you know. To me, you know, actually retainyourbrain.com is 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 it is, 11 or 12 in the afternoon. I am not allowed to drink coffee after 11pm Based on my time's up. Time's up, know, because you know, caffeine lasts for 5, 6 hours, the half life. So if I'm drinking coffee at 2 or 3 or 4 o' clock in the afternoon, I still have caffeine in my system as I'm going to bed. So, so, 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. Just earplugs and eye shades. Yeah, exactly. Weighted blankets. Some people really like those like you know, cooling temperature.
- [93:14]
A
Like I like cold rooms and hot heavy blankets.
- [93:16]
B
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.
- [93:24]
A
Reinstalling my air conditioning while you're here because it's an older house and it needs updating and it wasn't cooling down when I put it at 65, was only getting the 70. I'm like, that's not good enough.
- [93:31]
B
Yeah, 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 9:30pm my alarm goes off as a reminder that says power down your electronics. So at 9:30 I try to wrap up and by 10 I try to put, you know, like our biology. Wasn't meant to have two cell phones like, like this, you know, at all times with the light and whatever else. And there's my, there's my, there's my Grateful Dead bear. Got the Bobby and the Wolf Brothers show a couple years ago.
- [94:15]
A
For those who don't know what he's talking about, it's Grateful Dead and Bob Weir and his. His band called the Wolf Brothers.
- [94:21]
B
I was waiting online to get into the show. Someone miracled me with that.
- [94:26]
A
So too many inside jokes.
- [94:27]
B
Yeah, old deadhead jokes. But like, why are we on our cell phones right before bed? Like that causes rumination. If you want to fast forward brain aging, worry, worry about everything. Like that will make rumination or worry is the number one thing that basically fast forwards cognitive decline.
- [94:45]
A
I have two more things I want to cover 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're going to link to all your papers, all the media on you. People can learn more. There are two other pieces. One is what about pharmacologic interventions? Because drugs, drugs have a role and kind of one of the star players here. And also what about brain exercises, like brain games, learning new language. So those are the two things we need to talk about. But I think there are key pieces of keeping and retaining your brain.
- [95:28]
B
I'm equal opportunity. I got no skin in this game. I take no funding from pharmaceutical companies, anything like that. I'm equal opportunity. If it's a drug, a vitamin A supplement, and it's relatively safe and I would be willing to take it myself or give it to a family member, it is on my list of potential interventions. So I'm not pro or con 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. These papers take years and years and years to publish. The general categories of drugs, drugs that worked the best. Well, we talked about hormone replacement therapy and we talked about GLP1s and those drugs, drug categories worked honestly, amazingly well. Like, it's just, it's just I was, 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 Ezetimibe or Zetia, which is a plant sterol inhibitor. And we've broken out groups into statin use versus Ezetia 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 serotonin reuptake inhibitors. And then the final category was anti amyloid drugs. So these are drugs that we've studied and these are things that we've studied in our cohort.
- [97:06]
A
But you're also talking about, talking about GLP1s too, are part of this.
- [97:09]
B
Oh yeah, yeah. Oh yeah. GLP1s and hormone replacement therapy are definite check marks. And I would say in our, in our study, multimodal interventions work the best. GLP1s and hormone replacement therapy, I would say work the next best. And then there's these four other categories which we studied and across a variety of biomarkers, but maybe not as like not home run grand slam. There were statistically significant improvements across select blood biomarkers.
- [97:37]
A
Basically what you're saying is the basics work better than these fancy drugs that we spent billion dollars researching and have shown very incremental benefit. Yeah, and not like zero, but they're, they may be additive to an overall package of interventions.
- [97:49]
B
True. And in the right person, at the right dose, Ezetimibe, the plant sterol inhibitor. Never in a million years would I have ever said that. I would be saying something like this. But we're developing these blood tests and we talked a lot about Alzheimer's today. But alpha synuclein. Alpha synuclein is a pathologic protein that builds up in the brain brain of a person with Parkinson's disease and Lewy body dementia. We are working on these blood tests. This is crazy. Never in a jillion years would I have ever, regardless of my family, my brother, my brother's son, my brother's brother in law, we see these drops in alpha synuclein protein using some of these things. And these are Parkinson's related things. I don't fully know what this means yet, but what I would say is the cholesterol drugs in the right person, at the right dose, in the right duration, your mileage may vary work. And it's improving what I believe to be brain health risk and brain health outcomes. Statins. Let's talk about statins. The people that start on statins in our cohort are not your typical, you know, Crestor, Rosuvastatin, 20 milligrams. Like the amount of people I see on high dose statins, it like just blows my mind. 85% of the cholesterol lowering effect of Rosuvastatin are Crestor comes at 5 milligrams.
- [99:05]
A
Of the dose so you get 80% of the benefit at the lowest dose.
- [99:08]
B
Yep. And no one knows this. And like, and I think that's correct. I mean, that's what I've read and that's what I've been taught. But like, if the majority of the effect come at low dose, like, why do we keep, like to get an extra 5 or 10% benefit when you like keep pushing and pushing and pushing these doses that are just like really.
- [99:26]
A
High to me, when those cause mitochondrial injury. And that is important in keeping your brain healthy, is having healthy mitochondria.
- [99:32]
B
Yeah. And, and the side effects go up and across 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 over producer of statin, genetically or biologically. So lower dose statins do show brain positive effects in our research.
