128-Is Alzheimer's Reversible?

Are you ready to challenge what you think you know about Alzheimer's disease? This episode presents a conversation with Dr. Dale Bredesen, a highly respected neurologist and author of the best-selling series, the End of Alzheimer’s. We dissect the complexities of this disease and explore the revolutionary understanding that has emerged in recent years. You'll be gripped as we reveal how factors like genetic programming, lifestyle choices, and changes in our telomeres, methylation patterns, and stem cell population can influence both the aging process and Alzheimer's disease progression.

Stress, nutrition, and immune responses - we're delving into the intricate science behind Alzheimer's disease. Dr. Bredesen offers an audacious claim that Alzheimer's is optional, asserting the power of early detection and targeted treatment. Hear about this profound shift in perception and how it can potentially safeguard future generations from this disease. 

Wrapping up, we journey into the realm of precision medicine and its potential to treat complex chronic illnesses. The importance of early diagnosis, and how the body's response to these illnesses can be addressed with targeted treatments, forms a critical part of our discussion. Prepare to have your perspective on Alzheimer's disease completely transformed. Join us for this insightful discourse!

ReverseAgingRevolution Summit June 20-22, 2024 https://robertlufkinmdcom.ontralink.com/t?orid=49&opid=2

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Transcript

Speaker 1: 0:01

Welcome back to the Health Longevity Secret Show, and I'm your host, dr Robert Lufkin. Today we'll be speaking about the important topic of Alzheimer's disease and some of the remarkable breakthroughs that are being made in our understanding of this important disorder. We'll be joined by my co-host, Dr Steven Sideroff, and we're going to learn not only about the many causes of Alzheimer's disease that weren't really appreciated even a few years ago, but also how some of these can even be reversed. So be sure, and stay to the end to hear it. Our guest for this discussion is Dale Bredesen, md. Dr Bredesen is a respected neurologist and author of the best-selling book series the End of Alzheimer's, which I highly recommend.

Speaker 1: 0:53

One of the most common questions I get asked are which blood tests I rely on most heavily for myself and that's really a whole topic unto itself and I'm going to cover it in future programs. But, simply put, there are about 17 or so biomarkers that I check on myself on a regular basis. Now, the way I do it is from my home, with a simple finger stick like this, and then I just mail it in. It costs less than $10 per marker and I get the results right away. If you want to try this test for yourself. You can check my website, robertluffkinmdcom under Secrets and use the code SAV10,. Save the number 10, for $10 off. Try it. Let me know how it goes, if you like it. And now, please enjoy this conversation with Dr Dale Bredesen.

Speaker 2: 1:53

And I'm very pleased in this session to have a fellow professor from UCLA, dr Dale Bredesen, who's a pioneer in brain health research and the author of the best-selling the End of Alzheimer's. Dale, welcome to our program. Thank you for being here.

Speaker 3: 2:12

Great to be here, Steven. Thanks so much to Rob and to you for having me on.

Speaker 2: 2:18

So your area in Alzheimer's I know you've said that it's the third leading cause of death and, of course, our program is about aging and longevity. How did you get into this field in the first place? What inspired you?

Speaker 3: 2:36

Yeah, it's a great point. Of course, nobody wants to live to 100 and have 20 years of dementia as their last 20 years. I got interested in this as a neurology resident because, you know, as a medical student I thought you know, if you don't have your brain functioning, what do you really have? That's the thing that's really critical to be a human being. And as I went through my neurology residency, the striking thing to me was we neurologists have so little to offer our patients therapeutically. And if you look at, of course, the history, neurodegenerative diseases from Alzheimer's to Lewy body to frontotemporal dementia to ALS and on and on and on, represent the area of greatest biomedical therapeutic failure. As everyone says, you know there's, everyone knows a cancer survivor. No one knows an Alzheimer's survivor, and so I wanted to understand the fundamental nature. So my laboratory for 30 years was all about what is the fundamental nature of the neurodegenerative process? Can we understand that so that we can begin to fashion effective preventions and treatments?

Speaker 2: 3:41

Beautiful, beautiful. That's great. And can you give our audience your perspective and this is something we ask all of our guests your perspective on the process of aging and longevity?

Speaker 3: 3:55

Yeah, you know, this is a fascinating because there are so many things now that were that are coming out from the epigenetic studies, looking at biological aging and actually seeing that you can move biological age backwards, as I'm sure you've talked about, but you can also move it forward to more rapidly with things like ongoing inflammation. So we're really getting at what is the nature of this, and you know and I was at an aging research institute for years the Buck Institute was founding president and CEO there and so we were looking at what are these processes and it really boils down to essentially three things. Number one you have a genetic program that gives you a lifespan. So, in other words, if you're a mouse, it's very hard to get to 100. If you're a human, it's a lot easier to get to a human. You have a pre-programmed length. If you're a human, it's very hard to get to 500. But we want to understand why that is.

