The idea that Alzheimer’s disease can be prevented, and even reversed is transforming the medical world. Today we get to speak with one of the key people responsible for this revolution. An internationally recognized expert in the mechanisms of neurodegenerative diseases. Dr. Dale Bredesen’s research explores previously uncharted territory in explaining the physical mechanism behind the erosion of memory seen in Alzheimer’s disease, and has opened the door to new approaches to treatment. This work has led to the identification of several new therapeutic processes that are showing remarkable early results.

Dr. Bredesen is a prodigious innovator in medicine, with over 30 patents to his name. Notably, he put most much of his findings and research into the 2017 New York Times bestseller book, The End of Alzheimer’s. His most recent book, the first survivors of Alzheimer’s also prevents presents the stories of seven individuals who reverse their cognitive decline using his recode protocol. Dr. Bredesen graduated from Cal Tech and earned his MD from Duke University and served as chief resident neurology at the University of California San Francisco before joining joining Nobel laureate Stanley prisoners laboratory at UCSF as an NIH postdoctoral fellow. He has held faculty positions at UCSF, UCLA and the University of California, San Diego. Dr. Bredesen also directed the program on Aging at the Burnham Institute before joining the Parker Institute in 1998, as founding president and CEO.

LINKS:

  • The End of Alzheimer’s Book – LINK
  • The First Survivors of Alzheimer’s – LINK
  • Apollo Health – LINK


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Robert Lufkin  0:00   

Welcome back to the health longevity secrets show and I’m your host, Dr. Robert Lufkin. The idea that Alzheimer’s disease can be prevented, and even reversed is transforming the medical world. Today we get to speak with one of the key people responsible for this revolution. an internationally recognized expert in the mechanisms of neurodegenerative diseases. Dr. Dale Bredesen, his research explores previously uncharted territory in explaining the physical mechanism behind the erosion of memory seen in Alzheimer’s disease, and has opened the door to new approaches to treatment. This work has led to the identification of several new therapeutic processes that are showing remarkable early results. Dr. Bredesen is a prodigious innovator in medicine, with over 30 patents to his name. Notably, he put most much of his findings and research into the 2017 New York Times bestseller book, The End of Alzheimer’s. His most recent book, the first survivors of Alzheimer’s also prevents presents the stories of seven individuals who reverse their cognitive decline using his recode protocol. Dr. Bredesen graduated from Cal Tech and earned his MD from Duke University and served as chief resident neurology at the University of California San Francisco before joining joining Nobel laureate Stanley prisoners laboratory at UCSF as an NIH postdoctoral fellow. He has held faculty positions at UCSF, UCLA and the University of California, San Diego. Dr. Bredesen also directed the program on Aging at the Burnham Institute before joining the Parker Institute in 1998, as founding president and CEO. And now please enjoy this interview with Dale Bredesen, and D. Hey, Dale, welcome to the show. 

 

Dale Bredesen  1:58   

Thanks very much, Rob. Great to be here. 

 

Robert Lufkin  2:01   

Yeah, well, full disclosure, I think you and I overlapped a little bit when we were both professors at UCLA. I don’t think we met them. We’ve we’ve met we’ve met after that and been working together on on a few projects. Since then. I’m, I’m so excited to talk about the work you’re doing about changing the world of Alzheimer’s disease. And also, I want to mention your new book. First survivors of Alzheimer’s, I highly recommend it to everyone, as well, as well as your your other two books. They’re probably my go to books on Alzheimer’s disease, I recommend them for everyone who wants to get up to speed with the latest best thinking on it. Thank you. But before we dive into those, perhaps we could set the stage and maybe tell us you could set the stage and tell us a little bit about maybe when you knew that you wanted to work in this area. 

 

Dale Bredesen  3:08   

Yeah, that’s a great point you so I got interested in the brain. I was an undergrad at Caltech years ago. And I got interested in how the brain functions and how it’s similar to a computer. And then from there, I got interested in you know, what brain diseases how does this work, and so I became a neurologist. And of course, as you know, the area of neuro degeneration is the area of greatest biomedical therapeutic failure. So if whether you’ve got ALS or Frontotemporal dementia, or Alzheimer’s disease or Lewy body or PSP are so you just go right down the list. This has been an area where medicine has had nothing to offer. And unfortunately, these are horrible diseases, as we all know, and they are you know, they’ve been death sentences for so many people, and they’re very common. So Alzheimer’s is Professor Christine Jaffe from UC San Francisco has pointed out, now the third leading cause of death in the United States, it’s actually the second leading cause of death in the UK. So it these are very common. And just for comparison, for perspective, we’ve now had over 700,000 people in the United States die from COVID 19, the pandemic nearly 100 times as many will die of the currently living Americans will die from Alzheimer’s. So this is a very common problem, and there just hasn’t been anything. So I got interested in basic research, could we understand the fundamental nature of the neurodegenerative process well enough so that we could begin to fashion the first effective treatment so we’ve been interested in so we spent years we’ve published over 220 papers in peer reviewed journals on what actually drives the degenerative process. And so right back in 2010 2011, we realize okay, this is driving us to a completely different model of what 

