This Is Causing Alzheimer's & Dementia: Diet & Lifestyle Habits To Reverse It | Dr. Dale Bredesen

We're going to talk about diet in a little bit, but I want to talk about the widespread nutritional deficiencies that you're seeing and how those play a role in the brain and cognitive decline, and what are the most important nutrients we need to be focusing on.

Yeah, it's amazing to me because we've got so many things working against us, and obviously you've written probably more on this than anyone, looking at the critical nature of nutrients for your health, looking at all changing the world one bite at a time and all these fantastic things that you've done. Again, it just fits perfectly with the science that we've studied over the years. And so, Paul Clayton from Oxford has pointed out that we don't even have the nutrients in the soils that people had 100 years ago, 200 years ago. When we were thinking, these people, wow, they didn't know what they were doing. They were doing much better than we are because they actually, he's pointing out that Henry VIII had better nutrition than we do. Of course, he ended up being obese and had problems with arthritis and things. But the key is that they actually had better soil. So we've got essentially a triple whammy. Number one, we have poor soils and therefore we have poor overall nutrition. Number two, we're eating food that's way too high in sugar, obviously, and way too high in processed foods and all these issues. So we're eating stuff that's toxic. And then number three, we're not getting enough, nearly enough fiber, nearly enough phytonutrients. So we have this system. It's as if you took your car out and you're trying to drive this car that needs appropriate fuel and you're putting stuff in that is very low octane. It's just sputtering, it's spluttering, it's having trouble getting out of the block. It's just, you know, you might go a little way, you might, and that's what we're all dealing with every day. So if you start- Crappy fuel. Crappy fuel. You optimize those things. You get people into some ketosis, you get them appropriate fiber for detox and for their microbiome, you get them appropriate low-carb diet, you get the appropriate phytonutrients, and by the way, one of the most common deficiencies, choline. As you know, choline is needed to make acetyl choline, which is a critical neurotransmitter for memory, and is reduced in people with Alzheimer's And, a, I've checked myself on chronometer and I realize I'm not getting enough chholine in my diet. You know, we should be getting around five hundred and fifty milligrams or so of coleline each day.

We should get our eggs and get.

Our eggs and from yes, some sardine from liver obviously, organ meats, things like that, from oysters, things like that, a number of vegetables as well. or you can, if you're not getting it from there, take some citicoline. This is why Professor Wurtman from MIT found that citicoline is so helpful for synapse formation. Yeah. So, you know, lots of ways to get choline, but please make sure that you get enough. So all of these things are critical.

So what besides choline is so important for the brain?

Oh, nutrient.

What nutrients?

I'll take flavanols, flavanols and flavonoids, those alone. Study that just came out showing that over thousands of people, those who were in the highest quartile of flavonols had a much lower dementia risk than those who were in the lowest quartile of flavonols. So things like strawberries and things like grapes and things like that, all helpful to give you the flavonols and then the flavonoids, things like blueberries and things like that, all critical.

So those are like 25,000 different phytochemicals in plants.

Exactly.

And flavonols and flavonoids are part of those. and so eating a rainbow colored diet where half your plate is vegetables is a simple take home to protect your brain and pretty much everything else that could go wrong with you. So we've got choline, we've got flavonoids and phytonutrients. What other major nutrients are an issue?

Well, you know, the minerals. So the key ones that almost all of us are deficient, as you know, in zinc. And zinc has become a huge issue because of COVID-19. So many of the people who are deficient in zinc are reduced and have an increased poor outcome, increased risk for having a poor outcome from COVID-19. So zinc, magnesium, iodine, potassium, those are the big four that most of us are deficient in. And then of course, vitamin D, as you know, the study that just came out about 10 days ago showing if you take the people who are low in vitamin D, they have a much worse outcome in COVID-19 than the people who have sufficient vitamin D. And of course, Alzheimer's is no different. The same thing you see. people who are low in vitamin D, more likely to get Alzheimer's, people who are sufficient vitamin D, and of course, same thing in multiple sclerosis, high vitamin D associated with better outcomes. So as you said, it's multiple diseases that all depend on these critical factors.

Some of the most important things I found are B vitamins. I once had a patient who was about 80 something years old, she was on multiple boards, very successful woman, but was noticing depression and really severe cognitive decline and been diagnosed with MCI or pre-dementia, told to get her affairs in order. She came to see me and I'm like, checked her levels and found she had really high level of something called methylmalonic acid and homocysteine, which are things that most doctors don't check but reflect your status of B12, which is methylmalonic acid and homocysteine, which is the folate and even B6. So I basically gave her B12 shots, high doses of methylfolate, which is a particular kind, saw she had some genes that made her need a special kind of folate. And she called me back and was doing amazing and all of her symptoms had gone away. and then a few years later, maybe four or five years later, she called me up and I thought, oh, I saw my schedule. I'm like, maybe she's not doing well, she's declining. I kind of worry about her a little bit. And, and she's like, Dr. Hyman, you know, I'm going trekking in Bhutan and I wanna know what I should do to prepare and what I should be taking with. So I was like, okay. And I think, you know, sometimes it's that simple, but it's not always that simple. But I think understanding the role of nutrients and nutritional deficiencies is huge. It's far more common than we think. you can't get everything you need from food. I think a lot of the reason the studies on vitamins have failed in large trials, whether it's for cancer or heart disease, is because they're not dealing with the whole system. They're just like if you're eating donuts all day, you can take all the fish oil or vitamin D you want, it's not going to do anything to fix your risk of heart disease, right? So you have to look at everything together. Absolutely. So let's talk about this concept you talked about called keto flex. We've touched on it a number of times, but what is the diet that's best for your brain? and what is the diet that's best for your brain if you actually have Alzheimer's?

Yeah, great point. So let me preface this by saying I know far less about nutrition than you do. So, you know, I'm really talking to someone who's an expert here. I'm looking at the neurochemistry. So I'm interested in synapses, how they're made, how you keep them. And so this is Ketoflex 12-3 is nothing more than what's the thing we can use to drive your biochemistry toward an optimal biochemistry for making and keeping synapses. And so what do you need? to have ketosis, you need to have all the nutrients we were just talking about for support, you need to have high fiber because you need to help yourself detox, you need to improve your microbiome, all those sorts of things. You need to have appropriate probiotics to support your microbiome, and you need to have fasting periods for autophagy, fasting periods for helping you to get into ketosis. Fasting periods for all the great things that fasting does, even in things like lowering your blood pressure, hypertension is another big risk factor for Alzheimer's. So if you put all that biochemistry together and you mix it up in a blender and you say, what's the diet? We named it Ketoflex 12-3. It's ketotic, it's mildly ketotic, it's plant rich. This is not a bacon related keto, ketotic diet, ketogenic diet. This is a plant rich, high good fats, intermediate proteins, low carb, and no simple carbs. It is flexitarian. And I realize flexitarian means you have to eat some meat and fish. It's really more about flexibility. You want to be a vegetarian, no problem. Make sure to check your homocysteine and your vitamin D and things like that, but fine. If you want to have some meat, have some fish.

It's hard to be, I think, keto if you're not eating animal protein. I mean, you can do it as a vegan or vegetarian, but it's harder because you harder to eat, reduce the carbohydrate load because you need the protein.

From beans and grains and things like that. So how do you do that with those patients? Yeah, that's a great point. And so, you know, again, because getting into ketosis is so critical for supporting brain energetics, we tell them, just start by taking some exogenous ketones. Do it for a couple of months.

No problem, because we need to get.

That energy up after. Taking it as a supplement. Exactly. Then you can get yourself into endogenous ketosis. And we do that by increasing the fat consumption and all the appropriate oils and the nuts and the seeds and all the things that you've written about that are excellent sources of good dietary fats. And then again, and then if they can't get into enough ketosis, okay, we can supplement that a little bit to get them where they need to be. So it's then, so that's the flex part. And then 12:3 is 12 hours as a minimum. And if you're APOE4 positive, you should really make it 14 to to 16 hours of a fast between when you finish your dinner, when you start your breakfast, brunch or lunch, and then the three is for three hours before you go to bed. You don't want to be eating right before bed because it'll spike your insulin, reduce your growth hormone and your melatonin and so forth and so on. So, this is why Ketoflex 12-3 is essentially our attempt to take the neurochemistry of synaptogenesis and to put it into a diet.