Speaker 3: 4:55

And then, within that, you basically have two processes. One is a process that's just about you suck at living. In other words, the thing that's driving aging in many of us is we're eating horrible processed foods, pro-inflammatory foods, we're exposed to all sorts of toxins, we're doing everything wrong, and that is part of it. Then if you do everything right, there's still an underlying change changes in your telomeres, changes in your methylation patterns, changes in your essentially in your stem cell population. So there is that underlying. So I think of aging as being those three things together a genetically pre-programmed lifespan. You're going to live about X plus or minus. Then on top of that you have are you good at living or not, are you doing things wrong or right, and then on top of that there are these underlying processes that are part of the aging of our somas.

Speaker 2: 5:59

Basically, so maybe, as we focus more on your area of Alzheimer's, we can sort of tease apart some of these considerations that you're mentioning. And to start off, I'm wondering you have a notion that the standard model of Alzheimer's has gotten some things wrong. Can you explain that to the audience?

Speaker 3: 6:27

Yes, I think you've been very kind to the community to say that they've gotten some things wrong. I would say I've taken a step further. The entire field is backward because of the fact that this disease has not been understood for what it actually is. And so we're told this is a disease and, by the way, there are dozens of theories. It's a disease of misfolded proteins, of aggregated proteins that are now interacting with each other. It's a disease of prions, of amyloid, of tau, of herpes simplex, on and on and on, of reactive oxygen species, of DNA damage, on and on and on. And the reality is it's none of those simple things. When you look at the epidemiology, you look at the neuropathology, you look at the genetics, you have to come away with an understanding that fits all of these. You can't just say, well, it's just this, and then it turns out that the epidemiologists show that you're completely wrong. You have to have an internally consistent model. And when you look at all the different things and there are, of course, there are dozens and dozens of things that we know contribute, and, of course, air pollution being in LA, you've got to be concerned about air pollution. There's a lot of information over the last few years on increased risk with air pollution, but, of course, insulin resistance, and on various toxins and various inflamogens and various pathogens and leaky gut. So how the heck does all this fit together?

Speaker 3: 8:00

Well, the way it fits together is ultimately what we call Alzheimer's disease is a network insufficiency. You have a beautiful plasticity network within your brain and you can go right down to the molecular species level. Ameloid precursor protein, the parent of a beta of ameloid, is a molecular switch that responds both to positive things and to negative things, and so when it is seeing that you've got ongoing inflammation or you've got toxin exposure or too little energetic support or too little trophic support, it will now essentially change your brain, put your cells into a protective downsizing mode. Essentially, it's switching you from making and keeping synapses to pulling back to protect yourself, and there's a direct analogy to what happened to our country when we entered the pandemic, so early 2020, as we all know, you have a path. In this case, you have an insult. We respond to it. They say shelter in place. Socially, distance don't go to work all this stuff and, of course, the country went into a recession.

Speaker 3: 9:18

Your brain is doing very much the same thing when things are good and you can trace, for example, estradiol, one of dozens and dozens of different molecule and molecular species. Estradiol binds to its receptor, enters the nucleus, alters the transcription of hundreds of genes, and one of them is the alpha secretase that cleaves your APP into the two fragments SAPP, alpha and alpha CTF, which signal growth and maintenance. At the same time you can look at NFKappa B, which is responding to inflammation. So anything that's inflammatory also enters the nucleus, affects hundreds of genes, and two of them are the beta and the gamma secretase, which now take your APP into this downsizing mode. So you're literally saying am I allowed to grow and maintain or do I have to downsize and really put my resources into protection? So the amyloid that we have vilified in this disease is a protective agent that is antimicrobial, as professors Robert Moyer and Rudy Tansy from Harvard showed a number of years ago.

Speaker 2: 10:33

So I love what you just said, because we're learning in a lot of different areas that the brain, body have two choices One is to grow, the other is to protect. Exactly, and I'm wondering if the conclusion from what you just said is it's not a particular process, it's how it's what determines which of those two directions the brain or body or cells take. Is that correct?

Speaker 3: 11:04

Absolutely. And so, again, we keep hearing the discussion as if this is a pathology. Oh, it's a dysfunction. Oh, you're making amyloid for some reason. We better get rid of that amyloid. You're making tau, let's get rid of that tau. No, you have to back up and say why is the brain, your body, is not trying to kill you, it's trying to heal. So why is it responding that way? And there's a lot known about this.