Alzheimer’s is. So as you You know, the standard idea was Alzheimer’s is because somehow you collect amyloid in your brain. And that’s bad for your brain, and it’s, quote misfolded proteins. And what we found was completely different. The research shows that this is actually a response to various insults. So you have this amazing molecular switch in your brain, which is amyloid precursor protein, it’s the thing that gives rise to the little fragment of amyloid. But literally, this thing will switch back and forth when things are good. And there’s a direct analogy, of course, to what happened with COVID-19, where we were all told there’s an insult, SARS, cov, to, we’re going to socially distance, we’re going to shelter in place, we’re going to not go to work as often all these things and what happened, the country went into a recession. So your brain does very much the same thing. When times are good, and you’ve got enough nutrition, and you’ve got enough hormonal support and nerve growth factor and BDNF and all this all the good things going on. Your brain makes a decision it’s going to make and keep synapses and you can make new memories and learn new things and all that when things are bad. You have ongoing systemic inflammation, infections in the brain, exposure to toxins, poor nutrition, you low menopause, with very low estrogen, or any of those things, you now have a mismatch between the supply and the demand. And so your brain switches to a mode of protection. And when you make the amyloid, the amyloid is a beautiful anti microbial peptide. And that’s been very well shown by professors Robert Moyer and Rudy tansy from Harvard showed a number of years ago that this is an anti microbial peptide. So this thing that we vilified as the cause of Alzheimers is really a response to these various insults. And that tells you to prevent it and treat it, you have to do something completely different. You have to determine for each person, why is the brain defending itself? What what is the what are the insults that it is responding to, then you can go after those. And we have better results that have ever been published previously, we’ve done a number of papers. This is why I also put in the book that we’ve just finished a a the first clinical trial in which instead of predetermining, a treatment that is a one size fits all, which has never worked. We’re looking for each person and all of the different parameters. Do they have unrecognized pathogens? Do they have unrecognized toxins? Do they have insulin resistance? Do they have leaky gut and just go down there dozens and dozens of things. But you see then that what we call Alzheimer’s is really the brain defending itself. 

 

Robert Lufkin  7:51   

So So Alzheimer’s disease is really much more complex than we thought it was. And it’s this this reaction to things and I wonder, what is it about Alzheimer’s disease that’s, you know, arguably resisted the efforts of some of the greatest minds in science and medical care and, and essentially unlimited financial resources over the last 20 years to come up with any sort of effective drug for it 

 

Dale Bredesen  8:20   

is a great point. And the answer is because we all understand the concept of systems medicine and systems biology, but virtually nobody practices it. So everybody is making the assumption that there’s one thing that’s causing the problem and we’re going to go after that whether it’s amyloid, tau, prions, misfolded, proteins, reactive oxygen species, you name it, people’s people have thought about is it herpes is a type three diabetes, we are all sorts of ideas. But everybody wants this to be one thing. And of course, all the pharmaceutical development has been around a single small molecule. So imagine that you have all sorts of issues, the country’s in a recession, and there are all sorts of things that are driving that. And that everyone was saying, well, what’s the you know, the one person we’re going to hire, that’s going to make it so that the recession just disappears? It’s just not that simple. So I think we’re all understanding more and more that the idea of treating something with penicillin, because there’s a simple pneumococcus. That’s a 20th century approach. This is now the 21st century and we’re dying of complex chronic illnesses. This type two diabetes, cancer, cardiovascular disease, Alzheimer’s, all the neurodegenerative diseases, so we have to change. We’ve switched from checkers to chess, and we have to change the way we evaluate and treat patients with cognitive decline. 

 

Robert Lufkin  9:50   

It’s almost as if our failure with Alzheimer’s to find a single drug is representative of a bigger failure in treating Essentially all chronic diseases that we’re failing at, but but the other chronic diseases like stroke, like diabetes, like hypertension, like a heart attack, all have some sort of identifiable mechanical or biological symptom, you could treat like, you know, a heart attack, you put in a stent, or you replace the plumbing. But it really doesn’t fix the root cause, which is metabolic disease. And with Alzheimer’s, there’s no symptom really, cognition is really hard to, we still don’t even know how the brain works. And so it’s especially hard to do anything about that. But, but, 

 

