Become an Alzheimer’s Survivor: Dr. Richard Isaacson’s Breakthrough Approach

Mark Hyman, MD

Full Transcript

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Dr. Mark Hyman
Forty seven million Americans are going to get dementia if we don't do something about it.

Dr. Richard Isaacson
People think of dementia and neurodegenerative disease as an older person's disease, and it's not. Wow. We can detect changes in the brain decades before a person is gonna develop dementia.

Dr. Mark Hyman
We spent $2,000,000,000,000 over 400 studies and ninety nine percent failed. So we're thinking about this wrong. Doctor. 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. He heads the NIH funded Retain Your Brain program about retraining your brain and retaining your brain by doing specific practice that help you preserve your cognitive function. Take us down to 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.

Dr. Richard Isaacson
Forty five percent of cases of dementia may be preventable.

Dr. Mark Hyman
When someone comes into your office, what are you looking at? What are you testing?

Dr. Richard Isaacson
We do this all now digitally. 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.

Dr. Mark Hyman
How do you approach diet with all this?

Dr. Richard Isaacson
Women that have increased waist circumference, Noretta, 39 higher risk of dementia.

Dr. Mark Hyman
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? Well, Richard, welcome back to the doctor 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.

Dr. Richard Isaacson
Things are things are very different now. It's only been five years, but,

Dr. Mark Hyman
And man, it's there's a lot more to tell about this whole topic of neurodegenerative diseases, which is a crippling problem. It's the most expensive condition is Alzheimer's, more than heart disease, cancer, diabetes, because of the long term care and issues we have with it. The entire research enterprise had 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 $2,000,000,000,000 over 400 studies, and ninety nine percent failed. So we're thinking about this wrong. We're 100% thinking about this problem wrong. And so I wanna sort of share a little bit about for you what is sort of the current thinking that's flawed, and how should we be thinking about this from a both prevention and treatment perspective? Because no one is an Alzheimer's survivor.

Right? I mean, but there's cancer survivors. There's heart attack survivors, but we don't really hear about this. But there are, and I've certainly had them in my practice. And I know other doctors who are working in this field on the fringes are doing this.

But you came from Cornell. You're you're an academic. You're, you know, trained at Harvard in neurology. You've got the street creds, and you've come at the same thing that I came at decades ago.

Dr. Richard Isaacson
Tomatoes getting thrown at us.

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

Dr. Richard Isaacson
I'm still bloodied and bruised.

Dr. Mark Hyman
So so take us down your, you know, this sort of this framework of of our current thinking and why it's flawed in the in the 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.

Dr. Richard Isaacson
So, you know, we we don't live in a health care system, we live in a sick care system. The medical system is is really positioned on treating disease. And what does disease mean? Well, disease means to most doctors a symptom, a problem, memory loss, dementia, treat them. 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, oh, Alzheimer's prevention clinic. Start. You can't use Alzheimer's and prevention in the same sentence. That's that's cookie talk. And this is, over fifteen years ago.

And and what I wanted to do was not just treat people with cognitive decline and treat people with early dementia, but I wanted to see their family members and treat their family members. And in 2009, I got kinda kinda taken away in a in a hallway saying, Isaacson, I know you got you got four family members with the disease. What do you what do you can we do anything to prevent like, what what should I do? He was a son of a patient of mine. And we we spent forty five minutes in the hallway discussing what what he and I could possibly do, and then next week, I saw his sister as a patient, and that was the first Alzheimer's prevention, consult, in in The United States that that I did, and and that kinda changed everything to me.

And and to me, we're thinking about things wrong. We're we're doing things all wrong, and people think of dementia and neurodegenerative disease as an older person's disease, and it's not.

Dr. Mark Hyman
We used to joke and call it Alzheimer's disease.

Dr. Richard Isaacson
Right. I get

Dr. Mark Hyman
it because we see people

Dr. Richard Isaacson
with dementia, and they're older. Right? But but these diseases start silently in people's thirties, forties, and fifties, and sixties, and seventies, decades before symptoms. And there are forty seven million Americans and hundreds of millions of people globally that have these pathologic features, these blood markers that you can now check-in these, you know, some cognitive assessments that you could do from the comfort of your own cell phone. We can detect changes in the brain decades before a person is gonna develop dementia.

So let's go then. Let's do it then. Let's see the person then, but our our health care system is, like, so broken that, like, I can't see a person to try to prevent dementia or reduce risk for Alzheimer's or reduce risk for Lewy body disease or dementia because there's no billing codes for it. I can treat someone with a disease after you have a heart attack or a stroke or dementia, but we don't get paid for it because our, again, our I'm not a believer of this, but our whole health care system is broken. So so to me, we just gotta get ahead of things, and the evidence you know, the the totality of evidence is overwhelming that we can do something.

And last time we talked, I feel like was doing cool stuff back then, and now it's just totally different. Like, the objective markers, like, the proof is in the pudding. Like, we're able to do things today that are just like science fiction even five, ten, or fifteen years ago. So, yeah, I'm excited about the progress, but, you know, it's hard to keep pushing things forward.

Dr. Mark Hyman
It is. You know? And then you talk about the 47,000,000 Americans. Forget globally. Yeah.

Forty seven million Americans are going to get dementia if we don't do something about it. And yet there is nobody pretty much besides you and a few others who are actually thinking this way. I did the math, and if we left leave this unchecked, the bill for Americans over the next thirty years is going to be $18,000,000,000,000. That's basically the amount of our annual GDP in one year. It's a huge amount of money.

And what you're saying is that it's it's really preventable. Now I want to kind of harken back to the flawed paradigm because in medicine, we have this idea that you have a single disease, Alzheimer's, that's caused by a single pathway, amyloid deposition, which is this gunk that gunks up in layman's term, gunks up the brain and makes it not work. But it's really the body's band aid where there's inflammation. And we've tried to find anti amyloid drugs for decades, and we spent $2,000,000,000,000, like I said, 400 plus studies, and massive failure. Why has that failed, and and what's wrong with that thinking?

And why should we look at a different framework that looks at al each Alzheimer's patient differently? You you say if you've seen one patient with Alzheimer's, you're seeing one patient with Alzheimer's. Right?

Dr. Richard Isaacson
You took the words in the sentence right out of my mouth. I'm a clinician. Right? I'm a doctor. I I see patients.

I talk to patients. Patients are my petri dish. I don't study mice. I don't I don't do basic science stuff, you know, over my head. You're an old old time family doctor.

I'm an old time neurologist, you know, carrying the We're calling old. Oh oh, I'm calling myself old too, so it's a we're all we're all hippies. We're all deadheads in the room, so, you know, we're we're we're old in in in a good sense of the word. But when you think about neurological disease and brain disease, and what I was taught in medical school was, like, Alzheimer's is, like, this protein called amyloid, and amyloid, like you said, is this this sticky protein that builds up in the brain of a person with Alzheimer's. And when you look at the brain of a person with Alzheimer's, there's amyloid in it.

Okay? But, like, why are there up to a third of people that have amyloid in their brain but didn't have dementia? Well, that's interesting. Well, how does that make sense? And then in the textbooks, I remember I remember the graph.

And then the amyloid goes first, and then the tau protein, other next protein, and then brain inflammation and 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, the 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. Yeah.

And medical students say that. So so to me, there's buckets, and different people present different way ways, and and the way that I view Alzheimer's, and also the way I view neurodegenerative disease as a whole, is it's very heterogeneous. There are so many different types and manifestations, and

Dr. Mark Hyman
and Even though this if the ends of dermatology and the diagnosis is the same, each of these patients might have different causes They can and need different treatment.

Dr. Richard Isaacson
Yeah. You can take different roads to Alzheimer's, you know. Women, you know, for example, missus Smith, she may be, you know, perimenopause, the estrogen is dropping, she may have a a variant, a genetic variant called APOE, which we could talk about, APOE four, and you have the APOE four and the estrogen drops, well, missus Smith, she's gonna need therapies a b and c. Mister Jones, he's totally different. You know, he doesn't have the gene, he's different, he has a big belly, has a belly size that's larger, the memory center and the brain gets smaller.

He needs a kind of more metabolic health and a different plan. He's gonna need therapies x, and z.

Dr. Mark Hyman
The bigger your belly, the smaller your brain.

Dr. Richard Isaacson
That's, smaller the memory center of your brain. Exactly. And there's lots of things we 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 is not how this works, and we need to take a one size fits one approach.

Dr. Mark Hyman
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 one research trials, but it it still hasn't kind of permeated the funding, really. It hasn't permeated the thinking at all.

Dr. Richard Isaacson
No. And and, you know, our

Dr. Mark Hyman
This is what you call it as precision neurology, precision prevention.

Dr. Richard Isaacson
That's exactly it.

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

Dr. Richard Isaacson
Taking this individualized approach, it's it you know, he people hear the term precision medicine. Oh, that's that's fancy, expensive tests. And and and no, actually, it's just like talking to the person and figuring out what road they may may be on. And whether it's doing a genetic test or doing some blood markers, which, you know, the cost has come down, doing cognitive assessments, we do this all now digitally. We all and it's and and it's free.

It's like people can go right now and and get an assessment and, like, learn about themselves and get, you know, a way to, like, have automated brain health preventative care, preventive neurology care. And doctors just don't realize, and it's not doctor's fault. Like, in medical school, I was taught one thing, and and the fields change, and the fields change so much in five years. So so to me, you've seen one person, you've seen one person with with Alzheimer's. And what we've done recently is now not just studied people with at risk of Alzheimer's disease.

My brother's a Parkinson's specialist. My brother's brother-in-law is a Parkinson's specialist. My brother's son is a Parkinson's specialist. So I got the Parkinson's movement disorders thing covered on one side of the family, and and we bring everyone into the same research database Yeah. Or research cohort, which is a a research group.