Speaker 3: 11:29

Now, when you have pathogens within your brain, you make amyloid because it kills them and surrounds them. So it isolates these pathogens. And what are they finding? Well, we're finding P gingivales. The neuropathologists have been showing us for years. You find, for example, pathogens from your mouth, p gingivales within your brain, herpes simplex from your lip, within your brain, of course, various fungi that can be coming in through sinuses. You can also have things like spirochetes. That can come either from the mouth or can come from systemic circulation.

Speaker 3: 12:07

Tick-borne illnesses are associated with cognitive decline, but then, as you mentioned, you're always you're also making this judgment. So, when you have sleep apnea, you don't have enough support for your brain. It's got to go into that protective downsizing mode, and we see this all the time with people who have low oxygenation at night. Beautiful study published a few years ago showing that just tracking the average sp02 at night correlates beautifully with your hippocampal volume. So all these things, you've got to have that support and I should.

Speaker 3: 12:40

Coming back to what you said about the choice, there are four major components, groups of things that will trigger you to go toward the protective side or the growth side, and they are enough energetics, you know, mitochondrial function, oxygenation, blood flow huge blood flow is critical here and ketosis, the ability to burn a substrate. Second thing is trophic support. You need that BDNF if you're going to be making synapses, things like hormones and nutrients. You need the estradiol, the vitamin D, the you know, the androgen, all these things. And then the third thing is inflammatory genes or anything that's. Inflammation is going to be a problem, it's going to push you toward the protective side, all these different organisms, for example. And then the final thing is going to be the various toxins, and those are inorganics, organics and biotoxins. So those are the big four.

Speaker 2: 13:41

So this is, this is great. Can we take this down to a behavioral level, in terms of how we translate what you just said into the optimal behavior and thinking patterns and things of this nature that may influence those four different categories?

Speaker 3: 14:01

Yeah, that's such a good point and in fact behavior is extremely important in cognitive decline and in fact most of us could prevent this. You know, my argument is that Alzheimer's is really now optional. If you, if everybody, gets on appropriate prevention or earliest treatment, we really shouldn't have a lot of Alzheimer's. Currently, 15% of the population dies of Alzheimer's. So you know, the nice study by Professor Christine Yaffe a few years ago, who did serial autopsies, show that it was the third leading cause of death in the United States. Now, to be fair, that was just pre, pre pandemic, so it is a very common cause of death and it actually dwarfs the COVID-19 pandemic, probably 45 to one in terms of the currently living Americans who will die of Alzheimer's disease. So, as you indicated, behavior is huge.

Speaker 3: 14:52

Stress one of the most important factors. If you are undergoing lots and lots of stress, you are first of all going to shrink your brain, as you know. Second of all, you're going to affect your immune system and a lot of Alzheimer's, interestingly, is about a mismatch between the innate immune system and the adaptive immune system. So just again, as in COVID, you die of cytokine storm because you've got this innate system that's just cranked up and the adaptive system has not cleared the virus. In Alzheimer's it's slower. You die of cytokine drizzle. It's years and years of mild activation of the innate system without a clearance because you have continued exposure to these various things. So, no question about it, behavior is critical and, of course, behavior on the side of compliance, getting the right things, doing the right things to address these different areas, which is why, you know, health coaches have emerged as such an important part of our health care system.

Speaker 2: 15:58

You mentioned two different kinds of immune responses. Can you explain that to our audience?

Speaker 3: 16:05

Yeah, this is a great point and it's so important because these are fundamentally important to many illnesses, starting with COVID-19 and Alzheimer's disease. So when you first have a response to a new pathogen, a new challenge, you have a nonspecific response. In other words, you just sense that there's danger. These are the so-called PAMPs, or pathogen-associated molecular patterns, and so these are typically through the. You know the toll-like receptors and things like that. So you're now, your body is alerted, something is wrong, but it hasn't you know, it hasn't characterized the, you know the bad actor yet. So it's like the police saying okay, everyone, just go into your house early at night. You know you want to have a curfew, you want to lock your doors.

Speaker 3: 16:54

It's a general signal and that's the innate immune system. It's the older part of the immune system and interestingly, that turns out to have a very interesting form of memory. So once you've been inflamed, you're at increased risk for future inflammation, which is a really critical piece here. But then, in a perfect world, what happens and normally what should happen is now your adaptive system, your T cells, your B cells. You're now going to recognize and characterize and present the antigens from this. Now you know aha, we know who the bad guy is. You're going to develop a beautiful response with antibodies and T cell activation, and part of that development is to turn off the innate response, so that you have a beautiful system where you get inflammation, you turn off the inflammation and now you have a very nice adaptive response and then, of course, you have a long term memory so that if you ever get exposed to that again now the problem is for reasons that are critical for pathophysiology in Alzheimer's disease you're not completing that loop, and there actually is.