Dale Bredesen  10:42   

and if you’re planning on that, this is a really important point. Because what happens is, we used to think of this as a disease of old age, what’s now become clear is that the that the pathophysiological changes started about 20 years before a diagnosis of Alzheimer’s. And as you well know, that’s been picked up both by longitudinal PET scans, but also by cerebrospinal fluid. So you can see the beginnings of changes. So really, this is a disease of your 40s 50s and 60s, diagnosed in your 60s 70s or 80s, and can be even into your 30s that you can pick up these abnormalities. So what you really want to do is look for those things as early as possible. And one of the big problems is everyone’s trying to treat this in its last stages. And think about it when someone says you have mild cognitive impairment, it includes the term mild, this is like telling someone you have mildly metastatic cancer, it is a late stage. So in Alzheimer’s, as you know, there is a stage that in which it is asymptomatic. Then there’s subjective cognitive impairment, which lasts about 10 years from epidemiological studies. So the window is huge for us to treat. And the virtually everyone with sei can get better if you do the right things. The third of four stages is MCI mild cognitive impairment. And it’s that final stage that we call Alzheimer’s disease. So that’s been the few years you know, you have to begin to lose your activities of daily living. So this is a late stage of decline. If people would simply switch to getting this evaluated early and think about all the great improvements that we had with colonoscopies and pap smears and Mahmad Ruffy. We need to do the same thing for cognitive decline. 

 

Robert Lufkin  12:32   

Yeah, and I want to I want to talk about prevention in a second. But before we leave, before we leave the the overall Alzheimer’s issue, I have a confession to make. My mom was diagnosed with Alzheimer’s a few years ago, and we got the best medical care in the world at the time, which was to basically put her in a room and wait for her to die, which she did a few years later in 2017, which is incidentally the year that your New York Times bestselling book, and your work became widely known. The problem is that I’m I wonder about is currently, the state at most, many, if not most patients with Alzheimer’s disease still received the treatment that my mother got and why you’ve you’ve published clinical trials, randomized clinical trials showing the effectiveness of this work. And you know, other people are, you know, there’s a groundswell of, of evidence, scientific evidence of how effective this is. I wonder why is there so much resistance from our colleagues? Is this some sort of is this been politicized somehow? Or why aren’t people shouting this from the treetops and giving everybody ketogenic diets in nursing homes? And, you know, these are simple things? 

 

Dale Bredesen  13:56   

Right? It’s a good point. And there are a couple pieces to the answer. And it really shows you know how medicine changes, it takes time, as you know, the the phenomenon of scurvy, there are people each century, 16th century, 17th century, 18th century, 19th century came up with something to do about scurvy. And each time, the experts said, no, no, that’s not it. And so 1000s More died of scurvy until 100 years later, they did the same thing. It’s really a sad history, unfortunately. But one of the issues is that there’s a fundamental change in the way we think about medicine. That 20th century medicine that you and I went to medical school for was about we’re to determine what it is, is it a brain tumor? Is it Parkinson’s? You know, what is it and then we write a prescription or we send people to surgery. That’s medicine. 21st century medicine is about why is it? It’s a systems medicine approach, where we’re looking at all the different things, and it’s interesting you already see this, you know, Google knows where you shop They know what you do, as they say, they probably know a lot more about you than you want them to. Because they have sophisticated computer based algorithms that follow you around? Why aren’t we doing the same sort of thing for looking at all these physiological parameters, that’s where medicine is headed, it’ll be much better when we can say, here are all the things that are causing your cognitive decline, your hypertension, your renal failure, you know, what have you, we will do much better. So we’re asking people to abandon the way that they were trained in medicine, that’s very hard to do. But the second thing is actually quite interesting. If you look back at the opioid epidemic, and the opioid scandal that really came to a head and there are now these multiple documentaries, you can almost place it on top of what’s currently going on with Alzheimer’s. What happened, there were a company making billions of dollars that use that to create a coercive infrastructure to tell doctors, this is what you’re supposed to do. And they then did things which unfortunately, resulted in unnecessary deaths. We’re in the same situation. Now. There is a coercive infrastructure as a very nice op ed recently, from one of the experts who said that everyone who wrote a very positive review of advocate Emad the drug that was just approved, was paid to do so. So everybody was a paid consultant, the Alzheimer’s Association was paid over $1 million by Biogen to say that their drug was a good drug. And this is really sad, because as you know, it doesn’t make people better. It doesn’t halt the decline. What it did was only in one trial, at one dose, it slowed the decline by 22%. So we need to do better than that. And unfortunately, we’ve got the unfortunately, it’s it’s been more about incomes than outcomes, we need to focus more on the outcomes and less on the incomes. 

 

Robert Lufkin  17:03   

So yeah, very, very good point. I mean, what you’re saying, I guess is is is part of it language matters, and how we what we call the disease matters, like, we have a symptom separately a disease but fever, and fever can cause because by a pneumonia or an infection, or you know, many different things can cause fever. And if we look for a treatment for fever, giving an aspirin will lower the fever, but it doesn’t take care of the root cause. I wonder and with what you’re saying with Alzheimer’s disease, if we do you think there would be value in renaming 

Alzheimer’s disease, if we have like mold related Alzheimer’s disease or inflammation related all timers disease? Or are they too interrelated. To for that, to really be valuable? 

