Neurscientists Found the Fastest Way to Reverse Brain Aging (And It’s Not What You Think) with Dr. Paul Thompson

Dr. Mark Hyman
What are the factors that seem to have the strongest influence over brain function, brain health over time?

Paul Thompson
When we looked at brain scans of people that were maybe obese, overweight, their brain would look eight years older. So people who had below normal estrogen and testosterone, their brain aging was faster. But when they were treated or when their nutrition was back in balance, all of these brain systems were restored. I mean, the food is the fuel of of the mind.

Dr. Mark Hyman
Welcome, Paul, to the podcast. So good to have you.

Paul Thompson
Appreciate it.

Dr. Mark Hyman
I am sort of in awe of your work. I think, you know, you're one of the few scientists out there who's connecting the dots in ways that most scientists don't because we're learning to be tunnel vision in science. We pick one topic. We have one trajectory we're working on our whole career. We're reductionists to a fault.

Sure. And you've zoomed out and you created this extraordinary project called the Enigma Consortium, which is a global brain mapping collaboration involving 2,500 scientists across 47 countries. And you're looking at brain imaging of all sorts and biomarkers, blood biomarkers. And you're you're you're kind of doing something that's kind of heresy in medicine, is looking at psychiatric diseases by looking at the brain. The joke in medicine is that psychiatrists pay no attention to the brain and neurologists pay no attention to the mind.

Paul Thompson
Yes.

Dr. Mark Hyman
Yes. And you're paying attention to both, the mind and the brain and how they relate. And they're not the same exactly. And how the rest of your biology plays a role. And you're you're not just looking at the typical neurologic diseases like Alzheimer's and Parkinson's and so forth, but you're looking at psychiatric conditions, which typically have been just diseases of description.

You get these symptoms, you get this diagnosis. It's basically the DSM five, which is a... We all call the diagnostic and statistical manual number five. There'll be a number six soon, I think. They used to have visitation from the gods and things like that, but I mean, they've updated it.

But it's not any better than that, honestly. My opinion opinion, I asked Thomas Insulla, who you probably know is the head of the NIH for the National Institute of Mental Health for a while. And I said, Thomas, what what do you think of the DSM five? He said, well, he said, it has a 100% accuracy, but 0% validity. I mean, it's very accurate in describing and putting people in groups and categories according to their symptoms, but not at all about understanding the cause or mechanism of the disease.

And for the first time, I think... I don't know too many people doing what you're doing, which is you're looking at the biology of mental illness in a way that's not just... It's a chemical imbalance and takes serotonin reuptake inhibitors, but really a much more nuanced view of how the structure and function of the brain work together, and and how to how it can help us understand these conditions, how it can and start to kind of bring about novel treatments that we haven't thought about before, make discoveries we never thought of before. I don't know how you got into this, but like, you you were kind of a Greek and Latin major at Oxford. And I don't even I don't even know where you go with that.

I'm becoming a classics professor. What took you down this road and how did you get this that we should be looking at things a bit differently?

Paul Thompson
Well, first of all, Mark, I really appreciate your invitation to be to be here today. I admired your work for many, many years. And it's it's fun to be able I

Dr. Mark Hyman
was hoping you'd say yes. I didn't even know who I was. I was like, I hope he comes on this podcast. He's he's a real scientist. I'm just kind of a quacky doctor.

You you

Paul Thompson
do incredible work, Mark. So I was just... First of all, the classics. If if we... We were joking about this.

If we meet any ancient Greeks, we're gonna be fine. We'll be able to look after them. But I I grew up in England, as you can probably tell from my funny accent. And I had the chance to work at UCLA during my PhD in my twenties here in in Los Angeles. And they had a brain mapping center, a brain mapping center.

And so what you could do at UCLA, and now this is available across the world, is you could have a three-dimensional picture of the brain, not just what it looks like, but the the activity of the brain, what is the molecular content of the brain, is the activity in the normal range, is it depressed like in depression, is it deteriorating, like in dementia? So I just got absolutely fascinated by this. And, I mean, you know, Mark, in your own work, you can use these technologies to give you insight into whether someone is doing okay, whether they need some medication or lifestyle intervention. Or for that matter, in a drug trial, you can use these as a readout of whether or not the medication is is working.

Dr. Mark Hyman
That's incredible. You know, and, you know, you have been part of this consortium and collaboration across 47 countries, done 200,000 brain scans, which is a staggering number of brain scans, over 30 different brain disorders. What are you seeing? What are the patterns that are emerging?

Paul Thompson
So I can tell you a little bit about the different brain diseases. And and I know your listeners are gonna be very familiar with with some of these, perhaps less so with others. So in old age, a lot of people get dementia. And one of the kinds of dementia, Alzheimer's disease, is a huge problem. And so as you know, maybe among 70 year olds, maybe five percent of them have this.

But every five years after 70 years of age, its incidence doubles. So that... That's that's pretty incredible. I mean, at 75, ten percent of people at 80 years of age, twenty percent of people. So this is this looming epidemic hazard that is coming.

Yeah. So one of the early results with brain imaging that really showed its value was that if you scan people as they progressed with Alzheimer's disease, there was this wildfire of tissue loss in the brain. And you you could take a scan a little like a Polaroid. You'd take a scan, you know, a month later, two months later, and you could make a time lapse movie where you could see the propagation of the disease. So it starts in the memory system.

It attacks your language systems. Eventually, it attacks the frontal parts of the brain involved in planning and making decisions. So that started to be used in drug trials. So people say, Well, I'd like to see if a treatment, it could be a pharmacotherapy, it could be a lifestyle intervention. Does that slow this relentless, you know, forest fire of change?

And so then we got into psychiatry. So Lilly, just to tell you the story of how it came about,

Dr. Mark Hyman
they The drug company.

Paul Thompson
The drug company, Lilly. They were

Dr. Mark Hyman
testing Not your friend, Lilly.

Paul Thompson
Not my friend, Lilly. They were developing drugs for schizophrenia. So schizophrenia's very different. It's a mental illness where people hallucinate. They have a distorted perception of reality.

They have so called psychotic outbreaks. But there are some medications for it. Not always successful, but moderately successful.

Dr. Mark Hyman
And with lots of side effects.

Paul Thompson
And with lots of side effects, one of them being obesity, which we'll get into. Lily said, Could you come up with a kind of brain imaging where we can see the drug is doing. Because there was an older drug, haloperidol. It was an antipsychotic. And the results of that trial were that the medications seem to be slowing down the spread of schizophrenia in the brain.

And you say, well, what does it mean, the spread of schizophrenia in the brain? You could see physical changes in the brain tissue. And if someone was scanned today and in three months, the people that were taking that particular medication would have a slower rate of tissue loss. So you can begin to see how, you know, in Alzheimer's where pretty much all scientists agree there's a degeneration of the brain, you could say, well, look, you're maybe 10% below the normal range for people of your age and background. And the drug trials started to use these measures.

Mark, you're very pioneer in the area of biomarkers. So you can think of a brain image as a source of physical evidence of disease in the brain. And there are plenty of others. I mean, someone's not gonna just use the image. There'll be clinical assessment.

There might be blood marker assessment. There could be whole body physical assessment, as you are doing. But the big picture of it all is that each of these is sort of an indicator, either to rule out or rule in a disease, and then even to see if an intervention is successful.

Dr. Mark Hyman
Yeah. This is really important. I think I think, you know, this is sort of novel, the idea that you can see schizophrenia on a brain scan. Right? I think what's really interesting to me is...

And I always say this. The body has only so many ways of saying ouch.

Paul Thompson
And

Dr. Mark Hyman
there are a lot of different things that happen. But often, the pathology is similar. Some of the manifestations are different. Right? So inflammation, oxidative stress, mitochondrial dysfunction, these are common phenomena across the spectrum of brain disorders.

Metabolic dysfunction, schizophrenia, these patients have inflamed brains. They have mitochondrial dysfunction in the brain. And there's different types of causes. There's scientists, for example, at Harvard and other places doing metabolic psychiatry, like Chris Palmer, and putting people on keto diets and seeing schizophrenia resolve without medication. So that, like, makes me wonder sort of what you're looking at with this brain imaging.

We can start to look at inflammation. We can start to look at mitochondrial function. We can start to look at, you know, metabolic function in the brain through various kinds of imaging.

Paul Thompson
Absolutely. And I think that line of work of functional psychiatry, metabolic psychiatry I saw your interview with Ian Campbell, a interview. I think it's opening a door to therapy for patients that they really haven't known about. I mean, if they've read your work, they know about it. It's a new window on how to come into these disorders.