Speaker 3: 18:04

There are phagocytic defects in Alzheimer's disease, things we don't quite understand. We also know just poor nutrition, poor resilience, poor overall health is increasing your risk for Alzheimer's, and part of that is because you're not able to get rid of it. If you're continuing to be exposed to changes in your oral microbiome you've got this in your brain if you're continuing to be exposed to pathogens, to air pollution, to things that are in flammage, you're never getting to the point of turning that thing off and responding completely. And so that's what happens Now in COVID. It's really interesting because the virus itself prevents you from having an early cytokine response. That's part of its MO and therefore you suddenly have this burst where you finally recognize oh my God, I've been overrun by COVID. You have this massive cytokine storm which, as you know, can be lethal.

Speaker 2: 19:03

Wow, yeah, you know, Dale, you mentioned that Alzheimer's is optional. That's quite a bold statement. Can you elaborate on that statement please?

Speaker 3: 19:17

Yeah, and when I say that I'm not saying for 100% of people, I'm saying for the fact that we currently have about 6 million Americans who have Alzheimer's and what I'm saying is for the upcoming generations. They don't have to deal with this, they don't have to allow this to happen, because we know so much more now about what can increase your risk, how we can prevent decline, how we can reduce risk and how we can prevent you from developing Alzheimer's. And then, if you just begin to get it, we can treat things early on. So when you get Alzheimer's, you go through four phases. Everyone is focused on treating the last two. If we simply move to the first two, you can basically prevent this in everybody. So first, as you know, you go through a phase where you're asymptomatic Already. Your PET scan can be abnormal 20 years earlier than you get a diagnosis of dementia due to Alzheimer's. But you have changes in your spinal fluid, for example, and of course, there are multiple new markers that are coming out looking at phosphotide tau in the blood, looking at A beta 42 to 40 ratios, looking at epigenetic changes all of these. So we can look at this better and better.

Speaker 3: 20:32

Second phase of Alzheimer's is called SCI, subjective cognitive impairment and unfortunately our doctors always tell us, yeah, this is just normal aging. You know, you're just going through normal aging, you're getting a little older. I had a guy contact me the other day who has relatively late stage Alzheimer's and was told by his doctor that it's just normal aging. I mean, we just have to get away from this. You shouldn't be losing all these things just because you're 45, 50, 55, 60, 60, 70. You know, they're a sharp hundred year old. So that's SCI. Now SCI, the epidemiologists have shown us lasts about 10 years. So we have a tremendous window of opportunity to prevent people from getting to that final fourth stage, which is dementia.

Speaker 2: 21:18

Yeah, let me interrupt for a moment and ask you because, as a psychologist, there are emotional, psychological states that can mimic some of the things you're talking about. Someone with trauma they can get what we call brain freeze, in which they're having cognitive difficulties. People who grow up in childhood environments that are dangerous they're on guard and their brains just don't function as well. People with anxiety they're gonna have cognitive, some cognitive impairments at times as well. So it's interesting, a lot of things can mimic the same kinds of symptoms.

Speaker 3: 22:06

And that's why it's critical again to determine what's actually driving the cognitive change. And in some people it's really easy. You don't have to do a lot. In some people you do need to go all the way to a PET scan or to some of these newer tests to determine this. And so once you understand what's driving the problem, then you have the best chance to deal with it.

Speaker 3: 22:27

The problem has been that so many people have tried to treat Alzheimer's as one problem let's just get rid of that amyloid with an antibody and as we know, it simply does not work. So just to finish that previous part, the third phase of four is what we all call mild cognitive impairment, mci, and it really should be called relatively late stage Alzheimer's disease, because it's like telling someone don't worry, you only have mildly metastatic cancer. It is a late stage of the problem. It's really too bad that the term MCI was used, because it's really the third of these four stages. And then the final one where you begin to lose activities of daily living, of course, is dementia.

Speaker 3: 23:15

The dementia phase of Alzheimer's pathophysiology. And so if we simply get people in those first two stages, get them on prevention, get them on earliest reversal, virtually 100% of these people do very, very well, and that's why I say Alzheimer's is now optional. If people will still simply get in in those first stages, this is not gonna be a problem. So we really need global programs, just as we had for polio, just as we had for other situations like smallpox. We need the same sort of program to reduce the global burden of dementia.

Speaker 2: 23:57

Yeah, we started the conversation today talking about how others have gotten the model wrong. Dale, can you give us the model that you work by?

Speaker 3: 24:11

Yeah, again, we spent 30 years in the laboratory studying the underlying molecular drivers of the neurodegenerative process. What we found is that literally there are molecular signals that come from different areas. It can be you can get the same phenomenon by having anything that is pro-inflammatory. One of my colleagues, by the way, dr Alexei Karakhan, also at UCLA and we've published a number of papers together points out that this is really, if you look at the changes in Alzheimer's, it really focuses you not only on this idea of the innate system over the adaptive system, but even further on what's called trained immunity, which is essentially the memory part of the innate system. His point was this typically affects the endothelial cells. You have a pro-coagulant state, you have activation of microglia. These are all the things we see in Alzheimer's disease. His argument is it's really even more focused on that sort of thing, but there are many things that get you there.