- [99:56]
A
But you're not just throwing it at everybody. You're doing tests to say, oh, you're somebody who produces. It's more cholesterol.
- [100:01]
C
So you.
- [100:01]
A
And I don't. So statins wouldn't be good. And even I have the gene that makes it. Me have myopathy or muscle damage if I take a statin, I have that gene, I tested it. So statins are not good for me. And they also cause mitochondrial damage. And if you do the test, this helps you personalize or precision approaches, you're gonna get a better effect with less side effects. And there's a friend of mine, David Fagenbaum, who created a company called Evans 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 ezetimide or zetia. 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.
- [100:51]
B
Exactly. And, and, and you know, these are, again, these are.
- [100:53]
A
Am I catching on?
- [100:54]
B
You are. You're catching on. You got. You've been to this rodeo before. So anyway, I would say cholesterol drugs, when used in the right person at the right dose for the right duration of time, are protective against dementia and Alzheimer's pathology, and maybe even Lewy Body and Parkinson's. But I want to be really conservative. Not fully published yet. We're just learning. Ssri, selective serotonin reuptake inhibitors, Prozac. Yeah.
- [101:15]
A
So in our cohort, does that category of drugs.
- [101:17]
B
Actually, we have zero people in our cohort on Prozac. The only people in the. Our cohort that are on SSRIs. I think this is because Escitalopram or Lexapro, it's all generic. Now, Escitalopram has been shown of all the SSRIs in a study that came out in neurology, like a few years ago to have the best lowering or attenuation effects on amyloid. So in our little group, we have a group of preventive neurologists, preventive cardiologists, preventive medicine specialists, internal medicine doctors that treat the patients in their own individual clinics and whatever. And then they're in our research study and we track the biomarkers. We all have gotten the memo that Escitalopram. I'm gonna sound like a broken record at a pretty low dose. You know, we have a guy now on 5mg. I almost never go. I mean, I don't usually go high. And by the way, we're not treating, you know, you know, I'm not a. I'm not a psychiatrist, you know, mild depression versus major depression, those things. I'm not gonna get into the. The nuance. But the majority of people in our cohort that are on SSRIs are on escitalopram or Lexapro. Five milligrams, I would say, on average. And in our cohort, it's a small group, but we also saw some, but not, I would say, slam dunk, robust effects from low dose Escitalopram, low dose Lexapram.
- [102:35]
A
So this is really important. I just want to step back because we kind of have to wrap up. But I think that for those of you listening. 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 one ones that are already and are available. And you're seeing change in brain structure, growing brains and the function of brains, improvement in cognition and you're not using the old paradigm of a single drug for a single disease, using over 50 different things that you pick from, depending on how you want to personalize the treatment, that if you see one person with Alzheimer's, you're seeing one person with Alzheimer's, and that this field is changing radically in such a way, way that will actually be able to help us avert this catastrophe of 47 million people who are in the presymptomatic stage of Alzheimer's that are measurable by these blood markers that is going to cost us $18 trillion over the next 30 years. This is revolutionary. And if anybody's listening, who cares about this issue, who wants to help? And again, I have no affiliation with you other than being your friend and having a bond over the Grateful Dead following your work for years. This is where the money needs to go. This is where the philanthropic dollars need to go. This is where NIH funding needs to go. If you're listening to Jay Bhattacharya, this. This is the future. Because it's what I have seen over 30 years in the practice of functional medicine from a very amateur scientific perspective. I'm not a researcher, although I've done some research studies. It's what I wrote about in my book the ultra mind solution. 15 years ago or more than 15 years ago ago now. And I think we're at this, this transitional moment in history where for the first time, we're. We're getting a handle on this horrific condition. You know, yeah, you get a heart attack. Okay. You have chest pain, you get a bypass, you get a new heart transplant. You're still you. When you get Alzheimer's, it. You lose. You. You lose your family members. It's a catastrophic disease. And no. And everybody's terrified of getting it. And nobody should be afraid of doing the diagnostic test to figure it out. And now at Ezra, which is a company we bought with Function, we actually, you can do brain imaging, and we can do quantitative brain imaging, which is a more advanced service we offer. But we can actually start to track these things over time. And so you can begin to do these things. You can go to retainyourbrain.com and start to kind of get ahead of the game. So, Richard, I just want to say thank you for what you've done. Thank you for the insights, for the aha moment you had in the hallway with that guy with a patient with dementia. We never know how we get doing what we're doing, but I hope that you were content. 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.
- [105:59]
B
Thanks so much.
- [106:00]
C
Snyder Heim when it comes to supplements, you only want the best for your body. The kind with the highest quality, cleanest and most potent ingredients you can get.
- [106:07]
A
That's exactly what you'll find at my.
- [106:09]
C
Supplement store, where I've hand selected each and every product to meet the most rigorous standards for safety, purity and effectiveness. These are the only supplements I recommend to my patients and they're also what I use myself. Whether you want to optimize longevity or reduce reduce your disease risk or you're looking to improve your sleep, blood sugar, metabolism, gut health, you name it, Dr. Hyman.com has the world's best selection of top quality premium supplements, all backed by science and expertly vetted by me, Dr. Mark Hyman. So check out Dr.hyman.com because when it comes to your health, nothing less than.
- [106:39]
B
The very best will do.
- [106:40]
C
That's Dr. Hyman.coM-R-H-Y-M-A-N.com if you love this podcast, please share it with someone else you think would also 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 guests 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. 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 wellness center center.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare 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. Thanks so much again for listening.