And I'll give you an example. So a lot of radiologists look at brain disease as if there's got to be some lesion or, you know, very obvious visible difference. So the techniques that tended to be used, know, an MRI would say, Look, in a stroke, we see vascular event. That's what we're looking for. In Alzheimer's, we're gonna use a PET scan.

A PET scan can look at the buildup of amyloid, which is a toxic protein in the brain. And maybe in Parkinson's, which is a disorder of motor function where people have disturbances in their ability to walk or things like that, you look in the scan for an atrophy of the motor systems of the brain.

Dr. Mark Hyman
Yeah, the

Paul Thompson
basal ganglia. So in neurology, that kind of works. It's not the full picture, but it kind of works. So you can

Dr. Mark Hyman
say Well, tells you about the structure, not the function.

Paul Thompson
Yes, it deals yeah, absolutely. Now, in psychiatry and I think you hit the nail on the head. When we were first publishing neuroimaging studies of schizophrenia, there were a lot of skepticism. And these were studies with maybe a dozen people. And they said, look, it looks like there's a change in the memory system of brain, the hippocampus.

But I think what we were missing, and you said it, Mark, is that there are physical, biological processes going on in the brain all the time. Some of them are functional. They have to do with the activity and the synchrony of parts of the brain. These are visible with newer imaging technologies. Functional MRI is gonna look at the blood flow.

Is your blood flow healthy? Is your lifestyle enabling you to have the activity of the brain that you need? And I think part of the blindness to this was to treat the brain as something that we could assess with an X-ray.

Dr. Mark Hyman
Right.

Paul Thompson
I mean, you know, an X-ray is pretty good. If you break your leg, we could have an X-ray. But the brain's complicated. And if you were a pilot flying over Los Angeles and you were trying to figure out what was going on, the map isn't all there is to it. You wanna have a look at the traffic flow and if there's anything blocked or, you know, what's going on.

Yeah. And I think these functional neuroimaging methods functional MRI is one of them PET, which is another type of brain imaging, looks at the metabolic activity of the brain. And these are slightly less used. In psychiatry, it's opening a whole new window into the synchrony of the brain. I've heard you interview people about the so called resting state networks of the brain.

On an X-ray, you're not gonna see any resting state networks. And what we see is that in An x-ray meaning an MRI or an Exactly.

Dr. Mark Hyman
Or x-ray. Because those really static images.

Paul Thompson
They're static images. And that's the secret, isn't it? Because if someone is very depressed, it might not be evident in the physical structure of their brain. I mean, they could... And I've heard your guests say this.

I mean, someone, I think Ian Campbell had a mental health condition. He went to a doctor. He had an MRI of the brain.

Dr. Mark Hyman
Yeah.

Paul Thompson
And they said, well, this looks like you're fine. I mean, there's nothing any different than other people's. You can't

Dr. Mark Hyman
fight bipolar disease on an MRI.

Paul Thompson
That's right. But what he is doing, and what we're also doing in our Enigma project, is we're trying to collect assessments of the brain that can look at the metabolism, is your blood flow as it as it should be, and it's complicated. I mean, in in something like depression, maybe the interactions among the brain's networks are are slow or they're sluggish. And, you you... You've done a lot of work on, bipolar disease.

So at certain times of day, someone's brain networks might not be functioning exactly as a healthy person would. But with the right intervention, maybe a metabolic intervention, maybe a keto intervention, even with classical pharmacology, which some people respond to, you could see a resetting. You know, they get back into the normal range. So they feel like these two things go together. One is having a giant reference of what healthy people's brains do Mhmm.

Which includes getting the right assessments.

Dr. Mark Hyman
Yeah.

Paul Thompson
And then in a sense, you know, making sure that the therapy, as you know, is matched to the kind of illness that they have. So if they have a neurodegenerative disease, you know, something like Alzheimer's or Parkinson's, you know, there's particular treatments for that in pharmacology. There's also particular lifestyle interventions, as you've pioneered, for metabolism. On the other hand, if you have bipolar or major depression, these brain scans can give you a readout of whether or not the the intervention has been beneficial.

Dr. Mark Hyman
Yeah.

Paul Thompson
And I mean, that's it it doesn't get more personal than that. You have a Mhmm. A physical picture of the result

Dr. Mark Hyman
of the... It's a whole new era. I mean, in fact, even the whole distinction between neurology and psychiatry is sort of artificial. It's it's kind of a fallacy that they're separate because they're so connected. And and you know, I find so fascinating is that...

And functional medicine is really good at describing this. What are the fundamental physiological processes that underlie There's all not that many of them. There's the microbiome, there's the immune function, there's your mitochondria, there's your communication systems and networks, hormones and so forth, are transmitters. There's your circulatory vascular system. There's your detoxification system.

There's your structural system down from the membranes all the way to your biomechanical structures. Disturbances in these fundamental processes are what's driving all the downstream illnesses.

Paul Thompson
Yes, absolutely.

Dr. Mark Hyman
And so when you look at the science, and you know what's interesting is as a functional medicine doctor, like, I'm not a quote specialist, but I... I'm a super generalist. So I'm looking at everything all at once. It's like everything ever all at once. Like the movie.

So I'm like, oh, gee. If you look at the literature on depression, it's brain inflammation and mitochondrial issues. If you look at the issue... The the literature on Alzheimer's, it's the same thing. If you look at literature on autism, it's the same thing.

If you look at the literature on schizophrenia, it's the same thing. So all these diseases are like like leaves on a tree and they have common roots and and often common therapies. But the common therapies aren't like the same drug for the different diseases. They're like the fundamental lifestyle and causal corrective causal systems.

Paul Thompson
And I think, Moe, you have the perspective to see all of the connections among these things. Because if someone is an Alzheimer's doctor Yeah. And they don't necessarily see patients with diabetes or with other psychiatric conditions, They won't see the connections between the things that were helpful. Some of the people that you've interviewed, they said, you

Dr. Mark Hyman
know,

Paul Thompson
the dietary change that I did, I noticed a big change. And that wouldn't have been on the radar for people that were doing the conventional treatment.

Dr. Mark Hyman
What's interesting to me is that, like Suzanne Go has

Paul Thompson
done

Dr. Mark Hyman
a lot of brain imaging around autism, she's like, there's a lot of mitochondrial dysfunction. Or can look at the same thing around schizophrenia. So the manifestations in an individual depend on their genetics, lots of factors, some of which we understand, some of which we don't. But it's, you know, like David Deutsch said in The Fabric of Reality, you can treat diseases even if you've never seen them before if you follow fundamental principles and be successful. And that's what I've done in functional medicine.

I've treated diseases I've never seen before successfully because I just follow the fundamental laws of biology. And what we're what we're discovering here, and your work is so key to this, is we're discovering these fundamental principles of human biology that were heretofore never unpacked. Yes. And now they and now they're like, wait, you know, what does OCD or schizophrenia have to do with Alzheimer's? Absolutely.

A lot.

Paul Thompson
Absolutely.

Dr. Mark Hyman
And and so...

Paul Thompson
I I think you're so right right, Mark. I mean, one one example, and you've written about this, is is cardiovascular health. So cardiovascular health, and people are familiar with it. I I wanna avoid a heart attack. I wanna avoid a stroke.

I'm gonna have a better lifestyle, better diet.

Dr. Mark Hyman
I I would kinda rephrase it as cardiometabolic.

Paul Thompson
Cardiometabolic health. That's but that that that's better. Now, a doctor who's treating Alzheimer's disease

Dr. Mark Hyman
can

Paul Thompson
say, oh, you know, the scan shows that you're not doing so well. There's amyloid plaques building up in the brain. The treatment for amyloid plaques is I mean, there's a vaccine that's experimental. Do you want to try that? But you know, Mark, that at the same time, sixty percent of people that are diagnosed with dementia have cardiometabolic issues and problems that, to some extent, are treatable.

They may be very treatable. And even going over to mental health and mental illness. We had a colleague, Thomas Hayek, and he treats a lot of people with schizophrenia and bipolar. And he said, Do you know that the cardiometabolic health of these patients makes all the difference in the world? And he said, some of the treatments for schizophrenia, as you know, you put on weight, it's part of this.

And he noticed

Dr. Mark Hyman
It's ironic. The very drugs that treat schizophrenia cause the very It's down. Caused the very problem that causes schizophrenia, which is mitochondrial dysfunction. Yeah.

Paul Thompson
Absolutely. And he noticed by looking at brain imaging, he said, look, I've seen the differences in people with schizophrenia on brain imaging, this tissue loss. But the people with high body mass index, or the people with cardiometabolic problems, they have worse brain Worse. He was very interested in it. He said, you know, in Enigma, let's start collecting that data.

