The 7 Lifestyle Habits That Can Protect Your Brain At Any Age with Dr Dale Bredesen #592

29:28You have to have data for all these things to show, yes, this is possible. Yeah. Let's go back to genetics for a second. We've mentioned APOE. People have heard APOE4, APOE3. Can you just take us through genetics, what they actually mean, and why you think it's important that we all know our own genotype with respect to this? Yeah. So as I mentioned earlier, everybody should know their genotype. There are actually about 100 different genes that increase your risk or decrease your risk for developing Alzheimer's disease. But as you mentioned, APOE4, so the apolipoprotein E, which is a fat-carrying protein, is the one that's the most common, and it's the most important genetic risk factor for cognitive decline.

30:20Now, if you have zero copies, so for example, I checked myself, I'm an ApoE3, which is kind of vanilla. It's the common one. Three quarters of the population is ApoE4 negative. My risk throughout my lifetime is about 9%. It's not zero, but it's not terribly high. Is that 9 % based upon current modern lifestyles? Yes. Yeah, because I think that's a key point. if you weren't proactive about your health and your brain, if you just lived as most people live, if you're an APOE33, it's only 9 % risk of getting Alzheimer's. That is correct. And it is important to point out that all these numbers have been collected with epidemiological studies that have had people doing, you know, old-fashioned lifestyles and those sorts of things and not being treated appropriately.

31:11Our hope is, of course, to get this as close to zero as possible. Now, if you have a single copy, and that's one quarter of the population. So here in the U.S., about 75 million people have a single copy. Most don't know it, unfortunately, until they get symptoms. Your risk, lifetime risk, is about 30 % that you will develop Alzheimer's disease. And if you have two copies, you are homozygous for AboE4, and that's about 7 million Americans, then your lifetime risk is about 90%. Most likely, you will develop Alzheimer's disease. And therefore, we'd like everyone to know and everyone to get on active prevention so that they reduce that 90 % as close to zero as possible.

32:05I want to add one thing. We've just documented, which again, I believe is the first, where someone is APOE44. This is a 67-year-old man. APOE44 already had MCI. He's been treated for the last few years on the protocol. He's done very well. His ASL, so his symptoms have improved, but what's striking is his ASL, this arterial spin labeling, very sensitive test for Alzheimer's, highly abnormal in the past, is of this year, it is completely normal, a completely normal ASL. So that was so striking to see. I hope to see that many more times. Yeah, this is amazing, Dale. That case in particular is fascinating given what you've just said.

32:52So APOE44, so you have two copies, there's a 90 % risk of getting Alzheimer's. Hence the belief, don't get your testing done because you don't want to live knowing that there's only a one in 10 chance you're not going to get this condition. That was based on old science. The new science says, no, no, no. It's even more important to know if you're ApoE44 because you need to get in the cognition game early. So that chap was already at stage three, right? Symptoms get better and brain scan gets better, utterly remarkable. I'm pretty sure, Dale, when I first met you, you told me that APOE44 increases your risk of dementia in the West.

33:40But did you say to me that maybe in Africa and in different environments, it lowered your risk and it was all to do with infection risk and the terrain? Remind me what you told me. Yeah. So the point was that APOE4 turns out, it's not just the butcher who carries your fat. It is also your senator who's making the laws of the land. That is to say, it's a transcription factor. It is a transcriptional repressor. So, it actually changes the programming in your cells toward being more pro-inflammatory. And this is actually, this appeared with evolution as we went from the simians, which do not have APOE4, they have a chimp version of APOE, to the hominids, where there is now APOE4 was the primordial APOE.

34:30In fact, for 96 % of our evolution as hominids, APOE4 has been the only one. APOE3 just appeared 220 ,000 years ago in our evolution, and APOE2 just appeared about 80 ,000 years ago. So in fact, this pro-inflammatory effect, if you are a chimane in Bolivia, you actually do better if you're ApoE4 positive. You've got that ability, for example, to eat uncooked food full of microbes. If you're going to puncture your feet and you have a wound, then you're gonna do better as an ApoE4. If you go for periods of starvation, you're going to do better as an ApoE4. But in the first world, where we don't typically have those problems, at least they're not lifespan limiting, then in fact you have that pro-inflammatory state, which does give you a slightly shortened lifespan, a shortened brain span.

35:31And so we can do something about that, understanding what's going on. Now we can do something about that. It's so thought-provoking thinking about that, right? That for the bulk of our evolution, we had ApoE4 and it actually helped us in an environment where there's infection risk everywhere, where we need to have the immune system on high alert. ApoE4 is fantastic. But you flip that into the modern Western world with the food environment, the toxin environment, the sedentary environment the chronic stress environment the sleep deprived environment in this landscape it suddenly becomes problematic you can make the same analogy with many things from our evolution so our ability to store fat was fantastic in a different era when we would go for periods of time without food we needed that that probably helped us survive and be in this current era but that ability to store fat in hard times becomes a problem in a food landscape where you know there are never any hard times where there's always a surplus of food it's the same kind of principle isn't it yes isn't it interesting all the little pieces that we found in the test tube over the years fit exactly in what we're seeing in functional medicine again and again the evolutionary mismatch that you just described comes up again and again and again.

