Is Alzheimer’s Preventable? The Power Of A Personalized Medicine Approach

Speaker 1:
Coming up on this episode of The Doctor’s Farmacy.

Dr. Richard Isaacson:
If your listeners take home one thing from this podcast, hopefully it’s that they’re not powerless. But if they take home two or three things, I hope that they take home the fact that everyone should know their blood pressure. Everyone should know their waist circumference. Everyone should know their body fat. Everyone should know these numbers.

Dr. Mark Hyman:
Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman, that’s Farmacy with an F, a place for conversations that matter. And if you have a brain, this conversation is going to matter to you because you’re going to learn how to take care of your brain in ways you never thought possible. In fact, you are going to learn potentially, how to prevent, stop, and maybe even reverse dementia. So, let’s get into it with our guest who is extraordinary scientist doctor, Dr. Richard Isaacson, I have been dying to have him on the podcast for years, finally got him to agree. He’s the director of the Center for Brain Health and director of Alzheimer’s Prevention Clinic now at Florida Atlantic University Schmitt College of Medicine. He was previously the director of the same Alzheimer’s Prevention Clinic at the Weill Cornell Memory Disorders program and Assistant Dean Faculty Development.

Dr. Mark Hyman:
He also is an Associate Professor of Neurology at Weill Cornell Medicine and New York Presbyterian and he just does so many cool things. But that is the least of it. He has literally been diving into an area of research that a few have feared to tread, which is, can we using a very radically different approach than the drugs which we’ve used to try to deal with Alzheimer’s, actually, stop, prevent, reverse Alzheimer’s? We’ve spent, I don’t know, billions literally, I think maybe two or three billion dollars in over 400 studies to try to find the cure for Alzheimer’s, much of it funded by the government. And honestly, most of it has failed. Over 99.6%, the studies failed and the ones that succeeded were like, “Well, you can maybe keep them out of the nursing home for an extra couple of months.” So it wasn’t like a slam dunk. So I’m so excited to have Dr. Isaacson on the podcast. Welcome.

Dr. Richard Isaacson:
Dr. Hyman, thank you so much. It’s a privilege to be here. It’s great to be here, lots to share. I just want to know, I have so many people that are fans of yours that are just going to gaga, that I’m finally talking to the Dr. Hyman on his podcast. I got Christina S. I guess I got a couple of Christina Ss. I can keep name dropping, but I’ll stop for now.

Dr. Mark Hyman:
See I don’t get excited by talking to celebrities, I get excited by talking to people like you. I get nervous. I’m like, “Oh, Dr. Isaacson does all this amazing work.” And I’m so excited to learn about what you’re doing and share it with everybody.

Dr. Richard Isaacson:
Sure.

Dr. Mark Hyman:
Let’s just get right into it. We are in a kind of a pickle, our brains are getting better, not worse. There’s 46 million Americans that have Alzheimer’s that is actually starting up in their brains, and that don’t have symptoms. Most people don’t even know that you can actually detect the changes in the brain with Alzheimer’s 20 to 30 years before you forget your keys. Right?

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
So we’re going to get into research, which is really extraordinary, that shows that… And I’m going to sort of give the punch line away that a disease that we previously thought untreatable is now potentially treatable, but not in the traditional ways we have thought, which is medication, or typical medical treatments that manage the typical things that we do. It’s really a radical approach using a systems model what we call functional medicine, which is essentially looking at multimodal interventions with multiple causal factors applied at the same time in a personalized way to radically change your biology, which changes your brain. So your body affects your brain, and you’re treating all the factors that affect the brain. And as we learned in medical school, the brain obviously has nothing to do with the rest of the body, right Richard?. It’s just disconnected, there’s this blood brain barrier, and nothing passes between except maybe some sugar.

Dr. Mark Hyman:
We’ve learned that’s just nonsense. So take us down, what are… Just to get right in, what are the top things that determine a brain healthy lifestyle, and a brain healthy diet that people can do to prevent preclinical or pre symptomatic Alzheimer’s. In other words, what is this whole field of preventive neurology that you’re talking about?

Dr. Richard Isaacson:
Yeah. You used the term radical, right? And it’s not radical, it’s just straightforward. And there’s all these terms that are flying around. Like when we publish, we talk about precision medicine, and we use the terms individualized care, and there’s all these terms and you can call it what you will in semantics, but it’s just regular, what should be regular medical care. It just doesn’t turn out that way, because our medical system is sideways and you can’t spend time talking to patients. I’m actually like you. I’m a clinician, I talk to patients. I wasn’t really a researcher, I kind of went into the research through the side door, this academia kind of thing just sprouted upon me. But what can people do? I think people can grab the bull by the horns, and say I can make a difference in my brain health by making incremental changes today.

Dr. Richard Isaacson:
And you don’t have to start tomorrow, you don’t just start next week, you can start today. And there are little incremental changes people can make to really promote their brain health over time. And I just want to just reiterate something you said. Alzheimer’s disease starts in the brain over 20 to 30 years before the first symptom of memory loss begins. This leaves an ample amount of time, this critical window of opportunity for people to just get educated and get informed. So if someone had to do something today, I would first say take a deep breath. There’s a lot to-

Dr. Mark Hyman:
Huh, okay.

Dr. Richard Isaacson:
Yeah, there we go. Deep breath. Right before we were starting the podcast, we each took… We had some tech difficulties [inaudible 00:05:51] the best of us, we took some deep breaths, everything was cool. But take a deep breath because Alzheimer’s is among America’s most feared diseases. It is a terrible condition. It’s sad…. I have four family members with Alzheimer’s. It’s a sad, terrible, horrible, I hate the disease. I hate… It’s a strong word, but I hate Alzheimer’s. I hate what it’s done to my family members, my patients and their family members or caregivers. But I think it’s important to take a deep breath and understand that there are so many things that we can do to put the ball back in our court, to write this script and tell our own story.

Dr. Richard Isaacson:
Can you definitively 100% prevent Alzheimer’s in every case? Well, no, there are certain pretty rare genetic causes where basically just about anything you’re going to do, you’re going to get Alzheimer’s, and it’s going to probably start early. And that’s unfortunate. But that is an exceptionally rare number of cases. Most cases of Alzheimer’s, you can do something about it based on the 2020 Lancet Commission.

Dr. Mark Hyman:
Hmm.

Dr. Richard Isaacson:
An amazing study based on 12 modifiable risk factors, we can, the person makes brain healthy choices prevent four out of every 10 cases of Alzheimer’s disease.

Dr. Mark Hyman:
Wow!

Dr. Richard Isaacson:
We didn’t learn that in med school.

Dr. Mark Hyman:
No.

Dr. Richard Isaacson:
Medical students now aren’t learning that in medical school, it takes 10, 15, 20 years for something to be learned in medical science to be translated into clinical practice. And I think it’s important for this podcast and people like us to share this news because there are so many things a person can do. So you asked me what can a person do? I want them to know there’re so many things.

Dr. Mark Hyman:
At least 12.

Dr. Richard Isaacson:
At least 12. Yeah. So, in our study-

Dr. Mark Hyman:
I think there’s more, but there’s at least 12.

Dr. Richard Isaacson:
At least 12. In our study, we recommended on average 21 Different things that a person can do. And those were individualized per person. In our whole universe of our study, we recommend almost 50 things that a person can do.

Dr. Mark Hyman:
Hmm. 50 things that influence the brain that you’ve identified.

Dr. Richard Isaacson:
Yep. And it’s… This isn’t radical. This isn’t rocket science. This isn’t like… I’m a simple man, I did not graduate first in my med school class, I did pretty good and I work pretty hard. But I try to just see things from the patient’s perspective. And there are so many things that are evidence based and safe. The two categories I would start with, just to kind of set the stage, are pharmacologic and non pharmacologic. And I want to get granular because the word pharmacologic doesn’t just mean drugs and prescription drugs.

Dr. Mark Hyman:
Uh-huh (affirmative).

Dr. Richard Isaacson:
It also means-

Dr. Mark Hyman:
Means food is medicine?

Dr. Richard Isaacson:
Well, food is definitely medicine, although that got sidetracked in non pharmacological, but I can-

Dr. Mark Hyman:
Vitamins are medicine.

Dr. Richard Isaacson:
Well, vitamins-

Dr. Mark Hyman:
I actually would challenge you, Richard, because I think that food is actually real medicine. The phytochemicals, the compounds in food are biological response modifiers for signal transduction changes, and they have similar effects as drugs. In fact, many drugs come from the phytochemicals in plants.

Dr. Richard Isaacson:
Right.

Dr. Mark Hyman:
So, I would just kind of make a sneak about that a little bit.