 

Dale Bredesen  17:53   

This is a great point. And as you know, Alzheimer’s was defined pathologically by Dr. Alzheimer in 1906. So this has always been a pathologically defined disease. And what we’re now understanding is that there are many things that contribute to that pathology. And there are there are four basic groups. But what we what we did was we subtype this, we can find that there are six different subtypes. So there’s a more inflammatory form of Alzheimers, there’s a more a trophic form, you can get to the same place by doing different things by withdrawing support. Since this is really about supply and demand, you can either make the demand higher, which is what happens with inflammation and toxicity, or you can decrease the supply which is what happens with energetic loss and trophic loss. So you do see people as I said, inflammatory, Alzheimers a trophic. And then glyco, toxic so many people have insulin resistance, as part of this is one of the most common contributors to cognitive decline, as you know. And then there is toxic, and that could be three different types of toxins in organics. And of course, anyone who’s been in the California fires has an increased risk now, with because of this air pollution, of course, anyone who has a lot of exposure to air pollution, some very nice work on this, at UCLA, and USC on looking at air pollution, and its increased risk for cognitive decline. And then the organics as well formaldehyde and, and benzene and things like that, by the way, the people who are in the World Trade Center, who were first responders, over 15% of them now have cognitive decline. And so definitely this being exposed to these very poor air quality is a huge issue. And then the third group is toxins. And these are, these are bio toxins, things like mycotoxins, as you indicated, you know, I was never trained as a neurologist that toxins produced colds had anything to do with cognitive decline, but it’s become very, very clear. And there are many reports now, especially people who are exposed to Traco theses from Stacie buttress, often will have some degree of cognitive decline. So that’s what we call type three toxic then type four is vascular, and type five is traumatic. And so all of those things can lead to this pathology that we recognize as Alzheimers disease. 

 

Robert Lufkin  20:24   

And one of the hallmarks of your approach is being very open minded to different strategies to to do whatever it takes to address the these multiple factors in there. And wondering what what what’s your take on the you rapamycin has been used for longevity now as an off label FDA use for suppressing mTOR and it’s, it’s having a lot of very interesting effects in very different areas. And there’s a, you know, the University of Texas study is beginning to look at rapamycin for Alzheimer’s disease. What are your thoughts on that? 

 

Dale Bredesen  21:01   

Yeah, Joe, it’s really interesting to me. And again, all of these kind of just as we talked about Mano Ed, illogical ideas about Alzheimer’s, these Mano therapeutics tend to unfortunately ignore many of the critical features that are actually driving the illness. I think the place for these drugs and I would include rapamycin is as part of an overall protocol as opposed to just mono therapies. rapamycin is not going to do much for people who have, you know, extreme exposure to mycotoxins. It’s not going to do a lot for people who have ongoing pathogens that you have to deal with, unfortunately. So it’s interesting, if you look at the longevity drugs like metformin and rapamycin, you really have three different major pathways for longevity. And they all have something to do with energetics and food. And so you know, you want to get a MP kinase activated, for example, you want to inhibit mTOR, that sort of thing. These are all about food and really come back to the fact that we’re all eating inappropriately, and with high simple carb diets, unfortunately. And that’s what’s driving. So the idea, you know, you can try to make your longevity greater with metformin. Or you can just quit eating all the simple carbs. And you don’t have to do the Metformin. So of course, we always want some way to get around doing the wrong thing. But in fact, the good news is, I think we’re all beginning to agree on these critical pathways for aging and for cognitive decline. And you may have seen a fantastic paper by Dr. Kara Fitzgerald just came out a couple of months ago, where she used the methylome, which is a very good look at aging, very good association with biological aging. And she was able to just by essentially doing the right things for people, she was able to get them to reverse their aging by about 3.2 years compared to the control group. So we can show now a 

backwards age and now no one’s seen Benjamin Button yet. You’re not going to go back to zero. But you definitely can age in reverse for at least some period of time and do better than you would have otherwise, which I think is really exciting. 

 

Robert Lufkin  23:15   

Yeah, that’s that’s fantastic work. Yeah, Kara was on this show. And we also lutea Ronica up at UCSF is another investigator that’s using DNA methylation, epigenetic clocks, with ketogenic diets to wind wind it back. It’s so, so fascinating. And and it’s, it’s all these things are, we’re seeing these relationships at a fundamental level, even with Alzheimer’s disease, and all it’s, it’s, it’s so so fascinating. There, there are so many things going forward, be picking up people on the show, we had one other person loose Parrish, who is the CEO of bio Viva sciences, which is a gene therapy company. And they’re, they’re investigating a number of gene therapy projects in humans. But one, one thing they used was a gene called clavo. Looking for cognitive impairment, and they they’re just publishing a paper that showing some improvement with cloth on there. And obviously, this isn’t, like you say, there are better ways to improve your cognitive impairment going all the way to gene therapy, but yeah, any thoughts on that? 