It's so incredible. So you're saying you don't have to be keto if you're not having Alzheimer's for prevention. This is more for treating the patient, right?

It's a great point, and this is one of the things that we've been arguing about lately. If you're just there for prevention, do you want to get yourself into ketosis? It depends on how concerned you are. If you are really concerned about prevention, then you probably want to get at least part-time getting yourself into some mild ketosis, but you're right, you don't have to. For someone who's trying to reverse, absolutely, it doesn't reverse well if you don't get into ketosis because you're missing that energy gap.

Yeah, I've seen that with my patients when I put them on ketosis if they're struggling. Because often people get better without it, but it's on a low glycemic diet. But then you really want to push that envelope. They seem to do a lot better. And what about APOE4? Because this is a common gene. that increases your risk and you have one or two copies. And there may be some interesting data that I'd love to explore with you because historically there was concern that these patients should not eat saturated fat, that they may have more problems with cardiovascular disease and dementia. What is the current status of the data on these APOE4 patients, which are a lot? I mean, they're, what, about 45 million or something in America?

Yes, 75 million. So here's the thing. three quarters of the population is ApoE4 negative, and one quarter of the population is ApoE4 positive. So it's incredibly common. And there are some advantages you have to have it to being ApoE4 positive. And so in third world countries, it actually gives you a big advantage because you have a more pro-inflammatory state, you're better at fighting off pathogens, and you're actually better if you have a starvation diet, if you're starving, you want to be APOE4 positive because you are better fat absorber. So 75 million Americans have one copy and they are at 30% lifetime risk for Alzheimer's. If you're negative, about 9% lifetime risk. One copy, 30%, two copies, well over 50%. Most likely you will develop Alzheimer's and that's 7 million Americans. So critical for all of these people to be on prevention, absolutely. And As far as the fats, it's a good point, and this is a controversial area still. Some arguments would say, yes, a limited amount of saturated fats, okay. I think most people who are APOE4 positive would like to stick with the monounsaturates and polyunsaturates and stay away. So typically we don't recommend, for example, coconut oil, MCT oil. We recommend if you want to take some, want to get into ketosis exogenously, just take some exogenous ketones, take ketone salts, take ketone esters, those sorts of things. You can do that a couple of times a day. and get nice spikes in your ketone levels. And then ultimately, again, you want to get into it endogenously. So, you know, if I had to say one way or the other today, I would say the preponderance of the evidence today is on the notion that you would want to stay away from saturated fats. Having said that, there are people who do have some saturated fats in their diet and have beautiful lipid profiles despite the fact that they are APOE4 positive.

So you want to check your blood work and see how responding to your.

Diet, not just guess, right? Absolutely. Check your LDL particle number. Try to keep that between 800 and 1200. Or if you want, check your calcium score to make sure that you don't have any cardiovascular disease. Of course, there's an increased risk for cardiovascular disease as well with people who are APOE4 positive.

So as you said, check to see where you stand to make sure you're doing well. Now, a lot of people listening, and if they're medical professionals listening, they probably think it's heresy to say that we can reverse Alzheimer's, that it's providing false hope, that we don't have the science behind it, and it's really not possible. But you and I both seen that it is possible, and it's not always 100%. But the question is, you know, really, to what degree in your experience is this reversible? And how far along can you be before you can, you know, be confident that it's going to be reversed? In other words, is there a time when it's too late? so can you talk about what that is? Maybe a case or two that explains, you know, really how this works in practice.

Absolutely. So we can think of this in four phases. Phase one is where people are asymptomatic, but they already have the pathophysiology ongoing. And those people are the ones for prevention, and they do very well. And let me ask you a question. Have you ever had a person who came to you for Alzheimer's prevention, who then developed Alzheimer's while on your program?

I think I've had people progress slowly over 10 years. I've had people kept them good for 10 years and then sometimes if they slip off the program, that's when they get into trouble.

Well, exactly, slipping off the program. So I ask this to many functional doctors. Typically, very few people have seen this. When you're on prevention and you start when you're asymptomatic, you do very well. Then the next phase is SCI, Subjective Cognitive Impairment, which actually lasts about 10 years where you know there's something wrong, often your spouse but you're still scoring well on the testing. Those people, virtually all of them get better because these are still early stages. Then the next stage is mild cognitive impairment. These are people who are scoring 23, 24, 25 on the MOCA scores, or 26. This is Montreal Cognitive Assessment scores out of 30. Dr. Yeah. So they clearly have significant early Alzheimer's, but we call it mild cognitive impairment at that point. the majority of those people will increase their scores. And we wrote a paper on this with 100 documented improvements and published it in 2018 with 15 different laboratories. And the average improvement in score was 4.9. So if you came in at 22, you ended up around 27 typically. So that's clearly improving and they typically sustain it. Then the ones who then are all the way to Alzheimer's, they're now losing activities of daily living. Calling someone Alzheimer's is like saying late-stage cancer, metastatic cancer because it's a very late stage of this process that's been going on typically for 20 years. Some of those people improve and we've had people with MOCA scores of zero improve, but when they improve, they go from zero to five. They dress themselves again, they speak again, they interact with their families again, they can even do emails again, but they're not normal. So we're not so far not able to take someone from zero to 30. And that's one of the big research questions right now. what is missing? They come to a next plateau. What do we need to get them to a higher plateau? Is there a rate limiting step that's preventing or is it just the massive loss of synapses? Do we need to then think about stem cells, intranasal trophic factors, methylene blue, all these sorts of things that are coming. Ewot, that's another thing we've been interested in, exercise with oxygen therapy, all the things that we can bring to bear. So the bottom line is the farther along, the harder it is and the less complete the improvement. But if you catch people early or even in mid-stage, you can do a lot just as you've indicated.

Absolutely, I've seen that. So can you share maybe a story or two of a patient you treated, what you found and what kind of things you did and how they improved?

Yeah.

Oh, absolutely. There are hundreds and hundreds like this. So, you know, simple example of a woman, an amazing lady who's a psychiatrist, who was having major problems. And in fact, her husband said to her that, you know, he said, you, memory is disastrous. She got to the point where she just couldn't remember anything. She's 73 years old. And actually she contacted me by email a few years ago and we started going back and forth and she started checking all the various things. And she had initially had a lot of the type 2, reduced estradiol progesterone, no surprise she was 73, reduced vitamin D, poor thyroid, all those. So all those were addressed. She then improved and she actually went from nine, so she was in the ninth percentile on her initial cognitive scores. She's now at the 97th percentile on her cognitive score. So she just dramatic. She got very, as you've seen yourself, people get into this and she started doing this game called Elevate as well as Brain HQ. These are brain training programs and she just got into this stuff and started working it. She started dealing with all these brain exercises. Brain exercises. Interestingly, she optimized her various nutrients and then it turned out, said, wait a minute, we haven't checked all the pathogens here. She ended up having Ehrlichia. She was from the New York area and she ended up having exposure because of a tick bite. When that was treated, she continued to improve and she's just done well. Interestingly, she had not only improvement in her MRI hippocampal volume, she also had a PET scan her first PET scan was diagnosed as looks like early Alzheimer's. Her latest PET scan looks like no Alzheimer's. So, she actually improved her PET scan, improved her MRI, improved her cognitive scores. And as she said, her significant other said to her, you went from disastrous to just plain lousy and then from just plain lousy to normal. And so, she now plays, she goes out and plays golf with her friends and they can't cheat on her. They can't cheat her anymore. She knows how many strokes they've taken.

Incredible. And what did her neurologist say?

