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Open the Podcasts app and search for The Doctor’s Farmacy. If you’re viewing this site on your phone, you can just tap on the

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Episode 462
The Doctor's Farmacy

Surviving Alzheimer’s: A Functional Medicine Approach To Prevention And Reversal

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If you had thirty-six holes in your roof and only patched three of them, you’d still have a very leaky roof. This is how we have to think about brain health—we need to address all the various insults to create lasting healing.

And despite what the conventional medical model has taught us about cognitive decline and Alzheimer’s, these disorders are actually within our power to reverse, which means tackling all the holes in the roof. Beta-amyloid plaque is not the only issue that needs to be addressed.

There’s no better person to talk to about reducing the risk of cognitive deficits and supporting optimal brain health than today’s guest on The Doctor’s Farmacy, Dr. Dale Bredesen.

This is such an important episode for all of us, considering that global rates of dementia are currently projected to triple by 2050. Dr. Bredesen is providing hope and a new way of looking at the brain, proving with his research that adding in the right inputs while taking out the offenders can actually reverse the devastating symptoms of cognitive decline.

You might be wondering if this is possible even if you have genetic variants that predispose you to Alzheimer’s, and the answer is yes! We discuss the stages of cognitive impairment and the different actions that might be required for those with the severe forms of ApoE4.

Some of the steps Dr. Bredesen has found imperative to healing his patients might seem too good to be true. Eating a high-fiber diet low in simple carbohydrates, intermittent fasting to induce autophagy, and reducing toxic exposure are just some of the accessible but powerful changes we talk about. He shares some truly amazing success stories from his patients, as well as the reasons he’s seen people fail to improve.

It is possible for those who are struggling with cognitive decline to regain brain function and take back their lives. This episode reframes the possibilities of healthy aging; I hope you’ll tune in.

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I hope you enjoyed this conversation as much as I did. Wishing you health and happiness,
Mark Hyman, MD
Mark Hyman, MD

Here are more of the details from our interview (audio):

  1. Why Alzheimer’s is a systems biology disorder that needs to be treated from a Functional Medicine perspective
    (7:13)
  2. Four main drivers of cognitive decline
    (12:01)
  3. The ineffectiveness of seeking just one cause of Alzheimer’s
    (13:05)
  4. Personalizing Alzheimer's treatment and prevention
    (19:42)
  5. The 4 stages of Alzheimer's
    (21:19)
  6. Eating and fasting to prevent, slow, and reverse cognitive decline
    (27:51)
  7. The importance of exercise, sleep, and stress reduction in relation to brain health
    (32:31)
  8. Reversing Alzheimer’s and pre-Alzheimer’s disease
    (39:38)
  9. Patient stories of cognitive improvement after Alzheimer’s diagnosis
    (47:04)
  10. Breaking through the conventional perspective and approach to Alzheimer’s disease
    (54:01)

Guest

 
Mark Hyman, MD

Mark Hyman, MD is the Founder and Director of The UltraWellness Center, the Head of Strategy and Innovation of Cleveland Clinic's Center for Functional Medicine, and a 13-time New York Times Bestselling author.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

 
Dr. Dale Bredesen

Dr. Bredesen is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s disease, and the author of the New York Times bestsellers The End of Alzheimer’s, The End of Alzheimer’s Program, and his latest book The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words. He has held faculty positions at UC San Francisco, UCLA, and the University of California San Diego. He has directed the Program on Aging at the Burnham Institute before coming to the Buck Institute for Research on Aging in 1998 as its founding president and CEO. He is currently a professor at UCLA.

Show Notes

  1. Get a copy of Dr. Bredesen’s book, The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words

Transcript

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

Dr. Dale Bredesen:
For virtually everyone, Alzheimer’s and pre-Alzheimer’s can be reversed.

Dr. Mark Hyman:
Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman and that’s Farmacy with F, a place for conversations that matter. Given the burgeoning epidemic of cognitive problems, particularly Alzheimer’s disease and dementias, this is going to be a very important conversation for anyone who’s suffering. Honestly, so many of us are suffering because not only are individuals getting affected, but dementia and Alzheimer’s affects families terribly.

Dr. Mark Hyman:
So we’re really lucky today to have a colleague of mine, a good friend, an incredible scientist, Dr. Dale Bredesen, a neurologist who has really specialized in neurogenerative diseases like Alzheimer’s, and he’s the author of a number of books, including The End of Alzheimer’s, The End of Alzheimer’s Program, and his latest book, The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words, which is, wait a minute, are there Alzheimer’s survivors? I mean, there’s cancer survivors, there’s heart attack survivors, but we’ve never really heard about Alzheimer’s survivors. If this is real, and it is, then really you need to pay attention.

Dr. Mark Hyman:
Dr. Bredesen has been a faculty at UCSF in California, UCLA, UCSD in San Diego. He’s directed a program on aging at the Burnham Institute before coming at the Buck Institute for research on aging in 1998 as its founding president, CEO. He’s currently a professor at UCLA. Welcome, Dale.

Dr. Dale Bredesen:
Great to see you, Mark. Thanks so much.

Dr. Mark Hyman:
Okay. So we’ve talked about this before in the podcast, but I really want to get into the details of what we’re doing using this new approach of precision medicine, functional medicine, whatever you want to call it, to not only slow, stop, but potentially even reverse the symptoms and the disease itself, which is staggering because most of the things we’ve done really haven’t worked. So it’s really one of the most significant global threats we face. It’s the most expensive disease in America, believe it or not, because of all this collateral damage that it causes. It affects so many people worldwide, and the increase in the rates of Alzheimer’s are staggering.

Dr. Mark Hyman:
I think there’s going to be 14 million people with Alzheimer’s in this country by 2050, maybe more, and so many people have pre-Alzheimer’s, which you’re going to talk about that, maybe tens and tens of millions. We are taught by mainstream medicine that it really can’t be prevented, that it’s really untreatable, it’s progressive, and that if you’re lucky, you’d live three to 11 years, but it’s pretty much hell.

Dr. Mark Hyman:
So how is your work challenging this orthodoxy and, and tell us about why you got into this and how it really is changing how we think about an approach to neurocognitive and degenerative disorders?

Dr. Dale Bredesen:
Yeah. That’s a great point, Mark. Just for perspective as you indicated, it’s so common. So nearly 100 times as many as have died from COVID-19 in the United States, we have over 700,000 now, will die from Alzheimer’s, somewhere around of the currently living Americans, somewhere around 45 million Americans, so many, many times the pandemic, unfortunately. It is a huge problem. I got into it for exactly the reason you mentioned because there hasn’t been anything to do with these neurodegenerative diseases. They are the area of greatest biomedical therapeutic failure.

Dr. Dale Bredesen:
30 years in the lab, we looked at all sorts of molecular species. We looked at networks, what is actually driving the loss of the synapsis and the loss of the cells. To make a 30-year story very short, what we found is that this is, when you get to the core of Alzheimer’s, it is fundamentally a network insufficiency. In other words, just as you would have scurvy, if you didn’t have enough vitamin C, if you don’t have enough support for this neuroplasticity network, and that includes dozens and dozens of different things from hormones to trophic factors, to nutrients, to oxygenation, to mitochondrial function, as you know, it is a perfect disease for functional medicine because when you look at it, there are all these things that contribute.

Dr. Dale Bredesen:
So unfortunately, all of the scientists had been going after, “Let’s get that one molecular species. Let’s get the misfolded protein. No, let’s get the amyloid. Let’s get the tau. Let’s get the prions. Let’s get the herpes,” whatever.

Dr. Mark Hyman:
It’s all reductionist. It’s all reductionist.

Dr. Dale Bredesen:
Exactly. So you really have to look at this as a systems biology disorder and treat it with functional medicine. When you go after all those things, you not only see people prevent the decline, but they also absolutely reverse the decline. Now, it’s harder and harder the longer and longer you wait, of course, but we see tremendous reversals. As you know, we have a pre-print on a trial where 84% of people actually improved their scores, which is unprecedented. Now, we’ve just published another followup on 225 people, who also improved their scores and improved their metabolic status as well. So we’re very excited about this approach.

Dr. Mark Hyman:
So I just don’t want to just gloss over what you just said because you said that 84% of people on this trial that you did improved their cognitive scores.