Speaker 3: 25:24

Again, our model, which has to be internally consistent and has to be predictive of treatment. You can throw out any model you like. It means nothing until it's predictive of treatment. You treat someone and say, ah, this proves our model and that's what we're showing. Our model is that what we call Alzheimer's is a network insufficiency, and this network is about neuroplasticity. It has the four fundamental things that I mentioned earlier. The inflammation affects it, etc. A trophic activity it's about your system trying to fight these various insults. We know that we get these. It fits beautifully with inflamaging, as we have some degree of inflammation and some degree of aging.

Speaker 3: 26:12

Your brain is dealing with changes in hormones, changes in oxygenation, changes in air pollution exposure, changes in mycotoxin exposure, changes in microbiome oral microbiome, sinus microbiome and even brain microbiome. You're dealing with all these things. It is now having to go into this protective downsizing mode. As long as you don't discover what's driving it into that mode, it's just going to get smaller and smaller and smaller. Your brain is essentially saying I can't exist with 500 trillion synapses, but I can put out all this amyloid tau. These things are antimicrobial. I can exist with 400 trillion synapses or something like that. Unfortunately, you just keep going and unfortunately get to mention die If you can identify those things and address them appropriately, create resilience and then regenerate. Things like stem cells are around, things like intranasal trophic factors and things are available. The armamentarium which we have been told over the years is zero. There's nothing that will prevent, delay or reverse cognitive decline is actually huge. There's a tremendous amount, and the earlier you do it, the easier it is to do.

Speaker 2: 27:32

Well, I know you put your money where your mouth is, because you just had a study published in the Journal of Alzheimer's Disease on your clinical trials. Can you share with the audience something about that study, what you believe were the key ingredients to the success?

Speaker 3: 27:54

This is such a good point. Thank you for asking that. We were very fortunate to have support from the Four Winds Foundation to do a trial Now. We tried initially to do our first trial in 2011. It was turned down by multiple IRBs because it's multi-factorial, it's a multimodal trial and they kept saying, well, you just have to have one change. But that's not the way the brain works. This is not a linear system. That's clear to pretty much everyone. We continued and we published some anecdotes just to show that, yes, there's enough reason to do a trial. We've actually published in 2018, 100 people with documented improvements. We were finally given the green light in 2019.

Speaker 3: 28:37

The idea was to do two trials. We've done the first one and now we're just starting the second one. The first one is a proof of concept trial that uses historical controls. It flips the script With all other previous trials. You tell ahead of time here's what we're going to do. We're going to give this drug or this change in behavior. Whatever you're going to do, this instrumentation, whatever In this one we're saying for each person, we will identify the factors that are contributing to the decline.

Speaker 3: 29:06

Typically, we find between 10 and 20. People have insulin resistance or they have changes in their oral microbiome or sleep apnea or what have you. We're going to address each thing in each person. This is a personalized, precision medicine approach. We then published this, as you said, in Journal of Alzheimer's Disease just a couple of months ago, and 84 percent of the people showed improvement in their cognition. Now the important thing is here when you look at the successes with anti-amyloid antibodies, what they don't make you better, they don't even keep you the same. What they do at the best is when you're going downhill, they have a modest effect to slow the rapidity of the decline. We're talking about something completely different. These people actually improved their cognition. By the way, we have people who've been on this approach for 10 and a half years and continued their improvement. We have people who sustained their improvement.

Speaker 3: 30:07

This was a fundamentally different approach, a precision medicine type of approach to people who have cognitive decline. We did take people with both MCI and early dementia. What I'd like to do is do this now for the people with SCI, because I think we can do even better with those, but these people had a personalized approach which included things like brain training, which has been shown by Professor Mike Mersnik and his group to be so helpful and healing leaky gut and optimizing their oral microbiome and reducing their stress just what you were talking about earlier and then fighting the specific pathogens that were identified. Some of them had specific pathogens that were undiagnosed, which we see so often, and so those were treated and these people did very well and, by the way, this has worked for people who clearly have Alzheimer's. One of the questions is what about the people who had more of a vascular dementia pattern? And so far this looks like the same approach may be useful for vascular dementia and Lewy body dementia as well.

Speaker 2: 31:17

So your approach is you're showing some nice results. Why do you think there's any pushback to what your approach is?