Dr. Richard Isaacson:
Well, actually… So I’m glad you brought that up. I would say that, traditionally speaking, and let’s talk through this, this is a great opportunity. So traditionally speaking, I’ve always framed it, and I’m open minded. So this is great. Pharmacologic includes-

Dr. Mark Hyman:
I’m just teasing.

Dr. Richard Isaacson:
No, this is exactly why we’re doing this. This is exactly a meeting of the minds. Gloves are off, let’s go. So, drugs, vitamin, supplements and medical foods are the classic things that I personally have categorized in the pharmacologic session. And then in the non pharm section, I’ve included diet, exercise, sleep, stress, a whole bunch of things, learning new things. But what you bring up is important. And I have a colleague named Dr. Robert Krikorian. And he’s an amazing guy. He’s a neuropsychologist and he’s fought the good fight. Kinda like us, he’s… I don’t want to say he’s had… Yeah, in some ways he’s contrarian views because he’s tried to do randomized studies using nutrition. He’s done studies on the ketogenic diet in Alzheimer’s and Parkinson’s and he’s done studies on blueberries and omega threes and what he’s done is he’s taken the food and he said, “Okay, it’s not just about the blueberries, we did a study in wild blueberries are better.” Well, why? Because of this… It’s called anthocyanin. And then he gets down deep into it.

Dr. Richard Isaacson:
So I completely agree that food is medicine, 100% agree. I completely agree that the specific chemical nutrient compounds can be isolated. But I think it’s too reductionist to just say, let’s just put a pill of anthocyanin and prescribe that.

Dr. Mark Hyman:
100%.

Dr. Richard Isaacson:
Because it’s the meal you. Right? It’s like with caffeinated coffee is good for brain health. Well, is it the caffeine? Is it the coffee? Well, no, they think it’s like some substance X during the brewing process. Right? So, depending on which way you look at the science, I would prefer that food is medicine. Sometimes-

Dr. Mark Hyman:
I agree with you. I understand the bucket. So I’m just kind of playing with you.

Dr. Richard Isaacson:
I love it.

Dr. Mark Hyman:
But I think. When I put a patient for example, on a ketogenic diet with Alzheimer’s, and they wake up and their brain becomes alert, and they remember their son and their daughter and I’m like, “Well, how is that less a drug than some other drug that doesn’t even work that we’re using like Aricept?” Right?

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
It’s impressive.

Dr. Richard Isaacson:
Yeah. No, I just feel like all of the different paths… Some people call nutrition, I don’t know. Not mainstream medicine. To me as a Western doctor, that doesn’t make any sense to me. Nutrition is… I got very little nutrition education in medical school, and I think that’s a terrible thing. I learned a ton and I had to… My better half has a master’s degree in nutrition from Columbia and she’s taught me a lot. I think through osmosis.

Dr. Mark Hyman:
That explains everything.

Dr. Richard Isaacson:
Huh, there we go. It’s always the better half. And she informs the less enlightened one. So I guess what I’m trying to say is nutrition is the cornerstone of how we practice. Physical exercise, and precision exercise, precision nutrition, these are all the things that are developing and really become the cornerstone of our care.

Dr. Mark Hyman:
So you’re talking about the 12, then the 21, and then the 50. Maybe there’s going to be 100. Tell us more about the granularity on that?

Dr. Richard Isaacson:
Sure.

Dr. Mark Hyman:
You were using these and I just want to sort of frame it for people. You did a study that you published, I think in 2019, which surprised even you, where using this approach, looking at a personalized assessment of these biological factors that could be modified. And then individualizing the treatment, that you not only slowed the decline, you not only stopped the decline, but you reversed the decline, which is something that has never really been seeing, except in a couple of trials like the finger trial. And I think there’s a new one coming out the pointer trial. So those are also lifestyle trials. And so you really have sort of crackED the egg and published something that should have been on the front page of every major newspaper, the lead story in every evening news, and yet, it was like crickets.

Dr. Richard Isaacson:
Yeah. Well, we got the Wall Street Journal and CNN and some others. So, I’m okay with that.

Dr. Mark Hyman:
Okay. But for me, it should have been like the NIH should have gone, “Oh, Richard, here’s $10 billion to get going on this.” That’s what you should have.

Dr. Richard Isaacson:
I have to be careful, but the NIH doesn’t really fund what we do. And that’s been… It’s very hard. And listen, the NIH I’ve engaged with the NIH over the last year or two and there’s definitely been more interest. But talk about crickets a decade ago, when I started this whole thing, 15 years ago, there was nothing, there was no funding for any of this. So what I would say is, what our work shows is that when you individualize care and you give people a plan, and I know you’ve asked me at least three times now, what should people do? What I’m trying… Why I’m delaying things is because it really truly needs to be individualized. And what we use is a term we call the ABCs of Alzheimer’s prevention management.

Dr. Richard Isaacson:
Based on the data, we get data on As, the Bs and the Cs, A stands for anthropometrics, anthropometrics is basically a fancy A word for body composition. What is your body fat? What is your waist circumference? What is your muscle mass? Depending on these factors, we’re going to change the recommendations we give. The B stands for blood based biomarkers. We’re going to look at markers of lipids, cholesterol markers, also advanced markers that preventative cardiologist use for example, that most neurologists honestly don’t really pay attention to. We look at metabolic markers, insulin resistance, we look at inflammatory markers, we look at nutrition markers. Instead of saying, “Okay, well go eat fish, it’s good for you,” we’re going to look at the markers in the blood, we’re then going to tell you based on your blood and based on your genetics, how much fish you should be eating, what types of fish. So, the take home point is we’re going to get granular with every patient.

Dr. Richard Isaacson:
The other thing we do is in the blood based biomarkers, we look at genetics, we look at the APOE4 variant, it’s the most common risk gene, it doesn’t mean you’re going to get Alzheimer’s if you have the variant, but it increases your risk. Well, if I know that you have the APOE4 for variant, they check for this and 23andMe. Millions of people have gotten this checked, I’m going to personalize your care differently. If you have the variant, I’m going to give you plan A, B and C, if you don’t have the variant, I’m going to give you a little bit modified plan X, Y and Z. If you have two copies of the variant, you have a different plan altogether. That’s only 1% of the population. So the take home is we take all these markers and then the C is cognitive function. And we understand a person’s cognitive baseline. We look at memory function, language abilities, learning abilities, speed of processing, attention and executive function, which is higher order processing.

Dr. Richard Isaacson:
We take all of this and the patient’s medical history, we learn about the patient, we learn everything we can about them about their family, and then we personalize a plan. So those 21 different things are based on that person individually. And there’s a lot of overlap. If you want me to say, “Okay, well, what are the core things?” Well exercise on a regular basis. Okay, exercise on a regular basis is good, but every person gets a different plan. If we’re putting someone on a plan for body fat loss, we’re going to give them a different plan. Steady state cardio for example, some people would call that zone two training. Steady state cardio at 60 to 65% of your heart rate. There’s different ways to do this through lactate testing through a variety of things that we do more precisely in our clinic. But we put people on these steady state cardio plans, fasted in the morning as long as they can tolerate it, because that way it jumpstarts body fat loss.

Dr. Richard Isaacson:
If we have people that don’t do any muscle strength training because they don’t like it, we educate them to say, “I don’t like it either.” I’m not Mr. Big muscles over here, but I have to do strength training once or twice a week minimum, because if you don’t have muscles, you can’t boost metabolism. So we put people on these very specific plans, high intensity interval training. I really believe that high intensity interval training is almost necessary for people with at least one copy of the APOE4 variant. And this is what has been studied down in a couple of studies. And yes, we need more research and studies out of Norway, we’re good. But we need to personalize an exercise plan. We need to personalize a nutrition plan, we need to personalize a vitamin and supplement plan. In some people we do use drugs… Drugs are actually not commonly used at all in our research. Although we do use them on occasion.

Dr. Richard Isaacson:
We’ll use a variety of drugs usually at much lower doses than maybe the regular community uses. But when it comes to management, I’m equal opportunity. If there’s data and it’s relatively safe, I’ll entertain it. So we recommend cognitive activities that will have a spillover effect, learning something new, learning how to play a musical instrument, learning a new language. These are things that may have a protective effect build backup pathways. Believe it or not, even learning how to play a musical instrument in midlife has protective effects on cognitive outcomes in late life. And that’s just-

Dr. Mark Hyman:
There’s hope for me yet.

Dr. Richard Isaacson:
There’s hope for you yet. I got my bass guitar over there. I got blisters on my finger.