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
That’s incredible because that just is impossible given our current approach. So to me, this is something that should have billions of dollars, some NIH funding to look at as opposed to all the ways we have been looking at it, which is looking at the reductionist approach of looking for the single drug to affect a single pathway. This is a multi-system disorder. The beautiful part about your work, Dale, is you’ve really gone into the details of all the things that affect the brain.

Dr. Mark Hyman:
So the brain is, as we learned, we went to medical school, we learned that, basically, there’s this blood brain barrier and then basically, it’s an isolated system above the neck, which is just nonsense. We know that everything that affects the body affects the brain, and vice-versa, but also, we have to really understand how do we leverage those things.

Dr. Mark Hyman:
In your work, you talk about three key, major things that are causing problems that may need to be addressed. One is insulin resistance, one is inflammation, and one is lack of what we call trophic factors, which are things that help the brain grow and work. So can you talk about from a big picture perspective, then we’ll get into details of actually what is causing these three things because these three things are driving all these other pathways, and there are many, many ways to get problems within some resistance or inflammation or lack of trophic factors, but can you just talk about these three things in general and how they affect the brain?

Dr. Dale Bredesen:
It’s a great point. Really, we have to flip, completely flip the way we think about this disease because as you know, it has been thought about as, “Why did you make this bad amyloid? The amyloid is bad for your brain. We just have to get rid of it.” That’s not the way this disease works. As I mentioned, it’s an insufficiency. So what’s happening is your brain is under attack, just as you indicated. This is a systems problem. This is a whole body problem, and it is under attack.

Dr. Dale Bredesen:
As you mentioned, inflammation. Any sorts of pathogens or leaky gut or chronic sinusitis or poor dentition, any of those things, will give you this ongoing inflammatory process and anything that does that will make your body respond by creating amyloid because the amyloid is actually an antimicrobial agent. So you are literally responding to these insults by making this stuff that is great for killing the bacteria, the spirochetes, the fungi, the viruses, but also is damaging your mitochondria just as we hear from a number of antibiotics.

Dr. Dale Bredesen:
So what’s happening now is your brain literally switches to a downsizing protective mode. Your brain is going from a mode of functioning, making synapsis, keeping synapsis to, “Uh-oh, I’m under attack. I’m going to go into a protective downsizing mode,” just as the world did with COVID-19. It went into a downsizing mode, protective mode. Same idea.

Dr. Dale Bredesen:
As you indicated, it’s really four big areas. So it’s anything with inflammation, toxins. So as you have talked about many times, these toxins, whether they be inorganics, organics or biotoxins, are absolutely crucial for that downsizing. Your brain responds by downsizing once again. The third area is energetics and that’s oxygenation, blood flow, mitochondria, and ketones, the ability to have a substrate to burn. Then the fourth area, as you indicated, trophic factors, things like insulin resistance, critical, loss of estradiol, loss of testosterone, loss of nutrients like vitamin D, loss of NGF or BDNF, brain-derived neurotrophic factor. These are all critical for keeping your brain functioning optimally. So you can literally write an equation and see where the brain is for each of these people when they are having cognitive decline.

Dr. Mark Hyman:
Yeah. It’s so important because the things that you looked at were so different than a traditional neurologist, right? I mean, in the study that you just preliminary published, called Precision Medicine Approach to Alzheimer’s: Successful Proof-of-Concept Trials, this is a pre-print publication, should be published and peer reviewed, it’s not yet, but it was very interesting to read about the design of the study, the things that you looked at, and how you address them, which is quite different than the traditional medicine, right?

Dr. Mark Hyman:
I’d love to go through some the details about how we start to look at these things because it wasn’t one thing. You looked at genetics, you looked at biochemical markers, you looked at MRI and brain imaging, you looked at infections, you looked at all so many different things.

Dr. Mark Hyman:
So can you walk us through because I think what many people need to understand is that if you just do one thing, it’s not necessarily going to work. You have to look at all the factors, and you always say, “If your roof has 36 holes in it, if you patch three of them, it’s still going to rain inside your house. So you got to deal with all the holes,” and essentially, that’s the approach, and then people go, “How do you know it works? How do you know it’s working? Is it this or that?” In a way, you need everything.

Dr. Mark Hyman:
If you want to grow a plant, you can’t just have sunlight, but no soil or water or you can’t just have water, but no sunlight and soil. You need all. So I think that’s a disruptive idea in traditional medicine, which is we have to use multisystem approaches for multiple factors that are being addressed at the same time. So can you walk us through at the kinds of things we look at on the diagnostics?

Dr. Dale Bredesen:
Yeah, of course. You have been pioneering this for many years. You and Jeffrey Bland and others have been pioneering this approach where you say, “Okay. We’re literally …” I mean, interesting to me. This is an inflection point in the history of medicine. Up until when you guys got going with functional medicine, everything was about, “Okay. We’re going to find that one thing. We’re going to write a prescription. We’re going to find that one thing and, hopefully, things will be a little better,” and that works great for pneumococcal pneumonia.

Dr. Dale Bredesen:
Now, for these complex chronic illnesses, and neurodegenerative illnesses are probably the best example, but, of course, cardiovascular disease, osteoporosis, so many others. Now, instead of just finding that one thing, you have to go from the other direction, ask what are all of the things that are failing in that network, in that system. Of course, what’s interesting is this turns, again, completely backward, the way we do these trials. All previous trials, you decide ahead.

Dr. Dale Bredesen:
I mean, isn’t this crazy, you decide ahead of time what you’re going to do to treat it. When someone comes in with cognitive decline, we’re going to give them drug X. Well, we don’t want to decide ahead of time. We want to look to see why did they have cognitive decline, and then we want to go after those things.

Dr. Dale Bredesen:
So as you indicated, yes, we look at their genetics. We look for example, are they APOE4 positive or negative? There’s a whole other set. There are dozens and dozens of genes that play on this, but as you’ve indicated before, these are not your fate. They simply increase your risk.

Dr. Dale Bredesen:
We look at that, and then we look at their hormonal status, their nutritional status, their gut status. We look at their status of all, all of the inflammagens. We look at their oral microbiome. We look to see whether they have chronic sinusitis. Do they have a leaky gut? What is their gut microbiome status? All of these different players, and then, of course, we look at, do they have mycotoxin exposure? Do they have organic-

Dr. Mark Hyman:
Molds. That’s from molds, right? Yeah.

Dr. Dale Bredesen:
Molds and mold-related toxins. Of course, many people have been exposed to air pollution. That’s another big one now that currently has been shown to increase risk for cognitive decline. So we look at all of these different features. The good news is we know from the research, what is that set of things that tend to cause cognitive decline? It’s not an infinite set. It’s a set of dozens and dozens of things.

Dr. Dale Bredesen:
So we want to look at all of those things and the diagnosis, if it’s Alzheimer’s or if it’s Parkinson’s or something else, tells you, “Here are the things that are likely to be causing those”

Dr. Dale Bredesen:
So, for example, in Parkinson’s, it’s more likely to be organic toxins like TCE, but in Alzheimer’s, it’s more likely to be things like mycotoxins or reduced vitamin D or reduced hormonal support or NGF or BDNF, things like that.

Dr. Dale Bredesen:
So then we address those things with a functional medicine approach, and the results are unprecedented. As we indicated, probably most important in the paper, not only did their cognitive scores clearly improved, but their MRIs actually improved. There’s a long history of following MRIs in patients with cognitive decline. On average, if you have cognitive decline, your gray matter volume shrinks each year by about four and a half percent.

Dr. Dale Bredesen:
If you are a normal person and you’re actually doing quite well, you still have a slight shrinkage, about 1.7%. These people, actually, their gray matter volume actually went up. It actually got higher instead of going down. So they did even better, even though they had Alzheimer’s or pre-Alzheimer’s, they actually did better than a normal person at that age.

Dr. Mark Hyman:
Wait, wait. So what you’re saying is, in general, everybody’s brain declines, Alzheimer’s declines more. The average person declines a little bit. What you’re saying is people with already damaged brains, not only didn’t decline, but they got better, that they improved the size and function of their brain.

Dr. Dale Bredesen:
Absolutely. That’s exactly what we reported in that paper.

