#209 The End of Alzheimer’s w. Dr. Dale Bredesen

Jul 15, 2023 | DISEASES, The Gabby Reece Show

Episode 209: The End of Alzheimer’s

Dr. Dale Bredesen MD on Breakthrough Treatments for Cognitive Diseases, Protocols & Practices to Revive Your Mind & Reverse Cognitive Decline + Practical Pillars for Brain Health

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Hi everyone. Welcome to the show. My guest today is an expert in neurodegeneration, Dr. Dale Bredesen. What if we didn’t have to worry about Alzheimer’s anymore? Well, Dr. Bredesen has been working in this area of Alzheimer’s and dementia for over 40 years and has come up with many programs. He’s written a book called “The End of Alzheimer’s Program” and other books, and he now has case studies of people who have been in cognitive decline and are now, through lifestyle changes, medication, and certain treatments, not only seeing improvement but getting back to normal. 

Not only that, but what are the things we can do right away when we’re small children in our twenties, thirties, and forties to avoid this process altogether? There are tests. There are things that you can find out about your genetics. There are things you can do in your lifestyle habits. There is supplementation that you can do to protect your brain. And I hear about Alzheimer’s, but I wonder, “What is it?” There are so many variables, not a million, but quite a few, that impact the reasons why people have this type of cognitive decline. And there is now a way to avoid and improve it.

He is dedicated to this space and has been doing this work for a long time. You can see his passion; I just really appreciated Dr. Bredesen and all he had to say. I hope you enjoy it.

Key Topics:

  • Who is Dr. Dale Bredesen?
  • The Challenge of Alzheimer’s Study
  • What are the Types of Cognitive Decline & How Do They Differ?
  • New Protocols and Programs to Manage Cognitive Decline
  • How Do Patients Die From Alzheimer’s?
  • How to Get People on Prevention Before Alzheimer’s
  • The Four Stages of Cognitive Decline
  • Reversing Cognitive Decline
  • Common Misconceptions About Alzheimer’s
  • Supplements & Nutrients for Alzheimer’s Patients
  • Sleep Apnea and Cognitive Decline
  • The Impact of Stress on Cognitive Decline

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Welcome to the Gabby Reece Show, where we break down the complex worlds of health, fitness, family, business, and relationships with the world’s leading experts. I’m here to simplify these topics and give you practical takeaways that you can start using today. We all know that living a healthy balanced life isn’t always easy. Let’s try working on managing life a little better and have some fun along the way. After all, life is one big experiment, and we’re all doing our best.

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Your generation should be the first generation not to fear Alzheimer’s because there’s a tremendous amount you can do. This was a big fear for my generation, but you should be able to avoid this pretty much a hundred percent for your life. We’ve all been told there’s nothing you can do about this disease. There’s a tremendous amount you can do, but you’ve got to do the right things for the right people in the right way and in the right order.

DR. DALE BREDESEN

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As you know, in health, it’s just an incredible time right now. The hundred-foot wave of global health is neurodegeneration. So, it’s always been an area where you, if you have Alzheimer’s, frontotemporal dementia, Lewy body dementia, go right down the list. ALS, you’re going to die – it’s a hundred percent. And we are the first to reverse cognitive decline in Alzheimer’s disease. So, we got the beginning of a hundred-foot wave. We need to know that we can do it for everyone in our trial; 84% of people got better. That was freely available online and published last year. We need to make it so that they get completely better. And we need to ensure all other diseases are the same.

So, Dr. Bredesen, it’s natural to wonder what led you down this path. Do you have any personal connections to this line of work? Did you have a grandmother or someone close to you who struggled with the conditions you now work on? What inspired you to pursue this particular field?

I picked this field because I was a freshman at Caltech and read a book called “Machinery of the Brain” by Dean Wooldridge. This is Thompson Ramo Wooldridge Fame. I was interested in computers then and thought, wow, the brain is such a fascinating physiological computer. There are distinct differences between how a computer chugs through its data and how the brain does.

But there are some similarities, and how the brain works is fascinating. And what I found very quickly when I went to medical school then to pursue neurology is that the area of greatest medical failure therapeutically is neurodegeneration. So, as they say, everybody knows a cancer survivor. Nobody knows an Alzheimer’s survivor. So we described the first back in 2014, and some of these people are still doing very, very well, almost ten years later. Very excited about that. So that’s how I got interested in it.

And it was like a no-win game when you started.

Oh, absolutely. And much of it still is.

You’ve done all types of things around this topic, but when you’re researching and trying things, there’s not a bullet approach to things, but there is this buckshot approach. How do you maintain that kind of drive and faith when you’re in something that we’ll never be able to figure out?

It’s a great point. And when the first person got better in 2012, she called me up on a Saturday morning at my home, telling me how much better she got. We’ve been in the lab for almost 30 years, which is the most depressing thing. And worse than that is when you get something that looks pretty good, and your colleagues say, no, we don’t believe it anyway; look at the science. But this is working. That’s the worst.