We have a clinical Bio RAN study, the the biorepository for Alzheimer's and neurodegenerative diseases. And when you start putting these people that have similar ish diseases in the same group, and look at the signatures, the biological signatures, they need to be studied together. How many times have I thought someone has like Alzheimer's ish? Yeah. They have a different protein or a different pathology.

Or someone has a diagnosis of Parkinson's, it's Oh, wait a minute. Something a little different. You have to study these things together, and there's so

Dr. Mark Hyman
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 it in functional medicine all the time that are fundamental to understand, and and the question is why. And and you've been asking why.

It's not all we do in medicine. We say, okay. What disease do have? What drug do I give? Why do you have this?

And how are you different from everybody else who has this? And what do you need differently in terms of diagnostics and treatment that'll help you get better?

Dr. Richard Isaacson
Yep. And what are we gonna do about it exactly? There there was an old saying, neurologists don't treat disease, we admire it. Adios and diagnose. Like, no, not not anymore.

Yeah.

Dr. Mark Hyman
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.

Dr. Richard Isaacson
Yeah. And that's just that's just plain wrong. 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

Dr. Mark Hyman
a if it's You have four family members.

Dr. Richard Isaacson
Yeah. Oh, yeah. Oh, yeah. And I've seen this I mean, I I have a family member with some Parkinson's like syndrome that I still can't understand despite having, like, hundreds of blood tests that we're developing to try to figure it out, like, and it it makes me sad, and and it just motivates me to just keep going. And there's so much confusion out there, but it's it's it's all about one thing.

What road could a person be on? If it's evidence based and safe, let's go do something about it. And we can't do we can't be, like, tricked into thinking, oh, you have to do a randomized controlled double blind study where everyone gets, you know, one group, they get one treatment, another group, they get a placebo. Like, no. Different people need different treatments.

So we've kind of turned the paradigm, the research paradigm, on its head, I believe, and we use that person as their own control. And just like you said, this n of one paradigm, we're following over 250 people over the last five years, and each person's getting their own different plan. And then what we do is we then group them together, we say, okay. The people that got the multimodal lifestyle interventions of 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 for everyone on a, you know, one of the GLP one, the 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, like, recognized the way it should be.

Dr. Mark Hyman
Well, I agree. I mean, I think what what the challenge is is that in each person, there are different causes, and you have to map them out. And if you give a person a drug or a supplement that they don't need, it's not 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 drug probably isn't gonna do anything.

So you've gotta customize the treatments. One of the failures of medicine is is you know, we have a rule in functional medicine called the Tac Grills we talked about last night at dinner. If you're standing on a tac, it takes a lot of acid to make you feel better. So if something's in your system that's bothering you that's irritating you you mentioned a case, for example, someone got a herpes lesion on their lips and a herpes virus, which is linked to Alzheimer's in some cases. So the end pathway is the same.

It's inflammation. It's damage to the brain. It's amyloid deposition. That's just a reaction to various insults. The insults could be toxins.

They could be allergens. They could be crappy diet. They could be too much sugar. They could be alcohol. It could be mold.

They could be other factors that they don't have that they need, like deficiencies of vitamin D or omega threes and various things that 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 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, sorta. I mean, with Louis Pasteur, we got the bacteria.

We saw 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 in that model, we basically treated all chronic diseases in the same way, which is a massive failure because chronic diseases are complicated and 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 And and then you're having to do investigations to figure that out.

And then you're doing diagnostics to help you map that out into the blood testing, and we call these new blood biomarkers for dementia, which is I want wanna talk about in a minute, and imaging, brain imaging. And then you start to treat these people individually, and you see remarkable changes and lowering of these biomarkers of dementia. Improvements in brain function, and improvements in their subjective function, and their objective neurocognitive tests, measure, you know, their brain function. And these are things that are real heresy because you talk to any neurologist, say, well, I've reversed the effects of Alzheimer's, they're gonna just laugh in your face.

Dr. Richard Isaacson
The tools that we have are not tools that are radically expensive, are radically unobtainable. It's just having the wherewithal to try to do something about it. And, you know, when we identify that a person is at high risk due to a gene or 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 and to me, I don't care if it's a vitamin, a drug, or a supplement. If if there's evidence and it's safe

Dr. Mark Hyman
You're agnostic to the treatment.

Dr. Richard Isaacson
I don't care what the treatment is. Right? Like, yes. I'd rather people you know, food is medicine. I I couldn't couldn't couldn't say that enough times, and, you know, I'm I and I wasn't trained that way.

I was I was not trained in medical school. I didn't learn about that stuff. And in residency, I didn't learn about that stuff. But I don't care what it is. Just just just try it, and then just recheck markers and whether the markers are blood markers, cognitive assessment markers, which, again, it's easy to do now, or brain volume markers.

And then some of the slides that I sent you not yet fully published, and, I mean, people's brains are growing. Like Yeah. That's, like, that's heresy. That doesn't make sense. And I'll be honest, a decade ago or twenty years ago, I would say that's not true or BS, but but I see it.

And when everything is going in the right way, when everything about his everything improves, you know, that's that's evidence for me.

Dr. Mark Hyman
Yeah. It's true. I mean, I think you're you're you're gathering data that is really solid. What I wanna sort of dive into now is is this idea of, you know, this 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 test the function that are also very big risk factors, like lipoprotein, little language, is genetics.

So you can actually map a person's trajectory by knowing their biomarkers. We do the same thing for metabolic health. We can measure glucose or insulin or a one c and see the trajectory of it going up before they get diabetes.

Dr. Richard Isaacson
Yeah.

Dr. Mark Hyman
So this is there's a so there's a proxy for this in medicine. But with dementia, we don't really do that. And what's really remarkable about your work is that you're you're not just doing neurocognitive assessments. You're not just measuring normal things like omega three fats or vitamin D or blood sugar or cholesterol or blood pressure, which are all important and have to be managed if you're gonna reduce risk. But you're you're finding that these particular blood biomarkers, these you're developing new tests that are from protein signatures expressed in people early decades and decades before they even forget their keys for the first time.

I'd love you to sort of break down some of the things that we're looking at now that are blood biomarkers. And and function health, we basically have a blood biomarker panel that helps identify that risk, including APOE four testing and APOE testing, which is a gene for risk for Alzheimer's. Looking at p tau two seventeen, which is another marker, eighty forty two forty, which is amyloid biomarkers. But you're going way deeper that.

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

Dr. Mark Hyman
Well, there's a lot of Alzheimer's disease. That that's what well, that's

Dr. Richard Isaacson
what they call it, and they should should be called something else.

Dr. Mark Hyman
Joke Bruce Ames, who's a very famous scientist, said on epidemiology with just population studies, he says, if you did a study of of population in Miami, everybody be born Hispanic and die Jewish.

Dr. Richard Isaacson
Uh-huh. I can I can say that that's true from the evidence I've seen? We had to create a lab. We had to go deep on the blood test. Like, I I'm not a basic science guy, like, I I never like, centrifuging blood and and developing at home testing using different devices and develop starting with a panel of, say, a thousand and now coming we're we're we're down hey.

We're down to a 150 tests, we're getting it down. And my goal and our goal, you know, at IND and and and elsewhere, we are trying to develop what will one day be termed the cholesterol test for the brain. And, you know, if we're talking baseball analogies, we're still in the first inning, in in my opinion, of of a nine inning, you know, baseball game, where the tests we use now, I think, are are are are are good in certain ways and I think can be helpful. For example, if a person has symptoms, and the doctor and the the person with symptoms is wondering, are those symptoms from Alzheimer's disease? Then then, yeah, there's this the p tau two seventeen test is a very good test.

It's not a perfect test, but it's a good test. But we're just just taking things with a very different lens, and we're looking at people ages 21 and up to understand what the signature of proteins should be, what is the normal values of these proteins. Because when you start doing a regular cholesterol test to prevent a heart attack or stroke, and you start doing those tests in people's say 60 or 70 and above, that's 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, you know, our work will will help, you know, inform this, but people in their twenties and thirties and forties and fifties and sixties and seventies and beyond before they have symptoms will get this panel of tests and we're just starting to like I think that that we're in the black and white television phase. I think we're we're now in the color television phase where I can kinda see what the five to seven, maybe 10 markers will be, And we can track these tests, and we can do it in a way that we can, you know, lower cost, improve increase access

Dr. Mark Hyman
Yeah.

Dr. Richard Isaacson
And then give people digital tools to, like, help interpret it and and give that person care. So what what we what we believe is that we need to look earlier, and we need to look more deeply Yeah. And we need to look at other markers. And then the other problem is that some of these markers that may be positive uh-oh. Got a positive Alzheimer's blood test.

What if the person had a virus that morning? What if the person got a blood draw in the afternoon rather than the morning? You know, these are things and and and what is a normal value for someone in their twenties or thirties versus someone in their forties or fifties versus someone in their sixties or

Dr. Mark Hyman
What are the reference ranges? What are the

Dr. Richard Isaacson
reference ranges? And and, you know, most of the research that's been done are people with dementia, people age 55 or 60 and above, and we need to start earlier. So the focus of our research is to to figure out what is this cholesterol test for the brain gonna be.

Dr. Mark Hyman
These these tests, we're gonna talk a little bit about them in detail. They're the way I think about them is they're they're kind of early warning signs. They're not necessarily the cause, but they're they're the things we can look at that are resulting from causes that drive those biomarkers to be abnormal.

Dr. Richard Isaacson
Yes. To me, the the word is biomarker. It's a biomarker. It's a marker of a biological condition or disease. Amyloid, to me, does not cause Alzheimer's disease.

I've just never felt that way. Why are there people without amyloid that have a clinical meaning like, you know, talk to the patient, looks like they have Alzheimer's, they don't have amyloid. Oh, I wonder why. I guess amyloid didn't cause Alzheimer's in that person, but by definition, you have to have amyloid to have Alzheimer's. Like, our our instruction manuals are, like, totally wrong.