37:00This switching from a system's biology of connection to protection. We see these changes. We see these changes that are throughout the system that are coordinated so that your body responds to various insults. The same sort of themes arise again and again and again. Okay, I want to get to the three big buckets which cause Alzheimer's, so energetics, inflammation, and toxins. I want to get to the treatment strategies, you know, the seven basics and the two specifics. Before we do that, though, I just want to really make sure we've addressed this key point, which I think we both tried to address at the start, which is that the way you manage this complex disease is by addressing multiple factors.

37:59So, and I know this is one of the problems you had initially when you submitted your first trial for publication. I think they came back to you and said, yeah, Professor Bredesen, this is great, but you've changed more than one thing, right? Because I think you changed three or four things in that trial from recollection. And this is the kind of paradigm shift that's required in our profession and with the public to really, for them to really understand just why your work is working so well. It isn't a case of you have Alzheimer's. Let's just change this one. Let's try this drug. Does it work?

38:36Does it not? and I think one of the best ways of describing it is your 36 holes in the roof analogy which which I always thought was beautiful so can you just speak to that because I still don't think the public and our profession really have made that paradigm shift yet in how they look at disease yeah this is a really good point so of course we're all trained that if you're going to go out and do a scientific experiment or a clinical trial, you change one variable. So you have one group that doesn't have the variable, one group that does have the variable, you compare them and say, aha, this is what that variable did.

39:14Okay, that works great if you have a system that is a simple linear system. But now we're looking at network function. The brain is complicated. You have about 500 trillion synapses there. we're now saying that the supply is not meeting the demand. So we'd better determine all the things that are reducing the supply and all the things that are increasing the demand, just as you were saying, various inflammatory processes and toxic processes and energetic processes. We'd better identify those and address them. And so we're now looking at network. It's a little bit like, Rangan, if you took your car in and you said, hey, my car just stopped.

39:56I have no idea why. It could be that you've run out of gas. It could be that you lost your oil and you've got a problem there. It could be that you've got problems with your transmission, all sorts of things. So if everyone said, well, what we do when a car comes in that's not working is we just fill up with gas. And some of the cars start working again. Yeah, some of them do, but most of them don't. So you've got to look at all the different possibilities. And what we find is, as you know, some people, it's more that they have a pro-inflammatory state. For some people, they've had a lot of toxic exposure.

40:32Interestingly, in almost no one is it one thing. They usually have some metabolic problems. They often have gut damage that you have spoken so eloquently about over the years. They've got chronic infections. We'll find people, for example, who have, you know, P. gingivalis, a change in their oral microbiome with some periodontitis, which has been associated. Some people, they've had a lot of exposure to air pollution. Just on and on and on. Sleep apnea, a very common one. And people, it's been pointed out that about 80 % of sleep apnea goes undiagnosed. And so with all the many things that that increases risk for hypertension and cardiac disease and all this sort of stuff, it also increases risk for cognitive decline.

41:20So what we do then is with each person, we're going to look at your network, look at all the different things that contribute to it, and then we're going to optimize each of those. We want to improve the energetics, reduce these inflammatory inducers, these inflammatory markers. We want to reduce the toxin exposure. We see it all the time. By the way, just recently, Bill Shaw, who's the one who started GPL toxicologist many years ago, pointed out, he looked at our first trial with just some data mining and showed that the mean of the ocratoxin A in this, so this is a toxin from mold species, was 50 times higher, actually it was the median in his case, was 50 times higher than normal background.

42:11So these were people who had a very much of a high exposure to these particular biotoxins. And by the way, those particular ones, ocratoxin A, that particular one happens to target the hippocampus of all places, the very area that is often abnormal in Alzheimer's disease. So you've got to look and you've got to address those things to get the best outcomes. Yeah. And I think a key point there is that sometimes people will say things like, oh, I tried that. It didn't work. But actually, even that statement is misinformed, not willingly misinformed, but unknowingly misinformed. Because it's not like, oh, I tried that one thing.

42:54It didn't work. Let me try something else now. It's like, no, no, hold on. maybe that thing that you tried was 12 % of it, right? And maybe you need to do something else. So it's another 7 % of it. I know it's not linear like that, right? The body doesn't work like that. But, you know, one of the things I always remember about this analogy that you used, you know, there's 36 holes in the roof. A pharmacist might address one of those holes, but what about the other 35? The other thing you said, which I think is really empowering, is that even if there are 36 different causes, you probably don't need to address all 36.