We tried to start very simply. I set up my lab initially at UCLA in 1989. I have worked for two different Nobel laureates. I was very excited about the work that they did. They changed the world of what’s going on in the brain. And so, when we set up the lab, the idea was straightforward. We wanted to understand the fundamental nature of the neurodegenerative process: why is Alzheimer’s so common? What happens to people’s brains when they get Alzheimer’s? One of every seven people dies of Alzheimer’s in the U.S. It dwarfs the pandemic. COVID killed over a million Americans: Alzheimer’s will kill about 45 million currently living Americans if we don’t do something about it. Now we’ve gotten to the point that we can pretty much say if you start early, it’s optional. We can do a great job if we get everybody on prevention or the earliest protocol. It’s the fact that people wait. You feel so sad for people like, poor Bruce Willis, where people knew there was something wrong for years, but they didn’t do something about it. (Now, to be fair, He, unfortunately, has frontotemporal dementia, which is different than Alzheimer’s.) But again, it’s part of that neurodegenerative group, and we better understand what drives that process.

So when we were studying this, we got to the point where we could see specific signals that come into brain cells, and as you mentioned, it’s the buckshot. Each one has to be hitting the right thing. And so we started to be able to do that and said, “Okay, let’s see if we can do a clinical trial with a drug that changes you from the bad side to the good side.” We realized very quickly one drug is not going to do it. So we started asking, “What could we add to one drug to target those other things?” We identified 36 holes in the roof; it’s 36 different pieces that are all critical to give you that synaptogenesis so you’re getting away from losing the synapses.

Now you’re restructuring and making new synapses. We found that exercise alone hits several of these. And a plant-rich, mildly ketogenic diet hits a couple more of these things. And good quality sleep with appropriate deep sleep and REM sleep hits a couple more. We started realizing we could construct precision medicine for each person, a personalized protocol that hits all the different things.

When I was a little boy, I was in a surf club, and there was a lot of discussion about what it would take to ride a 60-foot wave at Kaena Point. It was impossible. No one had ever done it. It was pointed out, “Hey, you just can’t paddle into these things. So, of course, your husband and his two buddies, Dave and Buzzy, change the world by inventing tow-in! So the tow-in for medicine is precision medicine. It allows you to do things never done before. So, unfortunately, 99% of doctors are still practicing the old way. Gabby, if you went in today and said, “You know, I’m having trouble with my memory; things are not good,” they might check your B-12 level, vitamin D, and a few other things. But then they’ll say, “Gabby, you’re in the earliest stages of Alzheimer’s disease. We’re sorry. Nobody knows what causes it. There’s nothing we can do about it.” Well, that’s the old way. Now we can look at all the different informatics, the whole genome, and your epigenome. We can look at specific markers; we can look at your tendency toward inflammation. We can look at your HSCRP, your homocysteine, go right down the list. Right now, we look at 150 different variables, but it should be millions, and it will be millions soon. And therefore, we can say, “Ah, Gabby, here’s what’s driving this.” You may have changed your oral microbiome. You may have a leaky gut. You may have some chronic sinusitis. You may have a chronic infection that you didn’t know about. Now when we address these things, that is the silver buckshot. People get better like never before. So that is the tow-in of medicine, and unfortunately, it hasn’t caught on in part because third-party payers don’t want to pay, as you know. So we need to change the fundamental practice of medicine.

It’s a push-and-pull dynamic in this industry, and unfortunately, money is made when people are unwell. It’s crucial to break down complex information and encourage individuals to invest in themselves. Regularly assessing inflammation markers and other indicators through blood tests can help identify potential health concerns early. By committing to these preventative measures, we can take steps towards improved health outcomes.

You said something about there’s difference between Alzheimer’s and frontal lobe degeneration. How are those different?

There are several different neurodegenerative diseases. Alzheimer’s is by far the most common, which is why we hear about it so much. But with frontal-temporal degeneration (FTD) or frontal-temporal lobar degeneration( FTLD), instead of hitting your temporal lobes and your parietal lobe (which is the main place you get affected in Alzheimer’s), it hits your frontal lobes and your temporal lobes. And it’s different in terms of what you see under the microscope. These diseases are classified pathologically by 19th-century pathologists looking under the microscope. Alzheimer’s was 1906, just after the 19th century, but shortly after that. So when, when you look under the microscope at Alzheimer’s, what you see in addition to the loss of brain tissue, you see this amyloid material, it’s a little piece of a protein, a little peptide that collects in the brain, just dramatic increases in this stuff, which turns out interestingly to be part of your innate immune system. It’s the stuff that’s fighting the microbes. So the old view was we want to get rid of that amyloid. And that’s, unfortunately, what the drugs do. They’re getting rid of your ability to fight these microbes. So you really want to find out what they are fighting and what you can do about it.