And I mean, Mark, you do this. So as well as the brain scan, let's collect data on their cardiometabolic markers in blood. And I mean, you knew this, and in your work, you pointed this out. In addition to whatever it is that is going on in their brain, their systemic, their bodily health, when that is treated, it can make a whole world of And difference their this was true in depression, it was true in bipolar disease, it was true in schizophrenia. And just to be really precise, the amount of difference in their brain on a brain scan was far greater if there was metabolic disease or if there cardiovascular disease.

And said, you know, this is revolutionary because we don't I mean, we will certainly use antipsychotics, but we don't see all the time this other path

Dr. Mark Hyman
to health. Yeah.

Paul Thompson
And I mean, the patients are extremely interested in this, as you know, because it's another path. And he said it's a little like a bank account. I mean, let's say my bank account is getting low. But there's plenty of ways that that bank account can be topped back up.

Dr. Mark Hyman
And

Paul Thompson
we used to use this one, and it worked for some people, didn't work for one another's. But if there's another route, as you know, to replenish or protect Mhmm. Or bolster the other processes that are going on, I mean, can make the world of difference.

Dr. Mark Hyman
Yeah. And it's so true. And I think that we we really we really don't think about treating the body to treat the brain. And that was the subtitle of my book, Ultramind, which was fix your broken brain by healing your body first. Yes.

Or something like that. I don't know what I would call And you know this, but

Paul Thompson
this is true in people that are sick and true in people that are healthy. So if you look in these brain scans of people with different mental health conditions, the people that have an intervention that protects their cardiometabolic health do better. The scan can show you it. Mean, we know that this is also relevant to, you know, everybody. Mhmm.

But particularly in these illnesses that we blamed on something else, it seems to make the world of difference.

Dr. Mark Hyman
Yeah. You know, you studied the spectrum of psychiatric and neurologic conditions.

Paul Thompson
Yes.

Dr. Mark Hyman
What, you know, they have all these different labels. Yes. What's in common?

Paul Thompson
Kind of interesting. So you mentioned the DSM-five, which is the way that doctors categorize a person's mental health condition. And people have heard of things like, you know, major depression, bipolar disease, schizophrenia. There's conditions like post traumatic stress disorder. There's addiction.

And they can be grouped. So there's a lot of mental health conditions with emotional blunting, lowered affect. There's sort of a depressive aspect of this. And on brain images, you very often see metabolic issues in the so called limbic system. So the center of the brain, we often think of it as the gas pedal, the motivation, the reptilian part of your brain.

The reptilian part of the brain. And this is a deep part of the brain that you could maybe think of as kind of the gas pedal, the motivator. What drives us to get out of bed in the morning? What what what motivates us?

Dr. Mark Hyman
It's the fight or flight or feeding

Paul Thompson
kind of Exactly.

Dr. Mark Hyman
We call it the four f's in medical school. Fight, fight or flight, feeding, and reproduction.

Paul Thompson
Yes.

Dr. Mark Hyman
Yes. The four f's.

Paul Thompson
Yes. Yes. So so you can see this part of the brain on neuroimaging. And a lot of the mental health conditions that are associated with poorer emotional flattening I mean, loss of motivation and volition, and that would include depression, it would include, in some cases, anxiety the depressive side of bipolar disease, which is very low emotion You'll see on the brain scans that there is, in some cases, structural deficits there, but also metabolic. I mean, you know glutamate, for example, the neurotransmitter that's very important to brain excitation, you'll see abnormalities in glutamate too.

So that is one group of disorders where there's depression. We sometimes call them internalizing disorders because they're disorders of thought, they're emotional disorders inside us. There's another group of psychiatric disorders that are associated with compulsion, addiction, substance. OCD is one of them. I mean, these are disorders.

And on brain scans, you can often see these compulsive, even aggressive disorders associated with abnormalities in the frontal parts of the brain, the frontal loads of the brain. So these are sort of two systems. There's the gas pedal, the motivator, the primitive brain. And the frontal part of the brain, you'll often see damage, and the brain scans show this, in people that are disinhibited, that they might be manic, they might have even in ADHD, where there's sort of overactivity. And so these are a very simple classification of the disorders into ones where there's depression, blunted affect, or the ones where there are compulsions.

But you'll see similarities. So if someone who's addicted to a substance of abuse, you know, alcohol or meth or opiates or cocaine, you'll often see damage and this is visible on the brain scan in the frontal lobes of the brain. And the frontal lobes are kinda like the brakes. So if the limbic system is the gas pedal, frontal lobe is a little bit like the brakes. And if you've damaged the brakes, there's often an out of control aspect to behavior.

So these patterns, they're not just physical pictures of how these brain diseases look. They're sort of becoming diagnostic tests as well. So if someone wants to know if someone has anxiety or depression Are

Dr. Mark Hyman
these not functional MRIs? These are

Paul Thompson
They are actually both. So to make a distinction, the functional MRIs are more useful in psychiatry, because we tend to think of these as more disorders of behavior, of emotion. We may not see a physical loss of tissue. But like you said, Bart, there may be molecular changes, there may be physiological changes that we can interrupt or block or restore that the readout on the functional MRI shows a benefit.

Dr. Mark Hyman
So for Beulah, you just kind of help distinguish between what is a regular brain MRI

Paul Thompson
and

Dr. Mark Hyman
what is a functional brain MRI.

Paul Thompson
Okay. So a regular brain MRI looks bit like an X-ray. And the reason we don't use X rays is a X-ray. It's a fancy X-ray. The principle of how it works is a little different.

So an X-ray is radiation wherever this bone or fibrous tissue. You can see it. If you've broken your bone, you can see the problem.

Dr. Mark Hyman
For

Paul Thompson
the brain, a lot of the issues are with the tissue, the nervous tissue. Obviously, the brain's not made of the material that bones are made out of, so that's why we use MRI.

Dr. Mark Hyman
And

Paul Thompson
usually, the types of things a structural MRI will pick up is if there's a tumor or a brain bleed, if someone has an aneurysm, you will see on the MRI that there's a physical structural disturbance of the brain. Now, what happened was, round about thirty years ago, there were people tinkering around with an MRI. They said, you know what? Wouldn't it be interesting if this depended on how active the brain was? I mean, it's just a picture, but it is measuring physical process in the brain.

So they started to do experiments where somebody did a task in the scanner. Like, would tap their fingers or they'd look at a flashing light. And they found tiny differences in the oxygenation of the blood in the brain. And if you could subtract the image when someone was active from the image when they were at rest, you could pick up. They just really took off.

And so in the '90s, you'd get, you know, here's the map of language, or here's the map planning, or here's the map of vision. And the brain is a landscape. It's like a city. I mean, there's places that control these different tasks. So you're right.

The functional MRI is looking at the blood flow in the brain, which for many reasons can be disrupted, either because the blood vessels are blocked, as in stroke, or because there just simply isn't the metabolic supply to drive the blood into these key brain regions.

Dr. Mark Hyman
Basically, you're looking at the biological function of the brain versus just the structure of the brain.

Paul Thompson
That's right.

Dr. Mark Hyman
And you can tell a lot about the metabolic function, what's working, what's not working, how it's working. And that tells you so much about the psychiatric disease. So it's a way of, like, using imaging for psychiatric illness.

Paul Thompson
Absolutely.

Dr. Mark Hyman
When you you look at so many brains, like, are the things that you're finding? Because you're not just looking at brains. You're also looking at lifestyle factors. You're looking at blood biomarkers. What are the factors that seem to have the strongest influence over brain function, brain health over time?

Because we all know, okay, I know for my heart I should... 90 century fat. Oh, that's not right. Or I know I should exercise. I know I shouldn't smoke.

I know these things are important for my heart health.

Paul Thompson
But

Dr. Mark Hyman
people go, how do I take care of my brain?

Paul Thompson
Yes. Well, those same things, as you would know, matter for the brain. So when we looked at brain scans of people that were maybe obese, overweight, their brain would look eight years older. And you know there's this very interesting measure of brain age. So you've talked about this concept in your So the brain age would be, know, how old does my brain look?

And not just an opinion. Mean, a computer can identify the different features of the brain, the change as we age, and give you a score.

Dr. Mark Hyman
And what measuring? Are

Paul Thompson
Well, they can be based on a few different kinds of measures. So the ones based on brain MRI are usually measuring the structures of the brain that change the most as we get older. And so, you know, kids' brains grow, they reach a peak in your twenties. Obviously, there's a gentle loss of brain tissue throughout the brain, I mean,

Dr. Mark Hyman
the

Paul Thompson
of the brain. The shrinking of the brain. So you can make a brain chart. So you can sort of say, you know, a pediatrician has a chart of how, you know, the height of a child should be at different ages. And they're not all the same height.