Dr. Mark Hyman:
I’m dying to learn to play the guitar. I’m dying but I just… My big problem is I don’t know how to tune it and I am so musically inept that I… Probably there are good apps [inaudible 00:18:48] to do it.

Dr. Richard Isaacson:
There’s a website, it’s called, you got a pen? It’s called YouTube, YouTube.

Dr. Mark Hyman:
Oh, yeah, YouTube. [crosstalk 00:18:55].

Dr. Richard Isaacson:
Have you heard of it?

Dr. Mark Hyman:
I heard of…

Dr. Richard Isaacson:
Almost as many people watch YouTube as listen to your podcast, so you can learn how to play guitar on YouTube. I think you can do it.

Dr. Mark Hyman:
Okay, I’m going to try it.

Dr. Richard Isaacson:
For sure.

Dr. Mark Hyman:
As my December.

Dr. Richard Isaacson:
And January and February and March. So, the take home point is engage your brain. Treat your brain with respect. Love your Brain. Make a plan for your brain. What does that mean? Make a plan for sleep. If you exercise and exercise an exercise, some people say colloquially that that loosens the amyloid, the bad protein that gets built up in the brain of a person with Alzheimer’s. But if you’re burning the candle at both ends and you’re not sleeping during sleep, especially deep sleep, that’s when a person has the trash come, the trash man comes, they pick up the garbage and they take it out and they take it to the trash heap. That is the restorative part of sleep and if someone isn’t sleeping at least seven, seven and a half eight hours of sleep, is usually the goal as we get older. It’s part of the sleep that much. But making a plan for sleep, prioritizing sleep.

Dr. Richard Isaacson:
We have people that track their sleep, that track their exercise, I’m wearing a risk device here, I’ve nothing to disclose. But we’ve done several research using this device. I track people on my phone, I have my phone right here. And I can check how much exercise they’ve been doing, how their sleep, how much deep sleep, I can see their blood sugar control, I can see all these different things on my phone, because my patients share their data with me. And when I talk about data sharing, it’s not just about tracking sleep, it’s not just about doing exercise, it’s about tracking it, determining the response, talking to your physician about it. Granted, it’s hard to find physicians that will take the time to talk to you about this kind of stuff. Tracking your blood sugar, there’s at home devices called continuous glucose monitors.

Dr. Richard Isaacson:
In our program, we take a very, very deep dive and we learn about all of these different metrics, and we refine or fine tune the plan that we give them based on their real time measurements. So, I can keep going, there’s stress modification. Transcendental meditation. Bob Ross taught me a ton about this. What about mindfulness based stress reduction? You can take a course online, mindfulness based stress reduction has amazing outcomes when it comes to brain health. The list goes on and on. There’s no one magic pill or one magic cure, but there are a variety of… Huh, I was going to say pharmacological and non pharmacological, but you’re reevaluating how I say this now. There are a variety of interventions that are evidence based and safe that I think all of us needs to learn about, whether we talk about fasting. And I like the term time restricted, eating better, meaning not eating for 12, 14, 16 hours overnight, so at least four or five days a week. I use the term fasting for a more prolonged fast, 24 hours or more. And that’s a different discussion.

Dr. Richard Isaacson:
There’s the ketogenic diet, there’s the Mediterranean style diet, there’s the mind diet, there’s components of each diet, green leafy vegetables, wild salmon, grass fed beef is better than non grass fed beef, because the Omega threes. There’re so many [inaudible 00:22:01] in the details, half a couple blueberries and strawberries two to three times a week leads to better brain health outcomes and cognitive outcomes in the Nurses’ Health Study many years later on. There are dark cocoa powder, there’re so many things that I can drop in as key things. But a take home point is all of these things need to be individualized.

Dr. Mark Hyman:
So let me ask you this, because… First, I want to just kind of feedback because I’m listening to you thinking you’re a neurologist, but you’re also an immunologist, a cardiologist and an ecologist, a gastroenterologist, a nutritionist. Right?

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
You’re breaking down the paradigm of medicine.

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
Which is we should stay in our lane, focus on our organ, and leave the rest everybody else.

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
And your insight here is that the body is a system, that everything’s connected to everything. You can’t just pick out one thing and work on that like amyloid, or tau or whatever, and get to the problem.

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
It’s sort of trying to bail the boat while there’s holes in it, you got to fix the holes. And essentially, the holes that you’re talking about are all these ways in which our brain gets injured by our lifestyle and by our environment, and even mentioned toxins, but that also plays a large role. And so all of a sudden, we have to sort of rethink our whole approach, which has really been a reductionist approach, single disease, single drug with a single outcome.

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
There was an article in JAMA a number years ago called Shifting Thinking in Dementia, you probably saw it. And they said in that article that we combine categorical misclassification with etiologic imprecision. In English for those listening, that means we categorize dementia according to symptoms not the causes. And we are not very focused on the etiology or the causes, we’re focused on the symptoms. And we say, “Well, you can’t remember this and you fit this profile on your neurocognitive testing, you have Alzheimer’s, you have this kind of dementia, or Lewy body or blah, blah, blah.

Dr. Mark Hyman:
And the reality is that you could have 10 people with Alzheimer’s who need 10 different treatments. And that’s exactly what you’re talking about. That’s heresy, Richard, that’s heresy in medicine. Honestly, because we really have a very restricted reductionist view of disease that doesn’t let us actually even study these things. And I’ve literally had arguments with top leading researchers, heads of research at major institutions saying, these are all the factors that affect the brain. We want to study them together. No need to study one thing at a time, and then see how that works. And then one thing… So study exercise, and they study nutrition, they study vitamin D, they study fish oil, I’m like, “No, that’s not how things actually work.” It’s like, you have to use the whole picture.

Dr. Mark Hyman:
The other thing I sort of wanted to sort of touch on was that you’re sort of introducing a concept of personalization, which again, is very different in medicine. It’s not one size fits all and you’re talking about very sophisticated personalization based on a whole set of biomarkers and tests and things that are easily accessible, but that aren’t normally looked at and then aren’t normally tested. You get your typical panel, your thyroid, your B12, you get your spinal fluid done, you get your MRI and you go, “Okay, you got Alzheimer’s.” It’s a little bit more complicated than that, but it’s really a fairly narrow window of biomarkers and metrics. And there’s bazillions of them. And I think we’re just sort of touching the sort of tip of the iceberg on this. And I’ve seen in my patients when you start to apply these concepts of personalized care around food, around exercise, around sleep, around stress, around supplements, around everything, that you really begin to see dramatic changes in brain function.

Dr. Richard Isaacson:
Yeah. I often joke that I’m like a 1/3 neurologists, but a preventative neurologist at that. I’m a 1/3 make believe. I will, full disclosure, I’m not a preventive cardiologist, but I’m a make believe preventive cardiologist. I’m a 1/3 primary care doctor and make believe preventative endocrinologist. I don’t even know any preventative endocrinologist, if you find one introduce them to me. I was trained in an environment. I went to a six year medical program where I was in med school from day one University of Missouri Kansas City. I knew I wanted to be a doctor when I was five. 17 years old, wearing my white coat and I did so much internal medicine during med school. I had like an extra year of medicine, because that’s the way our training was. I don’t know if it was that or I’m not sure exactly what it was. But Alzheimer’s disease is a medical disease.

Dr. Mark Hyman:
Yeah.

Dr. Richard Isaacson:
Full stop. That’s it. There’s this thing called a skull, and it’s a hard thing that protects you when you fall. But it’s just like it… It’s like when you have medical conditions, it can affect your kidneys. When you have medical conditions, it can affect your eyes, it can affect your heart. The same thing, it can affect your brain. And I couldn’t agree with you more, people can take different roads to Alzheimer’s. And you have to figure out what rod they’re on and get them the heck off that road. Women for example are unfortunately many times in the fast lane to Alzheimer’s. Two out of every three brains affected by Alzheimer’s are women’s brains. And five, 10 years ago I would say I didn’t know why. And now I think I can answer that question. And it’s related to the perimenopause transitions, it’s related to specific life factors, it’s related to women being maybe a little bit more at risk if they have the APOE4 variant.

Dr. Richard Isaacson:
So the take home point here is if you understand a person’s individual risk factors, whether it’s biological sex, whether it’s medical conditions, whether it’s what’s floating around in their blood, whether it’s what is their cognitive function at baseline, you have to figure these things out. And then you have to target that plan and personalize that plan. And Alzheimer’s disease and brain health needs to be treated in a medical way. Because if it’s not, if you’re just targeting amyloid, you’re missing the boat. Amyloid is a marker and I think hopefully one day we’re going to have just like we treat diabetes with lifestyle interventions and exercise and as well as certain targeted drugs that honestly some of them actually do tend to work pretty well. I’m not the biggest fan of insulin. That’s maybe bad dating to me, that’s probably too late.