And then you see also this tau, which is the thing that is a bolt. So when you put out processes in your brain, you must keep them stable. So you bolt the microtubules together with tau. And so, no surprise when this pops off, things collapse. Frontotemporal dementia, you don’t see those things. You see something, a different thing that’s called TDP 43. It’s a different protein that collects and a different place in the brain.

Years ago, I had the opportunity to read “Grain Brain,” a book that resonated with many readers. The author, Dr. Perlmutter, was motivated by his father’s situation and explained how brain inflammation can be challenging to detect compared to joint pain or soreness. This condition is a chronic brain inflammation, which some call diabetes three. However, there are things we can do through new protocols and programs to manage this condition. Despite common misconceptions, Alzheimer’s doesn’t only affect individuals over 65; it can begin earlier in life. But one thing you said that jumped out was that the brain protects itself. 

It’s an entirely different way. So when you get down and look at the molecular biology of this disease, it’s not what we thought it was. It’s not that this amyloid is hurting your brain; it’s that your brain is under attack. And by the way, this can start in your twenties, so we don’t diagnose it typically until your sixties and seventies. Although one thing I wanted to mention, which is critical, is that epidemiologists have shown us that the most dramatic increases have been in people in their forties and fifties. So when I was training in neurology in the 1980s, we never saw people in their fifties with Alzheimer’s. It was a disease of typically sixties, seventies, eighties, and nineties. Now, one of the most common things we see is people in their early fifties developing Alzheimer’s. Someone called our home at 4:00 AM here from the east coast crying, saying, “My spouse has developed this and is 58.”

We hear it all the time. So, unfortunately, this is on the rise in young people, and here’s why. So what happens is you have insults to your brain, Just like anything else. David and Lee are our old friends; David’s done a great job with so many things in neurology and has been writing “Grain Brain” and other significant pieces about what’s going on in your brain for many years. So what happens is your brain is under attack from organisms, interestingly, from your oral microbiome; the neuropathologists who’ve looked in the brain find oral microbiome organisms in your brain. They find candida in your brain. They find Lyme disease bacteria in your brain. So our brains are under assault. And we’re also exposed to toxins like never before. From the food we eat, from the air we breathe. The whole disaster right now on the east coast, with the poor air because of the Canadian fires, is a disaster. We have the California fires here, which do increase the risk for dementia. And unfortunately, COVID-19 has already been shown to increase your risk for cognitive decline. And so what I’m talking about is not just getting Alzheimer’s; it’s about being sharp every day. Most people can be sharper just by doing the right things. So you’ve got these insults, mainly inflammatory ones, as David mentioned, but also loss of energetics and toxins.

So what we found in the lab is that Alzheimer’s is about two major groups of things, too little energy to support your brain, which is why it’s critical, and why I love EWOT (exercise with oxygen therapy) because it’s getting the blood to the right places and it’s oxygenating it appropriately.

It’s why if you have sleep apnea, you won’t be as sharp as you should be. Energetics is number one for Alzheimer’s, and 1A is inflammation, as you said. And it’s interesting; it’s the innate part of the immune system, not so much the adaptive part. It’s that older evolutionary part that gives you the inflammation. And it’s especially the memory component of that which lives in three places. It lives in your bone marrow and your endothelial cells; that’s why the blood vessels tend to become sticky, and you get some thrombosis in people who are getting Alzheimer’s. And then thirdly, it’s in the tissue macrophages, which in your brain are called microglia. They’re the little guys running around. They’re eating up the plaque and trying to get rid of it, but you, they don’t want to get rid of it until you get rid of the inflammation. So the idea of removing plaque; it’s just like saying, I’m going to paddle into the hundred-foot wave. I don’t care. You’re not going to survive. And this is the problem. They keep removing this stuff instead of getting after what’s causing it; then remove this stuff. I think that’s the future – combining targeted drugs with these personalized protocols is what Alzheimer’s is all about. And then, we can adapt this to all these other frontotemporal dementia, Lewy body dementia, ALS, etc.

 Dr. Bredesen, I realized I don’t understand why people die of Alzheimer’s. What actually happens when people die from this disease?

It’s a great point, and you’re right; It doesn’t affect your brain so much that you stop breathing.

So we all need to remember that you’re doing a lot today. You brush your teeth today. You got up today. You took care of yourself. You did all the appropriate things. When you stop being able to do that, what happens is you get infections, you get pulmonary emboli.

So Alzheimer’s patients lie in bed, get clots, and throw those clots into their lungs, causing them to die or get infected. Bladder infections are common, also. These infections become sepsis. You get this throughout your body, and you die. So unfortunately, it is the inability to do the daily activities that ultimately lead to the deaths of people.