Dr. Mark Hyman
Rudy Tansey, who's a friend of Orthoire, is an amazing guy. He's an Alzheimer's researcher.

Dr. Richard Isaacson
We just said amazing guy, like, in unison, so I hope he

Dr. Mark Hyman
hears that.

Dr. Richard Isaacson
And he's a deadhead,

Dr. Mark Hyman
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, you know, he said that there are patients who have brains full of amyloid but die old, cognitively intact, meaning normal. And he said what's unique about these people, and I love to hear 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 prediabetes or diabetes to molds to, you know, Lyme disease. I mean, Chris Christofferson had, quote, dementia and Alzheimer's, but trying to get Lyme disease, and he got treated with antibiotics, and his dementia went away.

So I think we we have to think more about what what the underlying pathology is, which is inflammation, and then why is there inflammation, and then hunt down the sources and the 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 they weren't really available. These things like p tau two seventeen or amyloid biomarkers like a a a b forty two forty, other p taus like one eighty one, two thirty one, neurofilament light chain, which is more for brain damage, or something called glial fibrillary acidic protein or g g fat, and beta synuclein, which you're you're actually developing the test for. So there's all these novel biomarkers that are gonna be available clinically, probably in the not too distant future, where you can go get a blood test, and you can say, gee, you know, where are my levels?

You know, it's like, is my blood sugar high? Is my cholesterol high? Is my blood pressure high? And those are risk factors. And then these that tell you that you need to do something.

And the question is, how do you figure out what to do in each individual? If you're treating everybody as an N of one or as a precision medicine or personalized medicine, what's the actual clinical workup? What are you looking for? And then how do you identify the targets, and what are you doing for those targets that you find?

Dr. Richard Isaacson
The way that I do it in my, in our research program in clinical practice, what I would call it the a b c d and e of Alzheimer's and neurodegenerative disease prevention. Okay? A b c d and e. And then when someone can't access a doctor or can't get into a research trial, we have, you know, five sites in The US and in The United States and Canada, and if you can't access one of those sites and if you can't see a preventive neurologist, then we do it through software, and I'll explain how that is. And we got funded by the National Institutes of Health.

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

Dr. Mark Hyman
Wait. I have a brain, I

Dr. Richard Isaacson
think. You I think you do you you def you definitely have a brain. It's it's a you you have a very robust brain. It's functioning. Checkmark.

Neurologist approved. I'm gonna give the Cliff Notes version. I'm in the a b's, c's, and e's. If there's anyone out there like, just spent six years developing, and this was before AI was cool. We just developed we put my brain, a, 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 and and, you know, does a risk assessment. It can do cognitive games, if you like games, whatever, and then the software will tell you what to do.

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

Dr. Richard Isaacson
Baby steps. Yeah. In time in time. But but right now, it's it's it's all it's all inaccessible, there's, you know, no cost. And and, you know, doing the blood test would just add another layer that that's amazing.

But right now, clinically, that's what we do. And from a research perspective, we do use the blood test for sure.

Dr. Mark Hyman
So so the retain your brain, which is what we all wanna do, is retainourbrain.com, is a platform that you've developed that basically has downloaded the your thinking into a a system that allows you to assess people, identify their individual issues, then make specific personalized recommendations that they can implement even without a whole bunch of diagnostics, and it's free. Exactly. Everybody should go check that out and do it. If you have a family history of any of these neurodegenerative diseases or you're worried about getting it, get on it, and it's free. Now what I'm talking about is when someone comes into your office or you're part of this 250% research study, how deep do you go?

What are you looking at? What are you testing?

Dr. Richard Isaacson
Oh, we go really deep.

Dr. Mark Hyman
Yeah. Tell us when you're because I think this is important because people don't know what to look for, and I think there may be many physicians listening to this podcast. Hopefully, there's some philanthropists who have family members with these diseases who under are gonna 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 I think that's that's the joke.

It's like you you have to treat everything. Right? If you have low vitamin d or low omega threes or you have prediabetes or you have heavy metals or you have mold or whatever you're finding or you have high cholesterol, you've gotta treat all those things. You can't just treat one thing, but that's what we do in traditional medicine.

Dr. Richard Isaacson
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 it. Nature Mental Health, January 2024 was the last time we kind of updated the paradigm. And it's all again, doctors out there listening, any healthcare providers, you can read the paper. But the a is simple. It's anthropometrics.

So what does a stand for? Anthropometrics is body composition, body fat, muscle mass. I also kind of throw bone density in there. Yeah. Density, grip strength, also an important proxy

Dr. Mark Hyman
for that. And why is that important?

Dr. Richard Isaacson
Let's Well

Dr. Mark Hyman
As you go through this, I'm gonna kind of have you go through and explain

Dr. Richard Isaacson
why

Dr. Mark Hyman
you want it important.

Dr. Richard Isaacson
For sure. And and by the way, I'm gonna talk about things, and people are gonna be like, wait, what what is this guy he's a neurologist. Why isn't he talking about

Dr. Mark Hyman
a belly fat. Yeah.

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

Dr. Mark Hyman
it is a disease of the brain or a body disorder that affects the brain? So I believe

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

Dr. Mark Hyman
talk That's a heresy, because most neurologists stop looking at anything below the neck.

Dr. Richard Isaacson
Yeah. Right? I'm I'm like I'm an old time family doctor. Like, I'm an inter you know, I I I feel like I practice one third internal medicine, one third preventive cardiology, and one third, you know, preventive neurology, which is a field that, you know, just barely exists. So so what I'm gonna talk about now is gonna be very medical.

So Yeah. I'm glad I'm with you because you can you

Dr. Mark Hyman
can I can translate if you can?

Dr. Richard Isaacson
Translate. Exactly. So so a, anthropometrics. Again, it's a fancy long term and I I couldn't use b because body composition is is the next letter, but everyone needs to know their numbers. Belly fat.

Especially in 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 their body organs. Women are at a thirty nine percent higher risk of dementia Wow.

That have fat around their visceral organs and and belly fat. And you know what happens to women during the perimenopause transition? It gets really really really hard to lose belly fat. Yeah. And there are things that we can do to to change that.

So so we track all these things, and we use belly fat, muscle mass, you know. People lose one percent of muscle mass per year. I mean, like like people like, muscle mass is not easy to build, and and doctors don't focus on it. Like, why are people talking about weight? Like, stop talking about weight.

Dr. Mark Hyman
Body composition.

Dr. Richard Isaacson
Talk about body comp everyone needs some these scales, okay, they're a couple $100, but, you know, everyone needs some of their body fat. We wanna lose fat. We wanna gain muscle. We wanna put on muscle. We wanna lose body fat.

A lot of people take these, you know, weight loss drugs. Okay. They have some really interesting features. They're maybe too high a dose. We'll talk about

Dr. Mark Hyman
Like the GLP one drugs. Yeah.

Dr. Richard Isaacson
The GLP one drugs. But we shouldn't be tracking weight. I don't wanna hear about someone's weight. I wanna hear about body fat, body composition, and and muscle and muscle, and bone density, which is really critical. So the a, all of these things in anthropometrics are brain markers, so we track those.

The b So measuring your belly fat is a brain marker is what you're saying. 100%. Yeah. Muscle mass, you know, and and and belly fat, absolutely critical risk factors to to prevent cognitive decline, dementia, in Lewy body dementia, Parkinson's, these are all metabolic factors that actually do influence these diseases. They're all connected.

They're all connected.

Dr. Mark Hyman
So what's b?

Dr. Richard Isaacson
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.

Dr. Mark Hyman
Metabolic markers meaning, like, looking at blood sugar, insulin.

Dr. Richard Isaacson
So fasting blood sugar, fasting insulin. You know, there's a lot of us may have heard of something called a hemoglobin a one c or glycosylated hemoglobin or h b a one c, and, you know, people say, oh, above 5.7 is pre diabetes, and 6.5 or whatever is is diabetes. M, metabolism, memory, if you want to have memory decline, don't mind your metabolic risk factors. Metabolism and memory is so critical.

Dr. Mark Hyman
Well, because they they even call Alzheimer's type three diabetes. Right? It's Alzheimer's diabetes of the brain.

Dr. Richard Isaacson
Yep. And there's a lot a lot of overlap with with the with the with pathophysiology, which is a big word for, you know, potentially why these disease happen. And and metabolic health, you know, if you wanna fast forward cognitive decline, we don't wanna do that. You know, high cholesterol, high blood sugar, high blood pressure, these are all things that can, you know, fast forward, cognitive decline. And also, cholesterol's really complicated.

I'm not how much time we have to get dive into this, but, like, there's good cholesterol, there's bad cholesterol, like HDL. That's the good stuff. Right? Well, maybe not. It's a little confusing.

There's there's a lot of confusing stuff with with cholesterol, and and

Dr. Mark Hyman
It is. And and it's unfortunately, Richard, most doctors, even cardiologists, don't fully assess cardiovascular risk. 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. Yep. His wife did function health and found she had a lipoprotein a of 500, which is a And

Dr. Richard Isaacson
no one's ever checked

Dr. Mark Hyman
She said no one's ever he's like, I the her doctor wouldn't check it. I wouldn't have checked it. And now we did a full cardiac workup. We can actually manage her risk and look differently at her health. And and at Functional Health, we do these very deep biomarkers for cardiovascular risk that are far just beyond a regular cholesterol panel, apoB, which never gets checked, hypoprotein a, particle size.

We look at function of HDL. You said HDL's not all the same. Some good's the good isn't just all good, and the bad isn't all just bad. It's a it's kind of a false false framework. And and so we're able to get the nuances of what's happening, and we look at insulin, which, again, is never tested.

So a lot of things you're talking about are things that now people can access for a very low cost.

Dr. Richard Isaacson
And accessibility is critical. And, you know, in 2007 was the first time that I ever had these markers checked in me, and that's like almost twenty years ago, and I I got my first calcium score twenty years ago. Yeah. Thank you, doctor Agatson. Yeah.