Dr. Mark Hyman:
That’s like discovering penicillin, right? I mean, this is a big deal.

Dr. Dale Bredesen:
Yeah. You and I both know there’s a long way to go still. We’ve had a few people with cognitive scores, MoCAs of zero, improved, but the majority of the people at the end stage don’t. So we need to understand, continue to develop this to understand what do we do with the people who are farther along, how do we make it so that every single person gets better.

Dr. Dale Bredesen:
Now, one other good thing that came out of this paper, 84% of the people improved, but the 16% who got worse, we actually looked at, “Okay. Why?”

Dr. Mark Hyman:
Why?

Dr. Dale Bredesen:
You could see in some of these people. So there was an example, one woman who had high mycotoxins in her home, in her urine. We said, “Okay. You got to get out of there. You got to remediate this.”

Dr. Dale Bredesen:
She said, “I’m not leaving my house. I’m not remediating it.”

Dr. Dale Bredesen:
Of course, part of the problem was that part of this was carried out during the pandemic. So when we started, the pandemic hadn’t started yet, but as we were going through the trial, the pandemic hit and people didn’t want to go out and they didn’t want to do some of the things that they would normally do. So they unfortunately had increased exposure to mycotoxins. So no surprise, she did not get better.

Dr. Mark Hyman:
Wow. So basically, what you do with these patients is you do a personalized approach, which is looking at all the variables that we talked about, just to recap a little bit. You really look at specific genetics around the APOE4, which is really the Alzheimer’s gene, but it doesn’t make sure you’re going to get it, just predispose you to it. You look at factors around detoxification and how we get rid of toxins. You look at our methylation, which is about B vitamins, and then you also look at the whole insulin resistance package because a lot of times doctors don’t look at insulin. They just measure your cholesterol or your blood sugar, your A1C, but that’s not enough. There’s ways to really look deeply at what’s going on there. We look at cardiovascular risk, inflammation, CRP, homocystine. You look at all the other factors around infections like herpes and Epstein-Barr, tick infections. You look at the gut, see what’s going on in there. Is there imbalances in the flora? All the hormones you mentioned, estrogen, progesterone, pregnenolone, DHA, testosterone, all these hormones are really important, thyroid.

Dr. Mark Hyman:
You look at all your nutritional status, the B vitamins, vitamin D, vitamin E, magnesium, zinc, copper, CoQ10, lipoic acid, omega-3s. You look at all the toxins, metals, organic pollutants like pesticides, biotoxins, mold toxins, you mentioned, and all the autoimmune markers, and immune function, and sleep studies and all these things that look at how you actually see what’s going on. So you’re basically taking a soil sample of everything going on in the body that may affect the brain, and then you see what’s out of balance and then you tune it up. So you’re really not treating the Alzheimer’s. You’re just helping people get healthy and clearing out all the stuff that’s bad for them and putting in the stuff that’s good for them.

Dr. Dale Bredesen:
Absolutely. We’re looking at all the things that are driving this. Mark, I think it’s really critical for people to understand. Doctors have been trying to treat Alzheimer’s after it’s been there for 20 years. So there are four stages. If we could get to everybody in the first two instead of the fourth one, and by the way, in this trial, we did people in the third and early fourth stages. So they were still very far along, but the reality is you go through a period where you are asymptomatic, but you already have abnormal spinal fluid and abnormal PET scans.

Dr. Dale Bredesen:
Then you go through what’s called SCI, subjective cognitive impairment, which lasts about 10 years. So we have a tremendous window, and those people, 100% of them, reverse and do beautifully, but rarely do people come in during that time because they know there’s something wrong, their spouse has often noticed, but they say, “Well, I’m not that bad yet. I’ll wait.”

Dr. Mark Hyman:
Yeah, yeah, yeah. Don’t wait.

Dr. Dale Bredesen:
Then the third thing is called mild cognitive impairment. It should be called relatively advanced Alzheimer’s disease. It’s the third of four stages. If people would simply recognize that, not wait till then, everyone could do better. Then it’s the fourth and final stage that we actually call Alzheimer’s disease.

Dr. Dale Bredesen:
So again, calling something mild cognitive impairment is like saying you have mildly metastatic cancer. It’s a late stage of the problem, and we’d like to get to people earlier and earlier.

Dr. Dale Bredesen:
So as you indicated, we look at all these different things, and what we’re saying really is that, yes, that’s what Alzheimer’s is. It is your brain’s attempt to deal with these ongoing insults by producing a substance, amyloid, and the other downstream molecules like phospho-TAL that actually fights the insults. It fights the infections, the things coming to oral microbiome, things like P-gingivalis, the neuropathologists find in the brains of patients with Alzheimer’s disease. Various mold and fungal species they find in the brains of patients with Alzheimer’s disease. Herpes simplex, of course, from the lip, we find in the brains of patients with Alzheimer’s disease. So this is a recurrent situation with these various pathogens and with the brain’s response to these pathogens.

Dr. Mark Hyman:
Yeah. So you’re basically taking all this understanding of the things that do affect the brain, and then you create a therapeutic plan that addresses it on an individual level. I remember this article years ago called Shifting Thinking and Dementia in the Journal of the American Medical Association. There was this great line in there where the author said there’s basically categorical misclassification and etiologic imprecision.” That means that we categorize people according to symptoms, you lost your memory, not according to the etiology or cause.

Dr. Mark Hyman:
This flips it upside down and is focus on medicine by cause not by symptom. That’s what you’re doing. So everybody doesn’t get the same plan. If someone has mold, they get that treated. If someone has diabetes, they get that treated. If someone has a toxin, they get that treated. If someone’s nutritionally efficient in this particular nutrient or that, that gets treated. So it’s very individualized. So you’re not just throwing the same treatment in everybody.

Dr. Mark Hyman:
So tell us about high level. There’s the foundational pieces and then there’s the more therapeutic pieces. So there’s diet, exercise, sleep, and stress management, and brain training, which are the foundation. Talk about what are the specific kinds of dietary strategies, exercise strategies, and the sleep strategies that you’re using to help these patients because there’s some really foundational research on how these things affect the brain and, of course, stress and then brain exercise or brainercise, which is brain training.

Dr. Dale Bredesen:
Yeah. It’s a great point. So as you know, when we were in the lab, this is way back in 2007, this guy named Mark Hyman wrote a book about, “Hey, you should be treating these brain diseases with these multi-factorial approaches.” The interesting thing to me-

Dr. Mark Hyman:
I wouldn’t listen to anything that guy says, by the way.

Dr. Dale Bredesen:
So the interesting thing to me is what we found in the test tube over 30 years fits beautifully with what you published back in 2007. So what we’re seeing is very much the same thing. As you indicated, the great news here is, whereas we’ve always been told there’s absolutely nothing you can do to prevent reverse or delay cognitive decline, and we hear this again and again and again, in fact, the arsenal is huge. We have a huge armamentarium.

Dr. Dale Bredesen:
Yes, it’s diet, exercise, sleep, stress, brain training, supplementation, and detoxification as the beginning, and then beyond that, there may be other things that are dependent on what we find, but those are the basics. As you indicated, you start with nutrition that probably of all the things is the most important in terms of getting a good output of getting a good outcome.

Dr. Dale Bredesen:
So if you look at, again, we’re coming this from the biochemical side, if you look at what is the biochemistry that it takes to make you start making synapses again and reforming those and start making your synapses work again, there are several features to it. So number one, you have to get the appropriate energy delivery. So what happens is you have both the ability to burn ketones, the ability to burn glucose. Well, when you have cognitive decline, you’ve lost both of those. So you are literally starving your brain. You’ve lost the glucose because you now have insulin resistance. You’ve lost the ketones because your insulin is high and it’s preventing you from making the ketones.

Dr. Dale Bredesen:
So you need to get those both back. You need to become keto-adapted and you need to get to ketosis, but you need to become metabolically flexible and be able to go back and forth between burning. So getting people to do that is a critical piece of this. Then it’s a plant-rich, low-carb, essentially zero simple carbs, mild-

Dr. Mark Hyman:
No sugar and starch. No sugar and starch.