Dr. Richard Isaacson:
I’m not the best, whatever. But some of these new things that are pretty interesting. I won’t get into specifics. But I hope that one day we treat Alzheimer’s disease and cognitive decline like any other chronic disease of aging, where we hit things with a multimodal evidence based and safe approach that requires a medical intervention.

Dr. Mark Hyman:
So essentially, what you’re saying to paraphrase is that Alzheimer’s is not a brain disease?

Dr. Richard Isaacson:
Correct.

Dr. Mark Hyman:
It’s a systemic disease that affects the brain.

Dr. Richard Isaacson:
Yeah, I really believe that. I have to be careful saying that. Is just being recorded? Oh, no.

Dr. Mark Hyman:
Yes. And it’s going to be broadcasted to billions of people around the world.

Dr. Richard Isaacson:
Great. I was just gaining some fans in my field and now it’s a decade of work.

Dr. Mark Hyman:
No, no, no.

Dr. Richard Isaacson:
What are you going to do?

Dr. Mark Hyman:
You are at the forefront of a paradigm shift that’s happening throughout medicine, which is the breakdown of the old concepts of disease from simply this reductionist symptom based model, to systems thinking and network medicine. And that’s really all you’re talking about. And you’ve touched upon some of the most easily accessible and modifiable factors, which is what we eat, how we exercise, how we handle and manage stress, how we sleep. Those four pillars are huge. And then there’s the fine tuning with managing metabolic risk factors or getting their nutrient levels up to a certain level.

Dr. Mark Hyman:
But there’s a whole treasure trove of stuff that I think still haven’t even dug into, it’s like I visited Ephesus in Turkey, and it’s the largest Roman city during the Roman Empire, it was incredible. It was all buried under dirt, rubble and they excavated it. But they’re still excavating it 100 years later, and it’s just fascinating to see that there’s so much we don’t know. And I would say, in my experience as a functional medicine doctor, I’ve seen things that have impact on the brain that aren’t really included, like heavy metals. Do even have a way of testing that is in conventional medicine, probably metal is not really, we just do a blood test, and then we don’t worry about it if it’s okay, but there may be total body burden of toxins we don’t look at. The microbiome is another huge factor that affects the brain in Alzheimer’s.

Dr. Mark Hyman:
And mitochondrial function is something you talked about but is often ignored. And we have latent infections that may be affecting the brain causing inflammation, whether it’s herpes two, maybe [inaudible 00:30:53], but there may be other things. Kris Kristofferson had Lyme disease and got diagnosed with dementia, there may be environmental factors like mold that have impact on inflammation. So we know that the brain with patients with dementia is inflamed. And then the causes of that inflammation can be multiple. And so part of the diagnostic die that you’re doing, that would just sort of encourage you, think about this, is that you’re getting to all the stuff that we do know that’s so clearly evidence based, but then there’s a whole treasure trove of things to look at, that we’re kind of ignoring.

Dr. Mark Hyman:
And I’m just going to take two seconds, it’s my podcast, but you’re talking, but I’m just going to just talk about this one patient because it was the first patient I had where came in a guy with Alzheimer’s. I’m like, “Can you do anything?” I’m like, “I have no clue, I don’t know. But I’m just going to apply the model of systems of biology in functional medicine, let’s see what we do.” We found he was severely insulin resistant. He had… Which is we talk about Alzheimer’s is type three diabetes in the brain. He had very high homocysteine levels and methylation problems. So his genetics were off around metabolizing B vitamins in the right way, which we know is a risk factor for Alzheimer’s. He had the APOE4, double four gene. So he’s the 1%. He was 70 years old, cognitively impaired, diagnosed with Alzheimer’s, basically home, not able to do anything, depressed, not functioning.

Dr. Mark Hyman:
He was the former CEO of his company. He also had other nutritional deficiencies like vitamin D, and he had been living in Pittsburgh, and in Pittsburgh it’s the capital of steel. And for a century, they’ve been burning coal for the steel plants. And they use cold air for the streets on the winter for ice, they put it on the field for fertilizer, what they do, it’s everywhere. And all my patients in Pittsburgh have high mercury levels. And he had very, very, very high mercury levels. So when we did a challenge test, he also had a mouthful of fillings. And we know that if you look at amalgam scores and surface area, and you look at animal studies, the more amalgams you put in their mouth, the more mercury ends up in their brain. And so I said, “Well, I don’t know if anything I’m going to do is going to work, but let’s fixture in some resistance, let’s fixture…” Also, he had terrible gut issues.

Dr. Mark Hyman:
He had irritable bowel for 30 years, he was on Stelazine for his stomach, which is a anti psychotic drug to calm his stomach down. And I fixed his stomach, cleaned up his diet, fixed his insulin resistance, I picked the B vitamin thing, I got rid of the metals, and the guy came back to life. And it was really, really markable. And he was able to go back to work and function again and be part of his family and be part of his society in a way that I was just shocked. And so I think that there’s a level of stuff that we’re looking at, and then there’s a whole bunch stuff we’re not looking at. So allow me to comment on that and what your thoughts are about all that other stuff that’s going on.

Dr. Richard Isaacson:
Yes. And thanks for sharing the story. Because every story is instructive, because this is-

Dr. Mark Hyman:
I’ll send you the article I described. It’s an editorial I wrote for a medical journal, I’ll just… Because you’ll go wow, this is interesting.

Dr. Richard Isaacson:
So, the thing that resonates me with the story is, when you have people with APEO4 fours those are just different eggs. And E4 fours maybe for example, E4 fours may be preferentially responsive to vitamin D for example. So, some studies show that vitamin D, maybe it’s not really that preventative, oh, some studies show, oh maybe it is more preventative. Well, people with two copies of the E4 variant which is again, not super common, those people really need to have their vitamin DS up. And that’s just an example there. But people with the APOE4 variant, pesticides, DDT and DDE, the interaction between E4 and pesticides increases Alzheimer’s several fold. If people don’t have the APOE4 variant, maybe they’re not as exposed or maybe they’re not as increased risk to Alzheimer’s.

Dr. Richard Isaacson:
So when you look at a whole population, you don’t tease out for E4 positive versus negative. The studies may not show any correlation. But in practice, we see the correlation and in other studies, you do see the correlation. So I think something… I was at a conference in Canada, you have a lot of fans in Canada by the way, just your name came up there. True.

Dr. Mark Hyman:
It’s everywhere. I’m in this symbol of the airport and some guy from the security comes running up to me, I thought I was going to get arrested for smuggling my Turkish delights back to America. And he was like, “Dr. Hyman, can I take a picture with you?” And I was like, “Oh, fine. Okay.”

Dr. Richard Isaacson:
International. So I was at this thing Canada, and amazing people, just smart people. And we were giving presentations. And of course, I’m the science guy. I’m a clinician, I’m like a regular doctor, I don’t want to say Joe Schmo like you and me, but I was thrown into this clinical research thing. And again, I had research resources, infrastructure, did work hard to learn, hire the right people. So yes, I’ve done research. And when you do research, you need to have objective measures to follow that you can track. I was at this group in Canada, this guy named Gary and Elizabeth, Elizabeth is a naturopathic doctor. And Gary is just really, really, really smart. And they were working together to present on a topic and it’s kind of like a light bulb came off my head and I said, “I’m so focused in the objective because I need to be because I’m a researcher. If I’m going to say something and think it, I need to then prove it.

Dr. Richard Isaacson:
Because if I’m in an academic environment…” I was at Weill Cornell Medicine for New York Presbyterian for almost eight, nine years. Now I’m at Florida Atlantic University doing a really exciting program in brain health and Alzheimer’s prevention, Parkinson’s prevention, dementia with Lewy body prevention. I get to do some really cool things. Maybe I’m missing the boat a little bit, because if I’m just focusing on the objective that I need to track and prove, there’s a lot of stuff under the surface that I can’t really track and prove because I don’t have a biomarker to do that. So I guess what I’m trying to say is, as I’ve… I know what I know and I don’t know no one I don’t know, I’m consciously incompetent about things. And this story that you say is… No, I am… There are people that are unconsciously incompetent and those people drive me a little bit batty. But I am-

Dr. Mark Hyman:
I’m with you. I’m on your team. I’m on the… I know what I don’t know.