You said that there are two modes: the protective mode and the growth mode. Many people assume that they can only be in protective mode with age, but this is not the case. It’s possible to develop new neuro pathways throughout life, and staying in the growth mode is essential to maintain cognitive function.

Professor Mike Masnick took on this problem years ago. He’s the father of brain training. He says when you do brain training, you have new interactions and things you can do for your entire life. It does not stop.

Getting people to be compliant to try something new is so difficult. Have you found a technique or way to reach people that they will, regardless of age, make a change or pivot? What is it that gets them finally to do it?

This is an excellent point because this has been one of our most significant issues. People typically don’t want to do what it takes for prevention because they don’t feel bad.

When you get cognitive decline associated with Alzheimer’s, you go through four phases. And, of course, everyone right now is talking about reversing aging and Ozempic. Those are the two things that are everywhere. But what good does it do to live to 140 if 70 of those years are dementia? So we want to make it so everyone stays sharp to a hundred.

The first phase is you’re asymptomatic. You can already show on PET scans that you’re beginning to lose those synapses. You’re beginning to have the changes associated with Alzheimer’s. What’s interesting is the loss of the ability to utilize glucose in your temporal and parietal regions. That’s step one or phase one.

Then phase two is subjective cognitive impairment. That’s when people will start to listen. You can’t remember phone numbers anymore. You don’t recognize the face of an old friend. You pulled up to a stop sign and didn’t know which way to turn. Things like that. That’s SCI. Interestingly, SCI lasts about ten years on average, so we have a tremendous opportunity, and we can basically make a hundred percent of SCI people back to normal.

It’s easy, but they won’t do it for prevention. So we’re encouraging everyone to get on prevention if you’re in your 40s. It’s easy to do: get a cognoscopy, which is to find out the basic things, like, what are your risk factors? If you don’t do that, then please do SCI, as you have those first changes happen. If someone tells you it’s normal for your age, that’s not doing you any favors.

The third phase is MCI, mild cognitive impairment by definition. Now you’re not scoring normally on cognitive tests. 84% of those people got better in our trial, but we worked hard to get that.

What does that look like? What do these tests look like? And what does it take to right the ship? 

When you take these cognitive tests, they will test several parts of your brain. They test your memory, ability to read, and ability to remember simple things and add and subtract. And then recognizing things and recognizing shapes. Interestingly, drawing a cube and then drawing a clock – one of the first things to go in Alzheimer’s disease is the ability to draw a clock and put the hands on appropriately, which I’ve always found interesting because that’s a pretty easy thing for most people to do. But because of the affected area of the brain, the parietal lobe especially, patients lose the ability to draw that clock. And it often is very frustrating. It’s what’s called posterior cortical atrophy. It’s one of the presentations of Alzheimer’s, a tremendous problem with shapes.

It’s just so great to see people with terminal illnesses get better and stay better. We have people over a decade now that have improved. So those are the things they typically check when checking your cognition.

When you say you got “84% of our people to improve,” – is it that combination of lifestyle change with medicine? What does that look like? And then when you say, “We had to work hard,” is it just really staying on top of people and ensuring their environment when they leave you consistently supports that recovery?

So number one, they have to do the right things each day. As a competitive athlete, you know if you took a year off, it would take some time to get back. No question. You may take a day off, but you’ll never take a year off. But this is what’s happening. You have to remember when we see these people; we’re seeing a process that’s been going on typically for 10 to 20 years. So we have first to figure out what’s been causing it. And some of these things, people don’t even believe it.

It’s like Sherlock Holmes. You have to look and see if there are infections. The woman that I mentioned with the PCA ended up having herpes simplex. We had to treat that. She ended up having a tick-borne illness that was undiagnosed. She ended up having mycotoxins. Found those, treated those. And then there are the basics. There are seven basic things that we do for everybody. 

1) So you have to have a plant-rich, mildly ketogenic diet. 

2) You have to exercise, especially blood flow oxygenation. 

3) You have to fix your sleep. So many people drop their oxygenation while they’re sleeping. 

4) So, you have to manage your stress. Stress damages your brain. 

5) You must do some brain training, 

6) Detox, and 

7) Targeted supplements. 

Those are the seven basics that help everybody. Then we look for the infections, and we look for the toxins that people are exposed to, and that’s when we can see the things that are driving synapses to be lost. Then we can stop everybody from progressing. But then it’s a different question: how do you regain the synapses you lost?

And that has to do with your hormones, and it has to do with your trophic factors, and it has to do with your stem cells. So it’s a different set of instructions to build them back up. But the good news is your body is pretty plastic. It’s doing this somewhat, so we want to support that.