There's range. So what about if we were to make a chart of the size of the brain's memory system?

Dr. Mark Hyman
Like the hippocampus.

Paul Thompson
Like the hippocampus. And for a long time, even in drug trials, that single measure was used. So if someone was designing a drug trial of an anti dementia drug, it would be common to say, Well, the primary endpoint of this trial is the person's memory function doesn't decline as much. I mean, that's the clinical endpoint. But we're interested in a physical biomarker as well.

So they would pick either the size of the hippocampus, which is a little two teaspoon Looks like a It's like a seahorse. Over the course of time, I think people realized that just a single measure wasn't really gonna cut it. It's not gonna cut it. So even if you stay within a brain MRI, you can say, well, okay, what are the other things that decline as we age? Maybe the language area and the the visual area and other things.

Let's measure all of them. So what people do when they talk about brain age is they say, well, okay. In a particular person, let's measure them all. And we're gonna see where this person is on a chart, like a percentile chart. And if the hippocampal volume is is kinda low, maybe in the lower 5%, let's look at some other things as well.

Let's look at the the the white matter connectivity of the brain. So there's another type of brain scan, a diffusion image. If those neural pathways are intact, that's another measure. And you could even put in functional imaging. You say, Well, the structure looks like there's a little bit of a problem.

What if we look at this other measure of blood flow? So what'll happen is, all of these individual biomarkers on their own, they can certainly flag an anomaly on their own. But imagine how great it would be if there was a holistic picture. I mean, even just with imaging. All these cool types of imaging.

And that has led to the notion of, for example, brain age. And so you could say,

Dr. Mark Hyman
well That's a composite number

Paul Thompson
from

Dr. Mark Hyman
multiple different structural Yes. Aspects of the

Paul Thompson
Yeah. Absolutely. And you, I mean, you know this, Mark, and just for your listeners, you could have a blood age. So you could say, look, we can measure proteins in the blood. We know things like cholesterol and lipids are very important to healthy function.

We want to look at hormones like estrogen and testosterone, maybe homocysteine, which is sometimes a sign of bad metabolism. Let's make a score. And there's several scores from blood. I mean, blood I mean, you know this. You can get a blood panel readout and flag things that are off.

But you can also have a summary, as you know, of cardiometabolic health. Are there any signs of Alzheimer's? Are there endocrine markers within range? And so I think as you've said, the The hormones, perspective The hormones as well. The nutrients, hormones, everything.

And these are also evident in a brain scan. So people who had below normal estrogen and testosterone, their brain aging was faster.

Dr. Mark Hyman
And

Paul Thompson
I mean, that kind of makes sense. If their thyroid hormone was too low, their brain aging was faster.

Dr. Mark Hyman
Too lower? Like low normal or low?

Paul Thompson
Out of range. And that's a good point. So there's some markers where they're too high when they're bad, something like homocysteine. So if someone was taking folate or the B vitamins, and it can lower your homocysteine. And these have been used, as you know, in clinical trials.

I mean, there's been tests that have said, look, if somebody has some of these nutrients out of range, there's not just a health benefit of fixing them, but there's a physical measure in their brain scans that their brain is getting better.

Dr. Mark Hyman
So brain brain age is is a useful tool to sort of see how you're doing. I wanna take a little digression around this because, you know, we often think that aging is a linear process. Like, we just decline gradually over time and then we die.

Paul Thompson
Sure.

Dr. Mark Hyman
It doesn't turn out that that's true. I can tell you that from personal experience. I've aged backwards and forwards many times. Yes. And not obviously willingly, I've had various conditions or illnesses that have knocked me back.

Yeah. But I I recently went to Mexico where there's a compound called Ibogaine, which is legal.

Paul Thompson
Yes.

Dr. Mark Hyman
And I took it as a sort of... As a way to enhance my neuroplasticity because I met with governor Rick Perry Mhmm. Who was the fifteen year governor of Texas. And we had dinner and he's like, you know, Mark, I did this and my brain size increased on MRIs. And that got my attention.

I'm like, oh, okay, well, I'm 66. I'm like, I could use all the help I can get. And I was like, let me try it. And I went down there and I and I was methodical. I did a brain imaging, a quantitative brain imaging.

Because you're doing an MRI, you can do MRI just a regular one and then you can measure ones that look at specific brain structures and actually measure quantitatively the size of them. And I did a quantitative before, a week after, and three months after. And my cortical thickness, which is sort of the size of your brain essentially, like went up 8%. And my white matter lesions, which is the level of inflammation, which tends to get worse as you get aged, went down 22%. I'm curious if you've seen this kind of phenomena happen before?

Paul Thompson
Yes.

Dr. Mark Hyman
And what can you talk about that can explain that? And what other things, other lifestyle factors or other things, drugs that you've seen that can help do this?

Paul Thompson
I mean, you know this, Mike. They make a huge difference. So there's dietary factors, there's physical lifestyle factors. And I mean, saw this from your own experience and in the scan. It's just not regularly studied.

I think, you know, you're seeing

Dr. Mark Hyman
this By way, didn't tell the neuroradiologist what I did. Just Yes. They had my scans and they were like, what the heck's going on here?

Paul Thompson
Yeah. Absolutely. And there are so many lifestyle factors as well. So one example that, mean, Mark, you've written about is sleep. So having good sleep.

Sleep, I mean, we think of it, your brain isn't doing anything at all. I mean, when you're asleep, that's just downtime. But on imaging, neuroimaging, the images kinda had a surprise recently. There's something called the glymphatic system of the brain. Neuroscientists kind of knew a little bit about this, but they'd never really seen it in action.

And what happens is, when you're asleep, there's these sort of waves, almost like a car wash, where the brain fluid is cleansing out toxic products from the brain. I mean, wouldn't be a surprise.

Dr. Mark Hyman
It creates a lot

Paul Thompson
of waste products. It creates a lot of waste

Dr. Mark Hyman
Like, oh god, you gotta poop at the end of the day.

Paul Thompson
That's right. That's And

Dr. Mark Hyman
your brain essentially has to get cleaned out at night.

Paul Thompson
Absolutely.

Dr. Mark Hyman
And we have a lymph system for cleaning out our waste But from our

Paul Thompson
Absolutely.

Dr. Mark Hyman
Our brain has its own lymph system. We call it the lymphatic system.

Paul Thompson
And it it... I mean, it comes back to what you said, Mark. If you weren't thinking about that or weren't knowing that there was anything there, I mean, you'd miss it. But what started to happen is people said, Well, if you have bad sleep, how does that affect brain decline as you age? I mean, something like Alzheimer's.

And a lot of these things are circular. If someone starts to have Parkinson's or Alzheimer's, their sleep is gonna be affected. And as you know, if you can fix their sleep or if you can fix the lifestyle factors, some of these other things come back into line. So we were able to see these brain scans the effects of bad sleep. But until you think about the mechanism, this sort of detoxification of the brain that goes on during sleep, you don't realize how important it is.

So in Enigma, our consortium, we have a sleep group. And they look at insomnia, I mean, people that have a sleep disorder. Then they have people that, you know, would benefit from better sleep. Maybe their job is very stressful. And you see these biomarkers come back into line.

Wow. I mean, as you know, I mean, you see them restore. And so sleep is important. As you know, a good quality diet is important. And I think the important thing you said, Mark, your brain restores.

I mean, we were looking with brain imaging at people with eating disorders, people with anorexia. And it had the greatest effect on the brain of any disorder that we've studied in psychiatry. So we studied depression, bipolar, schizophrenia, eating disorders. Now, you know that this is common sense. I mean, the food is the fuel of the mind.

But when they were treated, when they went to the hospital, when their nutrition was back in balance, all of these brain systems were restored. And one of the things that you're taught in medical school is the brain, you know this, brain doesn't regenerate tissue. And you think, wait a minute. The brain scan, like you said with Ibogaine, the brain scan shows the physical evidence list. So I think people shouldn't be so pessimistic about the potential for the brain to recover because it's just not not true.

Dr. Mark Hyman
Yeah. And I think what your work is doing by mapping the brain with imaging, by mapping the biomarkers, by looking at metabolic things and nutritional factors, hormonal factors, and probably, I don't know what else you're looking at, which I'd like to unpack. You're actually seeing how the brain can repair. And many of these conditions can be treated in a different way. And, you know, the thing that's so interesting to me is that you're seeing that there's like some distinct patterns in different conditions, but there's a lot of shared patterns.

Can you talk about Yeah.