You know, interestingly, her neurologist said, in fact, she went in, she said to me, she went in there and there were all these people, she said it was a very depressing kind of typical neurologist's office, everything's bad. And she said he came out and he was so excited because he saw how much better she was doing. And he started saying to her, you know, what have you been doing? This is incredible. And we hear this a lot. People will come out and say, whatever.

You'Re doing, keep doing it because something is working here. This is really exciting. What is on the horizon in terms of the research you're doing? Because clearly you and I have had experiences. We're seeing this over and over. Our colleagues who are doing this in functional medicine are seeing these results, but it's still pretty much dismissed by most traditional neurologists and Alzheimer's researchers and even all the Alzheimer's funding isn't going toward this.

Absolutely.

What is on the horizon that gives you hope around the research that we can show the data and begin to change the conversation.

You know, this is a great point because we really do have the opportunity now to reduce the global burden of dementia dramatically. You know, people wiped out things like polio and smallpox with vaccines, global programs. We need to have a global program to reduce the burden of dementia around the world by doing these correct things. And, you know, it's, this is not magic. This is our complex the next organism that we're dealing with, and you have to look at the right things and do the right things to do that. Where the research is going is to take these same principles. What we're finding, of course, is that the supply is being exceeded by the demand in all of these diseases. So we have to increase the supply, reduce the demand, and there's a unique chemistry for each of these, for macular degeneration, for frontotemporal dementia, for ALS, for Lewy body disease, and on and on. And adjusting this sort of approach to each of these We should be able for the first time to make improvements in all of these different neurodegenerative diseases.

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 kind of a perfect disease for functional medicine.

Yeah.

When you look at it, there are all these things that contribute. And so, unfortunately, all the scientists have 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.

It's all reductionist. It's all reductionist.

Exactly. And so you really have to look at this as a systems biology disorder and treat it with functional medicine. And 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 preprint on a trial where 84% of people actually improve their scores, which is unprecedented. And now we've just published another follow-up on 225 people who also improve their scores and improve their metabolic status as well. So we're very excited about this approach. Dr.

So I just don't want to just gloss over what you just said because you said that 84% of people in this trial that you did improve their cognitive scores.

Absolutely.

That'S incredible because that just isn't possible given our current approach. And so, you know, to me, this is something we should have billions of dollars of 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. And the beautiful part about your work, Dale, is you've really gone into the details of all the things that affect the brain. So, the brain is, as we learned, we went to medical school, we learned that basically there's this blood-brain barrier and there's basically it's an isolated system above the neck, which is just nonsense. And we know that everything that affects the body affects the brain. Everything that, and vice versa, but also we have to really understand how do we leverage those things. And 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 sort of from a big picture perspective, then we'll get into the 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. Can you just talk about these three things in general and how they affect the brain?

It's a great point. Really, we have to 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. 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 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 microbial 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. 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 synapses, keeping synapses to, oh, I'm under attack. I'm going to go into a protective downsizing mode, just as the world did with COVID-19. We went into a downsizing mode, protective mode, same idea. And 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. And 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. And so you can literally write an equation and see where the brain is for each of these people when they are having cognitive decline.

Yeah, it's so important because the thing 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. It 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 traditional medicine, right? And I'd love to sort of go through some of the details about how we start to look at these things, because there wasn't one thing, you know, you look at genetics, you look at biochemical markers, you look at MRI and brain imaging, you look at infections, you look at all so many different things. So can you kind of 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, you know, 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 it's, well, how do you know it work? How do you know what's working? Is it this or that? that in a way, you need everything. If you want to grow a plant, you can't just have sunlight but no soil or water. You can't just have water but no sunlight and soil. You need all. And so I think that's a disruptive idea in traditional medicine, which is we have to use multi-system approaches for multiple factors that are being addressed at the same time. So can you kind of walk us through the kinds of things we look at on the diagnostic 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, it's 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. That works great for pneumococcal pneumonia. Now, for these complex chronic illnesses, and neurodegenerative illnesses are is 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 the things that are failing in that network, in that system? And of course, what's interesting is this turns again completely backward the way we do these trials. All previous trials, you decide ahead, 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. 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. 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 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. Then, of course, we look at Do they have mycotoxin exposure? Do they have organic?

That's from molds, right.

Molds and mold-related toxins. And of course, you know, many people have been exposed to air pollution. That's another big one now that we 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. And 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. 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. So then we addressed those things with a functional medicine sort of approach. And the results are unprecedented, as we indicated, probably most important in the paper, not only did their cognitive scores clearly improve, but their MRIs actually improved. And 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 4.5%. If you are a normal person and you're actually doing quite well, you still have a slight shrinkage, about 1.7%. These people, their gray matter volume actually went up. It actually went higher instead of going down. 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.

Wait, wait. So what you're saying is in general, everybody's brain declines, Alzheimer's declines more, and 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.

Absolutely. That's exactly what we're looking for in that paper. That's like discovering penicillin, right?

I mean, this is like a big deal. And yet, and you and I both know there's a long way to go still. We've had a few people with cognitive scores, MOOCs 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? 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? And you could see in some of these people. There was an example of 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. She said, I'm not leaving my house. I'm not remediating it. Of course, part of the problem was that part of this was carried out during the pandemic. When we started it, the pandemic hadn't started yet. 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.

Wow. So basically what you do with these patients is you do a personalized approach.

Yes.

Which is looking at all the variables that we talked about just to kind of recap a little bit. You really look at specific genetics around the APOE4, which is really the 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 methylation, which is about B vitamins. And then you also look at the whole insulin resistance package, right? Because a lot of times doctors don't look at insulin, they just measure your cholesterol, 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, homocysteine, you all the other factors around infections like herpes and Epstein-Barr, tick infections, 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 really important thyroid. You look at all your nutritional status, right? The B vitamins, vitamin D, vitamin E, magnesium, zinc, copper, CoQ10, lipoic acid, Omega-3s. 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. I mean, 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. 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. 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. They were still very far along. The reality is you go through a period where you are asymptomatic, but you already have abnormal spinal fluid and abnormal pet scans, 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 it's relative. They know there's something wrong, their spouses often notice, but they say, well, I'm not that bad yet, I'll wait.

Don't wait.

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. 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 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 phosphotau that actually fights the insults. It fights the infections. things coming, the 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. 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, and there was this great line in there where the author said, there's basically categorical misclassification and etiologic imprecision. And that means that we categorize people according to symptoms, you lost your memory, not according to the etiology or cause. So this flips it upside down and is focused on medicine by cause, not by symptom. And 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 deficient in this particular nutrient or that, that gets treated. So it's very individualized. You're not just kind of throwing the same treatment at everybody. 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 sort of foundation. Talk about what are the specific kinds of dietary strategies, exercise strategies and the sleep strategies that you're using to 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 brainer size, which is brain training. Yeah, it's a great point.

And so as you know, 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 multifactorial approaches.

And the interesting thing to me is I wouldn't listen to anything that guy.

Says, by the way. 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. Yes, it's diet, exercise, sleep, stress, brain training, supplementation, and detoxification as the beginning. Then beyond that, there may be other things that are dependent on what we find. 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. If you're getting a good outcome, if you look at again, we're kind of 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. And so what happens is you know 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. You need to get those both back. You need to become keto-adapted and you need to get into ketosis, but you need to become metabolically flexible and be able to go back and forth between burning. Getting people to do that is a critical piece of this. Then, it's a plant-rich Low carb, they have essentially zero simple carbs. No sugar and starch. 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 for your glymphatics to act, in other words, appropriate time for sleep and appropriate time. Yeah.

So, tell us about autophagy and the fasting because that's really important too, right?

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. This is a critical piece. 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 can again measure your ketones. 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. 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. Surprisingly, high fiber diets are important for a number of reasons and really critical. 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 this in cognitive decline, restoring that insulin sensitivity, restoring the metabolic flexibility, getting the phytonutrients, helping with the detox, optimizing your gut microbiome. And as you know, lots of studies showing relationship between gut microbiome and brain function.