Dr. Richard Isaacson:
Yeah, I know what I don’t know. And I’m willing to have my eyes opened. And the stories that you say, it’s like as a physician you have to treat someone in a certain way to try to make them better, but we don’t always have all the objective evidence and the types of work that we do on patients it’s really hard to study. I have empathy for people in our boat, who are trying to study the rigorous… Rigorously study, because what’s moving the needle? To me, I don’t care what’s moving the needle. People were criticizing one of my research papers. “Oh, you recommended 21 things, what if 18 of them are helping and three of them are harming you’ll never know?” And I said, “Okay, but look at the results 18 months later, people with amyloid in their brain with mild cognitive impairment due to Alzheimer’s disease that followed this plan, 18 months later, the longest they followed 60% or more of what I recommended, had better cognitive outcomes 18 months later.” We were able to improve symptoms. There’s no drug that can improve symptoms, slowing decline is one thing, improving symptoms?

Dr. Richard Isaacson:
So, I’m Zen with not being able to precisely understand which of my 21 things are working. But I think as clinicians, I think we just have to do the best we can. And we want to promise not to over promise, I think that’s important too. You said at the beginning when you were seeing that patient. I’m not 100% sure yada yada, but I’m going to try all the usual things and something worked. So, I think as long as we have honest conversations with our patients and do the best… People like us that have academic appointments and are in that realm, I think it’s my duty in some ways at this time in my life in my career to try to prove as much as I can. But I think the field and I think people need to realize that some things are really hard to study and prove.

Dr. Mark Hyman:
Yeah. They are, but what’s happening now is with the acceleration of our understanding of how to map biology and things we couldn’t even measure before, we’re able to start to look at different diagnostics than we ever did before and find things we never found before. And within the diaspora of medicine, which is where I’ve been most of my life. There’s a lot of people doing really interesting diagnostics that are ignored, like heavy metal testing. For me that’s like a blood pressure when someone comes in and they have any kind of toxic or immune or cognitive or any chronic symptoms, I look at it because it’s often an annoying factor. Actually how I figured this all out was through my own mercury poisoning from living in China. And I had severe cognitive impairment and also immune dysregulation and gut issues. And I think the gut stuff is such a big deal. And that’s something we can start to understand what the microbiome and it’s effects and there’s data coming out.

Dr. Mark Hyman:
But the question is, as clinicians, we never learn, well, how do we repair a microbiome that’s off? Right? How do we do that? That’s… Well, we may know if you’re low in vitamin D, you take vitamin D. But like if we test the microbiome and there’s all this inflammation and dysbiosis, and the average doc has no clue where to start. So I think that’s part of the problem, is we just don’t have one, some of the diagnostics we need, or if we do, the average practitioner has no clue what to do with it.

Dr. Mark Hyman:
And I think all that’s going to change, I think what you’re talking about is managing something that until now, I don’t think has been able to be managed by the average doctor, which is, God, there’s 100 things we could find that could affect the brain. I think there’s probably 1000, or maybe there’s 10,000, but the average person, and the average doctor cannot process all that and make the connections. But with the advent of quantified self metrics, which you talked about, with the advent of advanced diagnostic metrics and metabolomics, and the understanding of even the microbiome metabolomics for example, nobody talks about that, but it’s metabolome of the microbiome in your blood, there’s probably 20 to 50% of the metabolites in your blood come from the burns in your gut, right?

Dr. Mark Hyman:
And how does all that work? Well, that’s going to require big data and machine learning and artificial intelligence to start to see the data and the patterns and connections. So, I think that’s where it’s all headed. And we have to stop this paradigm of being reductionist and saying, just take this one drug for Alzheimer’s. And I get so frustrated when I hear these studies come out, and they have big news articles, oh, this helps that helps, or that helps. I’m like, “What about all the rest of the stuff that Richard’s talking about?” It’s gonna be frustrating for you too, because you see it. You see your patients get better, and you go, “Hey, guys, why don’t you try this?” And what do your friends say, who are also neurologists or memory specialists? Do they think you’re a quack, or are they listening? Are they…

Dr. Richard Isaacson:
I’m a pretty resilient guy, I gave my first talk in 2007, about how MCI, mild cognitive impairment due to Alzheimer’s in this pre symptomatic… I didn’t like that term, I just felt it should be prodromal at risk… I felt like we should be treating people before they had dementia. And when I kind of set that stage and I wrote about this in one of my books, names, not naming names, and I didn’t name the name there too. But one of the giants in the field was sitting there and just, I don’t want to say rolled their eyes, but just there’s no evidence, there’s no evidence or there’s nothing you can do. There’s no evidence for data. There’s no evidence for this. There’s no evidence for this. But there was no impetus to even aim to study it. I started seeing Alzheimer’s prevention patients in 20009. Dr. Arthur Agatston was one of my mentors.

Dr. Mark Hyman:
Oh, yeah. Arthur.

Dr. Richard Isaacson:
Amazing guy. He was my attending at Mount Sinai Medical Center when I was an intern.

Dr. Mark Hyman:
Yeah, I liked him.

Dr. Richard Isaacson:
Yeah, before the South beach diet, before… He’s known us as the South beach diet guy, but to me, he’s the Agatston calcium score guy. To me, he’s the visionary that was one of the first preventative cardiologists. And preventing disease and starting before there are symptoms, it was so the tomatoes that were thrown at me were the big vine, ripe tomatoes. Now, I don’t know if my reflexes are better. I’ve cat like reflexes now, I have a cat behind me, but I can dodge the tomatoes better. My armor is thicker, the tomatoes are not being thrown. But it’s also because we’ve now published. We’ve published results.

Dr. Richard Isaacson:
And I would talk to a journal editor five, six years ago, and I said, “Well, this, this and this, and this, and this is what I see. And it’s clear.” And he said, “Well, it may be clear to you, but you need to prove it. And then you need your peers to review the article and accept that your thoughts and your observations are substantiated by evidence.” And I feel like in the last five years, it’s eight years actually, we’ve been able to do about as good of a job as possible with the limited resources that we have. Now, if 1% of the billions of dollars or 10% of the billions of dollars would have come in the prevention bucket, I can tell you, if someone drops a very large sum of money in our research program to prove this, we can do it, but it’s hard. Prevention studies are expensive because they take longer. Prevention studies need to follow people for years rather than six months or nine months or a year.

Dr. Richard Isaacson:
So I think the reason that my colleagues are coming around is because of the publications and building the body of evidence. I think the other reason that my colleagues are coming around is several of them have come visit. I’ve invited over 45 other physicians and other health care providers come visit me and sit next to me. And if someone isn’t willing to sit next to me and my… If someone is willing to criticize the work we do, but not willing to come sit next to me and spend a couple hours and just watch. Just look, it’s… Oh, this is only one patient. It doesn’t mean anything. When you see this once and you see it again and you see it at nine o’clock, 10 o’clock, 11, and then one o’clock, two o’clock and 3:30, you just… You’re like, “Okay, fine, prove it, I get that.” But there are still skeptics out there. There are still skeptics, I still get criticism every day. And I don’t want to say I’m jaded, but haters are going to hate, I’m going to keep doing my thing. And-

Dr. Mark Hyman:
Well, you know what Max Planck said, right?

Dr. Richard Isaacson:
No.

Dr. Mark Hyman:
He said science-

Dr. Richard Isaacson:
Haters are going to hate? He said that? Tat was him?

Dr. Mark Hyman:
No, no, no.

Dr. Richard Isaacson:
That was Max Planck?

Dr. Mark Hyman:
No. He said science, but you could say medicine doesn’t evolve by convincing your opponents and helping them see the light, because they eventually die and a new generation grows up that’s familiar with it. In other words, medicine progresses one funeral at a time. That’s kind of mean, but that’s what he said. And I think the other point is that the absence of evidence isn’t the evidence of absence. Right? If we haven’t spent billions of dollars studying nutrition and Alzheimer’s, how the heck do we know anything? We spent billions of dollars studying drugs that don’t work, but not the right things. And the other thing which I’m going to push back pretty hard on this for you, because you keep talking about preventive neurology and preventing Alzheimer’s. And yes, we should do all that. But your study, your own studies show that you can not only prevent it, but reverse the symptoms.

Dr. Mark Hyman:
Now, how far can we go to reverse it? How much can we reverse it? How far can these treatments work? What if we added 10 other things that maybe we haven’t even thought of that might be as or more impactful than the 25 things you’re already doing? I would push back and start to encourage you to think about treatment studies, not reversal studies, because those you’ll see outcomes much quicker. And if you can take a group of 10,20, 50 people and be really aggressive. And it’s not easy, because changing… And I have these patients, I’m treating many of them right now. It’s the roughest thing. Because if you have an engaged patient, someone who has had a heart attack, and you tell him to change their diet and eat their vitamins and exercise, they’ll go, “I get it.” But you got someone with dementia or cognitive impaired, they can’t remember stuff, you need a full time like bodyguard, literally with them, telling them what to do and helping them do it. But if you did those kinds of studies, I think you would see dramatic changes.