Speaker 3: 31:28

Yeah. So you know it pains me to say this, but we went through a period where big tobacco companies actually had an entire institute funded by them to show that there was no link between them and the other companies. There was no link between smoking and lung cancer. So, as you know, I mean millions and millions and millions of dollars were spent on research to show, of course for greater profits. Then we had the claim that sugar is not particularly bad for you and again money spent in Harvard professor years ago was paid to say that it's really about fat, it's not about sugar, it's about the amount of money that's been spent to untold numbers of deaths.

Speaker 3: 32:12

Unfortunately, now we have pharma that has spent now $40 billion on various failed trials trying to hang on to this idea that amyloid is the cause of Alzheimer's. Atacanumab failed in one trial. The other trial, they claiming well, we think it had a modest effect, the best has ever that it's ever been showed. Again, as I mentioned earlier, it's just a slight slowing of decline. Anyone who looks at this honestly for a few minutes will see that amyloid is a mediator, except for those few people with mutations in APP itself, where it really is. They're making amyloid inappropriately. And, by the way, we're working with some people there that are actually getting some good effects, but for the vast majority of us this is a sporadic problem.

Speaker 3: 33:17

Increased risk with APOE4, of course, but this is a problem in which the amyloid is responding to something. It is again, it's an antimicrobial peptide and so, unfortunately, when you have $40 billion paying all sorts of consultants, paying off people here and there the Alzheimer's Association was given $1.4 million and turned around and said, oh, the company that just paid us, they make a drug which we think is a good drug. Well, that's kind of transparently inappropriate. So the bottom line here is that when you have huge numbers of dollars and you have a medical system that is resistant to change and that's the history of the medical system so I think of tobacco, sugar and amyloid really in the same sentence we have situations where there's a lot of dollars going into preventing change and so we've had no surprise, a lot of pushback, and of course, more should be looking at can we do larger trials? Can we get other people involved? That's the way things are headed.

Speaker 2: 34:29

Right, right, Dale, you touched on inflammation in the process. Can you go a little bit more deeply into the role of inflammation please?

Speaker 3: 34:40

Yeah, this is a really good point, and I think, again, people have gotten this wrong because we keep hearing oh you just have to get rid of the inflammation, this is just an inflammatory problem. Well, that's a short-term solution. What you want to do in the long run is get rid of what's causing the inflammation, and so there are multiple pieces to this. So you want to know what's the organism or organisms. Or do you have a leaky gut? Do you have chronic sinusitis? Again, a great place where imaging is so critical to picking up things like chronic sinusitis. We do, in the trial, cone beams to look for undiagnosed abscesses that people have as well in their oral cavities. So these things are all critical. And then, looking at, it's typically the chronic pathogens that are the ones, and, of course, herpes simplex family and the herpes family as a whole EBV, cmv, hsv, hhv6a all of these things are critical. And then it's things, as I mentioned earlier, like P gingivalis and T denticola, that are coming from changes in your oral microbiome, and then, of course, things coming from leaky gut. All of these things and you could argue that one of the most common reasons to have systemic inflammation is metabolic syndrome. I just was reviewing these. We have a computer-based algorithm that looks at all these different pieces and we I was doing this actually from a Native American group where the diabetes type two diabetes is very high, and you can see why when you look at the metabolic profiles, all of the ones that I reviewed had metabolic syndrome, relatively advanced metabolic syndrome, and so this is another common reason. You see that high HSCRP, along with the abnormal, you know, the dyslipidemia, the insulin resistance, the obesity, these things all go together and, by the way, very, very addressable clinically.

Speaker 3: 36:40

So all of these things are about inflammation and, of course, lots of beautiful work from Professor Charles Cyrann at Harvard showing it's not just about an anti-inflammatory. You also have to look at resolution, and he coined the term resolvance. So for these resolvance that he discovered that help you to resolve the ongoing inflammation. So we do. You know we as a country have a horrible omega-6 to omega-3 ratio, typically about 15 to one. We should be closer to two to one or one to one or four to one, that range where our omega-3s and omega-6s are more in a good ratio. But so many of us, because of our diets and because of the way we live and the exposures and all these sorts of things have these very poor ratios and we have low omega-3 indices as well. So inflammation critical to resolve it, critical to prevent it, critical to understand where it's coming from and critical to remove it.

Speaker 2: 37:43

Right, great. Thank you for that answer. I'm curious what other diseases do you think would be amenable to this precision medicine approach of yours?

Speaker 3: 37:56

Great, point, and virtually all complex chronic illnesses should be amenable. So what we are now doing is something called the ARC project. So the ARC, of course, know, as ARC was two by two by two. So what we want to do, then, is take small numbers of patients with much larger data sets. So we want a few people who have Parkinson's, lewy body, frontotemporal dementia, als, psp, cbd, and the one we started with was dry macular degeneration, and we have some fantastic initial data showing improvements in people and, as you know, what happens when you get you know what happens when you get macular degeneration, and it goes back to Dr Lufkin's excellent book about the lies that he taught his medical students. What do we teach people? Wait for macular degeneration and then inject your eye. What a barbaric thing to do to people who are developing macular degeneration.