Paul Thompson
Absolutely.

Dr. Mark Hyman
Cross disease brain patterns. Yes. You described them.

Paul Thompson
Yeah. So one of the puzzles about the brain's function is very, very complicated. And the more imaging that's done, I mean, the more complexity you start to see. And it's just like layers of detail. So one of the things that you see is that the brain has synchronized activity in so called functional resting state networks.

And in something like depression, in something where someone's brain activity is less, even the switching between these networks is slowed. It doesn't work. And we talked about the X rays. Mean, you will never see this sort of X-ray. It just has to do with the ebb and flow.

I mean, if we were at the oceanside and we were watching the waves come in, there'd be something about the dynamic balance of these things. And we see this in depression. We see it in bipolar. The treatments are usually either pharmaceutical medication, antidepressants, SSRIs. There's something called TMS, transcranial magnetic stimulation, attempts to kind of reset the brain activity in a certain way.

It's been very effective in treatment resistant depression. Or neurofeedback. I know you've talked, Mark, about this in other episodes, where a person tries so maybe a patient with chronic pain or a condition that is really severe. They try and train their brain activity in a certain direction. And then, as you said, there's the lifestyle, metabolic, and other sources of fuel to the brain.

And very often, some of these things are like turning the dial way up. I mean, a stimulation gonna have a very radical effect on the brain. In fact, initially, people wondered whether that was safe. But the ability to influence your relative contribution of these networks is really important. And I'll give you an example.

So there's a network of the brain that's active when we're ruminating. So if you don't feel good about something, maybe you just regret

Dr. Mark Hyman
something,

Paul Thompson
your brain kind of fixates on this. So what is happening in the brain when you're doing it? Well, I mean, it's not we have a brain lesion. It's that there's a certain kind or pattern of activity. And this has been discovered to be something called the default mode network.

Yeah. It's a network that's kind of active when we're not really doing anything. You could say, well, could be useful, but it could become It could inspire you. Ego, right? It's like Yes, yes.

So one of the ways that the treatments are being evaluated for things like major depression, as we said, they can be behavioral therapy, seeing a psychiatrist. They can be direct brain stimulation or neurofeedback, which is kind of jolting the brain's activity, or lifestyle and cardiometabolic approaches as well. Every one of these has a role to play in shifting that balance of brain activity back into action. But it's very complicated. I mean, as you said at the beginning, this isn't something that would be evident from a standard brain It has to do with the ebb and flow of activity.

And I mean, there's even AI methods that are trying to identify exactly what it is about the brain synchrony that's off, and then tell us when it's back in balance.

Dr. Mark Hyman
I had a case of a patient. I'll show you the image and we'll put it up on the video on YouTube and link it to it in the podcast. But this was a patient I had a long time ago who was an ADD patient, ADHD, He really was 12 years old, really intractable, kicked out of kindergarten, on Ritalin for years, you know, just a mess. And he had all these other behavioral issues. He had anxiety and insomnia, but he also had health issues like gut issues and asthma and skin issues and just gut issues.

It's a mess. He's on seven different medications. And I and I... His mother came in and I treated him. And I I basically gave him, you know, whole foods diet.

He was eating only junk food, processed food. This is his only diet. He had so many nutritional deficiencies that I corrected with diet and supplements. His gut was a mess, I helped his gut restore. He had some lead, we kinda got rid of that.

But even before we did that, I I basically just did diet and lifestyle and a few supplements. He came back two months later and his mother brought his homework. That was before he saw me and then two months later. And the original homework was illegible. It was 12 years old and it was what we call dysgraphia, which is the common, you know, common symptom of people with brain dysfunction and these kids with learning disabilities or, you know, ADHD and so forth.

They they have bad handwriting. It's basically bad handwriting. Like, really bad. And he comes back two months later, mom's bringing his homework in, and I'm like, wow. It was perfect.

Perfect penmanship. And I was like, that was the moment for me. I was like, what is going on in the brain? Like, this wasn't a kid who had handwriting lessons for two months.

Paul Thompson
He

Dr. Mark Hyman
had something go from chaotic and coherent and dis synchronous in his brain to coherent and synchronized and organized. And I was like, oh my god. This is something that nobody's talking about. And that's what led me to write the book, The Ultramind Solution, which was this case. And I wrote about Alzheimer's and autism and many other things that are kind of incurable, that were curable.

If you understood how the brain worked and how all these factors from diet, exercise, sleep, stress, environmental toxins, gut health, nutrient deficiencies, all these things play a role.

Paul Thompson
And the

Dr. Mark Hyman
things you're looking at. So like, you're doing this massive study, getting massive NIH grants, you're looking at 47 countries, thousands of doctors and scientists, just so much And you're coming back to the same freaking conclusion, which is it's these fundamental things that matter and that we can modify, that we have control over, that can change not only the function of our brain, but the structure of our brain. And I'm glad you said that,

Paul Thompson
Mark, because it's so critical for mental health. I mean, whether someone's generally well or whether they have a mental health condition. Mean, you've described examples where this has made the world of difference. And I think one of the reasons that neuroscience sort of went the wrong way is, I want to say, Well, you know, everything is neurotransmitters. If we could just get the level of the chemical right for dopamine or adrenaline or serotonin.

And, you know, there's validity to that. I mean, there could be an imbalance, maybe a drug. I mean, an example might be, you know, if you're anxious, you could take a drug like propranolol, a beta blocker, and, you know, you'd feel a bit better. But that's missing the whole channel and stream of fuel that's going on in your brain. I mean, we know this.

I think, I mean, you've pioneered this line of thinking. Treating those things as well, the psychiatrists we worked with, and they all say the same thing, it can make the world a difference when all of the common remedies have already been exhausted.

Dr. Mark Hyman
Yeah. Drugs don't really solve these problems. It's like you're treating, you know, a problem with a a symptom suppression drug. And we we talk about this in functional medicine. We call it the tac world.

So we're standing on a tac. It takes a lot of aspirin to make it feel better. Take out the tac. Right? If you're have schizophrenia and your brain's

Paul Thompson
inflamed,

Dr. Mark Hyman
treat the source of the inflammation. Don't give them antipsychotic. Right? Change your diet. Get them on a keto diet.

Whatever the science is showing. And you're seeing, you know, your work is so important because it... You you... There's very few scientists as far as I can tell that that, as I said at the beginning of this show, they're not just reductionist. You're like zooming out and you're like, what are the common patterns?

What are the... What is like... You're looking at a... A tons and tons and tons of data? You're like, what are the emerging patterns?

And you're seeing these patterns and these common patterns across all kinds of neurologic and psychiatric diseases. And there are common treatments that really work.

Paul Thompson
And I think, Mark, you I mean, you you in your writing, you you have this perspective where you see that something is effective across so many different conditions, and it's because you're treating this systemic issue.

Dr. Mark Hyman
Right.

Paul Thompson
And and, you know, you're just looking at the brain. You say, well, I I don't see anything wrong here. And I mean, can you imagine the times when people have been told their brain is fine

Dr. Mark Hyman
Yeah.

Paul Thompson
But there's something else

Dr. Mark Hyman
that

Paul Thompson
could be the source of of of the melody. So, I mean, it makes a whole lot sense.

Dr. Mark Hyman
Yeah. Treat the system, not the symptoms. Yes. Right?

Paul Thompson
Yes.

Dr. Mark Hyman
Yeah. In terms of enigma and the work you're doing, how much is determined by genetics versus lifestyle environment?

Paul Thompson
It is among the... I mean, both genetics and lifestyle are are usually important. And just to give some examples, it depends on the disease. So there are some diseases of the brain that are genetic diseases. There's not many of them, but there's a few.

So something like Down syndrome, fragile X syndrome, Williams syndrome. These are usually developmental abnormalities of the brain where sometimes somebody's DNA, their genetic code, has a deletion and it doesn't develop in the way that we would expect. Now usually, what about the more common disorder, Alzheimer's or Parkinson's or stroke? Now, there's some puzzles there. So something like Alzheimer's disease, there's one form of it that is genetic.

So only two percent of patients have this.

Dr. Mark Hyman
You do the presenilin gene.

Paul Thompson
It's the presenilin gene. So that's interesting in and of itself. So if there can be a form of the disease that's genetic and you can point to a genome, that's already very interesting. And there there, as you said, presenilin, the the... There's an amyloid precursor protein gene where someone has a really serious genetic anomaly in that area of the brain overproduces these amyloid plaques, and that can lead to dementia.

But for the ninety eight percent of the other cases, the genes sort of tilt the scales a little. They're not deterministic. It's not deterministic at all. And there are some important ones. So I'll give you an example.