Dr. Richard Isaacson:
So I’m really cautious and I would use the term hesitant. And actually, I would use the term, I don’t use the term reverse. And the reason is, and let me explain my position here. Because I respect where you’re coming from. And I see why that term has been used in the past. But until I have definitive biomarker evidence that I am reversing the signs of pathology. Now, if I would have done my study, and we had the blood test, the amyloid blood test out, now it’s out, now it’s out. So of 2015, 2014, if we would have gotten the amyloid samples in the blood, and then 18 months later, we got them again. And if I would have shown not only did we improve symptoms, so you can either use the term symptomatic benefit, improve symptoms, you can use the term reverse symptoms, I don’t like that term, because-

Dr. Mark Hyman:
I understand.

Dr. Richard Isaacson:
The term reverse to me implies neuro pathological reversal. And I want to be… I’m trying to build bridges here, and I’m trying to bring my enemies closer, even though-

Dr. Mark Hyman:
N0, no, I get it. I get it. [crosstalk 00:48:35].I know where you’re coming from.

Dr. Richard Isaacson:
Yeah. But listen, if we can show that we can improve symptoms, and amyloid goes down in the blood. Well, then we’ve just reversed Alzheimer’s, I will be the first person to plant the flag in the ground and say we have just reversed Alzheimer’s, I would be the first person to do it. And my next-

Dr. Mark Hyman:
There are neuro studies that show that hippocampal volumes go up that you can improve the neurocognitive testing that you see all those hardcore biomarker changes. There’s not enough of that data, but there’s some of that data out there.

Dr. Richard Isaacson:
Oh, you’re preaching to the converted here. I have this amazing guy in Italy, who the first MRI baseline-

Dr. Mark Hyman:
Oh, by the way, hippocampal volume, hippocampus for those listening is the part of your brain that’s the memory part that shrinks as you get older and shrinks a lot when you get dementia and if it grows, it’s not supposed to grow.

Dr. Richard Isaacson:
Right? Yeah. Again, this is an anecdotal story, but there have been studies that have shown this also. I remember one of the first times I saw a guy’s brain, a guy from Italy, nice guy came in this really fancy Italian suit, who’s well dressed. He was skinny fat though. He was skinny fat. He had elevated body fat all that you couldn’t see it because of the fancy clothes. And after a year and a half, he came back and we looked at his brain, this was… You could see it through the eyes, you could see it through computer automated software, the memory center in the brain after following a comprehensive plan through exercise. I think exercise is a big driver of volume, brain size, making the brain bigger. But I think it was everything. But you could see with your own eyes, an untrained eye could see that the hippocampus got bigger a year and a half later, his cognitive function got better, memory function was better. He was no longer skinny fat, he gained muscle mass and lost body fat around the waist size.

Dr. Richard Isaacson:
The bigger the belly, the smaller the memory center in the brain. He got rid of the belly fat, the memory center in the brain got bigger. Now, this is an anecdotal study and some of the naysayers out there would say, “Oh, stop already, you’re just giving us N of one study.” But no, there’s actual research that shows this too, that exercise increases hippocampal volume. So, if… I think the Holy Grail and the next big study that we do, and it’s going to have to be multi site, and we were just starting to work on this before COVID and then COVID really mess things up and obviously for the world, but also for Alzheimer’s disease research. Our goal is to do… What we’re trying to plan is more of a telehealth telemedicine study where doctors can take care of people at risk for Alzheimer’s and we can do a lot through telemedicine so we can break down barriers, keep the cost low.

Dr. Richard Isaacson:
But then get blood tests, get amyloid at baseline, get amyloid at follow up, maybe get MRIs at baseline, MRIs at follow up and basically try to enroll people from all over the place rather than just one site because we were the main site that enrolled it in New York. We’re going to basically try to prove this time that not only are we improving symptoms, are we slowing decline, but I would love to be able to shout off the mountaintops that we were able to reverse Alzheimer’s disease and prevent it from a neuropathological perspective. And if we have those data, I really believe that the naysayers aren’t going to have any tomatoes to throw because it’s proven.

Dr. Mark Hyman:
Well, it’s not only about the naysayers, it’s about all the people suffering to have finally hope. People with cancer have hope. People with heart disease have hope. People with diabetes have hope. People with Alzheimer’s, it’s like, “Oh, wow, it’s like dropping a nuclear bomb on somebody.”

Dr. Richard Isaacson:
Yeah.

Dr. Mark Hyman:
And it’s kind of the worst diagnosis you can possibly get because you lose yourself. You could be in bed with cancer and waste away to nothing but your soul and your brain, who you are is still there. And that’s the hardest part about this disease and its impact on families and caregivers. And you experienced that, I’ve experienced that. It’s just devastating. And it’s scary how much it’s increasing. I think, am I correct to say that it’s not just because the population is growing, but the actual incidence per capita is growing. Is that true?

Dr. Richard Isaacson:
So again, it depends on how you slice the data. But we have an aging population, age is the number one risk factor for Alzheimer’s. I do think that some data actually show that in areas where blood pressure and diabetes is being under somewhat better control, maybe the incidence is coming down a little bit, but the data are what the data are, but what I would say is we have the power to make changes in our lifestyles today, we have the power to have conversations with our doctors today. Even for example, vascular risk factors, high blood pressure, high cholesterol, diabetes, these are things that fast forward Alzheimer’s disease, pathology, we can say it pathology as well as Alzheimer’s disease, but also cognitive decline.

Dr. Richard Isaacson:
Diabetes doubles your risk of having Alzheimer’s disease. When it comes to blood pressure, this is just… I actually really want to share this because if your listeners take home one thing from this podcast, hopefully it’s that they’re not powerless. But if they take on two or three things, I hope that they take home the fact that everyone should know their blood pressure, everyone should know their waist circumference. Everyone should know their body fat. Everyone should know these numbers. Yes, this is a lot to track, but these are things that are not expensive to track. Anyone can go to their doctor’s office or go to the pharmacy and check their blood pressure. And anyone can buy a scale at home that has a body fat metric. And yes, it’s a couple 100 bucks, but it’s a really good investment.

Dr. Mark Hyman:
It’s a ballpark one, it’s not-

Dr. Richard Isaacson:
Exactly, they’re not perfect, right. And there’s gold standard ones that-

Dr. Mark Hyman:
It doesn’t tell you where the fat is, if it in your butt or your stomach-

Dr. Richard Isaacson:
Correct. Actually anyone for no cost can measure their waist circumference. And if their waist circumference is more than an inch or so greater than it was in their early 20s during high school and college, that probably means that there’s a problem. So, that’s actually the poor man’s way to do it. And we talk about this-

Dr. Mark Hyman:
I think you actually have to pay for the tape measure. I have a cheaper one. It’s called the mirror test. You look in the mirror, jump up and down. And if your stomach jiggles, then you probably have a problem.

Dr. Richard Isaacson:
Great. You’re hired. That’s a great test. When it comes to blood pressure, this is something that people remember because blood pressure is just so important. The Sprint Mind study published a couple years ago showed that people that had a blood pressure in the 140s over 80s which back then was considered as normal, right?

Dr. Mark Hyman:
Normal.

Dr. Richard Isaacson:
That’s completely not normal. But that’s a different discussion. Topic for another day. But this whole concept of normal versus optimal versus, what 50% of the population has, there’s a big difference. When we’re talking preventative health, we want to go up most. So when it comes to blood pressure, people in a randomized study, they were randomized to 140s over 80s, or 120s over 70s or below, okay? In just three years, they stopped the study early. In just three years of tighter blood pressure control, which is 120s over 70s, but goal was below that, people were able to reduce their chances of developing the earliest phases of symptoms related to dementia by almost 20%. In three years, just by lowering blood pressure by 20 on the systolic, the top number and 10 on the diastolic. When you add the blood pressure control, plus the nutrition changes, plus the exercise, plus the other stuff and the vitamins and the… Once you add all these different things, this is when we can really put a damper on.

Dr. Richard Isaacson:
And listen, if we have again, I’m sorry to keep pandering to the naysayers out there. But if there are people that don’t believe, if you can even delay Alzheimer’s, delay it from happening by a year, two years, three years or five years. And in that timeframe, a blockbuster drug comes, okay, great, that drug comes. Well, great, then that person prevented their own Alzheimer’s. If we can delay it longer than that, unfortunately if they pass from something else, then at least they lived a better quality of life, and they never got Alzheimer’s. So whether you talk about prevention, or delay or reversal or symptom, let’s not get caught up in the semantics, let’s just all unite and say there are things that we can do today to improve our brain health tomorrow. And it’s things that are tangible and available for everyone.