Tell us about, you know, how you came to understand that what you learned as a neurologist and as a researcher around Alzheimer's corresponded with these emerging ideas around functional medicine and how that led to develop the Bredesen Protocol.

Yeah, you know, and thank goodness there was functional medicine or we would still be figuring out how do we put all this together. So, you know, we were interested for 30 years in the laboratory, and we're simply going in, as you said, people have been unable to treat these diseases, Alzheimer's, frontotemporal dementia, ALS, neurodegenerative disease has been the area of greatest biomedical therapeutic failure. So we were trying to study what are the molecular drivers of this process. And what we could see with research was that there is a central switch, APP, which is literally integrating over all these signals. So the big surprise was that Everybody who's talking about Alzheimer's had the wrong idea. They've told you it's misfolded proteins, it's reactive oxygen species, it's prions, it's tau, all this stuff. But the reality is when you look at it, at the heart of Alzheimer's is an insufficiency. You have an insufficiency of signaling, which is picked up by this molecule APP, which then is protecting your brain for downsizing. It's very much, by the way, what's happened with COVID-19. We have an insult, SARS-CoV-2, and of course we're supposed to be sheltering in place and social distancing, but what's happened with that, with less interaction, we have a recession. This is exactly what goes on in the brain of an Alzheimer's patient. You have insults, and these are everything from herpes simplex type 1, P. gingivalis from your mouth, various molds from your sinuses, leaky gut, as you know, on and on and on, dozens and dozens of these things. And these insults trigger your brain to say, okay, I need to downsize. I need to shelter in place, literally. And it produces something that is an antimicrobial, which is the amyloid. So as long as you don't find those things and correct them, you're going to keep downsizing, downsizing until you can't dress yourself, you can't speak. And unfortunately, when you go in to see some doctor, an expert in Alzheimer's, they don't look for those things. And this is a critical piece. so what we studied was, what is the fundamental nature of this problem and the nature of it? It is an insufficiency in the network that mediates plasticity. And so what happens, you lose that plasticity and you start downsizing just as.

You see with synesthesia. What is plasticity?

So plasticity is the ability to change, you know, from plasticose in the Greek, something that is moldable. So the ability to mold your brain, to add add new thoughts, to add new memories. This is exactly what is lost in this disease because that is the network that is now downsized. It's basically saying, okay, Mark, can you live with a fewer synapses so that we can fight these things? You're going to use your resources now to fight the various pathogens or toxins or, you know, changes in insulin sensitivity and things like that, but you're going to have to live with a smaller function, basically. just as we are stuck with with the recession here in the United States right now.

Yeah, so your neuroplasticity is essentially all the networks that tie everything together in your brain, all the connections between the cells, all the messaging, all the new wiring that helps you learn and grow, that diminishes with all these insults that cause your brain to, as you say, downsize.

Yeah, it is protecting itself.

And what we've always learned is that once you go down, you're not going back up. That once you lose your memory, it ain't coming back. And that the best we can do is maybe slow it down. And the best research, we're talking about billions of dollars, hundreds of studies over many decades, have really come up with a big fat zero when it comes to any meaningful result to stop, to slow, or to treat Alzheimer's or dementia. And we've spent so much money and got so little because we've been focusing on the wrong thing. So in your program, the End of Alzheimer's program, you talk about what we actually should be focusing on. And you talk about these metabolic factors that can literally trigger this downsizing. So what are those factors and how do we rebalance them so we don't end up having this decline in brain function?

Yeah, it's a great point. And so, you know, we could actually see people improve just as you described in your 2007 book. And so this shows that that there is a set of things that are synaptoblastic, making connections and keeping connections, and a set of things that are synaptoclastic, pulling back. And when you're young, there's this beautiful balance. You're actively forgetting the seventh song that played on the radio on the work yesterday and stuff, that sort of thing. But then what happens with everybody with Alzheimer's, too high on the synaptoblastic, too low on the synaptoblastic side. So what are the things that are synaptoblastic? Well, step one, there is an energy gap. This turns out to be one of the most important parts about the Alzheimer's brain. As you know, if you just look at a PET scan, an FDG PET scan, you see that there is a decrease in the utilization of glucose by your temporal lobe and your parietal lobe. That is the hallmark, the signature of Alzheimer's disease, and it's present for about 10 years before a diagnosis. So you have a critical energy gap that you need to change. You need to address that gap, and the best way to do it, of course, is with ketosis. And you can, as Stephen Cunnane showed years ago, you can those ketones up to 1-2-3 millimolar beta-hydroxybutyrate, and you can address that energy gap. That's the first thing. The second thing is when we used to grow the neurons— Dr. Dean so.

Basically using a ketogenic diet, you can increase the way the brain uses energy and make it basically have more energy by feeding it fat instead of sugar and carbs.

Dr. Justin Exactly. And there are two problems there. One is that you've lost the flexibility, you've lost the ability. Everyone's stuck on the glucose side, they're not able to use the ketone side. You have to have the flexibility. And then the second is that they have the insulin resistance. So that even though they're trying to use the glucose, which is what they've used for years and years and years because of the standard American diet, they're now unable to do that because you literally have changes in the ability of insulin to signal. You change your insulin signaling IRS1 molecule from tyrosine phosphorylation, which is active to serine and threonine phosphorylation, which is inactive. You literally shut it down. And, when we used to grow neurons.

In a dish, in the lab. That's what you're saying, is that sugar kind of screws up your brain's ability to metabolize energy. Is that what you're saying? That's exactly right. Okay, because I don't people know what tyrosine and serine is. I think that's a basic take-home point.

Is that when you eat sugar, your brain doesn't like it and starts to shut down.

And it leads to Alzheimer's.

It becomes resistant to it, exactly right. It resistant to the insulin effects, which are so critical for keeping your neurons alive. So the beautiful thing here is that what we saw in the lab reflected beautifully what you and David Perlmutter and Jeffrey Bland were saying clinically. So that if we hadn't had all the great work you did, we would have been stuck. Okay, what's the next step we take now from the lab? But here's this beautiful functional medicine already to plug in the underlying science of Alzheimer's disease. So in that sense, very helpful. And as you said, sugar damages your ability to support your synapses. So you've got to address with ketones, you've got to address the energy, you've got to adjust the insulin sensitivity, you've got to get insulin sensitive instead of insulin resistant, which virtually everybody with Alzheimer's is. And then you have to have, you have to reduce any inflammation. Your brain responds to inflammation by saying, I am being attacked, there's some organism out there, so I'm going to make this amyloid, which kills these microorganisms, but in so doing, again, I'm downsizing. So you've got to get rid of that inflammation, not just get rid of the inflammation, resolve it, but you also have to find out what's causing it and address that. So those are the first three things. And then you've got to have the support. You've got to have hormones and trophic factors and nutrients that are critical for rebuilding those synapses. Fortunately, before you actually lose the neurons, you first lose the efficiency of the synapses. The synapses don't work well, but they're still in place, thankfully. So when we do the right things, these start working well again.

Yeah, you know, it's interesting. I remember reading this article, because what you're talking about is multiple different factors that explain the phenomena we see as dementia, but that it's not one disease. that it's many diseases and many dysfunctions manifesting as a particular set of symptoms that are common among people, but it doesn't tell you why. So, everybody you look at who's got cognitive decline or Alzheimer's, you have to be a detective and find out what is their particular issue. Is it more insulin resistance? Is it more of an infection? Is it a mold? Is it a toxin? Is it some other nutritional deficiency or hormonal lack? Like too much of something, not enough of something else. and what's really striking is that the inflammation is this common theme in all brain dysfunction, whether it's depression or ADD or autism or Alzheimer's or Parkinson's or whatever, it's inflammation in the brain. And so a lot of your work has really been in understanding what is driving that inflammation, because the amyloid, like you said, is not the problem. It's actually your body's attempt to fix the It's the band-aid that the body uses and to deal with the inflammation and the microbial factors, which often can come from gut and other factors. So talk to us about how, you know, we need to rethink this because I remember reading this article years ago in JAMA, which was called Shifting Thinking About Dementia. And there was a great line in there that says, We combine categorical misclassification with etiologic imprecision. and what that means in English is that we categorize people according to symptoms, not causes. And we are not really good at finding the etiology or the cause. So we're kind of just throwing spaghetti at the wall, trying to see what works. And what you've done with the Bredesen Protocol and the End of Alzheimer's program is to really map out systematically the ways in which you can identify those factors that are harming your brain Right. We call them dementogens. And what are those factors that we need to provide the body to optimize and enhance brain function?