Dr. Dale Bredesen:
Exactly, mildly ketogenic diet. We encourage people to measure their ketones, whether you like to do it by finger stick or you can do it by breathalyzer to get in the appropriate ketone range. Have appropriate time for autophagy and figure glymphatics to act. In other words, appropriate time for sleep and appropriate time. Yeah. So we want to-

Dr. Mark Hyman:
So tell us about auto and the fasting because that’s really important too, right?

Dr. Dale Bredesen:
Yeah. Critical. So autophagy, you’re basically recycling components of your brain that are damaged, including things like mitochondria that aren’t working so well. In fact, there was a beautiful experiment a few years ago in which just preventing the autophagy of mitochondria, that alone led to Parkinson’s and this is in animal models, of course, but it shows how critical it is to get rid of the old batteries and make the new batteries. So this is a critical piece.

Dr. Dale Bredesen:
So yes, we want to get people to have autophagy, which we do 12 to 16 hours of fasting at night. If you’re APOE4 positive, we’d like to see it more 14 to 16. If you’re APOE4 negative, 12 to 14 is probably good enough. Then you could, again, measure your ketones, and then it should be, as I say, plant-rich. You’ve got to have the phytonutrients, but you’ve also got to have it so that you have a high-fiber diet.

Dr. Dale Bredesen:
It turns out this is critical. This improves your glucose loads, as you know. It improves glycotoxicity. It improves your lipid status. It improves your gut microbiome. It helps with detox. So surprisingly, high-fiber diets, important for a number of reasons and really critical.

Dr. Dale Bredesen:
So that’s the combination. We call this KetoFlex 12/3, but you can do it any way you like as long as the bottom line is you improve those parameters. That gets you the best outcome in cognitive decline, restoring that insulin sensitivity, restoring the metabolic flexibility, getting the phytonutrients, helping with the detox, optimizing your gut microbiome. As you know, lots of studies showing relationship between gut microbiome and brain function.

Dr. Mark Hyman:
So important. I think that the idea of the brain having type three diabetes is an interesting concept that scientists have revealed from Brown University. I think that it is what we’re seeing. So you don’t get fat in the brain, you get Alzheimer’s, and that’s what it looks like. So cutting out the starch and the sugar, you get people off gluten, dairy often, and then you get them on high quality protein, low-toxin, fish, pastured eggs, pastured meats, grass-fed meats, lots of organic produce, plant-rich, very important. The diet is so important.

Dr. Mark Hyman:
I remember I had a patient who I treated with Alzheimer’s for a while. She did really quite well, and then she relapsed because she’s had a stress event in her life. I put her on a ketogenic diet and she had a chef. She was able to afford it. It was amazing what happened. It was like Rip Van Winkle. The lights went on and I was like, “Whoa! This stuff works.” So that’s very important. The diet is so critical. So talk about the kinds of exercise that are important.

Dr. Dale Bredesen:
It’s a great point. As we do this, we’re learning what works best, what works less. So it’s clear that by different mechanisms, aerobic, that part and the strength training, they have different and complementary features, but there’s also the coordination feature, so-called neuromotor, and now we’re seeing there’s also an issue with blood flow. So things like KAATSU bands are turning out to be helpful. As you probably know, these were used by a number of the Olympic athletes who are training.

Dr. Dale Bredesen:
This is where when you’re doing your training, you have bands that are somewhat restrictive. They don’t cut off completely the blood or the blood flow, but they are somewhat restrictive. They’re basically telling your muscles, “You need to improve the flow.” So in fact, after you use these, people actually get improved flow not only to their muscles, but to their brains.

Dr. Mark Hyman:
Wow. Wow.

Dr. Dale Bredesen:
So that’s one way to go, and then, of course, EWOT, exercise with oxygen therapy, where you’re doing both. You’re doing the exercise, but you’re also delivering a higher oxygen to your brain because, again, this is a disease in which there is an insufficiency in support of this complex neuroplasticity network.

Dr. Dale Bredesen:
So as you indicated, getting the appropriate amount of insulin sensitivity, very important, but also getting the blood flow and the oxygenation. Of course, we’ve heard repeatedly with COVID-19, you’ve got all these and the same sorts of things are impacted. Now, you’ve got less blood flow, you’ve got less oxygenation, you’ve got more inflammation. So unfortunately, people who’ve had this are at increased risk for cognitive decline and really should all be on prevention for cognitive decline.

Dr. Mark Hyman:
I mean, exercise is key because that’s one of the very powerful drivers of neuroplasticity and neurogenesis. So when you want to increase your brain’s connectivity and function and cells, the best way to do it is exercise, and the high intensity training, the strength training, the various kinds of oxygen-supported exercises. It’s actually precision exercise prescriptions, too. It’s not just just take a walk. It’s more than that. Then sleep also is really important. A lot of people have sleep apnea. Many people miss it, poor sleep quality. Sleep has a huge effect on the brain. So talk about how we evaluate and assess sleep.

Dr. Dale Bredesen:
Yeah. Again, there are multiple things and multiple factors that will drive the sleep down and make it less helpful. Of course, starting with the amount of sleep, so many people waking up in the middle of the night ruminating about various things, that can be addressed. As you mentioned, sleep apnea, but there are also people who have other reasons for nocturnal hypoxemia.

Dr. Dale Bredesen:
So again, wearables are going to be very helpful here. So whether you like to use an Apple watch or you like to stick an oximeter on your finger, borrow one from your physician or you can get them online, very inexpensive, and you can check to see where your oxygenation is at night and you should be sitting up in the 96% to 98%.

Dr. Dale Bredesen:
We see people all the time that are down into the 80s and even into the 70s. These people are starving their brains for oxygen at night, and it could be from sleep apnea, but it can also be from upper airway resistance syndrome, another way, and by the way, that also increases your adrenaline, which then wakes you up.

Dr. Dale Bredesen:
So then, of course, people who have low hormones tend to sleep poorly. Especially if your progesterone is low, you tend to sleep poorly. So all of these can collude to give you a poor sleep, and that’s such a critical time. Of course, so many of us, we have situations where we say, “Well, we just can’t afford to sleep that much. We’ve got a lot of stuff going on at night. We got a lot of stuff going on early in the morning, so we’re just not going to get sleep.” Well, that’s a short-term solution. That’s not a long term.

Dr. Mark Hyman:
No. Then brain training and stress management, too, meditation, these things do affect the brain. I remember listening to some scientists talked about the ways in which meditation actually improves connectivity in the brain or plasticity, brain cells, reduce inflammation. So it’s not just just to relax. There’s actually science around how it actually affects the brain in a positive way.

Dr. Dale Bredesen:
It’s interesting. If you simply look at people’s cortisol levels, as the cortisol levels go up, the brain size goes down. So in fact, when we were developing drugs over the many years in the lab for Alzheimer’s, one of the thing that came out that was very interesting is that there is a cortisol or it’s a corticotropin releasing factor, so CRF1 receptor in the brain, in the hippocampus, and blocking this actually improved both the amyloid and the tau in the brain.

Dr. Dale Bredesen:
So in fact, the whole stress pathway is absolutely part of cognitive decline. Yes, fine to have some transient stress and then respond to it. That’s great. That’s what we’re made to do, but as you know, this chronic stress for many, many years is damaging to your brain, it’s damaging to your vessels, you get the hypertension, on and on with all these problems, poor sleep, et cetera. So addressing that is very helpful.

Dr. Dale Bredesen:
As you indicated, some form of meditation, whether it’s TM, whether it’s mindfulness, what have you, very helpful as well in this whole system, getting that stress. When your brain feels that stress and threat and amygdala is responding to this, part of the response is, “Okay. We can’t deal with the brain that we have. We’re going to have to downsize a little bit.” So you want to get rid of that as well.

Dr. Dale Bredesen:
Then there’s targeted supplementation and there’s detoxification, and then addressing the various things that you’ve identified such as mycotoxins, which can take years to reduce these things, but it’s well worth it because it keeps you out of a nursing home and keeps you sharp. The most common thing we hear from people is, “Oh, my gosh! My spouse is so much more engaged since he or she has been doing this.”

Dr. Mark Hyman:
Yeah. It’s true. So you go through all these various modalities like diet, exercise, sleep, stress reduction, brain training, which essentially is using basically I think about crossword puzzles, Sudoku, those kinds of things, but there’s actually software that allows you to really scientifically improve your brain. It’s like brainercise like Brain HQ. So you include that.