 

Dale Bredesen  24:28   

Yeah, no, that’s right. That’s Clutha was picked up as an association with better cognition. You know, now about 10 years ago, and I think it’s a it’s a very interesting phenomenon. Again, we’re beginning to build an overall look at what is this network again, what we see is Alzheimer’s is really a network disorder. And so yes, both those a part of that and methylation part of that, you know, shpp Alpha, all these different pieces come together and mTOR all these Things You look at things like resveratrol, I was skeptical at first, when it was very trawl first came out. But what’s very interesting about it, it enhances the cleavage of a PP at the site that’s going for the building side. So it’s very interesting, we can look now at what are the things that drive amyloid precursor protein to go to push your brain toward making and keeping synapses? And what are the things that push it toward pulling back. So you’re literally switching your brain to a protective downsizing mode. And it’s intriguing that these things are linked that the protection and the downsizing are unfortunately linked. So when we’re protecting our brains, we’re saying, well, we can’t support that the brain that we have, but we can support a smaller brain. So we’re going to down a little. And unfortunately, when you go to a standard center for Memory and Aging, they don’t get rid of the things that are causing the downsizing. So you just as you saw with your mother, unfortunately, you just keep going going going. So if we would all simply find out what our risks are for these different things, we really could dramatically reduce the global burden of aging. And that’s the goal. 

 

Robert Lufkin  26:12   

Yeah, yeah. What one thing I loved in your book was a chapter that that I hadn’t heard before was, you talked about normal cognition versus optimal cognition. And these would be people who may be just on a prevention protocol. And we want to talk about pre code and recode a little bit later. But before we do that, the normal cognition versus optimal cognition that is taking regular people and making their thinking even better, sort of clearing the subliminal fog they may not even be aware of that’s such a fascinating idea. You and you mentioned nootropics, for those Yes, as as possible path 

 

Dale Bredesen  26:56   

as part of it. Yeah. And you know what, just to explain a little about that. So you know, you brought up a really important point, this is the issue of our age, since the pandemic, what is everyone complaining about brain fog. And it’s, you know, so everybody knows that if they stay up all night, they’re not quite as sharp at work the next day. And so, in fact, this is what’s happening, most of us are not operating at our best, because of we may not get be getting enough sleep, we may not recognize that our oxygenation is not quite as good as it should be, we may have a degree of insulin resistance, we’re dealing with that we’re kind of keeping that at bay. But in so doing, we’re not at our sharpest. And one of the things is, you know, when people start getting on a mildly ketogenic diet, and start kind of fixing these various thing, we, we call them the 36 holes in the roof, so that people will understand that it’s more than one thing, they start noticing, wow, I have more energy, they often will lose some weight. In fact, a lot of the people in the trial that we did, were able to get off their antihypertensives their statins, and they’re anti Diabetes drugs, because they’re now having a more optimized metabolism. And these all are contributing, we may not get Alzheimer’s, but we’re certainly not doing the best we could. And so sharpening people up is a is a real goal here. And so yes, no tropics are definitely part of that. But there are all sorts of other things, just looking at the things that are driving this sub optimal decline. And we walk around thinking we’re normal, but we’re really not at our best. 

 

Robert Lufkin  28:34   

So in addition to the nootropics. I mean, when we think that the same things that would work for reversing Alzheimer’s and and preventing Alzheimer’s would also work for optimizing functions. What else do we add beyond what we would do just for normal prevention? If we want to optimize our cognition to this, this new higher level? It’s such a great concept. 

 

Dale Bredesen  28:58   

Yeah, it’s a great point. So you have to be careful because as an example, everyone knows, you know, you can be sharper as has been shown in papers for years and years and years. You can be sharper for a few minutes with amphetamines. You can be sharper for a few minutes with cocaine, you know, that you will go to the college dormitories. What’s everyone doing Adderall, left and right. And so you they have to distinguish between short term smartness versus long term, we want to give people long term your better sharpness. And so yes, the some of the no tropics are quite helpful for this. But also just improving things like BDNF can be helpful for people getting them you know, getting their homocysteine down to to optimal again, not to normal but to optimal. These often will, as you know, have a slightly excitotoxic effect. They have to be careful. Alzheimer’s is too much excitotoxicity can drive decline, but your model improvements are what some of these, of some of these in no tropics will actually do. And then, you know, people for 1000s of years have used things like shank push the things that come out of either Vedic medicine, and Bacopa and ashwagandha. And so, you know, adjusting these things and starting you basically, you can do this by following yourself on things like brain HQ, looking at your scores and seeing how you do and of course, there’s brain training everywhere. Now, you can do it through, you know, all sorts of different, you know, through all sorts of different, you know, brain training programs, I happen to like brain HQ, simply because not because I have anything, I don’t work for them. But they have the most publications that support their work. But any of these things. Doximity is another one, a lot of people like one called elevate. It’s, it’s fun for people to do. And you can see your scores doing better, not only as you practice, but by doing the right things. And by looking at the, as you said at the chapter in the recent book, where we went through all these different things that you can look at. Oh, that’s great. 