Exactly. So, you know, what happens in COVID-19 again is cytokines. And so, you know, cytokines are killing people. As you know, the cytokine storm is the problem. Well, part of the inflammatory cascade, part of your innate immune system activation, is amyloid. So we have to quit thinking of amyloid as the cause of Alzheimer's. Amyloid is just like cytokine storm, except it's longer. Of course, COVID-19 has compressed all the things that go wrong in Alzheimer's into two weeks instead of 20 years. But it's the same idea. As long as you have something that is saying, hey, something's wrong with your brain, you are going to continue to make that amyloid. That's part of the response. So you're absolutely right. You have to determine what these factors are. And it's often, there are often biotin toxins or organic toxins or metallo toxins, air pollution of course has turned out to be a big one. So all of these critical things and then various pathogens and there are several of these chronic pathogens from Babesia to Bartonella to Borrelia to various mold species to herpes simplex type 1 to HHV-6A, these are all chronic pathogens and typically as you know, we don't know that we have them. So as you said, you know, this is interesting to me that we used to talk about people dying of fever. You know, in the 1600s, people died of fever all the time. And so now people talk about people dying of Alzheimer's. It's no different than fever. You shouldn't have a period after fever and be fever due to what? And you shouldn't put a period after Alzheimer's. Alzheimer's due to what? That's the critical piece. And so the doctors have always put the period. They say, you have Alzheimer's, but we need to know why for each person. And it's not one thing. It's not like tuberculosis. It's always the tubercular bacillus. all these different things. So that's, it is a systems disease. That's the point. Yeah, it's so true.

You know, I think in, you know, in, in neurology, there's a famous joke that the, the, you see the doctor and it's basically diagnose and adios. Here's the name for the condition you have. And there's not much we can do about it. Goodbye. Get your life in order. And that makes me crazy because, you know, over 25 years of doing this and working with people's brains, I wrote about this 12 years ago. I've seen more and more systems. of how we can really impact these patients. I mean, I saw a patient who had dementia, she had Lewy body dementia, which is sort of a sort of combo of Alzheimer's and Parkinson's. She couldn't walk, she was in a wheelchair. She had real cognitive issues. She was trying to run her business. She couldn't function anymore. And we essentially did this detective work that you're talking about using the approach that's described in the end of Alzheimer's program in the British protocol. And we found she had tremendous gut issues, tremendous overgrowth of bacteria and yeast in her gut, massive nutritional deficiency. She was diabetic, poorly controlled. Her thyroid wasn't working. She was post-menopausal and had all these various issues. And we simply corrected those things that we found. And she came back incredibly. And her energy came back, her cognitive function came back. She was able to be in her business again. She was able she was a relatively famous person who was able to record another album and write songs and write a book where she'd been totally dysfunctional and non-functional before and was able to even get up out of her wheelchair and start walking. So it's quite remarkable. And this was even over 80 years old. So no matter where you are in the spectrum, we see these remarkable changes that people just don't think are possible. And when you talk to traditional doctors about it, they kind of dismiss it. But, you know, there has been research on this. You know, one, one of our colleagues, and you've, you published a number of papers looking at these case studies. But one of our colleagues, Richard Isaacson, did an incredible study that looked at similar kind of personalized interventions, not even the full protocol, and saw that he could not only stop, but he could slow it and he could also reverse some of the symptoms of cognitive decline. So, can you talk a little bit more about what kind of approaches you do to looking at the factors that are going on and maybe sort of list some of the key factors that you're finding that are common among these patients.

Yeah, and I think the best way to do that is to talk about the subtypes. So what we described back in 2015 is when you start to look at these, to do the very evaluation that you just talked about, then in fact what you find is that there are people, although there are multiple contributors, people tend to have specific subtypes. So type one, inflammatory. These are people who have exposure. They may have leaky gut. They may have periodontitis. They may have metabolic syndrome. Lots of reasons that they have have inflammation, and that's the critical driver. And you can literally follow the molecular pathway from NF-Kappa B activation, part of the inflammatory pathway, to where it's producing the amyloid, which, as I mentioned, is part of the inflammatory pathway. So that's the type one. And those people, you need to look for things like HsCRP, TNF alpha, things like that. And then you need to use resolvins to improve these. And then you need to identify where this is coming from and to pack that. So getting again upstream is critical. Then there's type two, which is atrophic. And these are the people where they have low vitamin D, pregnenolone, progesterone, estradiol, testosterone, you know, on and on, the critical supports for this nerve growth factor, brain derived neurotrophic factor, B12, all these things. It takes, as you know, it takes a lot to keep a brain functional. You have over 500 trillion synapses in your head. You've got an amazing supercomputer inside your skull, so you've got to keep that and prevent it from downsizing. Again, this is a disease of insufficiency. And by the way, one of the most common things we're seeing now, nocturnal hypoxia. People don't realize it. The doctors don't check it. They say, oh, I don't snore. I don't need to look at this. And it turns out that when you actually look at it, you see that the oxygen has crept down during the night into the 80s, even into the 70s, we see people in the low.

70S who don't realize that they have problems with oxygenation.

So sleep apnea, you mean? Sleep apnea. sleep apnea. It's often without sleep, that's the key. Some of the sleep apnea is the tip of the iceberg, but there's upper airway resistance syndrome as another one of these. And there are people who just don't get enough oxygen at night, even though they don't have full-blown sleep apnea. So that's critical to check. And then of course we talked about the ketones earlier. Then there's the type 1.5, which is glyco-toxic, and this is the people where they've got both inflammatory changes because of glycation of hundreds of proteins, and they've also got the atrophic effect because they now have resistance to the insulin. So that's type 1.5 or glyco toxic. Those are the factors. You got to look at their hemoglobin.

A1C, their home IR, stuff like that. And glyco toxic means sugar being toxic to the brain. And it forms these crusts sort of like a creme brulee on the top of your brain. So it can't really work properly. And that you talk about atrophic, which means lack of things to help the brain grow. Trophic factors are essentially the fuel or the food or. the ingredients that the brain needs to function, including hormones and the right nutrients and vitamins and fish oil, all kinds of stuff that the brain actually needs to function. So you talk about the way you identify this, and I thought this was brilliant the first time I heard about it. Now, everybody knows they should get a colonoscopy to check their colon, but you come up with this term called a cognoscopy, which I love, which is essentially, how do you do a deep dive into to your brain and all the things that affect your brain that cause risk of cognitive issues. And by the way, all the things that you measure with a cognoscopy are all the things measure for any chronic illness to look at. And some are more prevalent in different illnesses. But with Alzheimer's, you've really come up with a model of a cognoscopy. So can you talk about what is a cognoscopy? What should we be looking for? How do we get it? Can we get it with our regular doctor?

Or is this something that you really need specialized care for now. Yeah, it's a great point. And people have told me, don't use that term cognoscopy. It sounds so horrible. But it's simple. It's easy to remember, and we all know we should get a colonoscopy when we turn 50. So we recommend everybody 45 or older get a cognoscopy. And as you said, it is things related to chronic illness, but the key is to prioritize. I mean, that's the key. The people who are getting the best results, as you know, are the ones who are prioritizing the things that are the most important drivers. It's different for each person. For some person, you know, it's going to be getting at that Borrelia. For other person, it's going to be getting get that mycotoxin. And another person, it's going to be the glycytotoxicity. So today, it's very simple to get a mold.

One might be lime, one might be sugar, sugar, one might be mercury, might be mercury, right?