Dr. Mark Hyman:
Then what’s really fascinating is you then start to go into how do we facilitate the brain to grow and to heal and repair. You call these trophic factors. Trophic means to grow. So you use hormones, right? You use estrogen, testosterone, progesterone, and then nutrients. So you replace all the missing nutrients and the key things like vitamin D, omega-3, B vitamins. All these really help.

Dr. Mark Hyman:
Then you focus on the gut, right? You focus on fixing the gut if that’s a problem. You start dealing with the infections and the inflammation causes. You start addressing the toxins, the mold. So this is all part of a functional medicine approach. I found this incredibly effective for so many patients.

Dr. Mark Hyman:
What really I want to talk about is what you found in the study. Now, you did all these things with these patients and you did a followup to look at brain size, to look at cognitive performance on standardized testing. You looked at all the biomarkers. What were the big findings and takeaways from the study?

Dr. Dale Bredesen:
Yeah. I think the big takeaway from the study is that for virtually everyone, Alzheimer’s and pre-Alzheimer’s can be re reversed, that you can reverse this problem by addressing the things that are causing it. We’ve known now from people who’ve been on this since 2012, we had our first patients go on this in 2012, they’re still better.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
So again, this is something that was unheard of before because with the drug, you may get a little bump, but then you go right back to declining. Unfortunately, when you look out at five years, the people who went on these drugs typically are just as bad or worse than the ones who didn’t go on them. So with this, you improve and then you stay improved because you’re actually addressing the root cause just as you’ve mentioned.

Dr. Dale Bredesen:
So I think the big takeaway was the vast majority of these people could get better. Then secondly, the few who didn’t, you could see why they didn’t. You could see what wasn’t addressed. You could see if they stopped doing the right things. Then thirdly, we’ve got, as I say, the sustaining of this. Then, of course, the fourth takeaway would be that you’ve got to get the people to change their biochemistry. So you’ve got to get them into that mild ketosis. You’ve got to make them insulin-sensitive. So as the metabolism goes, so goes the cognition.

Dr. Dale Bredesen:
Of course, we now need to look at, “Okay. What do we need to do to make this even better, better, better?” but this is a wonderful start. We saw on average increasing in scores of 3.89 as opposed to, for example, the drug that was just considered a success, aducanumab, no improvement, no stabilization, but in one trial at one dose only, the decline slowed by 22%. That was the exciting result.

Dr. Mark Hyman:
So basically, none of these drug work and at best, they’ll slow you down a little bit. So maybe you won’t end up in a nursing home for six months more than you want, right? We’re not talking about any great breakthroughs here. Everybody gets so excited. We’re doing this drug and it’s billions of dollars and it’s so expensive and healthcare pays for it, but this kind of approach is not something that’s really funded by health insurance. So it’s pretty frustrating for people.

Dr. Dale Bredesen:
Absolutely. Then, of course, there are big discussions now, right now, about who is going to pay if aducanumab is now, since it’s been approved back on June 7th, who will pay if you go in and get this drug that may slow the decline slightly. Of course, your Cleveland Clinic has come out saying that they’re not going to pay for this. Medicare is still deciding. The VA has decided, “We will not pay for this.” It’s about $100,000 per year.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
$56,000 for the drug, and then additional for the infusions, for the PET scans, for the MRIs, for all the other things you need. So it’s extremely expensive. Of course, the people who develop Alzheimer’s spend on average $350,000 per person by the time they pass away, Much of that, of course, with nursing homes. So as you said, this is the most expensive disease. We’re over $300 billion now in the United States per year-

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
… because of all the lost wages, the people who are the caregivers, the medications, the nursing homes, all these sorts of things. It’s truly heartbreaking. So taking this approach, whereas you indicated, you look at all these things and now you address all these things that have failed. Get you back to a system that functions again makes all the difference.

Dr. Mark Hyman:
It’s amazing. I mean, you did very rigorous science looking at all the standardized tests that a traditional neurologist would look at like a CNS vital signs, what they call the MoCA test, which is the Montreal Cognitive Assessment. You looked at brain training scores that are objective scores, looking at how people improve. You looked at brain MRI. I mean, how do you even get something more objective than looking at someone’s brain size? You saw changes in brain size and in volume of the hippocampus, which is the memory center, which is really staggering when you think about it.

Dr. Mark Hyman:
So even if you’re only 10% right, it’s still a major breakthrough, right? I’m wondering why do you think you haven’t been able to get funding from the NIH or major Alzheimer’s groups. What do you think the resistances that’s behind this because it just seems like this is so obvious to me. The results are there. You’ve got preliminary data. Why don’t we just put our chips on that bet and double down and go for it?

Dr. Dale Bredesen:
Yeah, it’s a great point. I think that a system is in place. As you know, there is no place in the United States that is teaching, no medical school other than yours that is teaching functional medicine to par. I actually talked to the vice chancellor of one of the greatest universities in the country in terms of medical school who said, “We’d like to teach this new medicine, but we can’t do that until all doctors accept it.” Well, of course, all doctors won’t accept it until you teach it in medical school.

Dr. Dale Bredesen:
So we’re stuck in this loop of let’s do things the old fashioned way. I think it will take more trials to show that this is clearly superior. I do think in the long run it’s going to be combining targeted drugs with an overall protocol like a functional medicine protocol like this that’s going to get you the best outcomes because these targeted drugs are very good at what they do. It’s just that, as you indicated earlier, they close one hole out of the 36 holes. So still, you’ve got to a lot open, but having them for targeted things is going to be very helpful.

Dr. Dale Bredesen:
So I’m hoping at some point that the drug companies will understand that their drugs will work better on the backbone of these. I think when that happens, things will slowly start to improve, but look what happened, Mark, with the opioid scandal. There was coercion because there were billions of dollars at stake. There was a whole infrastructure set up. There was coercion for doctors, “Do this. Make us lots of money.”

Dr. Dale Bredesen:
To some extent, Alzheimer’s currently is the new opioid scandal. There is coercion. There is an infrastructure. People are saying, “Well, you have to do this. You got to do this drug.” There was a great piece a couple of days ago talking about this new drug. They were interviewing a guy who said, “Oh, this is a breath of fresh air. I’m giving this drug to all my patients.”

Dr. Dale Bredesen:
“Oh, who are you?”

Dr. Dale Bredesen:
“Well, I’m a consultant for the company.”

Dr. Dale Bredesen:
“Well, okay. Yes. If you’re a consultant for your company and you’re being paid …”

Dr. Dale Bredesen:
By the way, Biogen has paid the Alzheimer’s Association, and the Alzheimer’s Association in turn says, “Oh, we think it’s a good drug.” They’ve paid other foundations. This is just an unethical approach, unfortunately. So it’s going to take some time to break through that infrastructure that has been created by billions of dollars.

Dr. Mark Hyman:
Well, the good news, Dale, is that you’ve really done the work, and you’ve also written a number of books that I think, for people listening, lay out the protocols and what to think about, what to test, how to work with your doctor, including The End of Alzheimer’s, The End of Alzheimer’s Program. This new book, I want to dip into a little bit, The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words, because, really, we hear cancer survivors. We never hear of Alzheimer’s survivors. So tell us about some of the stories that you found striking and what are the takeaways that you had from some of these patients.

Dr. Dale Bredesen:
Yeah. This book was really a labor of love because it was so great when I started hearing these stories from the people and how it affects their families. For example, Julie, who talked about when she first told her son her diagnosis. She had been to a neurologist and she said, “I’m an APOE4-4,” so highest risk group, “and unfortunately, I have cognitive decline. Can you just at least help me stay where I am?”

Dr. Dale Bredesen:
The doctor looked at her said, “Good luck with that.”

Dr. Dale Bredesen:
What a horrible thing to say to a patient. She told her son, who started crying and said, “Mom, I don’t want you to die.” So she ended up doing these various same sorts of pieces and she ended up having a number of things. She had insulin resistance. She had inflammation, initially. She’s done so much better.