So in Alzheimer's disease, there is a genetic variant that triples your risk. And it's not rare. And so there's something called APOE, the apple

Dr. Mark Hyman
APOE

Paul Thompson
copies, yeah. Absolutely. And around a quarter of us have one copy of this. Three quarters don't have it. Around six percent of us have two copies.

And the risk can be nine to 10 times higher just from this gene. Now, that doesn't mean that someone's gonna get Alzheimer's if they have this gene. It sort of tilts the And a lot is beginning to be known about these genes. So one puzzling thing is, in people of African ancestry, the APOE doesn't matter as much. In people of Japanese and Chinese ancestry, it's really bad.

People of European ancestry, somewhere in between. Interesting. And it was originally sort of speculated that maybe in those countries, other things determining health. But more recently, it's been found that even the gene sequence in East Africans, there's a genetic variation that's near the ApoE gene that seems to neutralize it. Protect it.

It seems to be protective. Now that's interesting, because if you could somehow switch that on or introduce it I mean, maybe there's a kind of direct genetic approach to doing this. And so when we started to look at the genomes of people that had Alzheimer's disease, we knew that this gene mean, number one, it's not deterministic at all. I mean, you can have people that have this gene and they're fine, which is already interesting. There is a protective form of the APOE gene.

It's a little bit rare called APOE two. But the problem with that is they often have cardiometabolic problems. So they don't get the Alzheimer's, but they tend to get these other problems. But going back to your question, there are genome guided drug treatments today. So there are treatments that are being developed that target these genes.

They won't necessarily target the root cause of all these other things. You know, look at that one for you. Yeah. And I'll tell you a little bit how they work, because it's kind of interesting how they work. So there's something called polygenic risk.

And you know this. You can look at somebody's genetic code. Yeah. You can add up all of these different genetic variants that

Dr. Mark Hyman
matter

Paul Thompson
for a particular disease. And you can get a score. Yeah. And within these polygenic scores, there's different subtypes. So there might be a particular set of genes that have to do with inflammation, or amyloid or tau depositions, proteins in the brain.

Or immunity. Maybe it has to do with immunity. So there are actively approaches, one of them in our AI for AD project, that essentially take And that's

Dr. Mark Hyman
a research project. They're using AI to help understand Alzheimer's. Yes. We'll get into that in a minute.

Paul Thompson
Absolutely. So you can say, well, Okay, how do we influence these genes? I mean, the gene looks like its destiny, as we know it isn't. But can we influence what the gene is doing? So some of these genes produce protein products.

And there are known drugs that are already approved by the

Dr. Mark Hyman
FDA

Paul Thompson
that influence those genes.

Dr. Mark Hyman
Off label uses, yeah.

Paul Thompson
That's right. And some of them I remember your interview with Ian Campbell, you talked about the repurposing of epilepsy drugs in bipolar disease. It was very interesting. I mean, again, these drugs are not the whole story. They can help with the drugs or something.

Dr. Mark Hyman
Lamictal,

Paul Thompson
I think. And so genome guided drug repurposing has exactly that goal. It tries to find a drug that's already on the market. It's known through these databases of drug gene interactions to suppress a particular kind of protein product. These are very interesting, because if you could pair up a patient's genetic profile with a particular treatment that might be effective for them, it may be less effective for us.

Dr. Mark Hyman
This is personalized treatment.

Paul Thompson
It's

Dr. Mark Hyman
personalized treatment. Precision medicine.

Paul Thompson
It's precision medicine. And I started to look at the work. There's a person called Kyungka Chun. She's a neuroscientist at Boston University. And she, amazingly, she makes these genetically engineered stem cells that express a certain genotype, the genetic risk for Alzheimer's disease.

And this sounds like science fiction. It's kind of science fiction. Make these pluripotent stem cells that turn into brain cells called astrocytes and neurons. And they apply these treatments and see if it is effective at suppressing the gene products of the risk So this is an active genome guided drug

Dr. Mark Hyman
repositioning

Paul Thompson
This

Dr. Mark Hyman
medicine by thinking rather than just by reaction. In other words, this disease, this drug, it's like, is the pathway? What's the mechanism? What are the gene products? What are the proteins made?

How do we modify those? What are the other things we can do? And it's just creative thinking about the biology of a human being that's not just so linear. It's fascinating. I mean, I just...

I wanna jump to brain charts and diagnostic tools in a minute, but I I just wanna sort of double click on the APOE four gene Yes. Conversation because people are scared. People don't wanna test it. And we offer it at Function Health. We also offer p tau testing, which is a biomarker that actually looks at progression of brain degeneration around Alzheimer's.

Yeah. And it it's it's kinda like a cholesterol test. You can modify it by lifestyle. Alright. So let's talk about this concept that you've kinda developed called brain charts.

And also, what kind of new diagnostic tests are you actually discovering from this large scale brain imaging and genetic data and biomarker data?

Paul Thompson
So the first one, it focuses on the brain scan. And we'll talk in a minute about the blood markers as well. But the ones that focus on the brain scan. So let's say you and I go and get a brain scan. And you could get an MRI at most hospitals.

I mean, look

Dr. Mark Hyman
at

Paul Thompson
Now

Dr. Mark Hyman
you get it with function health. You can get a brain MRI and all the blood biomarkers we're That's

Paul Thompson
talk

Dr. Mark Hyman
terrific.

Paul Thompson
So the uninterpreted brain scan, mean, could ask a radiologist, but I mean, what can we do with a brain scan? So you can measure the components of the brain, you know, including ones that, you know, an automatic program can identify. And this idea has been around for a little while. So there's a company called NeuroQuant, which I Yes. Think you've is an accepted method.

I mean, you will basically say, let's run this on a huge range of people. And, you know, people have very different backgrounds. You wanna make sure you include people from other countries, people that have different backgrounds, people who are... They live in a city. They live...

I mean, you gotta have a very representative population to make this chart. And then just like a growth chart for a kid where you say, look, you seem like you're doing pretty well or the... And the beauty of these charts, and you know this, Mark, is you can come back again after making a change and see whether or not your percentile or, you know, where you are on this chart has improved or gotten worse. And I remember, you know, my first encounter of these things. My daughter was born prematurely.

She was born at 30.

Dr. Mark Hyman
And

Paul Thompson
they would plot her weight or, you know, you don't say height for a baby, the length of the baby. And it would go back towards the healthy kids. And in much the same way, I mean, like you said with your experience with ibogaine, you can make a quantitative map of how you are doing relative to this chart. And it can either be for a particular brain measure. It could be for your brain age, which is, again, it's sort of a overall summary of how old your brain looks.

Now, does the brain scan tell you everything? No. So the brain scan is a tool. There are other

Dr. Mark Hyman
So the brain is based on these quantitative measures of the brain, like with a neuro quant or

Paul Thompson
Exactly. And one of the reasons in Enigma we do this is that we have access to a very large number of brain scans. So obviously

Dr. Mark Hyman
And you can reinterpret it through the quantitative analysis.

Paul Thompson
Yes, yes. And it helps to have a representative population. So if you were going to use these charts in India or Africa or Britain

Dr. Mark Hyman
They're different.

Paul Thompson
I mean, want to make sure that comparable people are going to be in there. Maybe men and women are all different. You have to have a chart that adapters those. So the more data I mean, you know this. The more data that goes into compiling, the more accurate they are.

And so, you know, with 100,000 brain scans, you have a pretty accurate picture of what is going on. The other angle to this, as you know, is the blood panels. In research clinically it's a little bit different but in research there are panels that measure 11,000 proteins in the blood. Yeah, we

Dr. Mark Hyman
talked proteomics.

Paul Thompson
Proteomics. We talked about measuring people know about cholesterol. You measure cholesterol in a standard blood test. You can look at inflammatory proteins. You can look at measures of general hormonal or endocrine health.

You can even look for telltale signs of dietary. As you know, dietary abnormalities that are fixable. And also toxins. I mean, maybe someone was exposed to a toxin. And you know, disorders like Parkinson's disease.

Dr. Mark Hyman
It's very much toxin related. Is thought to

Paul Thompson
this is puzzle. It's thought to be, you know, people that were exposed to a lot of pesticides or a lot of hazardous chemicals have a higher incidence of Parkinson's disease. So these blood panels, I mean, they have multiple uses. One of the uses that is beginning to use AI and I mean, you know this, Mark is, you know, we talked about how on a brace, there isn't a single measure that on its own is gonna, you know, tell us the difference between, you know, recovery or not. I mean, there's a profile.