And might be vascular. A common one is people just don't have the vascular support for their brain. And this is why they are downsizing. And so if we return that support, we return the oxygenation and the blood flow, they better. So the way you can get a Cognoscopy in it is three things. It is number one, a set of blood and urine tests, easy to do. Number two, it is a simple online cognitive assessment. And if you're completely asymptomatic and doing great and you're just in for prevention, you can stop there, just those two things. If you have any symptoms or you're not scoring well on the cognitive tests, you want to include number three, which is an MRI with volumetrics. You want to know the volume of your hippocampus. you want to know the volumes of your frontal lobes and your parietal lobes and things like that.

And hippocampus is that little memory center in the brain tends to shrink. Right. And I've heard you present some cases that when you've done these cognoscopies, you start these interventions that are in the end of Alzheimer's program, your new book, which everybody should get, and you map out the changes over time when you implement the Bredesen Protocol. And remember the story you told of the neurologist, the neuroradiologist who looked at the scans and was like, this was before and this is after. This doesn't make any sense. I've never seen this in my entire life to go from 20% of what it should be to 70 or 80 or 90% of what it should be. Can you explain how that happens?

Absolutely. And, you know, we see this again and again and again. We're actually just publishing another paper showing not only increase in hippocampal volume but also improvement in PET scans where you go from a PET scan that shows Alzheimer's to a PET scan that doesn't show Alzheimer's. We also see improvements in electrophysiology, so improvements in EEG, improvements in evoked responses, and of course improvements repeatedly in cognitive scoring and testing. So this is happening because you are putting the things in that actually support the brain. You're getting hormones and trophic factors that are critical. So the brain is now making the synapses once again. Now we don't know yet, is it making more neurons? Is it making just more synapses? Is it changing in terms of its astroglialosis? We don't yet know what's happening at the cellular level, but we do know that that atrophy is improving in many of these people.

So you said two things there that sort of struck me. One is that your brain can grow. You can rebuild brain tissue that's been damaged by the insults and literally grow your memory center, which correlates with improved cognitive function on the brain cognitive and second, you said you can do a brain scan that you can see Alzheimer's on, you can repeat the brain scan and the Alzheimer's markers on the brain scan are gone. That's like what? Stop presses, headline news. Why isn't this on the COVID of New England Journal, JAMA, cover of New York Times, Wall Street Journal? What's going on here?

Yeah, well, partly because of course the standard is, you know, do a thousand people and then do the whole study. So, you know, at the beginning, you have to start somewhere. You know, we're just getting the airplane off the ground, you've got to start somewhere. So we're looking, as you said, at these various cases. We are in the midst, I should say, of the first trial in history in which we look at all the different contributors for each person and do all address all these different things. We'll be finished with that in December, so very enthusiastic about that trial. But yes, we do see in these anecdotes that we're now looking at, we see improvements in PET scanning and electrophysiology and hippocampal volume and all these things. when you are getting these people to improve and to do the right things. You're literally just restoring a synaptoblastic neurochemistry.

And what that means is you're creating a brain that likes to build new brain cells.

That is capable. It's over almost 30 years ago it was discovered. It was, of course, I was taught years and years ago that the brain doesn't make new neurons. You get the ones you have and that's it. And then about 30 years ago it became clear that, hey, there are neural stem cells and you actually do make new neurons throughout life. And so it's a question of which ones do you keep? And do you have them interact with other neurons? Do they become part of the functional network? So it turns out you do make more of them. And if you do the right things, you can keep them and you can keep their interactions. Now, one of the big topics that.

You cover is the microbiome, leaky gut, inflammation, Alzheimer's. And so most neurologists aren't saying, well, let me look at your digestive system. Let me look at your gut and seeing if there's inflammation there. And how does that connect to the brain. And, you know, we talked to a colleague of ours, Rudy Tanzi, who's been pioneering some of the work around finding microbes in the brain. We thought the brain was sterile. We thought the brain had a blood-brain barrier that prevented anything bad from getting in. Well, it turns out that barrier is only semi-permeable and that things can get in and, and they can be even microbes. So can you talk about this amazing new research on the gut and the and the microbiome and how that impacts what we have to do with patients with Alzheimer's. And by the way, that patient that I had who had really had brain dysfunction, her main issue was her gut and we fixed it up after decades of being constipated, needing enemas to go to the bathroom and laxatives and tons of bad bugs growing in there. It was just amazing what happened.

We fixed all of that. Absolutely. And I think that, you know, when neurologist makes a diagnosis of Alzheimer's or pre-Alzheimer's, best thing the neurologist can do is refer the patient to a functional medicine doctor to deal with all the things that are driving this problem. But of course, the neurologists have felt like, oh, this is our province. We have to give the drug and watch you go downhill, which is really unfortunate. I think that's going to change. So absolutely, the gut is a driver. And I think one of the most interesting studies that was done in the last couple of years was a group, they were actually studying rodents, but what they were doing was injecting candida. And they thought, they wanted to see how long does the blood-brain barrier keep the candida. They injected it into the blood vessels and asked, okay, what happens when it goes by the brain? How long can the brain keep it out? And the answer was it went in immediately. So there is, yeah, candida, this is in a normal animal. So the fact of the matter is there is much more communication just as you pointed out, and as Rudy has been pointing out, there is much more communication between the brain and the periphery than anyone thought possible? And what have the pathologists shown us? When they look in the brains of patients with Alzheimer's, what do they see? Herpes simplex in the brain. They see Candida in the brain. They see Borrelia in the brain. They see P. gingivalis from your dentition in the brain. All these different gum disease. So the bottom line is our brains are communicating with the periphery much more than anyone thought before. And as you said, we actually probably have a normal brain might as much as that kind of blows my mind. We actually probably do have a normal brain microbiome and we're gonna have to have probiotics for our brain at some point.

Cognobiotics, right?

Cognobiotics, yeah. There we go.

Wow, that's incredible. But, you know, the approach also that is needed is something we don't do in traditional medicine, which is how do you restore a healthy microbiome? biome. And, this is what the focus of functional medicine is. How do you take the symptoms that people have, or even they may not have any symptoms in the gut, but look at the environment in there and optimize it by taking out the bad stuff, putting in the good stuff, and using the functional medicine approach to really heal the gut. So, I think what you're saying is that each patient is different and some may have gut issues, some may have other issues. One of the other issues that really affects people is heavy metals. And, there's been a lot of talk in the past about aluminum and Alzheimer's, but it was sort of, you know, sort of ignored. And I remember a patient I had, one of the first patients that I was like, I don't know what I'm doing with Alzheimer's. This patient has been diagnosed with Alzheimer's dementia. I have no clue if anything I'm going to do is going to work, but I'm going to try my basic framework of functional medicine to see if we can just take out the bad stuff and put in the good stuff. So, I did a cognoscopy of sorts. Got rid of the dementogens. And what was really striking about this guy, the guy Dale was, he was seven years old. He was a CEO of his major family business, couldn't function at all. So, it was in the corner basically depressed and not functioning. Nobody wanted to be around him. And, he had pretty significant dementia. But, when I looked at his story, he grew up in Pittsburgh and he lived in Pittsburgh and there's steel plants there. And, almost every patient of mine from Pittsburgh is mercury toxic because they put coal ash on the streets. They put it on the fields, gets in the food. It's in the air. And he had a mouthful of fillings. And normally, you know, normally when you do a challenge test for mercury with a patient in functional medicine, you know, you see a level of 20 or 50. That's like, you worry about that.

That's high.