Dr. Dale Bredesen:
Interestingly, she then had a little bit of a back slide and it turned out she ended up having Babesia. She had had a tick bite and had gotten rid of the line, but didn’t realize that she had a co-infection. Now, it turns out she’s also got some micro toxicity. So that’s being dealt with. With each of these things, she’s getting better and better. She’s gone from 35th percentile on her cognitive scoring to 98th percentile.

Dr. Mark Hyman:
Wow. Almost normal, almost normal.

Dr. Dale Bredesen:
Yeah, very, very high normal. So she’s doing great. In fact, she wrote a substantial part of the second book, The End of Alzheimer’s Program, based on what she has been doing for her own lifestyle and diet and things like that. So she’s one of the seven stories. We have seven wonderful stories.

Dr. Dale Bredesen:
We have Frank, a guy who moved to Mexico because he knew he wouldn’t have enough money as he got demented. In fact, his doctor said, “Oh, you got mild cognitive impairment.”

Dr. Dale Bredesen:
He said, “There’s nothing mild about this. It’s ruining my life.”

Dr. Dale Bredesen:
He’s done very, very well. We have Sally who actually went on a drug trial. She had a positive amyloid PET scan. She was APOE4 positive. She went on a drug trial. As we’ve seen with a number of other patients, when she would get the drug, she would get much worse for a couple of weeks and then slowly improve slightly and then get almost back to where she was, and then get the next injection a month later because remember, this stuff is antimicrobial. So if you have an ongoing insult, getting rid of it is the last thing you want to do. So she would get worse.

Dr. Dale Bredesen:
Now, fortunately for her after her sixth injection, she said, “This is making me worse, not better.” She quit. She then went on the protocol and she’s now got a perfect MoCA score of 30. She’s done great.

Dr. Mark Hyman:
30? Complete normal.

Dr. Dale Bredesen:
Yeah, 30 out of 30.

Dr. Mark Hyman:
What was it before?

Dr. Dale Bredesen:
She started at 24.

Dr. Mark Hyman:
Very good.

Dr. Dale Bredesen:
So she had significant MCI. Again, you don’t start going down on your MoCA until you’re fairly far along in the disease. She already had the positive amyloid scan. She already had well into MCI, the third of the four stages, and she’s done very, very well. Now five years into this is still scoring 30 and doing really, really well. She had gotten to the point where she would forget to pick up her granddaughters at school and she writes about this. Then when she found out, “My God! I didn’t pick them up,” she would be just horrified, “Oh, my God. I’m going to lose my granddaughters because of my cognitive problems.” So she ended up having a tremendous amount of micro toxicity, actually had to get away from the source of that and go into a detox program, and she’s done very, very well.

Dr. Mark Hyman:
That’s interesting.

Dr. Dale Bredesen:
So we have a story after story after story of these people and how it affected their families and how much better they’ve done by doing the right things.

Dr. Mark Hyman:
This is an extraordinary deal. I think that people need to take home that, one, that if you even start to have symptoms, there’s something you can do. More importantly, there’s a lot of people who are at risk. So we say there’s 14 million people who are going to have Alzheimer’s in a few years. How many people actually have pre-Alzheimer’s or are headed that direction? Because it’s tens and tens of millions, right? This program, this approach is not just for when you get it. It’s actually an approach that you should do decades before you actually get any symptoms if you’re at risk, right?

Dr. Dale Bredesen:
Yeah. We recommend that everyone who’s 45 years of age or older get a cognoscopy, just like when you turn 50 you get a colonoscopy. When you hit 45, please get a cognoscopy. That’s a set of blood test that we’ve been talking. It’s online cognitive assessment. Very simple. Takes about 30 minutes. Then if you have symptoms already or if you’re scoring poorly on the tests, it includes an MRI with volume metrics. That’s it. It’s simple to do. I have to say it’s much more pleasant than a colonoscopy. Get that checked out.

Dr. Dale Bredesen:
Then get on appropriate prevention because, as you indicated, the numbers are staggering. So if you look across the spectrum and there’s a beautiful paper by Professor Kristine Yaffe from UC San Francisco, who showed that if you just follow serial autopsies, this is now the third leading cause of death.

Dr. Mark Hyman:
Wow.

Dr. Dale Bredesen:
So about 15% of people, so about 45 million Americans will die from Alzheimer’s disease if we don’t do something. If we don’t have active prevention and early reversal, we will end up with about 15% of the population dying from this. As you indicated, already about six million diagnosed, heading for 14 million, but then over 10 million that are on their way to get diagnosed. So we’ll end up with all people from zero to the oldest ages, about 45 million of the currently living Americans will die from Alzheimer’s if we don’t get on appropriate prevention and treatment.

Dr. Mark Hyman:
What’s striking, Dale, is that in the studies on brain imaging, you can see the changes that Alzheimer’s is wreaking on people’s brains decades before, 20, 30 years before they ever get any symptoms.

Dr. Dale Bredesen:
Absolutely.

Dr. Mark Hyman:
So that’s really impressive. It tells me that it’s really important for people to understand if you have any Alzheimer’s in your family, if there’s any risk factors, that we need to fix those. I mean, obviously, all these things people should fix anyway from diet, exercise, stress, and taking care of their brain, but how do you live a brain healthy lifestyle from the get-go? That’s really important because if you let these things slide, it’s harder and harder to deal with them.

Dr. Mark Hyman:
What’s even amazing is that even after you’ve gotten the symptoms, which is 20 or 30 years after you first start get the process going on your brain, you can start to stop and reverse it, which is what your work is showing. That’s actually helpful, but I encourage people to think about how do they get a cognoscopy earlier in your life, 45, 50, whatever. So just get these things fixed. This is what I do in functional medicine. This is what you do. It’s really, really so, so powerful.

Dr. Mark Hyman:
Tell us about the way in which you think that the current approach is so flawed because I think we’re spending billions and billions of dollars on hundreds and hundreds of clinical trials for Alzheimer’s and most of them have failed. So what is the breakthrough moment for this approach because it seems like it’s not getting the airtime it needs. It’s not getting the scientific attention it needs. There’s a lot of pushback against it. How do we break through that?

Dr. Dale Bredesen:
Yeah. It’s a great point. The problem has been that there’s a fundamental flaw in the thinking. Everybody is saying, “Okay. We don’t understand what Alzheimer’s is, but we’re going to try to treat it.” So I think a lot more needed to be put into what is this thing. It’s not a virus. It’s not like with SARS-CoV-2. With COVID-19, we know what it is. It’s a viral illness. We have these variants, we have sequence, we know how to deal with that stuff. People developed vaccines. They developed antivirals. They developed improved immune systems, all that.

Dr. Dale Bredesen:
With Alzheimer’s, the problem has been people haven’t understood what it is. So they’ll say, “Oh, it’s …” You mentioned type three diabetes and, yeah, that’s part of it, but it’s not the whole thing, right? They’ll say, “Oh, it’s all about herpes,” or “Oh, it’s all about amyloid, tau, prions, APP changes,” I mean, all of these, on and on and on.

Dr. Dale Bredesen:
So if you look at what it actually is and then go after that, it is a network insufficiency. So you’re fixing a network. So I do think that when people start realizing you can’t get away with a single prescription and, sure, hallelujah. If there’s a prescription one day that does all the different things we need, great, but there’s no evidence so far that that is the right way to go.

Dr. Dale Bredesen:
So I think that it’s simply going to be continuing to publish these studies. We’re now just getting ready to start a larger randomized controlled trial that will begin in January, February of next year, depending on when the IRB approves it. So in that case, we’re now also looking to see what needs to be added.

Dr. Dale Bredesen:
So one of the things we’ve now added is cone beams because we’re finding that some people have oral pathology that is not picked up by standard approaches, standard X-rays, and just looking at the oral microbiome. So we’re seeing what needs to be looked at further to get the best outcomes from these people. I do think that when it is standard, when people realize they can get much better treatment by going to places that do this as opposed to simply these centers that write prescriptions, I think that’s when things are going to start to change.

Dr. Mark Hyman:
So what is the next step in your work? Where do you see the next step of pushing this forward? We’ve talked about the study that’s going to be published. You’ve got a study of hundreds of cases in the community, not that you treated it in the study, but there’s a collective that show improvements. What is the next step in your work?