You’re just making that environment buoyant. That’s so amazing. Now the fourth stage, because I parked it on the third …

Yes. So you go from my mild cognitive impairment – Again, I would ask everyone don’t call it mild cognitive impairment because it’s like saying you only have mildly metastatic cancer – it’s a relatively late stage of Alzheimer’s. Still, by definition, that means you’re not doing well on the cognitive test. But you’re okay with your activities of daily living. When you lose your activities of daily living, that’s when you have dementia. That’s the fourth phase. And now you’re having trouble taking care of yourself, showering, etc. It starts with trouble taking care of your bills. You’re not going to be able to drive and things like that. That’s dementia. And unfortunately, as you know, pretty much everyone waits until that fourth phase. That’s the worst thing you can do. If we could get everyone on early phase, we could make, we literally could make Alzheimer’s optional.

And you know, your generation should be the first generation not to fear Alzheimer’s because there’s a tremendous amount you can do it. This was a big fear for my generation, but you should be able to avoid this pretty much a hundred percent for your life.

You are an expert in Alzheimer’s disease; you have written several books, such as “The End of Alzheimer’s,” “First Survivors of Alzheimer’s,” and “The End of Alzheimer’s Program.” Can you share any experiences of individuals in the fourth stage of Alzheimer’s who have benefited from your program? Or is it too late to make any significant changes at that point? Could you provide insight into how your program works for individuals in the later stages of Alzheimer’s?

There’s this thing called MOCA, which is Montreal Cognitive Assessment. It’s a 30-point scale, and it tests everything we discussed, like drawing cubes and clocks and memory and things like that. So when you’re normal, your score is probably 30 out of 30.

And most people are in that 28, 29, 30. Then, when you’re down at the 24s, 25s, that’s MCI; you’re abnormal on your testing. When you hit down in the low twenties and teens, that’s dementia, and we’ve had people at zero; that’s end-stage dementia.

Interestingly, a guy wrote to me, saying, “My wife has a MOCA score of zero and went on your program, and she’s come back; she’s doing well now.” The difference is we can take people now from 18 to 30. We cannot take people from zero to 30. We can take people from zero to nine, which is excellent. They can dress themselves again. They can speak again.

But two big problems: We can only get them partially back. That’s my goal while I’m alive. Can we get someone from zero to 30? It’s Kaena’s point at more than 60 feet – it’s tough. It’s going to take stem cells and things. But here’s the big problem. When you have the fourth stage of dementia, getting people to budge is harder. They’re not taking care of themselves; they’re getting infections. They don’t remember what to do. This is why I urge everyone to get in early. We can do so much more. Yes, we’ve got many cases where people get better with even very low MOCA scores. It’s just that it’s less common.

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What are some common misconceptions about Alzheimer’s disease that you have observed among people? For instance, some people may believe that Alzheimer’s is only prevalent in older adults and that there is no way to prevent or manage the condition. Are there any other inaccuracies that you frequently come across?

So, the entire world of Alzheimer’s is backward because there has been nothing to do about it in the past. So, what do they tell you? We don’t know what causes it. That’s B.S. We may not know in a thousand cases, every single one, but we know 990 out of them. We know what’s in your brain. We know what that amyloid is. Fight those infections. So that’s the first thing.

The second thing they say is that it’s probably just normal aging. We had a doctor recently who had gone to his neurologist because he was having trouble thinking, and his neurologist said this is just normal aging. This guy was already in the fourth phase! He had dementia, but his neurologist told him it was normal aging. So that’s the second misconception. You should stay sharp till you’re a hundred. You should be doing things because you’re doing the right things with your blood flow, oxygenation, stress levels, and all those things.

The third inconsistency is don’t find out your genetics because there’s nothing you can do about it. That’s ridiculous. In the United States, three-quarters of us are APOE4 negative. So that is the most common gene associated with Alzheimer’s risk. So I checked myself; for example, I’m a three-three. That’s the most common. My lifetime chance is about 9%. It’s not zero, but it’s not too high. If you have one copy of APOE4, and that’s 75 million Americans, your risk is now 30%. If you have two copies, that’s 7 million Americans, and most don’t know it. Your risk is about 70%. Most likely, you will develop Alzheimer’s. So everybody should know their genetics around this—at least their APOE4. If not, about another hundred genes are associated, but they’re not as common as this one. So everyone should find out.

And there’s a wonderful website started by an APOE4-positive woman doing fantastic, by the way. She’s improved. She reversed her decline, and she’s sustained it for over ten years. So it’s called APOE4 Info. For anyone who finds out that they are APOE4 positive, don’t give up. It’s not your fate; it’s just a risk. We’re where we were with cholesterol and lipids 50 years ago. Do I check my cholesterol? Yes. Check these things. There’s a tremendous amount you could do about them. You should not have cognitive decline. Again, it should be optional.

What role, if any, do different types of dopamine receptors play in cognitive function? Is that connected to hormones, or where does that live?