Yeah. A hundred, you know, I've had, you know, maybe 20 in my whole life of doing, pay me 10, 20,000 tests. His was 350. I'd never seen anything like that. I had one other patient, I think I had 400, but almost nobody like that. And I got rid of his fillings, we detoxed him from the mercury. He also had all these genes like APOE double four. He had methylation gene problems. It has to be vitamins. He had genes that affect insulin resistance. He had years of gut issues. He had irritable bowel for decades and was on stellazine for his gut. And so he had all these issues that we treated. So we fixed his insulin and blood sugar. We fixed his gut. We fixed his B vitamins. We got rid of the mercury. And the guy literally came back like Rip Van Winkle from the dead. And it was the most striking thing I'd ever seen in my life. I was like, holy cow. I just cured Alzheimer's. And I'm like, and this was like 15 years ago. And I'm like, what? And that was really began the process of me going, wait a minute. The brain is so fixable if we understand the insults, which you have mapped out so well in the end of Alzheimer's. Alzheimer's and if we understand how to actually repair and heal the system. So talk about mercury and the metals and how these affect the brain, because this is, this is not to say that everybody with Alzheimer's has heavy metals, so they don't. But I've had a number of patients.

That makes a huge difference when you deal with it. Yeah, but as you said, you know, a certain number of them, that is the key piece. And here's the thing, you know, I mentioned earlier, your brain makes amyloid when it is under attack by microbes because it's trying to kill the microbes. But interestingly, the gene itself that amyloid comes from, which is called amyloid precursor protein, is a gene that is responsive to metals. So there's literally a metal binding region on the RNA, this piece that's going to be making the protein. So it is. It responds to Mercury, it responds to copper, zinc, iron. So this thing is part of what's binding up those metals. So it actually binds up. So what happens is you can actually give Mercury, and as you indicated, Mercury is literally a cause of Alzheimer's, not in everybody, but in a small group of people, probably something like 3 to 5% of all Alzheimer's patients, which still, it's a lot of them, there are going to be 45 million people with it who are the currently living Americans, 45 million of us will develop Alzheimer's during our lifetime.

Five percent is a couple of million of people have metal issues.

Exactly, this is a big problem. So this is why, as you said, you want to check this on everybody, because if that's one of the contributors, you need need to deal with it. And when you do, they do better. And it does, it increases the production of the amyloid and it both, interestingly, it induces the amyloid and it induces the tau as well. So it is a great way if you want to give yourself Alzheimer's, take some mercury, eat some sushi. Exactly.

But the funny thing is, you know, that not everybody accumulates the mercury and it's a lot has to do with genetic variation. I personally had mercury toxicity and I had cognitive function. I felt like I had dementia. Really, I did. My level wasn't 350. It was 187, which is bad enough still.

Yeah.

And, still bad enough. And so, I understand from a personal point of view what this does. And, it's one of the most potent toxins on the planet, probably second only to plutonium. It is the most potent neurotoxin. And, it's inconsequential to me that we don't as a profession really think about the role of toxins. We check the blood levels, but that doesn't really reflect the total body burden of these metals. And so there are ways through functional medicine and the approach you're talking about to really do this. Let's talk about the next topic, which is, you know, hormones. And I think, you know, I've seen some really interesting responses to hormones around thyroid, sex hormones. This is what we call a trophic factor. So it's not something that's hurting you, it's something that you're lacking, that your brain needs to function.

So talk about some of the big hormonal findings and what you're seeing with these patients. Yeah. And there's some elegant work published out of the Mayo Clinic a number of years ago where they simply looked at women who had for whatever reason. Take their ovaries out.

I'd say take their ovaries.

Move it up the ovaries, right, at the age of 40 or younger who did not get BHRT versus one who not get hormone replacement versus those who did get hormone replacement. And even though the hormone replacement has been imperfect for many of these, there was a striking difference. The ones who did not get the hormone replacement had a more than doubling of the risk for developing Alzheimer's. Even though the Alzheimer's wasn't diagnosed till years later. goes perfectly with the science that we talked about earlier. This APP is looking for support, and when it does not get that support, it's flipping over to the synaptoclastic. It's saying, we can't support this brain. And it goes beyond just estradiol to progesterone and pregnenolone and testosterone and vitamin D and all these things, thyroid hormone as well. These are all critical. And so repeatedly, people have come upon the fact that you're getting this at the time often when you're losing those hormones or down the road from this. And we see a lot of people now, something I never saw when I was training, people who are in their 50s, women who are going through menopause or perimenopause who have their first symptoms at that time. So for a number of reasons, it's huge. Not only the support side, but also, as Dr. Chris Shade has pointed out, progesterone is one of the most critical parts for your detoxification apparatus. So when you now get this relative of so-called relative estradiol excess or estrogen excess. This is because you've lost both, but you've lost the progesterone to a greater extent. You are at increased risk for toxin-related Alzheimer's disease and you're now getting this synaptoclastic burst. You are re-releasing these toxins, including mercury, that you have sequestered for so many years. So by multiple mechanisms, having too low a support from your hormones is a critical risk factor. for cognitive decline.

Yeah, and there is controversy about hormone replacement, particularly around cancer. Do you worry about that?

Do, absolutely. And so I think it's critical to have people see experts in this area, you know, Dr. Ann Hathaway, Dr. Prudence Hall, and many people who are BHRT experts who look at, you know, when's the best time to do this, what are the best doses, where, you know, when, if you, can you improve, get you get the better outcome, than this worry. Yeah, there is a worry about cancer, although some of the studies have actually shown reduced with appropriate use of estrogen and progesterone, reduced likelihood of cancer.

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 things like Katsu bands are turning out to be helpful. As you probably know, these are used by a number of the Olympic athletes who are training. This is where when you're doing your training, you have bands that are somewhat restrictive. They don't cut off completely the blood flow, but they are somewhat restrictive. They're basically telling your muscles you need to improve the flow. In fact, after you use these, people actually get improved flow not only to their muscles but to their of their brains. That's one way to go. Then, of course, E-WOT, 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. Again, this is a disease in which there is an insufficiency in support of this complex neuroplasticity network. 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 same sorts of things are impacted. Now you've got less blood flow, you've got less oxygenation, you've got more inflammation. Unfortunately, people who've had this are at increased risk for cognitive decline and really should all be on prevention for cognitive decline.

The exercise is key because that 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 exercise. It's actually precision exercise prescriptions too. It's not just, you know, just take a walk. It's more than that. And then sleep also is really important. A lot of people have sleep deprivation. nocturnal apnea, many people are misfit, poor sleep quality, and sleep has a huge effect on the brain.

Talk to us about how we evaluate and assess sleep. Dr. Yeah, and 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. Again, wearables are going to be very helpful here. Whether you like to use an Apple Watch or you like to use a stick an oximeter on your finger, borrow one from your physician, or you can get them online, very inexpensive. You can check to see where your oxygenation is at night. You should be sitting up in the 96 to 98%. 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. night. It could be from sleep apnea, but it can also be from upper airway resistance syndrome, another way, which by the way, that also increases your adrenaline, which then wakes you up. Then of course, people who have low hormones tend to sleep poorly, especially if your progesterone is low, you tend to sleep poorly. All of these things can collude to give you a poor sleep, and that's such a critical time. And 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've 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 solution. Dr. No. And the brain training and stress management to meditation, these things do affect the brain. I remember listening to some scientists talk about the ways in which meditation actually improves connectivity in the brain, neuroplasticity, brain cells reduce inflammation. so it's not just oh, just relax. There's actually science around how it actually affects the brain in a positive way.

You know, it's interesting. If you simply look at people's cortisol levels, as the cortisol levels go up, the brain size goes down. And 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. 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 this, as you know, this chronic stress for many, many years is damaging to your brain. It's to your vessels, you get the hypertension, on and on with all these problems, poor sleep, etc. Addressing that is very helpful. 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 your 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. You want to get rid of that as well. Then, there's targeted supplementation and there's detoxification. Then, addressing the various things that you've identified, such as mycotoxins, which can take years to reduce these things. 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. engaged since he or she has been doing this.

Yeah, that'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 brainer size, like brain HQ. So, you include that and 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. And so you use hormones, right? And you use estrogen, testosterone, progesterone, and then nutrients. So you replace all the missing nutrients and the key things like vitamin D, omega-3s, B vitamins, all these really help. And then you focus on the gut, right? You focus on fixing the gut if that's a problem. 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. And I found this incredibly effective for so many patients. And what really I sort of want to sort of talk about is what you found in the study now. You did all these things with these patients and you did a follow-up 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?