 

Robert Lufkin  31:05   

Yeah, we’ll put those in the show notes for everyone. And once we’re talking about nootropics, and other things, what about psychedelics, the default mode network, it’s a whole different area, but you know, MDMA, psilocybin, it looks like they’re going to be, you know, fast. They are being fast tracked by the FDA now, and they have real uses and PTSD and depression. Any, any, any thoughts here in the work you’re doing? 

 

Dale Bredesen  31:33   

Yeah, it’s a great point. And there’s a lot of interest, as you said, I mean, they’re micro dosing. So the standard doses don’t seem to be helpful for cognition. At the micro doses, they may be and it’s so far, it’s looking more like for people who have these the exact overlays that you just mentioned, who have a bit of PTSD as a problem, some depression, things like that, we’ll see. I mean, time will tell whether these actually have an effect for people who don’t have those other Manda, psychiatric related manifestations in terms of just pure cognition, because they do often inhibit pathways that are involved with cognition. But this may be a kind of a hormetic effect, where you’re, you’re creating a mild stress, and then your your brain as you know, your body is coming back better. And this is one of the things by the way, you may have seen just some really recent interesting work from Israel, which I, which I heard presented, actually at Amazon a couple of years ago, where what they were doing is using hyperbaric. But they were doing it in cycles, where they would have people improve their oxygenation, which gave them one. So now improved energetics, and people would get some better, but then they would cycle them for about five minutes, where they didn’t go into hypoxia. But they went into a short term relative hypoxia, which then causes the production of more trophic factors. So by the cycling, they actually got quite nice results with their patients with cognitive decline. 

 

Robert Lufkin  33:07   

Yeah, oh, that’s spectacular. Well, back to back to prevention versus versus treatment, and you have programs. Pre code is for prevention, and and recode is for treatment. Given that Alzheimer’s disease, like you say, is present. 1020, even 30 years before mild cognitive impairment, it’s almost as if the prevention we’re really just treating subclinical disease, it doesn’t matter, or is it sort of academic I mean, the treatments are the same, right? So I mean, more or less? 

 

Dale Bredesen  33:42   

Yeah, so one is just more extensive. So we created initially recode, for reversal of cognitive decline. And yes, once you’re, you know, far down the road, there are all sorts of things you have to do. But we realize, okay, one of the people who is doing quite well said, Well, look, I’d like to have my whole family. But beyond prevention, we recommend that anyone who’s 45 years of age or older, just as we know, what do we all do, when we turn 50, we get a colonoscopy. Well, if you’re 45 or older, you should have a colonoscopy. And that’s basic three things. It’s a series of blood tests that we’ll look at these different features. It’s a simple online cognitive tests. And then if you’ve got, if you’ve got any symptoms, or you’re scoring poorly on the cognitive test, you of course, you want to include an MRI with volumetrics, that’s critical as well. So everybody should get a colonoscopy and especially anyone who has a family history of cognitive decline and that way it allows us just as everyone knows their blood pressure and their cholesterol but virtually no one knows what their risk is for cognitive decline. Most people don’t know their hscrp their homocysteine there C four a, there, urinary mycotoxins, these sorts of things that are actually risk factors. Now you’re armed with that, and so on. Pre code creates a preventive program. And so the good news is, when you’re preventing, you don’t have to do as much. It’s just like, if you start the ship out in the right direction, it’s a whole lot easier than once it’s steaming down to try to actually turn that ship around, much harder to do that. And so the good news is when people get on appropriate prevention, we have not had any cases of those people who now progress to dementia. So we believe that, you know, time will tell, but we believe that, that this is something where we can really reduce the global burden of dementia. And by the way, we have people, the very first people on recode, started in 2012. And they’re still doing well nine years later. So that when you are attacking the things that are actually causing the problem, you get a much better outcome. Whereas as you know, when people have gone on the drugs, they may get a little bump, but they go right back to declining. And in fact, there’s a paper showing that in the long run, they do no better than the people that weren’t on the drugs. 

 

Robert Lufkin  36:04   

Now, let me let me underscore that a little bit to what you said about pre code for prevention, that at least so far, in the patients in your pre Code program, none have progressed Alzheimer’s disease, and, you know, that may change in the future, but so far, that’s very dramatic, dramatic results and, and pre coded recode. Is that something they can sign up through to Apollo health? Or how do how do they get engaged with those programs? 

 

Dale Bredesen  36:32   

Yeah, it’s very simple. And in fact, there’s, there’s even mobile phlebotomy so it makes it very, very simple. So you can do it either through Dr Bredesen comm or you can do it through Apollo health co.com. And you can get you get the testing get initial. So we have a report and very much like a Cambridge heart sort of report that you’re getting for cardiovascular disease. This is typically about 55 to 65 pages of looking at, okay, here are all the things that represent your risk, here are the things you can do about it so that you can really reduce your risk for cognitive decline. 

 

Robert Lufkin  37:08   

Oh, that’s, that’s great. 