So I really believe that within the next five to ten years, we're gonna be able to at least diagnose all of the major neurological and psychiatric conditions using a combination of scans, the brain scans we talked about, and blood markers. Now, blood markers are not gonna tell you everything. As you know, if you have a stroke, maybe the scan is the thing to use. If you have a metabolic abnormality, maybe both or maybe the blood is gonna be the thing to use. But what's amazing about it is this data accumulates and the references get better and the ability of either AI or the charts or some way of combining this to flag the anomalies, it not only finds people where these treatments are gonna be useful, but measures the degree of improvement as well.

Dr. Mark Hyman
It's really personalized sort of brain treatment

Paul Thompson
Yes.

Dr. Mark Hyman
Yes. That affect psychiatry and neurology that are combining brain imaging with blood biomarkers

Paul Thompson
Absolutely. Absolutely.

Dr. Mark Hyman
That are looking for patterns that are unique among them.

Paul Thompson
Absolutely.

Dr. Mark Hyman
Absolutely. And so what are the suite of blood biomarkers that you're looking at that are most important?

Paul Thompson
So there's been a huge revolution in the last year in the dementia field. And so, you know all of the relevant processes to dementia. There is a test for amyloid beta, beta amyloid. Forty percent,

Dr. Mark Hyman
forty percent. Exactly.

Paul Thompson
And the FDA approved that.

Dr. Mark Hyman
Now,

Paul Thompson
as we've said, that is just one process. And some people with dementia have that as the main thing that's going on. But plenty of other people may not have any of So that going on at there are other inflammatory markers. There's also a measure of neuronal integrity. Neurofilament light is another measure.

There's glial fibrillary GFAB, which is looking at your astrocytic helper cells, how are they doing. And this idea that for each one of these channels of abnormality, there could be a targeted treatment. I mean, you know this, Mark. I mean, you've written about it for a long time. The dementia field is just coming around to this.

Dr. Mark Hyman
And p tau two seventeen.

Paul Thompson
And p tau two seventeen. A lot of these

Dr. Mark Hyman
are offered function health, forty two forty, neurofemin light chain, p tau two seventeen.

Paul Thompson
Absolutely.

Dr. Mark Hyman
Yeah.

Paul Thompson
So let me ask you, Mark. So are these tests you would recommend for everyone who's elderly or just people that are showing signs of a of a

Dr. Mark Hyman
I think if you have a family history, if you... I think as a baseline at some point to get. Yeah. Maybe when you're 50 or 60. I I I think we we don't really know.

Sure. Like when should you check your cholesterol? When you're five? When you're 20? When you're 50?

Like Yes. You know, we're seeing kids with abnormality. We're... We didn't mention it earlier, but, you know, from brain imaging, we can see change in brain imaging thirty years before you have Alzheimer's.

Paul Thompson
Absolutely.

Dr. Mark Hyman
So something's going on, and you can you can see the smoke signals. So I think we're going be learning more and more about these biomarkers, but I think there's a continuum of abnormalities from optimal to fully abnormal. And I think it's just like blood sugar. Our blood sugar cutoff is a 100. But we know from the data that if blood sugar over 85, you're starting to see a linear increase in risk of cardiovascular disease.

So it's it's not that normal is normal.

Paul Thompson
I think that's such a great way of looking at it. Because let's take something like Parkinson's. A fraction of people with Parkinson's, which is a movement disorder, have a lot of vascular abnormalities in the brain. And like you said, that didn't happen today. The scan that shows vascular damage didn't happen on the day of the scan.

And so there has to be a whole period of time, maybe years, maybe decades, leading up to that. I think it's a very different perspective. If someone had a scan that revealed that at an earlier time point, maybe some of the methods that you've been talking about could be proactive rather than just reactive to the scan.

Dr. Mark Hyman
You're talking about things like Alzheimer's and dementia, with these new biomarkers like neurofilament light change Yes. A a d forty two forty, p dash 17, g fap. Those are those are emerging biomarkers. And we're we're adding those in function or they're already in function. What about psychiatry?

Paul Thompson
Yes.

Dr. Mark Hyman
What are the biomarkers you're seeing? Because I think there are a lot of biomarkers of mental health. I think it's a whole unexplored area that I've been checking for a long time. And I think I'm curious to see what your research is showing.

Paul Thompson
Yeah. I think many of the same systemic biomarkers that you've been referring to, I mean, things to do with inflammation, all of the metabolome. I mean, this is a whole new landscape that's ripe for study. So I'll tell you a story. So one of my lab managers, Chris Whelan, he worked at Biogen and Pfizer.

And we were using a data set called the UK Biobank. They assessed half a million people in the And Chris said what you said. Why didn't they collect blood readouts, proteomics? Mean, all of these things that we know are useful to do. And he managed to get a group of people together.

It's called the PPP. I think it's the plasma proteomics project.

Dr. Mark Hyman
And

Paul Thompson
you can look at exactly what you said. I mean, did the people that had a mental health issue who recovered or had a particular diet or lifestyle... And I think a whole landscape of discoveries is gonna be made using that kind of thing. These are like proteomic metabolomic tests. Not necessarily

Dr. Mark Hyman
clinically

Paul Thompson
used now. They're not used now. And I think, you know, some of them need to be developed. And so there could be, as you've said, a metabolic process or an inflammatory process, good or bad immune process, that is dysregulated. And as you know, there are many, many ways of nudging that back into the zone it should be.

But by looking at this data, you could even have AI. I mean, I'm sure you do this. Even have AI. Find what is the signature of people that did well with this treatment, what is the signature that did well with a different treatment, and then is there a signature for just not great outcome? And it's immensely useful for people doing drug trials or interventional trials, because they have a plasma readout, and there's a pretty good chance that these people will do well, or that these people will have a side effect, you know ahead of time.

You can kind of prescreen. And neuroimaging is used for this. If there's a drug trial, you can often have neuroimaging be kind of a gate. It says, well, this treatment's probably gonna be good for you. We think in Alzheimer's, also in depression, this brain scan means that the probability is this is probably gonna be the right thing.

So I think that's a great way forward.

Dr. Mark Hyman
That's true. I would say that, you know, there's gonna be an emerging set of diagnostics to come out of things that are not typically clinically measured now, like metabolomics, proteomics, proteins, metabolites. And we're just kind of hitting the surface of that, the microbiome, so forth. But I think there are existing biomarkers, and we include these at function health, that that not necessarily, like, are directly correlated to mental illness, but play a role in mental health, like vitamin d, like iron, like omega three fats, like heavy metals, like your insulin levels and metabolic health, like hormones, like thyroid, like sex hormones. All these things we can actually measure, and we do homocysteine, methylmalonic acid.

These are these are measures of b vitamin status. These are all things that play a role in brain health, brain function, and mood, and cognitive function, and all of it. And and they're available to us, and doctors aren't checking them. Know, you mentioned that the the database in The UK. There's an American study that's called NHANES, which is the National Health and Nutrition Examination Survey done every year on a set of people.

It's about 5,000 people. 5,000 people. Measure about 40 blood tests. Function health, we have over half a million people. We measure a 160 blood tests a year in a longitudinal fashion that look at much deeper levels of these biomarkers that nobody's looking at.

And I think, you know, we're discovering all sorts of things and how sick our population is. And we have a health foreign population. These people are proactive, want to join, want to know about their health. And they're not the average American typically. Although we hit a broad demographic, there are people who are more proactive.

So even within that population, we're seeing such massive amounts of problems that are fixable.

Paul Thompson
And I think, Mark, you collect the right data. You have to ask the right question. You have to collect enough data. And if these panels hadn't been assessed, you'd miss this whole perspective on what's going We on in

Dr. Mark Hyman
collaborate because we're doing a lot of imaging now. We're doing brain imaging. We have Ezra, which measures brain MRIs, full body MRIs. We can do neuro quantum MRIs, brain age. And I think we're just beginning to kind of unpack all this.

And we want to come up with, I think, you like you can get a cardiovascular risk score. We should really get a brain health score. A brain health score. And I really like We should combine blood biomarkers, genetics and imaging in one informed data set that we can watch over time and learn and it'll be vehicle for scientific discovery and understanding. It's kind of an exciting time and I just want to finish by talking a little bit about your project called AI four AI four AD which means artificial intelligence for Alzheimer's disease.

And and, you know, we've we've hit a dead end. Mean, we've billions, literally billions of dollars of federal money on hundreds and hundreds of studies and have come up with buckets as far as I'm concerned. Like, just failure, failure, failure, failure. The, you know, great drugs now maybe extend the time to get in a nursing home by a few months. That's like a...

That's a win. That's ridiculous. So we're we're we're basically failing. And and and and we're not basically looking in the right place. The same is true with with this amyloid hypothesis.