That’s a great point. So if you look at how a country is organized, you know when a country’s having problems. By the way, this is similar to what happened in Covid 19. In early 2020, we knew that there was a new insult in the country: SARS COV two. What were we told? There’s an insult, so we’re going to shelter in place, we’re going to socially distance, we’re going to stay away from work, all that stuff. And the country went into recession. That’s the same thing that your brain is doing. It says there’s a problem, and I must pull back. I’m switching from a growth and maintenance mode to a protective mode. That means I’m going to make the amyloid. I’m going to activate my innate immune system. I’m going to kill the bacteria; I’m going to bind the metals. I’m going to deal with the toxins. So these things are all critical.

You can look at the different genetics, which tells you many things. Yes, the most crucial neurotransmitter for Alzheimer’s is not dopamine but acetylcholine. So most of us are low in our diets on choline. We need a little more choline, an essential neurotransmitter for making memories. If you give someone an anticholinergic, they lose their memory; if you give them for an extended period, they increase their risk for Alzheimer’s. If you give them benzodiazepines for an extended period, they increase their risk for Alzheimer’s. So there’s yes, acetylcholine, and then BDNF, brain-derived neurotrophic factor that increases with exercise, is also intimately related to your ability to make and keep synapses and to the Alzheimer’s processing itself. So there’s a real intimate relationship there between BDNF and Alzheimer’s. And then, interestingly, ketones, having that ketone level high, gives you the energy you’re losing in Alzheimer’s disease. And then hypercoagulable states. So the point is anything that makes this network not work optimally, it’s like having your car good with gas and grease and having everything work so it’s going well. That’s the same thing happening in your brain, so you must have all these different pieces.

That’s why this idea that it’s just one thing and we will eliminate that one peptide is so silly. You have to look at the entire function, and it’s also why something that helps one person with Alzheimer’s may not be the right thing for another person because there are different rate-limiting steps for different people, and this is just a fascinating disease in that way.

You can see all these different things. You can tease them out, find out about the BDNF, find out about the acetylcholine, and find out about the various pathogens and toxins. We had one guy in the trial who had turned out to have a hypercoagulable state, he would get on an airplane and be sitting there, and he would get to Europe, and he was, he was confused. And it turned out when that was addressed, which you can do pretty quickly, we have a tremendous armamentarium for these things where we’ve all been told there’s nothing you can do about this disease. You can do a tremendous amount, but you have to do the right things for the right people in the right way and order.

What about Neurotropics? Have you observed any supplements or nutrients that have been effective for your patients in improving cognitive health, especially when combined with other lifestyle changes and therapies? While I understand that you cannot prescribe supplements without a proper diagnosis, are there any general recommendations you provide to individuals looking to improve their cognitive function?

That’s the good news. The armamentarium is enormous. I mentioned EWOT before. Exercise with oxygen therapy helps people to perfuse. And yes, there are some supplements that I like. One of them’s whole coffee fruit extract – turns out to be very nice. It increases your BDNF. It helps just as exercise does help. The second thing is to make sure you can get into some ketosis. People talk about taking ketones; it helps their performance. They can do better on bicycles and things like that. Your brain has to burn one of two things: glucose or ketones. As we get a little older, we lose the ability to burn both of those, and that’s what the PET scan of an Alzheimer’s patient shows. You’re no longer burning glucose well in your temporal and parietal regions. So you’re losing that ability because you’re insulin sensitive. After all, you live in America. You’ve been eating processed food your whole life, and your insulin has been crazy high, and it’s horrible. And so you lose that.

Now, what’s interesting is because the insulin has been high, that prevents you from making ketones. So, you then lose both of these. When I see patients, this is an energetic emergency; I want to get them back. So, I start by telling them to take some exogenous ketones. Over time, we can get you into endogenous ketosis, but you have to remember this disease is a network insufficiency. You’re not supporting that network and demanding too much because of the inflammation. And therefore, I want people to go only a bit with fasting. They can be frail. They can hurt themselves. So, I love the ketones. I love a whole coffee fruit extract. And then I love resolvents. This beautiful work is from Professor Charles Serhan out of Harvard, who discovered resolvents related to omega threes. It’s your innate system’s memory. Your innate immune system has a set point, so when exposed to saturated fats and various organisms and things like that, it’s set to go off like a hair trigger.

So, you’re sitting there, and you’ll make inflammation at the drop of a hat. So, when you take omega three’s, it lowers the set point. Now the problem is if you continue to have organisms, it will be a problem. But we want to dial that down. We’ll find the organisms, get rid of them, and you’ll do better now. So I love the resolvents and omega threes because they are cousins of the resolvents. One’s more of an anti-inflammatory, and the other is more of a resolution of inflammation. Then, of course, vitamin D, so many people are low on vitamin D.