 

Dale Bredesen  37:11   

Sorry. Quickly, I would add, there are there are frequently people who say I’m here for prevention. And because this, this problem really sneaks up on you, as you know, and I’ll give you an example, one woman who came several years ago, she said, you know, this is in my family and turned out she had a single copy of a bow before, which is, which increases risk for cognitive decline. And there’s unfortunately 75 million Americans who have a single copy about 7 million Americans who have two copies. And when she, through her cognitive testing, her Moca score was only 23. So she was already well into mild cognitive impairment. And by the way, she’s done beautifully. For Moca scores now perfect 30. And she’s doing she’s continued to do well. So again, getting in, she was there for prevention, but she was really there for early reversal. So just as you said, there are similarities there. And there’s this kind of middle ground where people don’t quite realize how bad things have gotten. And they get tested. 

 

Robert Lufkin  38:11   

Yeah. Back to back to your book. I love reading your book. There’s one other chapter that I wanted to ask you about two, it’s it. I think it’s towards the end. It’s with Abraham Flexner and his his report on on medical schools in 1910. And he revolutionized medical schools with with his report. And can you talk a little bit about that? 

 

Dale Bredesen  38:35   

Yeah. Well, it’s a great point, because, you know, I call this flex nurse, right? Because he basically told all the rest of us but you know, unfortunately, is over 100 years ago, and it was a great thing at the time he did, he did a service. But as you probably know, he was funded by Rockefeller who was trying to sell drugs. So he came to the conclusion, what a surprise that we should close the medical schools that aren’t focused on drugs. And so this really, unfortunately, drove medical schools from that day forward. As you know, about half the medical schools closed, anyone interested in other forms of therapy, we got closed down. And I think on the positive side, what he said was medicine should be much more based on biochemistry and basic science. And I applaud him for that. And I think that this is why we all want to do the clinical trials and do the basic research and all that sort of thing. But imagine that someone instead 100 years ago, everyone is going to fly in a plane, it must be in a biplane. Well, at some point, you say, Wait, we want to fly jets now. And unfortunately, medicine has really become out of date, in part because that report hasn’t been updated. I would love to see a new Flexner Report that says what are the things that should be done for best outcomes because as we talked about earlier, we as physicians have done really well with Simple diseases like pneumococcal pneumonia, and tuberculosis and even HIV. But we have not done well with complex chronic illnesses like Alzheimers and ALS and things like that. And so it’s really a new day. And we need to reassess. If you think about it, Silicon Valley is all about disruption. How do we do the next thing, the next thing, the next thing, and the the advances in Silicon Valley have been spectacular. Medicine is more about tradition and permission than it is about disruption. We ask, Is it okay, if we do this? Can we get reimbursed for it? And they say, Well, you know, we’re not quite there yet. So it’s really an archaic system. And we need to look again, more at best outcomes. So I look forward at some point to a new Flexner Report. 

 

Robert Lufkin  40:51   

And it’s almost as if the Flexner Report was conceived in the intellectual climate of, of Louis Pastore with, you know, treating single illnesses with a you know, with with a single agent. And it makes me think that what made things so successful for the treatment of acute diseases and like rabies and Anthrax, at the time, also ventually laid the groundwork for what has become the failure to treat chronic disease that we’re facing today. And still, you know, maybe a little more Antoine Beauchamp and less Louis pass tour, you know, the Anton Bishopp was the soil versus seed and Louis Pasteur was the seed versus oil, hopefully, maybe a blend of those. But we’re seeing the pendulum swing back and and 

 

Dale Bredesen  41:43   

and I think it’s going to be both we’re going to have targeted drugs, pharmaceuticals, on the backbone of overall personalized precision medicine protocols. I think that’s where things are headed. 

 

Robert Lufkin  41:56   

Yeah, yeah. It’s, it’s an exciting time in medicine, I have to say that, you know, I’ve never been more excited about the things that are happening in the last 10 years in medicine than the last, you know, 40 years. It’s like, it’s, it’s a great time. You know, it’s so, so exciting. 

 

Dale Bredesen  42:19   

Isn’t it just I just, we just watched people die all these years, ALS and Alzheimer’s, I think we’re now at the point, seeing people get better from cognitive decline has been the most exciting thing I’ve seen, and just even getting the various emails. And that’s why I wanted to get this book, the first survivors of Alzheimer, so I had seven people who had all gotten better tell their personal stories, but they’re really heartwarming to hear, Oh, my gosh, you know, I was worried about my family. One of the people who wrote her story, brilliant attorney from Harvard, who her watched her grandmother die of Alzheimer’s, watched her father, who was a brilliant neurologist die of Alzheimer’s. And then realize that she also the three of them all had the same risk factor gene, she then find out she hadn’t she coarsely looked at her children and thought, oh, my gosh, what’s going to happen to future generations? She’s done beautifully. And it’s just it’s so great to hear this and hear her stories of you know, how she got better and how well she’s doing now. So yes, this is a great time. And it’s the beginning. There’s so much more for all of us to do to to reduce the global burden of these of these complex chronic illnesses. 