Yeah, I think the big takeaway from the study is that for virtually everyone, Alzheimer's and pre-Alzheimer's can be reversed. That you can reverse this problem by addressing the things that are causing it. And we know now from people who've been on since 2012. We had our first patients go on this in 2012. They are still better. This is something that was unheard of before because with a 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. With this, you improve and then you stay improved because you're actually addressing the the root cause, just as you've mentioned. So I think the big takeaway was the vast majority of these people could get better. And 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. And then thirdly, we've got, as I say, the sustaining of this. And 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. And 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. And we're seeing, we saw on average increasing in scores of 3.89 as opposed to, for example, the drug that was just considered success at a Canakinumab, no improvement, no stabilization, but in one trial at one dose only, the decline slowed by 22%. That was the exciting result. Dr.

So, basically, none of these drugs 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. It's like we're not talking about any great breakthroughs. who's here. Everybody gets so excited. We're in this drug and it's billions of dollars and it's so expensive and health care 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.

Absolutely. And then, of course, there's big discussions now right now about who is going to pay if atacanumab 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. And 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. About $100,000 per year, $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. And of course, the people who develop Altimmune Alzheimer's spend on average $350,000 per person by the time they pass away. Much of that, of course, is nursing homes. So it's, as you said, this is the most expensive disease. We're over $300 billion now in the United States per year 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. And so taking this sort of 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. And it's amazing. I mean, you did very rigorous science.

Looking at all the standardized tests that a traditional neurologist would look at, like at CNS vital signs, 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 look at brain MRI, I mean, how do you even get something more objective than looking at someone's brain size. And 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. So, you know, even if you're only 10, right, it's still a, it's still a major breakthrough.

Right.

And I, I wonder why, why do you think we, you haven't been able to sort of get funding from the NIH or, you know, major Alzheimer's sub groups, what do you think that's at a distances that's kind of 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?

Yeah, it's a great point. I think that there's 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 pardon. I actually talked to the vice chancellor of one of the greatest universities in the country in terms of medical school who said, you know, 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. So we're kind of stuck in this loop of, you know, let's do things the old-fashioned way. And I think it will take continue, you know, it'll 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 as you indicated earlier, they close one hole out of the 36 holes. So you're still, you've got a lot open, but having them for targeted things is going to be very helpful. 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, you know, 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. And 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've got to do this drug. And there was a great piece a couple of days ago talking about this new drug. And they were interviewing a guy who said, oh, this is a breath of fresh air. I'm giving this drug to all my patients. Oh, who are you? Well, I'm a consultant for the company? Well, okay, yes, if you're a consultant for your company and you're being paid, and 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. You know, this is just an unethical approach, unfortunately. And so it's going to take some time to break through that infrastructure that has been created by billions of of dollars.

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, end of Alzheimer's program. And this new book, I sort of want to dip into a little bit, the first survivors of Alzheimer's, how patients recovered life and hope in their own words. Because, you know, we really, you know, we hear cancer survivors, we never hear of Alzheimer's survivors. Tell us about some of the stories that you found striking and what are the takeaways that you had from some of these patients.

Yeah, you know, 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. And 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 APOE 44, so highest risk group and unfortunately I have cognitive decline. Can you just at least help me stay where I am? The doctor looked at her and said, Good luck with that. 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. 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 so much better. Interestingly, she then had a little bit of a backslide, and it turned out she ended up having Babesia. She had had a tick bite and had gotten rid of the Lyme but didn't realize that she had a co-infection. Now it turns out she's also got some mycotoxicity, 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. Wow.

Almost normal.

Yeah, so high, very, very high normal. 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. She's one of the seven stories. We have seven wonderful stories. We have Frank, a guy who moved to Mexico because he knew he wouldn't have enough money as he got demented. His doctor said, oh, you've got mild cognitive impairment. He said, There's nothing mild it's ruining my life. 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, and 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. If you have an ongoing insult, getting rid of it is the last thing you want to do. She would get worse. 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 MOCAT score of 30. She's done great.

What was it before?

She started at 20. She had significant MCI. Again, you don't start going down on your mocha 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. She's done very, very well. Now, five years into this, she's 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. She writes about this. Then, when she found out, My God, I didn't pay pick them up. She would be just horrified. Oh, my God, I'm going to lose my granddaughters because of my cognitive problems. She ended up having a tremendous amount of mycotoxicity, actually had to get away from the source of that and go into a detox program, and she's done very, very well. We have 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.

This is extraordinary, Dale. And I think that people need to take home that one, that if you even start to have symptoms, there's something you can do.

Yeah.

More importantly, there's a lot of people who are at risk. So we say there's 14 million people who have, are gonna have Alzheimer's in a few years. How many people actually have pre-Alzheimer's or are headed that direction? Because it's, it's tens and tens of Millions. Right. And this 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?

Yeah, we recommend that everyone who's 45 years of age or older get a Cognoscopy, just like we know when you turn 50, you get a colonoscopy. When you hit 45, please get a Cognoscopy. That's a set of blood tests that we've been talking about. It's online cognitive assessment, very simple, takes about 30 minutes. And then if you have symptoms already or if you're scoring poorly on the tests, it includes an MRI with volumetrics. That's it. It's simple to do. I have to say it's much more pleasant than a colonoscopy. Get that checked out and 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 Christine Yaffe from UC San Francisco who showed that if you just follow serial autologous autopsies. This is now the third leading cause of death. 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 6 million diagnosed heading for 14 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.

And 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. So, that's really impressive. And it tells me that it's really important people understand if you have any Alzheimer's in your family, if there's any risk factors that we need to fix those. And, 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? And that's really important because if you let these things slide, it's harder and harder to deal with them. And, you know, what's even amazing is that even after you've gotten the symptoms, which is 20 or 30 years after you first start to get the process going in your brain, you can start to stop and reverse it, which is what your work is showing. And that's actually helpful, but I encourage people to think about how do they get a cognoscopy earlier in their life, 45, 50, whatever, 60, just get these things fixed. And, this is what I do in functional medicine with you do. And, it's really, really so powerful. powerful. 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 sort of 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, you know, sort of pushback against it. How do we, how do we break through that?

Yeah, it's a great point. And 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 the this thing. You know, it's, 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 the, you know, variants, we have sequence, we know how to deal with that sort of stuff. People develop vaccines, they develop antivirals, they develop improved immune systems, all that. With Alzheimer's, the problem has been people haven't understood what it is. So they'll say, oh, it's, you mentioned type 3 diabetes, and, yeah, that's part of it, but it's not the whole Right? They'll say, oh, it's all about herpes or, oh, it's all about amyloid, tau, prions, APP changes, all these on and on and on. And 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. And 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 that does all the different things we need, great. But there's no evidence so far that that is the right way to go. So I think that it's simply going to be continuing to publish these studies and 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. So one of the things we've now added 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. And 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.

So what is the next step in your work? Yeah, what are you, where do you see the next step of pushing this forward? You'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've treated in the study, but they've been collected that show improvements. What is the next step in your work?

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 MOCAS scores of 0, 1, 2? 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. 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-stage neurosyphilis because you treat it early. And 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. Second piece is we need to continue to improve the overall approach, and this is why we've got the randomized controlled trial starting up. And then the third piece is we need to now adapt this. to the neurochemistry of each neurodegenerative disease. Each one affects a different subsystem of the nervous system. We need to be able to adapt the neurochemistry for each of those. We're actually starting with macular degeneration. We have the first few patients already who have early macular degeneration. They have a different chemistry. In fact, interestingly, APOE4 protects protects you against macular degeneration. Apoe2 is the one which protects you from Alzheimer's but increases your risk for macular degeneration. So, it's a slightly different strategy. You have to go after this.

I agree.

Okay, well, make sure that I'm sure you're on top of your doing the right things. You're not a smoker and you're not drinking alcohol. These things that will predispose you to macular degeneration. So that's, 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.

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