He was one of my old mentors. Like, I I mean, I I got thrown into this because I had mentors and people that thought differently, thought in a contrarian way. You know, doctor Agatson, for example, the calcium score, I think he invented that in, like, I don't know, 8990, and it became part of the guidelines, the physician, you know, consensus guidelines in 2018. Took thirty 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 so

Dr. Mark Hyman
By the way, you can have like, just the way you can have amyloid, but no Alzheimer's, you can have extremely abnormal cholesterol, and it's clean arteries. And I have patients like that. I know. I'm like, wow. Yep.

Your LPA is high. Your APOB is high. Your particle number's high. Your particle size is small. Clean as a whistle.

Yeah. Clean as a whistle.

Dr. Richard Isaacson
And and that's the thing, like, and and this is precision medicine and and personalized care. So so, anyway, we look at all these markers, and we look at APO B. We look at Lp. We look at h we look at LDL. We look at particle size.

I mean, if you have to choose one, like I choose ApoB is a good proxy, we always check Lp. Yeah. We look at markers of absorb like, is is someone you know, if someone has high cholesterol, instead of just throwing them on a drug that, you know, you know, in in the grand scheme of things may work for seventy or eighty percent of the population, what if you're in that twenty or thirty percent where you're not the right person? And I think you and I, whatever we may be I I I have a different version of of my cholesterol is 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

Dr. Mark Hyman
A statin.

Dr. Richard Isaacson
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 because 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 that's the one I

Dr. Mark Hyman
would choose. It's basically also called Zetia, but it it it's interesting because, you know, you know, I have genetics, and I've done my cardiovascular genetics, and I I'm have a very strong family history of heart disease, and I'm a hyper absorber. And when I actually started taking this drug, it was like a dropped like a like a stone.

Dr. Richard Isaacson
Because you had the right drug for you, basically.

Dr. Mark Hyman
It's that cholesterol I was eating from eggs. It's the cholesterol that's produced by your liver and bile, it's excreted in your bile. It gets reabsorbed that you kinda have to manage.

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

Dr. Mark Hyman
available now. Talked about just now is all available through Function Health for $499, and there's add ons for cardiovascular. You also are going deeper on blood biomarkers. I wanna stay on the b one because 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, neurofluid

Dr. Richard Isaacson
and light chain and other things. But you're going even deeper into these The stuff we're doing, like, you know, we're we're developing blood tests, like, that'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 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, they the person that probably shouldn't take a statin because it may or may not hurt x y or z, we're working on a blood test to figure that out. Like, by the way, I can't believe I'm saying this. Like, this is not me. I'm not like that guy.

I'm a clinical guy, but I had to do this because no one else is gonna do it.

Dr. Mark Hyman
And then for some patients with dementia, taking a statin might be a bad thing

Dr. Richard Isaacson
Yeah.

Dr. Mark Hyman
For certain genetics.

Dr. Richard Isaacson
And you need to track everything, and you gotta figure out which drug is the right drug for the right person. And, you know, we're we're working on this through ind.org, which is our nonprofit.

Dr. Mark Hyman
That's the institute for neurodegenerative diseases. Right?

Dr. Richard Isaacson
Yep. But ind.org, people can learn about all this stuff, and we have so much education, you know, all for free online. And we're trying to develop these these tests, and we're trying to, like, you know, figure this stuff out. And, 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 it's positive, but it's not really positive because of a variety of reasons.

So like, the 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 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 we're 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 GLP one drug because their doctor said, oh, they were overweight, and they had a little diabetes, and they wanna well, then we're gonna track these markers Yeah. And we can then show, is there a ground truth? Is there you know, in in using that person as their end of one control, can treating risk factors for cognitive decline actually impact in a positive way brain biomarkers of disease? And we're getting really close. So between ind.org, alslabs.org is one of the arms that we're investing a lot of money to try to figure this out and and and develop these blood tests.

And and then, honestly, once you have access to the testing and you have access

Dr. Mark Hyman
Will you be able to include your lab tests in that if you put that in as data?

Dr. Richard Isaacson
Yeah. I mean, in time, I I we're you know, for people without symptoms, for the panel that we want to deploy, I feel that we're not there just yet, but that's that's the future.

Dr. Mark Hyman
But you could I mean, you could have them check their blood pressure. You could have them do a body composition. And they

Dr. Richard Isaacson
do that.

Dr. Mark Hyman
Check their cholesterol or their insulin

Dr. Richard Isaacson
They type that all in.

Dr. Mark Hyman
Or the 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?

Dr. Richard Isaacson
Well so yes. So for example, the one of the key things about Retain Your Brain is there's, you know, there's tens of millions of people out there that have a gene called APOE four. So having one you know, twenty five percent of the population twenty five percent 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 we know lots of people that have been tested. About one percent of the population has two copies of e four. And honestly, one of the key drivers of why we created this, free, you know, automated software is because when someone has an APOE four variant, they're scared. Right? And they can type in what their genes what are they?

They got tested through '23 a

Dr. Mark Hyman
find that. It's like, shoot. I don't wanna know. Don't wanna test it. And doctor said, well, don't test it because there's nothing you can do about it, so don't don't make sure you don't test it.

And that's wrong.

Dr. Richard Isaacson
That's entirely wrong because, you know, if you have an APOE four variant, I'm gonna tell you to do all these different things, and if you don't have an APOE four, I'm gonna tell you to do different things. And if you have two copies of the APOE four variant, which is again one percent 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, you know, fifteen years has have studied to show may be effective, and then this software, you type in that you have the APOE four variant, and it's gonna tell you, you know, what you can do to reduce your risk.

Dr. Mark Hyman
So it's a it's

Dr. Richard Isaacson
more personalized. It's more personalized. Yeah. To help manage risk factors for Alzheimer's disease.

Dr. Mark Hyman
Long story short, there's a bunch of blood tests that are available now that you're already measuring that are easily accessible through through your doctor, by the way, might not order, but function health for $490, and things like your blood sugar, insulin, you know, cholesterol, particle size, LPA, APOB Yep. All the nutrients, omega threes, all that we we 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 neurogenesis diseases that we can measure and then are lowered or changed or improved by doing various interventions that are specific to that person. Yep. So it's not like there's one thing you do to fix all all that.

It's a whole bunch of things you do.

Dr. Richard Isaacson
Exactly. And and we while we are just starting to scratch the surface, and we're in the first inning of a nine inning baseball game, the fidelity and the accuracy, I'm telling you, in 2026 and 2027, these are gonna be amazing years because my belief, my hypothesis right now is that you, Mark, are gonna need these five tests to track over time. Me, I'm different. I'm gonna need these four tests. And a woman, especially during the perimenopause transition, two out of three brains affected by Alzheimer's disease are women's brains, and we gotta 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 eighteen months away or less from having this this road map clear.

Dr. Mark Hyman
And we can go a lot more into the blood brain. I think I think there's ones that we're even not looking

Dr. Richard Isaacson
Oh, so

Dr. Mark Hyman
many. Metals, like tick infections, like mold exposure.

Dr. Richard Isaacson
And and I I've only talked about kind of the some of the traditional ones, but, like, the these inflammatory markers that we're looking at and the immune you mentioned doctor Tanzi earlier. I mean, a third of our markers are focused on the immune system and inflammation. Like and we're I'm a neurologist. Right? We're supposed to be talking about brain proteins.

No. We look at inflammatory markers. We look at cascades. We look at interleukins. We look at CCLs.

We look at TNF alpha. We look at so many things, and then if someone oh, interleu

Dr. Mark Hyman
Those are all blood tests for inflammation.

Dr. Richard Isaacson
Exactly. Yeah. In our in our multimodal panel, you know, we have this guy who he has psoriasis, and it's mild psoriasis. Okay. It's mild psoriasis.

He can deal with it. He doesn't want to take a drug or change his diet or do whatever because it doesn't bother him. It's fine. Yeah. Well, this guy also has an ApoE four variant.

Okay? And this guy's 49 years old.

Dr. Mark Hyman
You're like, oh, there's inflammation on this person.

Dr. Richard Isaacson
So So wait a minute. And I look at the panel, and I say, but but call him Bob. Bob? Hey, bud. You got an APOE four.

You got a interleukin 17 a, 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 tau. Okay. Check mark. Okay.

Nothing 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 three fatty acids. His omega three fatty acids were in the toilet. And he's like, oh, I don't don't really like fish. I'm like Yeah.

Then take then take the cacti sardines. And sardines are albacore, and tuna is high in mercury, but like in a wild salmon, at least once a week, but wild salmon has all sorts of stuff in it too. So you take certain supplements that are high quality, and everything improved. The interleukins came down. The his inflammation came down.

His psoriasis gets better. The amyloid comes down. Like, everything about his everything improves through some mild changes that were personalized for him. Right? And and that's that's the key.

These we could talk about blood biomarker.

Dr. Mark Hyman
I mean, 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 and 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 gonna try to find a drug that's gonna 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, presymptomatic level, but it's still happening. And it's like it's like the Bogalusa Heart Study where they looked at fatty streaks in the arteries of teenagers who are eating crappy diets in Louisiana. They were were a prelude to heart disease that they were gonna get in their thirties and forties, but we could see it in their teens.

Dr. Richard Isaacson
In May 2024, there was a CNN documentary that came out, doctor Sanjay Gupta came down. You know Sanjay, and, you know, he officially joined joined my research study, and 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 they send a film crew, you get they get to know people, and they see people for years, and they get to know them.

And and if that guy that doesn't believe that the stuff that I'm doing and our team is doing is possible, he thinks it's it's it's heresy. He thinks it's not real. Well, Simon was followed for years, and we have his brain on the same MRI, the same magnet, the same software. We have it in 2022. We have an image in 2024, and we have an image in 2025.

And Simon is an APOE four four. He's got two little kids. Okay? He's in his early fifties, now in mid fifties. He's got

Dr. Mark Hyman
That's APOE four is the high risk.