 

Robert Lufkin  43:30   

Yeah, and get get the word out. We just interviewed Matthew Phillips, you may know as a neurologist in New Zealand, who did a randomized control trial with ketogenic diet and Alzheimer’s and got great results. But before that, he did it with Parkinson’s disease. And it was a crossover, partially blinded trial and even got some results there for neurodegeneration. So it’s amazing, amazing time. Well, Dale, I, before we run out of time, as an expert in this area, you’ve spent your career in science investigating the very basics of this and now your your understanding of these lifestyle choices and the decisions we can all make. I have to ask what what lifestyle choices do you make yourself if you wouldn’t mind sharing that, that you do in your own personal life? 

 

Dale Bredesen  44:19   

Yeah, for sure. And as I say, you know, my wife, who’s a family practitioner, and who actually told me 25 years ago, you know, whatever you guys find in the lab, it’s going to have something to do with basic things like nutrition and exercise, sleep, stress, things like that. And I laughed and said, No, no, we’re gonna find one molecule with one full and of course, I should have listened to her 25 years ago. And our two daughters, they do much better than I do. They they’ve been fantastic, but I try Yes, I try to absolutely and realize these are important. And the one thing is wearables. You know, we haven’t talked about wearables, they are changing the world. You can now find out what your oxygenation At night, you can find out what your heart rate variability is, you can make sure you’ve got enough exercise in, you can look at your VO two Max, you can look at your telomeres, you can look at your, your genetics, you can look at your microbiome, your your, the your continuous glucose monitoring, which we find one of the most helpful. So this has been fantastic. And I check my ability, and I check my oxygenation to make sure I don’t have any problems with that. So what I try to do is the basics. So for diet, I try to eat a plant rich, it’s not purely plant, I tried to eat a plant rich, call keto flex, 12. Three, it is a plant rich diet, I do it a time restricted eating for eight hours during the day, and then go 16 hours of fasting. Now, I don’t recommend that for people who are who are really, really thin and don’t have any body fat. I’m an old man, I’ve got some body fat to burn. So I can make some ketones, I often check my ketosis ketones with a with a breathalyzer very simple, something called biosense, see what I’m blowing for the ketones to see, make sure that I’m making some ketones, and that they’re not too high that they’re not too low, then make sure to get an exercise. Typically Do you know 10,000 steps, I usually do a little bit of weight training a couple in fact, I’ve just gotten some kaatsu bands, you know, these restricted bands, which actually are turning out I was very skeptical about the some of the Olympic athletes use these by the way, they actually basically slow down the flow to muscles just a bit. And so you when you’re finished training, first of all, it takes less training, and then you get better flow overall, which you know, is a huge issue for many people. And so exercise and then make sure that I’m getting eight hours of sleep at night. And of course, you and I when when we’re interns, we get virtually no sleep. And I’m sure that that has some damaging effects on my nervous system. But I’ve tried to then continue to get good sleep, and then try to keep stress to a minimum, you know, you should know it’s fine to have some stress, but you don’t want to have, you don’t want to have chronic stress. That’s the thing that kills you. And then I checked my blood pressure. And I can see very clearly, you know, when things are bad, it’s up, when I’m doing the right things, it’s coming down. And then I do some basic detox. So I get into the sauna. You know, typically, and I probably don’t do that enough, more like once or twice a week. As you know, the Finnish study showed that a men who were doing sauna five and six times a week lowered their Alzheimer’s risk dramatically. And it was striking. So due to basic detox, you know, filtered water. And then I’m very big on fiber. Because it turns out, you know, the prebiotics and probiotics, getting your gut healed, and then getting appropriate microbiome. And then I do the same thing. oral microbiome, there are now oral probiotics and prebiotics, or probiotics for the oral microbiome. And there’s again, you can check this with oral DNA simple way to look to see, as you probably know, there was just a trial on looking at the P ginger valus in the brain and basically trying to prevent one of its proteases called Ginger pain. And it’s interesting to trial failed overall. But it actually looks promising in that group that had the P ginger valus in their mouths, and not in the ones that didn’t have PG gels, which which makes sense. So those are the basic things that I do. And then of course, as far as brain training, just basically that, you know, trying to keep up with the latest literature and things like that. And so yeah, just like everyone else, I’m interested in avoiding cognitive decline. I always ask people, How many people here would like to avoid Alzheimers, and most people will raise their hands I think most of us would like to avoid Alzheimer’s. 

 

Robert Lufkin  49:00   

Well, thank you so much Dale for sharing your knowledge with us and and spending an hour of your time and and I just want to thank you also for the great work you’re doing to revolutionize the treatment of this disease. 

 

Dale Bredesen  49:17   

Thanks so much, Rob, and really love working with you look forward to continued work, I think, you know, imaging is a critical part of this. And as you’re indicating here, health longevity secrets. It’s amazing how much can be done today that we didn’t know, even a decade or two ago. 

 

Unknown  49:35   

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