We're just barking up the wrong tree. I'm wondering, you know, with with your work with a... AI four d, you're trying to look more broadly at genetics, brain scans, biomarkers, kind of not having such a prejudiced view of what the causality is to be able to understand actually maybe we're thinking about this wrong and how do we rethink this whole problem. So so I'm gonna be learning about this and tell us about, like, the fact that, you know, Alzheimer's is a name of a syndrome, but it... There's many causes, and there's many subtypes that you're finding.

And this is classic in functional medicine. We like... You just be... Because you know the name of the disease, you don't know what's wrong with you. It's just a label that we give people who share a set of symptoms or pathology.

So it's medicine by pathology and geography, not by mechanism or cause. So so tell us about, like, briefly, what what is this AI four d project? What are you finding? What are you learning?

Paul Thompson
Well, I I I think about... Mean, you you you saw the full perspective of this at a at a very early time point. I mean, you you know the the theory behind it and the evidence behind it. And each of these new observations coming from neuroimaging or from blood tests is sort of you know, validating and proving this is true. One of the points that you made on subtyping dementia.

Dr. Mark Hyman
So

Paul Thompson
if somebody has amyloid building up in their brain, I mean, that's one particular pathological process. But if you look at autopsy, people who have donated their brain to science, there's a number of things going on. I mean, some of these people don't have amyloid. They don't have these deposits that are the target of a lot of the therapies. They have other things.

There's something called Lewy bodies. There's a protein called It's kind

Dr. Mark Hyman
like a combo of Parkinson's and Alzheimer's. Yes.

Paul Thompson
And there's another one that's very, very, very recently discovered, TEP forty three. So there's something called LATE. It's a type of dementia that has a different pattern in the brain. So rather than the memory system being hit first, the frontal and other areas. Now, on a brain scan, you can say, Well, look, that doesn't look like the same thing as the amyloid treatments are able to treat.

That looks like a different thing. So one of the ways that AI can help I mean, AI is terrific at seeing patterns. Humans are pretty good at seeing patterns, but AI doesn't tire. It can look at millions of scans. I mean, it's got a lot of time on its hands.

So you could say, look, could you tell me if there's anything in the scan that would have found these Lewy bodies or the synuclein I or mean, you mentioned the metabolic, I mean, also evident there. And the AI can compare these things in I vast mean, vast numbers. And, you know, if you go to an airport and you come back in and there's a biometrics thing that tells it to

Dr. Mark Hyman
That freaks

Paul Thompson
me out. That tells it freaks me out. Well, the AI that does that, I mean, it's using a lot of information. It doesn't just say, how tall is this? Mean, there's a lot of information.

So in much the same way, can use the

Dr. Mark Hyman
scan,

Paul Thompson
pair it up with the pathology. Same kind of technology. So the reason I'm saying that that's very important is if the diagnosis is refined and personalized and subtype I mean, you know this the treatment that is most sensible to offer a patient with that particular type of dementia may be very different than what they're being offered today.

Dr. Mark Hyman
Yeah.

Paul Thompson
If they have amyloid, sure. If they have a primarily vascular type of dementia, you know, the cardiac, the metabolic, the lifestyle factors are gonna be important. And you said this. Even being proactive, if we know a certain fraction of people are likely to get these vascular diseases, I mean, you have exactly the right approach. And it's something they can do today.

It's not something they're gonna find out later only. I mean, they can look at this today and look at the readout.

Dr. Mark Hyman
It's amazing. So this whole project is using AI and large scale brain data, biomarker data to maybe genetic data, metabolomic data, proteomic data, basically to look at how to diagnose and create prognosis and treat a broad range of neurologic and psychiatric conditions. It's really a new era. You know, the joke in neurology is that the typical neurologist's basic way of practicing is diagnose and adios. Oh, no.

Have you heard that? No, I haven't heard You haven't heard that? Because there's nothing neurologists... They're really good at diagnosing, but there's not a lot of tools in the toolkit. You have Parkinson's, have Alzheimer's, you're kinda screwed.

And so, now, we're in a different era. It's no longer diagnosis.

Paul Thompson
We sure are. I think Mark's pretty well diagnosed

Dr. Mark Hyman
in Buenos Aires.

Paul Thompson
It's good news. And you have readouts that you can demonstrate the correction of many of these processes. I think it's terrific. And AI is helping us because it's so much

Dr. Mark Hyman
data, it's so much information, it's so much noise. Like it's, a human brain can't process all that. And so I think this is why it's such an exciting moment in medicine and science because we've been in the dark ages, like really dark ages. I mean, just to paint a picture. Like Norman Rockwell's doctor in the in the painting where, you know, it's just the stethoscope, listening to different parts of the body, maybe a physical exam.

Okay. We have some imaging. A few blood tests. Like, maybe 20, 30, maybe if you do a little more. I mean, we're really not looking at the scope of what's going on.

We have 20,000 genes. We have 5,000,000 variations in those genes. We have 6,000 metabolites. We have tens of thousands of proteins. We have a microbiome that's got 40,000,000,000,000 cells with 10 times as much genetic material as our own genes.

We've got the metabolites from all that in our blood, we have all these biomarkers we can measure now that we couldn't measure before. It's just so much data. And including me, I've seen more data than most doctors because I've done so much diagnostic testing on so many people over so many decades. And I have my own little AI pattern recognition thing, but it's very limited when comes down to it in terms of what AI can do and what it actually understands. And I think we're literally just at the beginning And I think function health is is really leading the way, I believe, to disrupt all this thinking and to collect large data sets.

I mean, you... I I would imagine, like, to get the data that you've got has been billions of dollars of investment to get all the imaging and genetic material and all this. Right? And yet and yet people now are paying $365 and giving us the information and it's their data, but we're able to kind of go, okay, what can we learn that can help you? How do we use this data to help you learn about your body and what to do about it?

It's so it's such an exciting moment. I I'm just I

Paul Thompson
It's amazing. And I I think you're right, Mark. I mean, you you know to correct... To collect the correct data. Like, you gotta look at the right things.

Like, you could collect a lot of information that is tangential. But if you look at these blood markers, if you have a database that is so rich that the patterns that matter can be pulled out, and then all of these different corrective actions, I mean, wonderful for scientists. I mean, a really great idea to be able to

Dr. Mark Hyman
do that. I believe that people should get their blood work and that's why Creative Functional Health should get a detailed panel. Imaging is a little more controversial and this is your life. What do you say to people who are saying, Oh, you shouldn't bother looking and it's a waste of money and time? Because I do think that it's valuable to get imaging on yourself.

I think

Paul Thompson
you're right, Mark. Mean, people who care about their health, who are healthy today might want to look into their future health. What is the downside? I mean, you've said this before. You know, if you have a brain scan and it finds something that you can treat, I mean, why not?

I mean, that seems like a useful thing to do. I have had countless times when I've had a blood test, and it's revealed something that is fixable for me. I mean, you know, vitamin is off or cholesterol was too high and now we're fixing it. And I feel like, you know, nobody would claim that you should just go through life oblivious to all of these things that you could fix. Nobody would just No.

People have different points of view on this. But at least you've made this landscape available to people

Dr. Mark Hyman
who

Paul Thompson
are interested in availing themselves of it. Yeah. And you have positive proof that it's testimonials of this.

Dr. Mark Hyman
It's true. It's pretty rewarding to see how many people's lives have been improved and saved just by knowing their data. And I'm really proud to have co founded Functional Health and be working with our team of 500 people to make this a reality for everybody. And, you know, I hope we can collaborate in this. I'm excited to kind of share more what we're doing.

And thank you so much for your work. And Enigma is such an incredible project. I just sort of overwhelmed when I first learned about it. And I think, you know, the fact that you're coming to the same conclusions that I did twenty years ago or twenty five years ago is like so rewarding.

Paul Thompson
So... Well, thank you, Mark. Thank you for what you do. I appreciate it very much.

Dr. Mark Hyman
Thanks so much. And people can learn more about your work where?

Paul Thompson
They can look up enigma. So if they put into the Internet enigma and brain and there might be a disorder or disease that they're interested in, they'll find us.

Dr. Mark Hyman
Enigma. So it's enigma... Just go enigma what?

Paul Thompson
Enigma... Well, enigma.ini, because it's the Institute of Neuroimaging and Informatics, dot USC, University of Southern California, .edu. Okay.

Dr. Mark Hyman
We'll put that link in the show notes, but it's it's an incredible project. Thank you for doing it, and thanks for all your work.

Paul Thompson
Thanks, Mark. Much appreciated. Thank you.

Dr. Mark Hyman
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