Speaker 3: 38:57

What we want to do is get into the earliest stages. That's typically dry macular degeneration. You're picking up the drusen. You're saying, aha, this person has an abnormality. Often at the beginning they don't even notice it, but already the first thing that's changing typically is dark adaptation, where normal dark adaptation is less than 6 and 1 half minutes. Most of us are going to be 2 and 1 half 3, 3 and 1 half 4 minutes.

Speaker 3: 39:25

The first patient we dealt with with, macular degeneration 13.7 minutes dark adaptation. He didn't even. He was picked up with drusen by an optometrist and it didn't know that, yeah, you're on your way to having some significant problem here. After one year on it we adapted the profile to, especially for the pathophysiology of AMD. Each of these things is different. He was at 5.38 for his dark adaptation completely normal. Now we'll see. Can we keep that going for the next 20 years? We'll see. But this is the way things are going to take the genetics and the biochemistry of each of these chronic conditions and target those with a personalized precision medicine approach. And I think this has obviously been very popular and very effective in tumor biology and in oncology treating people with cancer. Adapting this now for each of these neurodegenerative and other complex chronic conditions I think will be very successful.

Speaker 2: 40:31

Yeah, that's great that you're looking at all these other illnesses with your approach, and it seems to me that one of the key takeaways is checking early enough, diagnosing early enough, noticing early enough, because the earlier you do, the more that the intervention can benefit the individual.

Speaker 3: 40:57

No question. You know what's interesting to me. When we, all you know, went to medical school and learned about diseases, we saw and we were exposed to the success of 20th century medicine with acute illnesses. You know we're really good at pneumococcal pneumonia, simple illnesses like that. In the 21st century it's not that simple. These are now network diseases, it's multiple, it's systems biology now.

Speaker 3: 41:23

And the big problem, as you know, with complex chronic illness is that you don't develop the symptoms until a relatively late stage of the disease Because your body is responding with things like atherosclerosis and amyloid plaques and tau and drusen and all these sorts of things. So I remember being depressed when I was a medical student when I was told yeah, you get your first symptoms of renal failure when about 80% of your glomerular, glomerular filtration rate is declined and you get your first symptoms of Parkinson's when about 80% of your dopaminergic input to your striatum is lost. This is horrible. So we need to develop approaches to look earlier, which is why I like the dark adaptation in macular degeneration. These are early changes that we can look at and these, all of these diseases should be treated earlier.

Speaker 3: 42:14

But of course our healthcare system has said we don't want to do prevention. We don't want to pay for it, we don't want to get ahead of the curve, we want to wait until you get really sick. It's just, it's again. Everything is backward because of the old fashioned notion that we just can't do things about these illnesses.

Speaker 2: 42:33

Yeah, and the same thing is true in the area of stress and dealing with stress People, people. The stress process is a cumulative process. Yes, people really don't really deal with it, really motivated to deal with it, until they have some serious problems, even though they noticed symptoms a lot, a lot earlier in the process. So we can say the same thing there.

Speaker 3: 43:00

And I was going to say this is where wearables are going to change For the generation after us. The wearables are going to change everything. So I was surprised when I got my Apple Watch a few years ago to look at my heart rate variability A great way to look at stress and wow, the difference between when I'm doing deep breathing and getting it to bump up to 120, 130, and when I'm in the middle of some stressful event and it's 17,. It's just a huge difference and I think I actually think wearables are going to have a big impact on complex chronic illness. Look what we can do now. We can look at your heart rate variability.

Speaker 3: 43:41

I check my sleep parameters this morning. I check them every night. How much REM did I have? How much deep sleep, how much superficial sleep? You can now look at this. What's happened with the continuous glucose monitoring? The CGMs are changing the way we think about this. This is the future, and so people will be looking and saying you know what? I don't have to wait until I get Alzheimer's. I'm already seeing that something is wrong with my physiology. We can look at telomere length now. We can look at your microbiome. We can look at your oral microbiome before you get a lot of periodontitis and get the P gingivalis into your brain. You can find that it's there and use some dental side and get rid of it. So there is so much that can be done and these early warning systems are going to be helpful.

Speaker 2: 44:28

Yes, yes. So in my language we refer to that as greater awareness from a psychological perspective. Yes, absolutely so, dale, other than Alzheimer's, what is going on in the research in areas of longevity that excite you right now?