Dr. Dale Bredesen:
Yeah. Great point. So three pieces to this. Number one, to now look at people who are in the later stages. Can we do something about the people who come in with MoCA scores of zero, one, two? We’ve seen people who get better, although they typically don’t get all the way better. So they’ll improve. They’ll start to dress themselves again. They’ll start to do this. So we do need to have something for the later stages. Although I hope we will rarely see those later stages.

Dr. Dale Bredesen:
This is what happened way back in the days when I was in medical school. The old timers had seen late stage neurosyphilis. The new guys would not see late stages neurosyphilis because you treated early. So we want to get to the same point where you don’t ever see a late stage Alzheimer’s patient, but until then, we need to address that.

Dr. Dale Bredesen:
Second piece is we need to continue to improve the overall approach, and this is why we got the randomized control trial starting up. Then the third piece is we need to now adapt this to the neurochemistry of each neurodegenerative disease. Each one, it affects a different subsystem of the nervous system, and we need to be able to adapt the neurochemistry for each of those.

Dr. Dale Bredesen:
So we’re actually starting with macular degeneration. We have the first few patients already who have early macular degeneration. They have a different chem. In fact, interestingly, APOE4 protects you against macular degeneration, and APOE2 is the one which protects you from Alzheimer’s but increases your risk for macular degeneration.

Dr. Mark Hyman:
Oh, boy!

Dr. Dale Bredesen:
So it’s a slightly different strategy. You have to go after this.

Dr. Mark Hyman:
I have that.

Dr. Dale Bredesen:
Okay. Well, so make sure that, I’m sure you’re on top, you’re doing the right things, and you’re not a smoker and you’re not drinking alcohol, these things that will predispose you to macular degeneration. So I think that’s the third piece of this. We want to be able to do this to make it so that neurodegenerative diseases are things of the past.

Dr. Mark Hyman:
So this would work for Parkinson’s, ALS, and other things you think?

Dr. Dale Bredesen:
Well, we’ve already seen some good results in people with Lewy body disease. So Lewy body is, as you know, Parkinson’s and Alzheimer’s together. Those people typically turn out to have lots of toxins onboard, and they can be metalotoxins. They can be organics or mycotoxins. So that’s already looking pretty good. We need more. We need a whole trial on Lewy body, but, yes, the Parkinson’s is another one, typically toxin-related, and in some cases, pathogen related, and the same thing, frontotemporal ALS, right on down the line.

Dr. Mark Hyman:
Yeah. It’s quite amazing. I’ve seen so many patients. I had a patient with Lewy body recently, who couldn’t get up out of a chair, was motor impaired, severe cognitively impaired, unable to run her business. She just had so many things going on. One of her doctors was giving her steroids shots for energy because she was older and tired. She had blood sugar. A1C was eight or nine, which is really poorly controlled diabetes. She was a very small little woman, but she was a skinny fat woman, high-carb diet, had tons of yeast overgrowth in her gut, tons of B vitamin issues, and we just worked on them. We just fixed her thyroid. We fixed her diabetes. We fixed her gut. We got rid of the yeast. We optimized her nutritional pathways and it was amazing.

Dr. Mark Hyman:
She literally flipped right around and she was able to actually get back to work. She wrote a book. She recorded an album. She was able to function and get up and walk, which she hadn’t been able to do. It was really quite impressive. I think it’s just being methodical about looking at all these variables.

Dr. Mark Hyman:
I remember another patient, and everybody’s different. I had another patient with MCI and, basically, early dementia. Doctors told her, “Just get your affairs in order. There’s not much we can do. Take some Aricept,” which doesn’t work anyway and causes side effects. It’s just the main Alzheimer’s drug. It turned out she had low thyroid, she had adrenal issues, she had really severe mercury toxicity. She had all kinds of B vitamin issues, mitochondrial problems, gluten, dairy, sensitivity, bacterial overgrowth in her gut, lots of inflammation, mold exposure, all the things you’re talking about.

Dr. Mark Hyman:
We just did exactly what you said. We just personalized it. We got her on a low-glycemia, high-fat keto light diet, lots of phytonutrients, replaced all the nutrients she was missing, got her thyroids sorted, got her metals detoxed, and optimized her mitochondria.

Dr. Mark Hyman:
Literally six months later, she was just totally normal. I mean, just totally normal, and all her markers were normal. CRP went from 4.7 to zero. Over time, her metals came down, took a little while, but over a couple years came down from 100 to 13. She really did great and seven years later was still doing great.

Dr. Mark Hyman:
So there’s so much potential for people to actually get help. It’s not easy. I’s not easy. So you go to the doctor, “Oh, you have high cholesterol. Take this statin.” You just take a pill. It’s easy. This is a very complex disease to treat, and it’s part of the challenge because people are cognitively impaired. So it’s hard for them to remember what to do. They need some help, and it’s hard to do the diet, the exercise, the supplements, all of that.

Dr. Dale Bredesen:
Mark, how do we get the doctors and the patients not to give up because as you indicated, it’s methodical. You find the things, you address them one at a time. To me, one of the big breakthroughs is going to be when we can absolutely prioritize and say, “Okay. In your case, this is number one, this is number two, this is number three.” It’s not always obvious at the beginning what is number one, two, and three in priority. As long as you fix enough of them, people typically get better, but what will happen is the doctors will say, “Well, I work on these things, but I don’t really do these other things,” or the patient will say, “Look, I tried the first thing, it really didn’t help me that much.” No. You’re at the beginning. You’ve got multiple contributors. So they give up. So if we could just get people to say, “Look, don’t give up, get a health coach working with you, make sure that you do the right things,” there’ll be so many people who’d do so much better.

Dr. Mark Hyman:
I just want to point out the obvious here. You’re a neurologist and you’re treating people’s guts and nutrition and their hormones and toxins. So in a way, the way we’re trained as super subspecialists, we don’t know what to do. We don’t know how to optimize someone’s nutrition. If you’re a specialist and whatever you’re a specialist is, you don’t know how to balance someone’s hormones or treat these infections or fix someone’s gut or help someone detoxify.

Dr. Mark Hyman:
This is what functional medicine does. This is what functional medicine doctors do. They look at the whole picture, not just their little slice. So if you went to an infectious disease doctor, all he’ll do is focus on the Lyme or the viruses or if you go to a GI doctor, all he’ll do is focus on the SIBO or bacterial overgrowth. If you go to an endocrinologist, they’ll just treat your hormones. You need to do all of it. That’s the problem. I think the average physician is overwhelmed.

Dr. Mark Hyman:
So you you’ve developed a program called Recode and you’re building it as a platform where it’s easier for people to get all this data in to synthesize it and come up with an algorithm set of solutions that helps people decide what to do. Can you talk a little bit about that because it takes a lot of the painful work of learning all this away from the doctors, which they really don’t have time to do, but they can implement this by getting the support of this program, right?

Dr. Dale Bredesen:
Exactly. So what we realize, again, I’m treating dementia. That’s what I mean. So it’s whatever it takes to treat dementia and pre-dementia. So what we realized years ago is we need larger datasets. When you go in today and say, “My cognition is not great. Can you help me?” people check a couple of things. They’ll check your TSH. They won’t even check your free T3 and free T4 or your reverse T3. They’ll check your TSH, they’ll check your B12, they’ll check your RPR, and then they might check your sed rate. That’s it. Then they’ll do an MRI and say, “Yeah. You got Alzheimer’s. We’re going to put you on Aricept.

Dr. Dale Bredesen:
So we realize, no, we need to get these much larger datasets, exactly the things you’ve just been talking about. So we developed this so-called Recode. So this is a computer-based algorithm. So you look right now, we look at 150 different variables, but the reality is it should be 150 million, whole genomes. It should be many things. This should be part of your office helper. Everyone should have access, just as if you do someone’s genome, you don’t read that yourself. You get a nice readout that says, “Here are the genes that you have SNPs, and here are the concerns you have.” We need to have that for everything so that you can say, “Okay. Here are …”

Dr. Dale Bredesen:
One of the things it does, for example, is subtyping. So it says, “Aha! You have mostly inflammatory Alzheimer’s, whereas this person has mostly glycotoxic, and that person, the third person may have mostly vascular.” Different people have different subtypes of Alzheimer’s disease or pre-Alzheimer’s.