And you know what? It affects your brain. People who are low in vitamin D are unquestionably at increased risk for Alzheimer’s disease. Then other things, most people in the U.S. are low in four things. They’re low in. Choline. They’re low in zinc, they’re low in magnesium, and you can throw in potassium as a fifth as well. So most of us are low on these things.

Depending on what food we’re eating and how we’re eating, there’s a huge issue. And I wonder if you’ve interviewed Professor Rick Johnson from the University of Colorado. Still, he, David Perlmutter, and I published a paper just a few months ago on fructose. His work is beautiful, showing that fructose tricks your body. It’s telling you winter’s coming, so you dial down your ATP, which is horrible for Alzheimer’s.

Neurotropics? Do you think it’s gimmicky?

In general, what we’re trying to do is as physiologically relevant as possible. So help you to have optimal various things. These things are a little bit like adding a little flogging. A lot of the people who are developing cognitive changes will get some degree of ADD. Some argue it’s a bit controversial, and people say, well, you really had it when you were a kid, and you’re revealing it again. But we see it frequently. They don’t have the attention they did before, so they’re not storing the memories. And some of them will tweak with little bits of Adderall. You don’t want to do that every day, but for specific periods when you want to be focused, you can do that.

Neurotropics have been controversial, but I have no problem with them. Again, we’d like to see everybody be sharper. Most people don’t realize that their normalcy with their brains is not what they could be. It’s like what you see with people exercising; they’re not what they could be. They could do better if they would get out there and be jogging more, exercising, keeping nimble, and all those sorts of things.

The name of the game is: it doesn’t have to be everything all at once. It just has to be consistent. You don’t have to kill yourself and deny yourself every single day, but you have to move consistently, consistently try to eat well, get to bed, and find ways to sleep well. 

Regarding sleep apnea or disruptive sleep: what are some ways to get sleep regulated without heavy-duty medications?

Wearables are very helpful to all of us. And so, it’s easy. Now you can check with your Apple watch, or you can check with your aura ring and see where you got deep sleep. You want to have at least one hour of deep sleep a night. You want to have at least an hour and a half of REM sleep a night. And if you’ve got sleep apnea, you may see the oxygenation drop. There’s another condition called upper airway resistance syndrome, which is a little harder to pick up but relatively common. Of course, one thing you also can get is a dental device.

If you’ve got sleep apnea, it increases your risk, not just for Alzheimer’s, but also for heart disease, hypertension, esophagitis, and atrial fibrillation. So you want to address that. Get with someone who does that for a living. They may say you should get some CPAP, A-PAP, or a dental device. The devices are getting better for sleep apnea. It’s easier and easier to do this.

People are starting to look at what’s causing your airway to be small. Over time (a little bit like having braces), you can begin to open that airway up at night. You may have some chronic sinusitis. There are many options, but reports claim that 80% of sleep apnea goes undiagnosed. If you’ve got any questions, get it checked out.

In today’s fast-paced world, stress become an inevitable part of our lives. While lifestyle changes can help us improve our cognitive health, it is crucial to manage stress effectively to prevent it from taking a significant toll on our mental well-being. As a healthcare professional, you must have encountered several cases where stress adversely impacts an individual’s cognitive function. For parents with children at home, could you suggest some practical tips or lifestyle changes that they can incorporate to manage stress effectively and mitigate its impact on cognitive function?

We were made as human beings, evolutionarily, to have periods of stress and then resolution and periods of stress and resolution, and that’s okay. That is hormesis. You’re improving things. That’s what competitive athletics are. It’s stress and resolution, stress and resolution.

The problem is for so many of us, we have this chronic, unresolved stress. So you keep going for years and years with no resolution. During my first week as an intern in 1978, I was up all night, every night, and by the end of the week, I couldn’t get my shoes on. My ankles had swollen because I walked 24/7. It’s not a way for human beings to function. Now, it was later that the Libby Zion rule came into play. (Libby Zion, sadly, passed away because people were not thinking [about the stress]. But it turned out to be a massive stress. I ended up getting arthritis, essentially revealing an arthritic process.

So, I say to people, especially young people, take some time. The thing that’s tricky about being young is you can get over almost everything, so you only see the damage it’s doing to you once you’re older. So take some time away; take some time to do things that you love. The enjoyment is actually a huge positive for your brain. Your brain shrinks when it gets exposed to chronic stress. Find what you like. Some people like forest bathing (so-called shinroku). Some people like music, so enjoy some music. Some people like meditation, yoga, those things. I used to laugh at these things. I thought this didn’t move biochemistry. But I can’t ignore the data. It absolutely does move the biochemistry.

I also suggest getting some of these things checked out. You might be surprised that your telomeres aren’t as long as you thought they were; you might be surprised that you’re already starting to have insulin resistance. We have insulin resistance in eight-year-old kids now, so find out where you stand, and if you’ve got this, then the great news is you can do things; it’s easier and easier.