Speaker 3: 44:49

Yeah, you know I'm very excited about the epigenetic ability to look at biological age. Now again it's associations and of course I should point out, a lot of this came from Professor Horvath's lab at UCLA. So another plug for an excellent professor at UCLA and Professor Horvath has done just brilliant work over the years looking at epigenetic association with age. And now what's happening is there are different epigenetic associations with things like rapidity of brain aging. There's a really interesting group out of Kentucky called True Diagnostic, ryan Smith and that whole group. They're doing really exciting work looking at different associations, different programs and, I should say, doing all sorts of collaborations with a number of medical schools. So we can now actually say to someone and Dr Kara Fitzgerald published about a year ago that here's some people where she can actually make them about three and three and all about three and a half years younger biologically, essentially just by doing the right sorts of things, and so we're going to be able to see that what speeds this up, what slows this down, and then again, association with other parameters such as brain aging. So I think that epigenetics and, along with this, being able to look at things like detox, one of the things I'm really excited about is when we see Alzheimer patients, we lump them. So you've got PCA, which is essentially posterior cortical atrophy, and, by the way, described by another UCLA professor, dr Frank Benson so thank you, the late great Dr Benson and PPA, primary progressive aphasia, and then, of course, the classic kind of amnestic presentations. These are very different and yet we lump them as Alzheimer's disease. And so, in fact, the epigenetics may teach us a lot.

Speaker 3: 46:45

We've seen, just as a clinical observation, the non amnestic presentations tend to be associated with toxin exposure. So we recommend anyone who sees someone with a non amnestic presentation, please dig deeply into the possibility of toxin exposure or potentially some of these chronic pathogens exposure, but especially looking at mycotoxins and organics and inorganics. So I'm hoping that the epigenetics are really going to tell us aha, these are, you know, these have different profiles and that we'll be able to help guide us. Another thing that's coming up is the hypercoagulable states. Partly because of this activation, a beta binds complement, it is a pro coagulant and, by the way, it also invests vessels, not to cause them to leak but to patch the vessels. It's a flocculant. So I think we're being able to look at this disease in a very different way now and, looking at these things like epigenetics, it's going to tell us a lot about aging and about disease. So we're going to have a just a raft of things looking at aging, now being able to measure biological age yeah.

Speaker 2: 48:01

You mentioned Ryan Smith and True Diagnostics. They're actually one of our interviews in this program and I'm currently in discussion with Ryan about doing some research to see if there's a correlation between biological age and my model of resilience.

Speaker 2: 48:22

So, psychological resilience, so I'll let you know when we move along on that as well. Fantastic, this has been a wonderful conversation, dale. I really appreciate the time you're taking to meet with me and to share your amazing information with our audience. We've touched on a lot of things that people can do during the course of our conversation. Is there anything else you want to add to that about what people can do to reduce their chances of getting Alzheimer's?

Speaker 3: 48:54

Yeah, so we've developed actually programs. One's called Precode Prevention of Cognitive Decline, and the other is called Recode Reversal of Cognitive Decline, and I've published books on these so you can look at the details. As you mentioned earlier, we published an article recently, but it's detailed, so it's helpful to have someone to work with you like a health coach. We've trained over 2,000 physicians now in 10 different countries and all over the US to do this, and there are people all over the country so you can certainly get that If you look just look at my Cognoscopy. We recommend everyone to get a Cognoscopy if you're 45 years or older. We all know to get a colonoscopy if you turn 50. But get a Cognoscopy as well. Simple to do and these are important things. The bottom line is we really can reduce the global burden of dementia if we all work together. So I encourage people please get a Cognoscopy, please work with someone who knows what they're doing and let's make Alzheimer's a much less common disease.

Speaker 2: 49:56

Thank you for that. And finally, how can people reach you? How can people learn more about what you're doing, what's your website or other ways that people can connect with this amazing source of information coming from you and from your group?

Speaker 3: 50:14

Yeah, I mean you can look at me up on DrBrettisoncom. There's a Facebook, we have Instagram as well and we're on Twitter as well. So, dr Brettison and Dr Dale Brettison, for some of these so easy to do, have books out, as I mentioned, one called the End of Alzheimer's, now available in 33 different languages. So you can. You know the usual Amazon and Barnes, noble and all that sort of stuff. Or look at our papers, and the papers, I should say, are freely available online. So again, the tremendous amount to be done. Unfortunately, in the United States the average person with Alzheimer's spends $350,000 by the time he or she dies. Horrible to think that you can do much, much, much better by getting started, getting on prevention or early treatment, so that you can save yourself vast amounts of heartache, dementia and not allow your family to go destitute. We can, you know again, as a country we can do far better.

Speaker 2: 51:23

Thank you again. I loved having our conversation. I look forward to the next time and thanks again and have a good day.

Speaker 3: 51:33

Thank you, steven, take care. Bye-bye.

Speaker 4: 51:36

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