Dr. Mark Hyman:
Well, if anybody’s listening is got a foundation is a billionaire, has some… Is somebody from the government or the NIH, or anybody listening to this? IF what the two of us are saying Dr. Isaacson’s research is on the right track, how could we not put our resources toward that? How can we not focus on that instead of spending another billion dollars on other drugs study that’s going nowhere, because there’s a really simple rule in functional medicine, which is if you’re standing on a tack, it takes a lot of [inaudible 00:57:30] to make it feel better. And the second rule is, if you’re standing on two tacks, taking one out doesn’t make you 50% better, you’ve got to deal with all the factors. You can’t just say, we’re going to study food, or we’re going to study exercise, or we’re going to study vitamin D, or fish oil, or a flavonoids, or blah, blah, blah, we’ve got to really look holistically at how do we optimize health.

Dr. Mark Hyman:
And you said something that is also a little bit of heresy. Because in medicine, when your lab tests are in the normal range, your normal, the doctor goes, you’re fine. But what you’re talking about is treating to a standard that’s beyond normal, that’s optimal. So if your homocysteine is 13, it’s considered normal on most lab tests. If you look at the data, if your homocysteine is 14 and above, your risk of Alzheimer’s is 50% higher than the average population. So Should your homocysteine be 13 or 12, or 11, or 10? Maybe it’s six or eight. And how do you treat to that metric? And I think that’s what really we do in functional medicine. Is how do we create optimal function? People, what is function medicine? It’s pretty simple. It’s learning how to create health through optimizing function. And every aspect in all the areas of the body that are off balance and that’s essentially what your work has done.

Dr. Mark Hyman:
And it’s really so groundbreaking. And I know you might sometimes feel like a lonely warrior out there with arrows in your back and a bunch of bumps on your head and struggling, but I encourage you to continue because you are on the right track. And folks like you and Dale Bredesen who’s definitely got a lot of flack, you’ve shown that there is a possibility that this is not a disease that we can tackle that we can learn more about that we can’t actually have an impact on, and have hope for, because that’s the worst part. It’s just this devastating lack of hope. And I’m actually excited when I get to see a patient who’s got cognitive impairment because I know there’s stuff we can do. And I would say, sometimes I see miracles, sometimes I try everything I know how to do and it doesn’t work and I don’t know why. But we’re learning. We’re learning and it’s a really exciting moment in medicine, exciting moment in science, exciting moment in neuro, endo, cardio, immuno, gastro ology.

Dr. Richard Isaacson:
Preventative. Well, Mark, I really appreciate that. It’s striking to me that with the billions and billions of dollars invested in this field, our study that we published… Again, I was psyched it made the Wall Street Journal, but it didn’t make the first page. So you’re right, you’re right. Alzheimer’s is the most costly disease to our society. It is easily one of the most challenging, just sad, damaging, just obliterating the terrible disease. And you’re right, maybe that study should have made the front page. I want you to know that that study was funded barely between 10 and $12 million for a five year study. That’s it. Which is… $10 million is not a trivial amount of money. But it’s… This was paradigm shifting, this was a study that actually moved the needle and truly moved things forward. So, if there is someone out there, I’m not selling anything, I do have a book, but I just … I’m not trying to sell a book, I’d rather you help our research.

Dr. Richard Isaacson:
I’m an academic medicine, I still have student loans. I live in a very small apartment. In academics, I don’t make a lot of money. So if there’s somebody out there that wants to do something to help, please, we will make good use of the funds. I can give you a link. May I share the link?

Dr. Mark Hyman:
What is the link? We’ll put it in the show notes. What is the link?

Dr. Richard Isaacson:
Sure. So, it’s an amazing opportunity because I just started a new position at Florida Atlantic University. I have an entire building that I can use. I have equipment, I have… Now would be the time where a gift or support to our program could literally just fast forward progress. So the link, I’m going to give you the link. It’s F-A-U-F, Florida Atlantic University Foundation, fauf.fau.edu\alzp Alzheimer’s prevention. fauf.fau.edu\alzp. Sorry for the word salad, but if you remember that, it means that your brain is working pretty good.

Dr. Mark Hyman:
That’s okay. We’re going to put it in the show notes don’t worry.

Dr. Richard Isaacson:
Thanks a lot.

Dr. Mark Hyman:
This is amazing. And who else is doing this around the world? Because there are other people also. And we’ve got the pointer study that was being done, the finger study that was done. There’s people in Europe. Who else is on this?

Dr. Richard Isaacson:
Yeah. So, in Europe, I think Europe’s just a little bit more ahead in some ways. They have something called EPAD, the European prevention of Alzheimer’s Disease kind of program and they’re doing something pretty good. I have collaborators throughout the country that I work with. I’m the one talking to you today, but we had 31 collaborators that we worked with on that research study, we had a satellite program in Puerto Rico, we have collaborators in LA. There’s just the fact that there’s only a handful of people that are focusing that if someone wants to go to a doctor for Alzheimer’s prevention, Parkinson’s prevention, Lewy body, dementia prevention, we just started before I left Cornell Parkinson’s Disease Prevention clinic, we’ll be starting one in Florida soon, next year. But I think the fact that we’re only having like less than a dozen people focusing on the area of Alzheimer’s and neurodegenerative disease prevention, there should be one of these programs and centers on every corner in every community, because if someone wants to talk to a doctor about how they can protect their brain health and be proactive, they should have every right to do that.

Dr. Richard Isaacson:
And so while we do have a handful of people that are doing this we don’t have enough. I literally have trained 45 or more people. I’ve been asked to consult for different programs in Canada, in New York, in Australia, three different programs in Australia. But we just don’t have I would say the funding and the infrastructure to really make all these programs be able to talk to each other on a regular basis. And we just haven’t had enough support yet. And I think-

Dr. Mark Hyman:
Well, it’s coming [crosstalk 01:03:56]. It’s coming. It’s paradigm shifting. And I just congratulate you. And I like to sort of close by having you share a story or two, and I’d like to share one and just give people hope, and talk about what we’ve learned. And yes, it’s an anecdote. But I think what’s happening and even the NIH has now recognized and funding what we call NM1 studies, which is essentially looking at a person before and after treatment in a very sophisticated way that helps to validate the science about the change in their biology. And so to me, it’s relevant. And in fact, that’s how all good discoveries happen is through clinical observations and then extrapolating those and studying them and proving them. So tell us about your, a few cases or one case that you’d like to share.

Dr. Richard Isaacson:
Oh, boy. It’s a beautiful thing that there are so many that I can’t even think of just one. But I guess what I would say is, after COVID, COVID hurt us a lot because we were in-person, we did the blood draws, we did the cognitive testing. And then when COVID hit, we had to recalibrate. And what we did was we basically put everything online, and now we do the cognitive assessments online, we can get the blood draws remotely. So if someone lives out of town, a third of our patients don’t… Prior patients didn’t even live in the state we were in. So, we’ve moved to telemedicine, we’ve moved to remote care.

Dr. Richard Isaacson:
And I guess what I would say is it also allowed us to take a deeper dive and some things like genetics, and what we’ve done over the last year is when we truly have the resources, and time to go deep, and not just as deep as you and I usually go but go as deep as whole genome sequencing, look at mitochondrial haplogroup and look at pollygenic risk scores, having a neurogeneticist, a PhD in Alzheimer’s precision medicine. For a year and a half, we went-

Dr. Mark Hyman:
Now you’re talking baby.

Dr. Richard Isaacson:
Oh, oh, oh. I got to share with you some of this stuff. And we went deep on 17 patients and six of their family members. Now, remember, we spent a year and a half on 17 patients and six family members, which is not, that’s not feasible in the normal thing. But what I can tell you is what we’ve learned in the last year and a half. No, I have no publications yet on this. I have a draft manuscript on my desktop. I have Excel spreadsheets open on my desktop as we speak. At some point, I hope in the next year to year and a half, we’re going to publish a paper that has really I think, this will be my best or maybe second best contribution to science. Because there’s there’s a patient in his early 50s. Okay. So this is I guess, where it comes down to. So, patient’s in his early 50s, this is the first patient we ever did this on. He’s early 50s. And he’s a young child. A couple years old.