Dr. Richard Isaacson
APOE he's got So is it and and he's been totally public, he's obviously been in the documentary. If someone out there is listening to this and doesn't think this is possible, like, I I should call Simon

Dr. Mark Hyman
right now. We're gonna link to the documentary in the show notes. Yeah. We're gonna link to all your studies, all your research, all your websites.

Dr. Richard Isaacson
It's all there. It's all there. Like, this there's 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 the documentary stage, his amyloid improved, his his amyloid well, actually, was normalized.

His tau was still a little bit there. It's gone. Everything amyloid and tau are gone. His symptoms are improved, even though he still is doing great, and he had some subjective symptoms. His brain grew twice.

This is all real.

Dr. Mark Hyman
So just just for relisting, this doesn't happen. Right? Brains don't grow. They just atrophy as you age. That's orthodoxy.

Yeah. 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 the the brain itself and and reduce the atrophy, and and that leads to changes in cognitive function and improvement in outcomes.

Dr. Richard Isaacson
We have a saying, that we say it a lot, promise not to overpromise. And we're we're cautious, and we wanna, like, undersell just to be extra safe because we need to, like, really prove that this works. But my gosh, I mean, when you see it once, you're like, wow. When you see it twice, you're like, wow. And now I've seen it so many times, I'm still like, wow.

Right. Because I'm I'm in awe.

Dr. Mark Hyman
It's a mirror.

Dr. Richard Isaacson
It's a mirror.

Dr. Mark Hyman
Because compared to what we were trained in in medical school, it just doesn't happen.

Dr. Richard Isaacson
Yeah. 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 Take is

Dr. Mark Hyman
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

Dr. Richard Isaacson
are available. Sure. So actually so let let me finish on the a b c d and e first real real quick. The c is cognitive testing, and and again, like, a lot of people don't wanna do cognitive testing. A lot of people in our research don't wanna do it.

If someone, you know, wants to, you know, you know, we try to make, cognitive, activities. We call them cognitive activities at at retainyourbrain dot com. You you join, you get to know yourself, you can, you know, track or, you know, assess or whatever word you want to use with these cognitive, we call them, you know, activities because they seem less, you know, worrisome, but we do track cognitive function, in in our ABCD and E model. D is DNA. We do look at, some genetics, especially the APOE four variant, which is super, super, super important to personalize care, not to deduct or deduce, sorry, if you're going to get Alzheimer's, but it does help personalize care.

And the E in the ABCD and E is, emotional and social support and health, and and and, you know, stress management, staying socially engaged, having a meaningful life, mindfulness based stress reduction is something that we, you know, advocate for, you know, learning new things. The e is something we really, really, really take, seriously, and, we have to focus on the biological, the cognitive, and the psychosocial in order to get people off the road to neurodegenerative diseases.

Dr. Mark Hyman
And and you're talking about these social connections and relationships and having meaning and purpose and connection and belonging. And and and it even speaks to, you know, how things like hearing loss or visual loss will actually cause people to withdraw from these social connections, which actually accelerates dementia.

Dr. Richard Isaacson
Yep. Forty five percent of cases of dementia may be preventable if that person does everything right. And forty five percent to me is a very conservative number. I think that number's gonna be, you know, from a, you know, evidence based way, and then the next big study to come out, it's gonna be fifty percent or sixty percent or whatever magic number it's gonna be. But the the majority of cases, in my opinion, of dementia may be preventable if that person does everything right and we get ahead of things before symptoms.

And in that forty five percent, The Lancet 2024 paper, eight percent of cases of dementia are attributable to the modifiable risk factor of hearing loss. Eight percent. And now whether you have hearing aids if you can't hear this. Yeah. Yeah.

And if you're age 50 and above or whatever word whatever age you wanna use, get a hearing screen. You don't have to I mean, you should, you know, go to an audiologist and see a doctor, obviously, if if you can, but but you could do this on your headphones now. You could do it on a computer. You can get a hearing screen, and people that have hearing challenges you know, my mom I fought with my mom about this, like, for for for years. Like, wear a hearing aid.

You'll be more engaged. It it it may help prevent dementia. You know, that's that's that's not a pill. That's not a dietary change. It it's just have a hearing vision loss.

There's so many things that we can do to to screen and and intervene.

Dr. Mark Hyman
So so again, going back to, like, what what are the things that you're actually specifically using, and how do you kind of customize the treatments? And what are the what is the what are the cocktail of therapies? And what are the what's the what besides the things we've already talked about, you know, that are 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?

Dr. Richard Isaacson
So, you know, in our in our 2019 paper where we showed, really, back then, like, 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. 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 it's it's not like one or two things can do this because Alzheimer's and neurodegenerative diseases, they're they're complicated. Right? Any chronic disease of aging.

Right? Diabetes. Can you take a magic pill to prevent or cure diabetes? No. Can you eat a magic blueberry?

I love blueberries. I think blueberries are great. Right? Well, you can't eat a magic blueberry and prevent or cure diabetes or Alzheimer's or whatever. The people that did the best were people that followed greater than 60% of the recommendations.

So if we gave 21 on average, if you followed greater than 60%, people did better. People with mild cognitive impairment, the earliest symptomatic phase of Alzheimer's actually had improvements in cognition, like, again, heresy. It hadn't been shown like that.

Dr. Mark Hyman
So this is symptomatic early dementia?

Dr. Richard Isaacson
Symptomatic, not Well, to both. We had two groups. We had the the early treatment group and the prevention group. And I think the the the the take home for people listening is that there are so many things you can do. I'm gonna go through those in a second.

On average, we gave 21 different things. Oh, 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.

Dr. Mark Hyman
Benjamin Franklin. Right? Yep. Announced the prevention's worth the pound of cure.

Dr. Richard Isaacson
100100100% agree with that. But the people, before they had symptoms, whether they followed greater than 60% or less than 60% of the recommendations, they still had cognitive optimization. Their cognition improved at eighteen months in our 2019 study. So the earlier you are, the less you have to do to move the needle. The later you are, the more you have to do to move the needle.

So so that was our 2019 paper, and I think that was, you know, really critical. What are those 21 things on average? Well, those are average. In our whole universe of things, we've probably recommended right around 50 different things across all of the, you know, thousand plus people that we've seen. But the the two kind of categories that I put it on are in are, I would say, non pharmacologic and then pharmacologic.

And in the non pharmacological bucket, you know, for example, extras. Non drug. Yeah. Non drug. So non drug.

And and, you know, in the pharmacological bucket, I mean, I guess you could I don't know where to put the vitamins and supplements because those are, like, really important and critical, but, like, wherever you wanna 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 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 I do believe in them and 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 and and targets the thing that need they need to target.

Dr. Mark Hyman
And there's major papers published within JAMA, like, just walking prevents Alzheimer's.

Dr. Richard Isaacson
Yeah. Mean, anything is better than nothing. And and, you know, someone who's sedentary, I'd rather they walk. I think walking is physical activity, and physical activity is better than nothing, but to me, 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 gonna say, well, I'm gonna go walk three times a week and I'm gonna prevent Alzheimer's.

Well, not if you have excess belly fat and not if you have if you're under muscled. So someone that wants to use exercise as a primary lever to pull needs to figure out, well, what are they trying to do? So for for example, if someone needs to lose belly fat, you know, walking slowly is probably not gonna be enough. You need to get into a higher, you know, what we call zone two or steady state cardio where the the heart rate goes to 60 to 65% of of, you know, the person's maximum. The best way to kind of approximate that is if someone wants to get into fat burning mode is where they can still have a conversation with someone, but the person that they're talking to can hear that they're a little bit short of breath.

They they can hear that they're exercising, but they can still carry on a conversation. To me, that's in the zone two. And you need to get, I would say, least forty, forty five, sixty minutes of of that. And walking alone may not be able to do it, but fast walking sometimes with a weighted vest or up and down hills like that, that could be a way to get. In Austin, there are a lot of hills, so in Austin, 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 are fit and their doctors say, okay, doing fasted walking fast walking with a weighted vest early in the mornings before they've, you know, had any maybe maybe black coffee. But if you don't have any carbohydrates in the system, you may be able to burn fat even more efficiently. But again, some people, you know, shouldn't start like that.

Dr. Mark Hyman
But the belly fat, know, you're not gonna fix it by doing crunches or or ab exercises. It's basically sugar and starch that are driving it. And if you cut out sugar and starch, which is driving metabolic disease, which is a

Dr. Richard Isaacson
big part of Alzheimer's, you're gonna fix it quickly. In incredibly. And and I think, you know, if you're trying to just lose body fat, but not realizing that if a person has a lot of muscle, they're more metabolically active, and they can break down show break break down whatever, you need to build muscle mass. People should be doing strength training at least twice a week, you know, depending on their individual situation. Someone is trying to lose body fat, they should be doing zone two, you know, fast walking with a weighted vest, you know, three times a week for forty five to sixty minutes.

So exercise is not just like, you know, going for a walk is better than sitting on the couch, but being intentional about your physical activity and physical exercise routine is what it takes to really have an impact on brain health.

Dr. Mark Hyman
So exercise is one of the interventions. Diet. Let's talk about nutrition. Yeah. There's there's the MIND diet, which is Mediterranean.

Dr. Richard Isaacson
And, you know, like, the way I

Dr. Mark Hyman
think about it is is is, you know, if food is medicine, what's the drug? What's the dose? What's the duration? Right? And I think, yes, the MIND diet, which is a sort of modified Mediterranean diet, lots of omega three fats and anti inflammatory foods, Great.

But it there's there's different levels that you can push on the gas pedal to get more effect. I had a patient once who had MSCI mild cognitive impairment. She had a whole bunch of problems, the 21 things, and we fixed all of Her thyroid was off. She had heavy metals. She was pre diabetic.