One of the common things people say to me is, “I don’t want to eat this plant-rich, mildly-ketogenic diet. It’s too much of a pain. I got to go shop for things. I got to look to see what’s organic. I got to find the right things”. Okay, so we worked with Nutrition for Longevity, a great group. They do a fasting-mimicking diet. They have assembled our Keto Flex 12/3  plant-rich, mildly-ketogenic brain-supportive diet. You can get it from them. It’s easy. So the good news is: do some of these easy things and enjoy it. Enjoy life, and you will live longer. You will live happier and avoid these chronic illnesses that unfortunately don’t announce themselves symptomatically until they’re mostly over.

Dr. Bredesen, I cannot ignore that some people might consider certain aspects of your approach as “woo-woo” and prefer a more scientific approach. However, based on your information, I would like to inquire about your opinion on adaptogens and their impact on cognitive function. Many people consume adaptogens regularly to improve cognitive health, and I would like to know whether you believe this to be effective or just a waste of money.

There’s so much coming online here. Adaptogens are huge. I take them myself. They’re fantastic – things like ashwagandha, an adaptogen, and it is actually supportive. The change in medicine is it’s not about one thing killing you. It’s about a network that’s dysfunctioning. So we want to avoid hitting it with a hammer. We want to tap here and tap there and improve these things over time. The interesting thing is those are pro-synaptogenic. So they are allowing you to change your mind. But we’re interested in whether they will be necessary now that you’ve eliminated what’s causing Alzheimer’s. Will they be essential to help you reestablish the synapsis? We have yet to find out. The jury’s out on that. That’s a huge issue.

There’s so much you can do, and again, just being aware of these things and not letting yourself run into the ground. At the first symptoms, get on prevention; please don’t wait.

Finally, you mentioned telomeres, which makes me think of Dr. David Sinclair’s work. Could that give some buoyancy to what you’re talking about? 

I’ve known David for years, and his work is fascinating. He’s now interested in reprogramming, of course, and his argument is we can go from age 60 to 20; time will tell. I worry about some of these issues because things have changed. We know from Kara Fitzgerald’s work: Kara’s done some cool stuff where she’s made people about 3.2 years younger. So you can go backward a little bit, but can you go backward 40 years? We have yet to find out. Hopefully, David’s going to tell us over time.

But what we can do, when we’re in the new trial that we’ve just started, it’s six different sites around the country. We include brain aging, and we include biological age. So what we’ve been doing for the brain will make people a little bit younger, but it’s probably relatively small changes in making people younger.

But these are things you can do and absolutely. Studies showed that caretakers of people with Alzheimer’s are under tremendous stress, and they have telomeres that are shorter on average. So again, we’re understanding the whole network.

I appreciate your approach and the faith to plug along and create these programs. Please remind us, Dr. Dale, where everybody can find you.

Dr. Dale Bredesen on Facebook; you can find me there. Apollo HealthCo. I work with Apollo, a group from Apple that does exciting software. Then also, Instagram, Twitter, DrDale Bredesen.

Again, thank you so much for reminding people if you are in your twenties, thirties, or forties, it’s an excellent time to get things checked out, take a test, get your blood work done, and know a little bit about your genetics to give you that tool for prevention for this long-term kind of vitality. Thank you for joining us today. 

It’s been my pleasure. Thank you so much for having me on the show. Take care, everybody.

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About Dr. Dale Bredesen

Dale Bredesen, MD, received his undergraduate degree from Caltech and his medical degree from Duke University. He served as resident and chief resident in neurology at the University of California, San Francisco (UCSF) and as a postdoctoral fellow in the laboratory of Nobel Laureate Professor Stanley Prusiner. He was a faculty member at UCLA from 1989 to 1994 and was then recruited by the Burnham Institute to direct the Program on Aging. In 1998, he became the founding president and CEO of the Buck Institute for Research on Aging and an adjunct professor at UCSF. In 2013, he returned to the University of California, Los Angeles (UCLA) as director of the Easton Center for Alzheimer’s Disease Research, and he is currently a professor.

The Bredesen Laboratory studies basic mechanisms underlying the neurodegenerative process and the translation of this knowledge into effective therapeutics for Alzheimer’s disease and other neurodegenerative conditions, which has led to the publication of over 200 research papers. He is the principal investigator for the Alzheimer’s Disease Research Center at UCLA. He established the ADDN (Alzheimer’s Drug Development Network) with Dr. Varghese John in 2008, leading to the identification of new classes of therapeutics for Alzheimer’s disease. His group has developed a new approach to the treatment of Alzheimer’s disease, the MEND protocol, and this approach has led to the first description of a reversal of symptoms in patients with mild cognitive impairment (MCI) and early Alzheimer’s disease. Dr. Bredesen is the author of two New York Times bestsellers: The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline and The End of Alzheimer’s Program.