Dr. Dale Bredesen:
Then it also gives you an optimal program. As I mentioned earlier, we’re working on can we now tell people what is the highest priority to deal with, what is the second highest priority to deal with because, again, it’s different. If you deal with something that’s not a rate-limiting step, then you’re not going to see any improvement because that’s already good enough. You want to identify what are the rate-limiting steps for each person’s improvement.

Dr. Mark Hyman:
How do you figure out the priorities and the things that are the most important, that have the biggest impact?

Dr. Dale Bredesen:
It’s a great point. Partly, we do that by the subtyping. So as an example, the people who have type three, which is the toxic type, they often look somewhat different. They often have some depression as part of their initial feature. They often will have a non-amnestic presentation. So they’ll come in with executive dysfunction problem, with the organizing things or they’ll come in with problems with word finding or problems with recognition of objects, things like that. Then we’ll find high toxin levels.

Dr. Dale Bredesen:
So in that case, the toxins are the number one if they have that presentation. Then the ones that are more inflammatory, as you know, it’s the overweight, ruddy-faced guy in his 60s who’s got hypertension and metabolic problems. They are the inflammatory ones, and you go after that first.

Dr. Dale Bredesen:
Then you’ve got the different who have the sleep apnea or who have the oral microbiome changes. Then we have a different one where you have the 75-year-old woman, who’s got no hormones, no estradiol, no progesterone, low vitamin D, low everything, low pregnenolone, low thyroid. Those are the atrophic subtypes, and those you need to focus on that, get their BDNF up, get their NGF up. There are ways, of course, as you indicated earlier, to do that. So to some extent, it’s based on their presentation.

Dr. Mark Hyman:
So it’s very personalized. It’s very specific. It’s really quite amazing. I think this work is some of the most important work in science being done because it’s one of the few areas where we’re able to look at systems biology. I think autism is a very similar thing. I mean, they’re at opposite ends of the AIDS spectrum, but they’re often the same diseases. You haven’t treated a lot of autism patients because you’re a neurologist, an adult neurologist, but I have, and I’ve also treated a lot of Alzheimer’s patients.

Dr. Mark Hyman:
When you look at the biology of what’s going on, it’s the same stuff. Literally, you can literally do the same approach and fix these kids, fix their gut, fix the toxins, fix the infections, deal with the inflammation, get their diets straight, put them on ketogenic diets. It it’s actually incredible how profoundly effective it is, but it’s complicated, and it’s hard to do. Our system is actually structured to do it for patients. It’s structured for the eight-minute office visit with a prescription, take the pill, by the way, which most people I know don’t do anyway.

Dr. Mark Hyman:
So it’s really this moment where we’re beginning to rethink our whole approach to chronic illness based on systems, based on looking at all the variables, looking at every. So when people criticize you, what do you say? How do you answer their skeptical remarks?

Dr. Dale Bredesen:
Yeah. So I just say to them, “Look, if you’ve got something better, please publish it. Show me that patients get better.” We’re getting better results and publishing better results than have ever been achieved before or published before. So I hate to be that negative about it. Very interesting though, related to what you just mentioned, for the first time, so seven years after we published the first examples back in 2014 with the first 10 cases, the California Neurological Society has asked me to speak this year, and I actually wrote back to the person who emailed me and said, “Are you sure you want this? We’ve had a lot of pushback. There’s been a lot of controversy. You may get some screaming and yelling from the classic little neurologist.”

Dr. Dale Bredesen:
So she said, “No. We absolutely. We want to have some discussion and debate.”

Dr. Dale Bredesen:
So I think that’s a great first step, and I have to say I give great credit to the physician, the neurologist, who invited me and wants to have some dialogue, and she’s got all sorts of other speakers to talk about other features of neurology.

Dr. Dale Bredesen:
So I think this is just the beginning and people are just starting to think about, “Okay. Maybe we do this.” So what I want to encourage during the talk is let’s address the specifics. Let’s instead of focusing on politics, finance, and the usual stuff, one of the things that was written negatively was, “Hey, you guys are saying that supplements are a cure for Alzheimer’s.” That’s so silly. Nobody said that. That’s a straw man argument. You put up something that’s really worthless and then knock that down. Fine. I want to get into, let’s talk about the data from the people. Let’s talk about their MRIs. Let’s talk about their cognitive testing. No one criticizes those.

Dr. Dale Bredesen:
The other thing they say is, “Oh, you published in a journal we don’t like.” Come on now. Read the data, read the stuff, and then talk about what we actually wrote. If you want, go see some of the patients. We’ll be happy to set you up. Evaluate some of the patients. Make sure that what we’ve published is accurate. That’s all fine. I don’t have a problem with that, but this idea of saying, “Wrong journal, wrong study. We don’t like that,” that’s all political.

Dr. Mark Hyman:
Well, I want to finish by giving a little bit of hope because you’ve not only done the scientific work, but you’ve actually gone in the trouble of helping build a system that can help patients prevent and also treat, and you call it Precode and Recode, and it’s Apollo Health. So can you talk a little bit about Apollo Health, what it is, and how people can access it and what it offers?

Dr. Dale Bredesen:
Great point. Yeah. So you can get a cognoscopy, for example, at mycognoscopy.com. You can look at drbredeson.com. So the idea is we needed to build this ability to get larger datasets, to manipulate them, to figure out subtyping, and then to help all doctors. This is like a doctor’s helper, basically. So we work with a group from Silicon Valley led by Lance Kelly, who used to work for Apple. This is Apollo Health, as you mentioned. So they now look and make it very simple. You get a set of blood tests. Everything is basically very simple to have a community of people. There are over 5,000 people now that have gone through this. We also trained over 2,000 physicians from 10 different countries and all over the United States. So this makes it much easier for people to get their testing, to get their analysis, to get what we call a Recode report.

Dr. Dale Bredesen:
So it gives you very much as you’d have a Cambridge Health. You look at the heart, the cardiovascular report, it’s the same idea. This is about a 50-page report that looks through all the different things that could potentially be either risk for you or actually causing your decline.

Dr. Dale Bredesen:
As you indicated, Precode is for prevention of cognitive decline. Recode is for reversal of cognitive decline. So two related programs. Of course, if you’re just trying to prevent, it’s a little easier. You don’t have to have quite as many tests. You don’t have to do quite as many things. On the other hand, once you actually are suffering the decline itself, you really have to work harder to get things turned around as you know.

Dr. Mark Hyman:
Yeah. Well, that’s what Benjamin Franklin said, “An ounce of prevention is worth a pound of cure.” So you want the ounce of prevention not the pound of cure. That’s the point.

Dr. Dale Bredesen:
That’s exactly right.

Dr. Mark Hyman:
Well, this is such an incredibly hopeful conversation for so many millions of people suffering. I spoke to a young woman today who said to me, “Dr. Hyman, my family has a really bad history of Alzheimer’s and I’m really scared. What can I do?” I’m just so happy that I have an answer for her. I think that your work is so important. I hope you get a lot more funding. If anybody listening to this is working for the NIH or somebody, philanthropists, somebody, this is the work you should support because this is so important, one, not only helping with Alzheimer’s, but helping to establish the paradigm of science, where you look at multiple factors that are driving complex illnesses and addressing all of them, which is functional medicine.

Dr. Mark Hyman:
So it’s hard to do. It’s not easy, but this is just how the body works. We didn’t design it. God did or whoever you believe that created us did, but it is actually what we have to deal with. So whether we like it or not, we can’t be reductionist anymore. We have to zoom out and go, “How do we deal with the whole system?”

Dr. Mark Hyman:
So Dale, thank you so much for your work. Everybody check out apollohealthco.com. Check out Dale’s books, The First Survivors, The End of Alzheimer’s Program, The End of Alzheimer’s book. They’re really great. I think you will have so much to learn and it’ll help you and your family, hopefully, if you’re at risk or if you have somebody in your family with this problem.

Dr. Mark Hyman:
So hopefully, you like this podcast. If you loved it, please share with your friends and family on social media. Leave a comment. We’d love to hear from you how do you help maybe your own cognitive function using this approach. We’d love to know and subscribe wherever you get your podcast. We’ll see you next week on The Doctor’s Farmacy.
Speaker 1:
Hi, everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their Find A Practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner and can help you make changes, especially when it comes to your health.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

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