She had methylation issues and high homocysteine. She had low omega three 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, jeez, why don't we try a ketogenic diet? Because I've been reading about ketogenic diets and changing the metabolism of the brain by cutting out all sugar and starch and carbohydrates pretty much and eating 75% fat. And we did it, and, like, the lights came back on. And I was like, holy cow. So, again, how do you approach diet with with all this?

Dr. Richard Isaacson
Yeah. Well, so to, know, nutrition and and and dietary patterns versus single or multiple nutrients. Like, this is a this is a long topic, and you and I both have written books about this, and we could talk about this probably for an hour. But, to me, different diets you know, we're not in the realm yet where precision nutrition is like, easy off the shelf straightforward. But different people, I believe, need to follow different dietary patterns.

And and I too, back in, I think, 2007 was the first time that I put someone on a ketogenic diet, and and saw something that I just did not think was possible. But then I've had other people where I put on ketogenic diets and, like, things kinda went the wrong way. And and to me, you know, it we're not we're gonna 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 you think about the big buckets. So the Mediterranean style diet, fatty fish, brain healthy fats, omega three fatty acids, especially people with one or more copies of the APOE four gene, like, we have to have enough omega three brain healthy fats, otherwise people will have cognitive decline in the synapses.

Dr. Mark Hyman
Because a lot of your brain is made up of DHA, which is 60% as far

Dr. Richard Isaacson
as I remember, which And is and DHA and EPA are the two most brain healthy fats, and DHA is especially important for people with one or more copies of the APOE four variant. So brain healthy fats, that's PUFAs, polyunsaturated fat. Then you have monounsaturated fats. Monounsaturated fats, like, if you wanna drink olive oil, like, ounce or two a day, and your doctor says okay, that's like anti tau protein. Like, that is good for

Dr. Mark Hyman
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.

Dr. Richard Isaacson
Exactly. And 60%, one study I read of the alco of the of the Oh, wow. 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 moustached in different parts of the house and just

Dr. Mark Hyman
pour it on Me too.

Dr. Richard Isaacson
Pour it on whatever I can get it in because I I need and if it burns the mouth, yep, that's exactly the the proxy, has a taste to it. So avocados, olive oil, fatty fish, brain healthy fats are, like, so critical. Green leafy vegetables. So, you know, berries, you know, half a cup of strawberries or blueberries two to three times a week. Nurses' health study published over a decade ago showed you could delay cognitive decline just by eating berries on a regular basis by two years, just from one intervention.

Dr. Mark Hyman
That's why I gave you a berry shake this morning.

Dr. Richard Isaacson
You did. It was good. With with with goat milk whey, which was a first for me. That's right. So I I appreciate it, which is really nutritious and and actually tasted really good.

So, you know, green leafy vegetables, high antioxidants. People should be eating mostly plant based. You know, I I would call it plant rich. Yeah. Plant rich.

Yeah. Plant rich. Plant rich. And, you know, there's diff because plant based is vegan.

Dr. Mark Hyman
Yeah. No. No. Might be problematic for people who wanna build muscle.

Dr. Richard Isaacson
Mostly plant rich. Okay. Yeah. That's a better and I wouldn't maybe maybe yeah. I don't know the exact terminology, but, you know and then, like, meat is all not created equal.

Like like, red meat grass fed beef is totally different than other beef that isn't, you know, whatever. So I think people need to eat, you know, where they feel comfortable with, whether ethically or or otherwise. They need to get protein levels, whether it's through whey protein through goat or or whey protein through regular milk from cows. I think each person needs their own individual kind of thing, and some people may be more sensitive to one thing versus the other, and there's lots of different

Dr. Mark Hyman
And I saw you putting, like, cocoa polyphenols in your

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

Dr. Mark Hyman
So Richard Eisenhower starts his morning with a mocha.

Dr. Richard Isaacson
I do. A mocha for your a mocha for your memory in the morning.

Dr. Mark Hyman
And that's funny because mocha is actually one of the names for a test we use, the Monteral 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.

Dr. Richard Isaacson
Exactly. Yeah. We don't want people to do it too much at home because then they practice, and the doctors see the doctor, and they memorize a test. But I I don't disagree. Yeah.

For, yeah, for sure. Are definitely ways to to track track.

Dr. Mark Hyman
So fatty fatty foods, omega three fats, monosage fats, berries, leafy greens.

Dr. Richard Isaacson
Yep. You know, nuts and seeds. Antioxus nuts and seeds. Know, balancing the omega six with omega threes. There there's so much nuance with nutrition, but I think that's it.

Also, the elf diet.

Dr. Mark Hyman
What's that?

Dr. Richard Isaacson
Oh, my did Eating moss in

Dr. Mark Hyman
the Arctic I

Dr. Richard Isaacson
I just saw Doctor. Mark Hyman on a dietary pattern that he's never heard of. Wow. This is this is a great day. I'm never gonna forget this day.

Dr. Mark Hyman
I've never

Dr. Richard Isaacson
heard of it. The Olf diet. Eat less food.

Dr. Mark Hyman
Oh, eat less food. Yeah. Yeah. Like Michael Pollan, eat food not too much, mostly plants. Right?

Dr. Richard Isaacson
Yep. So just less. Like, people just eat so much in excess. Like, it's it's crazy. And, you know, there was a study out of Mayo that showed that people that ate, like I think the cutoff was, 2,100 calories a day, less than 2,100 or more, have, you know, delayed cognitive decline.

And and again, this is, like, imprecise So the Okinawa principle. Right? Hari Hachibu, which is eat percent full. Percent full. Exactly.

Hari Hachibu. That's exactly it. So the the take home here is, though, if you're trying to gain muscle, well, you better eat sufficient protein and and and calories because you need both carbs and protein to build muscle, and you don't wanna, like, just, you know, starve yourself, and there's good carbs and bad carbs and know the difference. That's really key. Berries and leafy greens are carbs.

Right? Exactly. Yeah. And and, you know, some whole grains in moderation, think, are okay, but but not if a person's not active. You know?

So so, anyway, yeah. Nutrition's, you know, tricky. You know, vitamins, we we talked about, you know, omega three fatty acids, but vitamin d, especially people with one or more copies of the eight zero eight four 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 a as an example, sixty percent of the people in Miami, even with sun exposure, are deficient in vitamin d. So we check vitamin d and

Dr. Mark Hyman
Well, you have to be naked between ten and two in the morning, two in the afternoon for twenty minutes. And if you're not, you're not gonna get enough vitamin D. If you're if you're if you're a lifeguard, you will. But otherwise, forget it.

Dr. Richard Isaacson
Exactly. People wear sunscreen now. People are indoors. And, yeah, you know, I usually tell people you need fifteen minutes of of twelve to fifteen minutes between the hours of eleven and one to try to split the difference. I don't wanna you know, it's it's it's hard to know for sure, but, you know, we we check vitamin d and and and supplement if needed.

We also talk a lot about b complex vitamins, and 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 Yeah. Homocysteine is high, the people that took B complex vitamins, b twelve folic acid, and a tiny little bit of b six, 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 of the total shrinkage of the total brain size. So Yeah.

Dr. Mark Hyman
There was a paper published a number of years ago in JAM or a New England Journal I read where if your homocysteine was over 14, you're fifty percent more likely to get Alzheimer's or dementia. And that's, again, something we test at function health, and also methamylonic acid, which is a marker of b 12 function. Yeah. And I I remember a patient who came to me who was, you know, a very successful businesswoman, was on multiple boards. She was in her early eighties, and she's like, I got diagnosed with MCI, mild cognitive impairment, early dementia.

And she was pretty upset. And I'm like, well, I don't know. Let's see what we find. And she had extremely high homocysteine and high methylmalonic acid, is a marker of b 12, which are better probably better than measuring folate and b twelve in the blood.

Dr. Richard Isaacson
Probably had a double MTHFR

Dr. Mark Hyman
She did. She had the genetics that made her having trouble

Dr. Richard Isaacson
with Yeah. Her metabolic

Dr. Mark Hyman
And she was older and probably not absorbing b twelve, 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 that made me crazy. I mean, there's the third most leading prescribed drugs after statins and psychiatric drugs is the acid blocking drugs, which are now over the counter.

And they they're they're dangerous to take long term. Fine short term, but long term. And so I said I found this, and I gave her b twelve shots, and I gave her high dose of methylfolate and some b six, 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 wanna know what I should be doing to prepare and take and blah blah blah. I'm like, okay.

Great.

Dr. Richard Isaacson
Amazing.

Dr. Mark Hyman
Yeah. What else supplements? What other supplements? Vitamin d, fish oil, the b vitamins? Yeah.

Dr. Richard Isaacson
I mean, turmeric, I think, you know, curcumin, the active ingredient in curry. I think in certain people, especially with, elevated, amyloid levels, in the blood, you know, we usually we we we sometimes use this. And I think in terms of, like, the the the big picture, those are, like, the one size fits many ones. Yeah. But, I mean, the list just I mean, the list is really long.

So, I mean, there's there's definitely other things people can do. But 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 is real nutrition and exercise are, like, critical critical levers. And, you know, in our research study that we presented data on that that I can talk about because we presented this at the, twenty twenty five 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. Stress management, keeping the brain engaged, learning

Dr. Mark Hyman
Social connection.

Dr. Richard Isaacson
Yep. Seeing a doctor on a regular basis to make sure their blood pressure, cholesterol, you know, blood sugar is all modified in in in in a in an optimal range for specifically for them. When you when you put all those together, but no drugs, if you look at the the groupings of of the the categories of the people we followed So intensive lifestyle intervention. Intensive lifestyle intervention of all the interventions that we tried moved the needle the most.

Dr. Mark Hyman
More than any of these billion dollar amyloid drug studies.

Dr. Richard Isaacson
Right? Our in our study that we've and now this hasn't been fully published, but I can talk about it because we present an abstract form. There are people that, for example, took GLP one drugs. And GLP one drugs are tricky because, you know, I believe that too high a dose, if you're not eating right and doing the right thing, you can, you know, lose muscle and have all other things lower dose. You know, I'm I'm more of like the microdose crew when it comes to GLP ones.