Dr. Richard Isaacson:
And he was diagnosed with Alzheimer’s disease, was diagnosed with mild cognitive impairment due to Alzheimer’s. And he’s in his early 50s. And he just had a child. Finally, he waited all this time, and he has a child. We went as deep as any person science, clinic research program could have possibly gone. And we found something in his genetics that explained, he’s had high cholesterol since his 20s and 30s. And his father passed away earlier as well. And we found the reason why he had high cholesterol. So he had been on a variety of different drugs, he was prescribed, go eat a healthy diet, go exercise on a regular basis, that’s what he was recommended. There was no precision, there was no details. What we did for him is we literally told him to do everything. He was insulin resistant. He didn’t know it. His belly fat wasn’t a big deal, but it was there.

Dr. Richard Isaacson:
He literally did every single thing we told him to do, we changed one of his drugs. Now again, this is one of the drugs we did use because of a genetic thing we found in his DNA. We added the drug, we changed, we took him off more drugs… Actually, he’s on less drugs now than he was. We added some supplements and vitamins. We changed his entire framework. He doesn’t eat breakfast anymore. He skips breakfast, and he feels great. And he’s lost a lot of weight. It’s not just about what you eat, it’s about when you eat it. It’s not just about how much time you exercise. It’s about what you do and how you structure it. So we put him on an exceptionally detailed plan. He’s no longer having mild cognitive impairment. He still has preclinical Alzheimer’s, he still has amyloid in his brain as far as I know. But he has no symptoms.

Dr. Mark Hyman:
Yeah.

Dr. Richard Isaacson:
He is functioning normally. He’s now to the point where he decided to have another child, when prior to meeting us, he decided that he was probably going to retire early. We just created life by prolonging someone’s brain health. And we have so many babies that have come out of the Alzheimer’s prevention clinic because women are coming to see us for brain health, but then they create light. And I guess what I would say is that we can really help people. And when you empower people to feel better, and they go on living their life, and you break the fear and you break the stigma. I had a young woman that said, “Well, I don’t want to give… Look what I’m going through with my mom, I don’t want to have a child. I don’t want to do this to someone. I don’t want to give my child an Alzheimer’s gene.” And when you just have honest conversations and you explain well, actually, that’s not exactly how these genetics work and Alzheimer’s is going to be a different disease for you in five or 10 years for your child. That is the absolute for this thing.

Dr. Richard Isaacson:
So, from whether it’s breaking stigma, education or helping people in real time. I don’t know. I’ve just seen… In some ways, it’s miraculous, but it’s just good, comprehensive clinical care.

Dr. Mark Hyman:
It really is, Richard. And I think that brings to mind a case that I had of a woman who was basically on her way to check out. She was kind of early 80s, had an extraordinary career, ran a massive business, and had Lewy body disease, which is sort of for those who don’t know what it is, it’s a combination of like Parkinson’s and Alzheimer’s, got dementia with motor symptoms. So she was in a wheelchair, she couldn’t walk, she came to my office, three people had to pick her up to put her on the scale to stand. And I said, “Let’s look at everything. Let’s get a map of what’s happening with your biology.” And we found she had type two diabetes, her A1C was nine, okay? And wasn’t really treated well. She was on Metformin, but her diet was kind of sugar and starchy. She had menopause and there’s some evidence that maybe hormones play a role. She wasn’t sleeping right on Klonopin, which we know affects the brain adversely.

Dr. Mark Hyman:
She had kind of marginal thyroid function, her TSH was 6.7, ideal should be one or two, right? It’s not the worst, but it’s not optimal. She also had terrible gut. She had severe constipation her whole life, laxatives forever, enemas every day. And we looked at her gut, she had very low short chain fatty acids, really bad bacteria gut, leaky gut, dysbiosis. She had rashes all over her. She had some doctor who was giving her steroid shots for energy on a regular basis. And she had, which by the way, shrinks the hippocampus and causes dementia. And she had yeast growing everywhere under her breasts and her butt, it was like a fungal mushroom all over ger body. She was taking acid blockers for years, which Block B12. And then many antibiotics over the years for all kinds of stuff, and she had all these immune issues and mitochondrial dysfunction. And we found also she had really low levels of B12 and high homocysteine and low vitamin D. And so I just kind of treated all that.

Dr. Mark Hyman:
I got her thyroid tuned up, fixed her diabetes, got her more keto diet, gave her the vitamin she needed, B12 shots, gave her an antifungal, fixed her gut. And again, I’m like, “I’ve never had a patient with Lewy body dementia.” I was like, “I’m not a neurologist.” We’re like, “Let’s just try this model of tuning everything up.” And she came back to life. She walks, she’s not on a wheelchair anymore, she is running her business again. And she recorded an album and wrote a book in the year after I treated her. I’m like, “Wow, that just shouldn’t happen.” But when you have even one patient like that, to me, if you have one patient like that in the universe, then the scientific community should go, “Oh, if it’s possible in one is it possible in man?”

Dr. Mark Hyman:
And we direct our resources and our thinking to reimagine research, to reimagine our approach to getting to the root causes of this problem and treating it in a very different way. So you’re a hero to me, I really admire you, Richard, I want to give you… If I was Jeff Bezos, or Elon Musk, I would give you $100 billion right now. At least 10. And I seriously think we are on the verge of a real transformation. And just anybody listening, Richard Isaacson is an extraordinary doctor. He’s not only a humanitarian, and a kind hearted guy, but he’s a brilliant scientist, and the work he’s doing is going to change the face of medicine. So I don’t say this very often on podcast. But if your work could get to the next level that you want it to get to, we see is possible.

Dr. Mark Hyman:
It’s going to create a paradigm shift that’s going to ripple throughout all of medicine, not just around Alzheimer’s, but for everything. Because every disease we treat the same way, whether it’s rheumatoid arthritis or heart disease, or cancer, is all reductionist, and you’re breaking that paradigm. So thank you so much for what you do. And I’m sorry if sound like a fan girl, but I just really love what you’re doing. I’m so grateful you finally agreed to be on my podcast.

Dr. Richard Isaacson:
Mark, I really appreciate the time and it’s been a pleasure. Thank you for helping me and us spread the message far and wide. I just… Just people need to know that there’s things that people can do for their brain health. That the brain is not just organ that’s like tucked away that you can’t have any control over. It’s not the next frontier, we can do it today. And I really appreciate you giving me the time and the platform to share this education.

Dr. Mark Hyman:
Yeah. And we’re going to put in the show notes the links to your recent research papers where you show this was the kind of diet they did. This is the kind of exercise, this is the supplements they took, vitamin D, fish oil, B12 and so on. These are the kind of plant compounds that can be beneficial, this is the kind of sleep therapies we do, the stress reduction therapy. So, it’s all in there for people wanting more granular detail, which I wish we had time to get into today. But I think it’s all there. And your work is out there in the public domain, and everybody’s going to find out how to find more about you in your show notes. And if you’re listening to this and you have the resources, please, please help Richard.

Dr. Richard Isaacson:
And when we’re in process, they should… I’m not sure when the podcast will be live. But pretty soon in a couple of months or less, there’ll be a multi 10 hour everything you need to know about brain health, all the questions you asked, but I had 10 hours to answer them will be live on our website at Florida Atlantic University. So stay tuned for that. We recorded it, now we’re just putting the finishing touches on that. Hopefully-

Dr. Mark Hyman:
So that’s a free consumer course-

Dr. Richard Isaacson:
Totally free.

Dr. Mark Hyman:
… how to take care of your brain?

Dr. Richard Isaacson:
It’s like… Basically they stuck me in front of a teleprompter and there was no teleprompter because there was no words. And I just talked for 12 and a half hours. And they got on a video. So everything that people need to know-

Dr. Mark Hyman:
Amazing.

Dr. Richard Isaacson:
… hopefully came out that day. And that’ll be live on the site free. Totally free available.

Dr. Mark Hyman:
So basically the user’s manual for your brain.

Dr. Richard Isaacson:
I hope it’s well received. I was bleary eyed at the end. And I was not reading off the teleprompter, so I may have been-

Dr. Mark Hyman:
That is hard. That is hard… I’ve done that. It is way harder than you think.

Dr. Richard Isaacson:
Yeah. Now we’re twelve and half.

Dr. Mark Hyman:
Congratulations, Richard. And thanks for being on the podcast. Everybody who’s heard this podcast. I think it’s your moral duty to share with everybody you know, because almost everybody in this country is impacted in some way by this disease. And everybody should hear this message. So please share it. Leave your comments how have you approached this in your family and yourself? Leave a comment we’d love to learn and share it and subscribe wherever you get your podcasts. And we’ll see you next week on the Doctor’s Farmacy.