GLP ones, positive effect on biomarkers, you know, in my opinion, based on the our results, you know, impressive results when used in the right person at the right dose for the right duration of time.

Dr. Mark Hyman
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 mean, before GLP ones were on the market, was reversing diabetes, getting people to lose 200 pounds, 100 pounds, 150 pounds. You you can do it.

It's just it's just and I think my guess is that they would do a head to head comparison of GLP ones and the same diet that you would eat if you were on GLP ones, there would be no difference in any of the biology. That's my feeling.

Dr. Richard Isaacson
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. So So

Dr. Mark Hyman
you're testing, not guessing?

Dr. Richard Isaacson
We test everything.

Dr. Mark Hyman
Okay. 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

Dr. Richard Isaacson
is a

Dr. Mark Hyman
bunch of questions. We try something. You're actually looking at blood tests that show changes.

Dr. Richard Isaacson
Try one thing. We repeat it. We don't try 10 things at well, for multimodal interventions, we try a group, and then if we're gonna try a drug, we're gonna recheck the 150 biomarker proteins. We check the proteins on different machines in duplicates. Every blood test we do, we run twice.

This is not normal. This is not cost effective. We do it anyway because we care about quality, not about anything else. But and and and we just try to do things as as as rigorous as as humanly possible. And what we show is that when we do these tests, we call these NF one studies, we'll try a GLP one, and we'll check.

We'll try hormone replacement therapy. Like, replacement therapy, bio identical hormones for women during the perimenopause trans transition. In the right woman at the right dose, the the women in our in our little hormone replacement therapy group, believe it or not, the age ranges from 42 to 67. We have multiple women that have actually started on hormone replacement therapy with approval and agreement by the GYN and the primary care doctor in our in our team. We've had, I'll just say what I feel like I should say, amazing success with using hormone replacement therapy.

And and when that rapid drop of estrogen comes in a genetically susceptible woman, You know, we did this whole women's brain imaging study at at Cornell and spent, you know, millions and millions of dollars on this. Women that had, you know, hormone replacement therapy on board had better brain volumes and less amyloid. Yeah. But it had never really been proven in a in a study that you could use h hormone replacement therapy. And then there's this that woman's health study that used, like, synthetic hormones and horse urine derived whatever.

Like, when you use a bio identical patch and you use progesterone, and we talk to the GYN, we talk to the doctors, hormone replacement therapy during the paramedial post transition has helped improve brain biomarkers associated with Alzheimer's and neurodegenerative disease risk. It's been striking. So So

Dr. Mark Hyman
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 and improve the the blood biomarkers that are associated with neurodegenerative disease. So that's a big deal. And and the other thing I I wanted to say is that the consensus most of that I've heard is that it's it's important to start right away after your menopausal transition. But what I hear you saying is that you can actually start it later.

Dr. Richard Isaacson
What what end early? I I wanna start any time.

Dr. Mark Hyman
Both. I see. Yes. Start early. Both.

Does that mean every woman should be on hormone replacement therapy? Like, what what are the implications here?

Dr. Richard Isaacson
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, to my knowledge because we have misogynistic research infrastructure. Like, it's it's just so it's demoralizing.

It's just so wrong that women are taught that like, oh, you're having night sweats. Oh, oh, you don't feel good. Oh, you're having brain fog. Oh, okay. Sorry, you know, we'll see you back in six months.

Perimenopause is a neurological disease. Like, you're just gonna have a woman suffer? These are these are symptoms that are treat oh, go change the temperature in your room, and maybe you'll sweat less, or maybe change your sheets, get better sheets. Like like, no. This is a medical condition.

Like, really or get, like, you know, the cooling thing. Like, okay. Or a weighted like, fine. Okay. Treat the problem.

And what we've shown is that, you know, through ridiculous amounts of time, effort, money spent, and research, which needs to be quadrupled or or probably increased even much more than that, we've shown that when we use hormone replacement therapy in the right woman at the right dose, 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 tau starts coming down. Even though the tau wasn't elevated to a degree where we're like, uh-oh, sky is falling, but the tau is higher than it should be in that woman who's 47 years old. And this whole concept of, like, you know, 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 and I think, you know, it's it's tricky. I think there's risks and benefits with every one of these decisions, but, you know, I've just seen too many women suffer, and it's just not fair.

Dr. Mark Hyman
So if they're symptomatic, or if you if you do evaluations, 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 even if you're not symptomatic Well,

Dr. Richard Isaacson
I think if you're symptomatic, it's it's like, how like, how could you not? I think it's like, you know, it's unethical not to try to figure out how to. In our cohort, we track estrogen, estradiol levels, and other hormone levels, you know I mean, women 21 and above. We also this is crazy, but like, you know, this hasn't been done before to my knowledge. We do multiple blood draws through the menstrual cycle to try to figure out, like, as estrogen and progesterone change during the cycle, guess what?

P tau two seventeen changes, and these other markers change too. How has this never been done before? So we have women. We have, like, vol thank you. Thank you.

I'm not gonna say their their code numbers in in our research study. They get six blood draws on day one, on day three, on day seven. Like, we get six blood draws during the menstrual cycle. We're just trying to figure out, like, what should the p tau be at what depending on what day the blood was drawn, we need to correct for what the tau level should be based on where the estrogen and progesterone is. Like, these are things that just haven't been figured out yet, and these are the types of questions we're asking, and these are the types of things that need to be figured out.

And when you take this approach, precision, personalized, individualized approach, we've seen women in their early forties, like 42 is the earliest we've started, where we've seen the estrogen going down and we've seen the amyloid going up. Well, maybe they're a little symptomatic, but it's not really bothering them, But we're gonna start on low dose hormone replacement therapy if everyone is in agreement. And guess what? She feels better. Her cholesterol comes down.

That's interesting. Her amyloid is improving even though it wasn't abnormal, and this is really the key. Like, we have to personalize these therapies, we have to you know, we also just monitor for a change. We've been monitoring these women for so long. We see the change, and then you intervene.

And so so to me, it's if symptomatic, like, please talk to your doctor. And and if your doctor says tough it out, like, to another doctor. If you're presymptomatic, follow it closely. I I think women pre menopause perimenopause should should probably get checked every six to twelve months for these brain biomarkers and hormones.

Dr. Mark Hyman
So essentially, what you're saying is if you're symptomatic, don't suffer. Right. And if you're not symptomatic and you have a lot of risk factors and some of these blood biomarkers that were that are emerging are abnormal, then it's better to get on early even if you're not symptomatic.

Dr. Richard Isaacson
I believe that specifically in people that are at the high women that are in the highest risk category, which are APOE four positive, especially women with two copies of the APOE four variant. Some of the most striking improvements actually, one one woman is actually lives in Austin, one woman is in California. I mean, know these cases, like, you know, the back of my my my my mind, like, I I you just start, and you see everything improve.

Dr. Mark Hyman
This this is honestly, Richard, why we cofound and function, and and I 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 APOE four and some of these brain biomarkers, and then you can kinda start to decide what to do and and take control of your own health. I wanna ask you about guys because two thirds are women, but then one third is guys. Yep.

Do guys benefit from hormone replacement therapy in terms of testosterone?

Dr. Richard Isaacson
Great question. I I think the literature has been I would say the literature has been not conclusive is is how I would answer this question. It doesn't mean it helps or hurts. It's just literate the the evidence has not been sufficient for, I would say, the vast majority of the times that I've looked into the data. I would say more recently, you know, I would say it's more likely than not, but not a certainty, that using, hormone replacement in men, specifically testosterone in the right man at the right dose for the right duration

Dr. Mark Hyman
That's right.

Dr. Richard Isaacson
For a different That's right. Different discussion, and and, like, which types, and how many times a week, and what version, and is it the cream, or is it inject like, there's a lot of confusion here.

Dr. Mark Hyman
Yeah.

Dr. Richard Isaacson
A lot of confusion. And then what else is going on? Like, what other hormones? Because sometimes when people use testosterone, they're also doing, like, five other things. What I would say is if hormone replacement is used judiciously in men, and the person is putting in the work, exercising and trying to build muscle mass in addition to taking, you know, lower end I mean, some of these testosterone levels I see are just like Super high.

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

Dr. Mark Hyman
You want a physiological level, because then your estrogen levels will go up because you convert testosterone to estrogen, then you start having sex you know, libido issues and other issues that are it's like it's a it has

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

I'm just not sure if it's strictly Alzheimer's pathology.

Dr. Mark Hyman
Well, it's it's kind of the motivation hormone. Right? And when people drop off in motivation, they withdraw from life. They stop doing the things they want. They might not wanna exercise as much.

It's kind of like a a dirty cascade. Okay. So we've got we've got nutrition. We've got exercise. We've got certain supplements 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. Yep.

So you have to be careful with sleep.

Dr. Richard Isaacson
Yeah. Sleep I mean, we could spend a whole podcast just on sleep.

Dr. Mark Hyman
Me a couple minutes on sleep.

Dr. Richard Isaacson
Yeah. So so, you know, everyone out there has to make a plan for sleep. You know, you could be burning the candle at both ends, pushing pushing pushing, sleeping five, six hours a night. If you're exercising, doing everything right from an exercise and nutrition perspective, but not getting adequate sleep, you will not have adequate brain health. It's not gonna happen.

So everyone out there needs to prioritize and make a plan for sleep. I have people where the only thing they changed after I've read them the riot act was their sleep patterns. The only thing they've changed and the impact on their brain biomarkers Objective blood test. Every I mean, objective cardiovascular test. I wear all these trackers.

We track everything in all of our patients. I mean, the only this is this is, like, crazy, but the only thing that changed in an otherwise optimized person, if you get sleep right, the amyloid can come down, the cognition can improve, sleep is so critical. You know, it's not just about getting what's the magic? In our study, we did a study on this. We tried to figure out, like, what's the optimal sleep?

And, like, 07:11, that's how I remember it. Like, 07:11. Seven hours and eleven minutes. The people that slept more than that did better cognitively. People that did less.

Dr. Mark Hyman
But Seven hours and forty eight minutes night. Great.

Dr. Richard Isaacson
Take it. That's that's good. And, you know, obviously, you know, it depends on the sleep quality. Yeah. Sleep is restorative sleep.

That's when the trash gets taken out. The amyloid gets, you know, taken out in the garbage. You know, REM sleep is when short term memories are consolidated or really formed into long term memories. So there's sleep quality and there's sleep sleep quantity. And the number one way to get more sleep quality is to sleep longer, to have more REM and more deep sleep.

Like, that's a cheat code. You know, to me, you know, actually retainyourbrain.com is the the actually, I'm 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, eleven or 12:12 in the afternoon, I am not allowed to drink coffee after 11PM based on my Time's up. Time's up.

You know, because, you know, caffeine lasts for five six hours, the half life. So if I'm drinking coffee at two or three or 04:00 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

Dr. Mark Hyman
Ear plugs and eye shades.

Dr. Richard Isaacson
Yeah. Exactly. Weighted blankets, some people really like those, like, you know, for cooling temperature.

Dr. Mark Hyman
I like cold rooms and heavy blankets.

Dr. Richard Isaacson
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

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

Dr. Richard Isaacson
I I agree. You know, my other routine that I got, the the brain healthy habit that the software recommend because, know, I typed in the thing, like, are my issues? And then 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 09:30PM, my alarm goes off as a reminder that says power down your electronics. So at 09:30, I try to wrap up, and by ten, 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

Dr. Mark Hyman
Yeah.

Dr. Richard Isaacson
There's my there's my Grateful Dead bear. Got the got the the Bobby and the Wolf Brothers show a couple years ago.

Dr. Mark Hyman
For those who don't know what he's talking about, it's Grateful Dead and Bob Weir and his his band called the the Wolf Brothers.

Dr. Richard Isaacson
I was waiting online to get into the show. Someone miracled me with that.

Dr. Mark Hyman
So Too many inside jokes.

Dr. Richard Isaacson
Yeah. Sorry. It's old old deadhead jokes. But but, like, why are we on our cell phones right before bed? Like, that causes rumination.

If you wanna 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.

Dr. Mark Hyman
And two more things I wanna 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 can link all your papers, all the media on you, people can learn more. The there are, you know, two other pieces. One is is what about pharmacologic interventions?

Because drugs have a role and kind of one of the one of the star players here. Yep. And and and also, like, what about brain exercises? Like, brain games, learning new language. So those are two things we need to talk about, but I think there are key pieces of of keeping and retaining your brain.

Dr. Richard Isaacson
I'm equal opportunity. I got I got no skin in this game. I take no, you know, funding from pharmaceutical companies, any any anything like that. I'm equal opportunity. If it's a drug, a vitamin, a supplement, and it's relatively safe, and I would be willing to take it myself or give it to a family member, it is on my list of potential interventions.

So I'm I'm not pro work on anything. I'm pro evidence, and I'm pro safety. That's all I am. In our research study that we presented in July 2025 at the International Alzheimer's Conference, paper is getting ready to be published, not gonna be published yet. It's gonna these papers take, you know, years and years and years to publish.

The general categories of of of drugs that, worked the best, well, we talked about hormone replacement therapy, and we talked about GLP ones, and those drugs, drug categories worked, honestly, amazingly well. Like, it's just it's just I 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 Zetia use.

That's the brand name, but it's all generic now. And then the other categories were, I think this was in the paper, SSRIs, selective 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.

Dr. Mark Hyman
And you're also talking about GLP ones too are part of

Dr. Richard Isaacson
this topic. Oh, Yeah. Oh, g l yeah. G l GLP ones and hormone replacement therapy are definite check check marks, and I would say in our in our study, multimodal interventions work the best. G l p ones 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.

Dr. Mark Hyman
So basically, what you're saying is the basics work better than these fancy drugs that we've spent billion dollars researching and have shown very incremental benefit.

Dr. Richard Isaacson
Yeah. And They're not like zero, but they're

Dr. Mark Hyman
Yeah. And I And they may be additive to an overall package of information. True.

Dr. Richard Isaacson
True. And in the right person at the right dose, ezetimibe, the plant sterol inhibitor, I I I never in a million years would I have, like, ever said I would be saying something like this, but, you know, we're developing these blood tests, and, you know, we talked a lot about Alzheimer's today, but alpha synuclein. Alpha synuclein is a pathologic protein that that builds up in the brain of a person with Parkinson's disease and Lewy body dementia. Like, we are working on these blood tests. Like, this is crazy.

Never in a jillion years like would I have ever regardless of my my family, my brother, my brother's son, my brother's brother-in-law, like like, we see these drops in alpha synuclein protein using some of these things. These are Parkinson's related things. So I don't fully know what this means yet, but what I would say is the cholesterol drugs in the right person, at the right dose, and the right duration, you know, your mileage may vary, work. And it's improving what I believe to be brain health risk and brain health outcomes. Statins.

Let's talk about statins. The people that start on statins in our cohort are not your typical, you know, Crestor, rosuvastatin twenty milligrams. Like, the amount of people I see on high dose statins, it like just blows my mind. 85% of the cholesterol lowering effect of rosuvastatin or Crestor comes at five milligrams of the dose.

Dr. Mark Hyman
So you get 80% of the benefit at the lowest dose.

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

To me

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

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

Dr. Mark Hyman
But you guys are throwing at everybody. You're doing tests that say, oh, you're somebody who produces more cholesterol. So you and I don't, so statins wouldn't be good. And even I have the gene that makes it me have myopathy or muscle damage. If I take a statin, I have that gene.

I tested it. So statins are not good for me, and they also cause mitochondrial damage. And if you do the test, this helps you personalize or pre precision approaches. You're gonna get a better effect with less side effects. And and there's there's a there's a friend of mine, David Faganbaum, who created a company called EviCure, 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 ezetimibe or Zetia. It works for Alzheimer's, but it was a cholesterol drug. But it has an an effect that maybe we don't even understand why, but it's working on some pathway that's independent of just the cholesterol lowering because it's not just about lowering cholesterol. Because you could actually lower cholesterol just as much with another drug, but not see the same benefit.

Exactly.

Dr. Richard Isaacson
And and and, you know, these are, again, are Am

Dr. Mark Hyman
I catching on?

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

Prozac. So in our cohort

Dr. Mark Hyman
Does that category of drugs

Dr. Richard Isaacson
Actually, we have zero people in our cohort on Prozac. The only people in our cohort that are on SSRIs, I think this is because escitalopram or Lexapro, it's an 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, you know, lowering or attenuation effects on amyloid. So in our little group, you know, we have a group of preventive neurologists, preventive cardiologists, preventive medicine specialists, internal medicine doctors 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 five milligrams.

I almost never go I mean, I don't I don't usually go high. And, by the way, we're not treating, you know, know, I'm not a sec I'm not a psychiatrist. I we're we're we're you know, mild depression versus major depress you know, those things I'm not gonna get into the nuance. But the majority of people in our cohort that are on SSRIs are on escitalopram or Lexapro five milligrams, I would say on average. And in our cohort, it's a small small group, but we also saw some, but not, I would say, slam dunk robust effects from low dose escitalopram, low dose Lexapro.

Dr. Mark Hyman
So this is really important. I just want to say a step back, so we kind of have to wrap up. But I think I think that, you know, for those of you listening who have a family history or who are suffering from memory loss or concerned about getting it. You know, what you're saying, Richard, Doctor. Isaacson, is that for the first time in history, we're actually able to do preventive neurology around neurodegenerative diseases, And that you can actually slow or even reverse the changes that happen that are measurable by new and innovative blood biomarkers that you're developing and that are ones that are already developed and are available.

And you're seeing change in brain structure, growing brains, and the function of brains, improvement in cognition, and you're not using the old paradigm of a single drug for a single disease, using over 50 different things that you pick from depending on how you want to personalize the treatment. That if you see one person with Alzheimer's, you've seen one person with Alzheimer's. And that this field is changing radically in such a way that will actually be able to help us avert this catastrophe of forty seven million people who are in the presymptomatic stage of Alzheimer's that are measurable by these blood markers that is gonna cost us $18,000,000,000,000 over the next thirty 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 and following your work for years.

Yeah. 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, Jay Bhattacharya, this this is the future because it's what I have seen over thirty 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 Ultramind Solution, fifteen years ago, or more than fifteen years ago now. And I think I think we're at this this transitional moment in history where for the first time, we're we're getting a handle on this horrific condition. You know? Yeah.

You get a heart attack. Okay. You have chest pain. You get a bypass. You get a new heart transplant.

You're still you. When you get Alzheimer's, you lose you. You lose your family members. It's a catastrophic disease, and no and everybody's terrified of getting it. And nobody should be afraid of doing the diagnostic test to figure it out.

And now at Ezra, which is a company we bought with Function, we actually can do brain imaging, and we can do quantitative brain imaging, which is a more advanced service we offer. But we can actually start to track these things over time. And so you can begin to do these things. You can go to retainyourbrain.com and start to kinda get ahead of the game. So, Richard, I just wanna say thank you for what you've done.

Thank you for the insights, for the moments you had in the hallway with that guy with a patient with dementia. We never know how we get doing what we're doing, but I hope that your work continues. I hope that you get it funded not to 10 or $20,000,000, 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 kinda is heresy, but it it's actually valid scientifically. And and we need to get behind it. So thank you for everything you've done.

Thank you for what you're doing. You're 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.

Dr. Richard Isaacson
Thanks so much, Snyder, Ham.

Dr. Mark Hyman
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