43:29You just need to address enough, maybe that's six, maybe it's seven, to start shifting the balance. That's absolutely right. And then that's why we've seen this systems biology flip. So you go from the connection to the protection. So now to flip back into connection, it is a threshold. You need, you've got the problem where the supply is too low and the demand is too high. You start working on this. And of course, as you said, early on, you're not seeing much change. You still haven't reached that threshold. You keep adding, you keep changing, and now suddenly you're on the right side of that.

44:03And this is why we're now seeing people get back. One of the first patients I treated got back her ability to speak Chinese and Russian. She had lost her ability to speak Chinese and Russian. She was on the protocol for about five months. She started noticing, hey, wait a minute, I'm starting to remember things better. Then she said she was driving her car, and suddenly all these Chinese words started rushing into her head. She had to pull her car over. It's like, wait a minute, I'm getting this back. Interestingly, she also got back the ability to read piano music and sit down at the piano and play, which she had lost.

44:37So if you get over that threshold and now you're seeing the ability to make and maintain these connections once again. Yeah, I love that. This idea of a seesaw, isn't it, where you've got this fulcrum point, right? On a one side, you've got a connection. You know, the brain is connecting neurons together. whether it's in a state of low stress, it's like, you know, the brain is functioning as it should. But if there's enough stress, and I don't mean, well, stress is one of the factors, but if there's enough insult to the brain, then the seesaw tips from connection to protection, the brain is trying to protect itself, it's starting to shut down, saying, hey, no, no, no, no, I don't need short term memory at the moment.

45:19I don't need this. I need to just bunker down. And of course, depending on how far that seesaw has been tilted and how long for will also influence how many of these holes in the roof you need to fix. So, you know, as you say, you keep doing things, you're not seeing a result, you're not seeing a result, and then suddenly, boom, the fulcrum shifted, the seesaw starts to switch, you're no longer in protection, you're going to connection, and then you start to notice these symptoms, which is a beautiful analogy. So, there's so many different causes of Alzheimer's, right? But I think you put it into three big buckets as a simple way for people to think.

46:01Could you just go through those three buckets and explain top line what they mean? Yeah. So there are three, as you mentioned, three major groups of things that contribute to this cognitive decline. The first one is energetics. So you need appropriate blood flow. You need appropriate oxygenation. You need appropriate mitochondrial function. You need enough support energetically to make that brain work with all its 500 trillion synapses. So no surprise, you can pick out the things that affect that. People with sleep apnea, that's no longer working correctly. People with reduced blood flow, people who are not exercising, people who have some degree of vascular disease, that is reducing the support.

46:52People with any sort of mitochondrial damage over the years from various mitochondrial toxins that people have ingested or been exposed to, biotoxins are common causes of reduced mitochondrial function. And by the way, we saw this in the trial that some of the people who are in the control group, because their doctors knew, oh, wait a minute, they're on this trial. I'm going to look for some of these things. There was a lot of cheating going on in the control group. So we had, understandably, people say, hey, I don't want to be part of the control group. I want to do the best I can. And so, for example, one of them found out during the time, oh, wait a minute, I do have sleep apnea.

47:32After all, I'm going to treat my sleep apnea. And boom, just that alone helped the person get some degree of improvement. You can see then optimizing these things is going to be even better. So energetics, that's the first big bucket. And anything that affects that, as I said, you know, vascular disease, sleep apnea, mitochondrial dysfunction, any of these things will change it. The second big bucket is anything that produces systemic inflammation. And as you know, a very common one is metabolic syndrome. There are about a hundred million Americans who have metabolic syndrome, where they've got increased insulin resistance, dyslipidemia, the kind of the classics, often some extra weight, hypertension.

48:18This runs together as part of metabolic dysfunction. And one of the things that is included there is a pro-inflammatory state. And this is a common, common contribution. In fact, if you have metabolic syndrome, you have a several fold increase in your risk for cognitive decline associated with Alzheimer's disease. So lots of ways that you can get systemic inflammation. We see it all the time with tick borne illnesses, Borrelia, Babesia, Bartonella, Ehrlichia, Anaplasma, any of the tick borne illnesses increase your risk for inflammation. Changes in oral microbiome, as I mentioned earlier, another one, leaky gut that you talked about so nicely years ago at our course.

49:05That's another one. So that's the second big bucket. You've got to look for those. You've got to address them. And then the third big bucket, as you mentioned, is anything that is giving you exposure to toxins. And they come in three different types. There's the inorganics, and there's a lot of evidence now that air pollution increases your risk. So here in California, the California fires, a big issue for us. We are during those times breathing in air that is actually potentially damaging to our cognition. And there's actually now a fair amount of research on this, especially the so-called PM 2.5, these small particulate matter that's associated with cognitive decline.

49:50So it's those, and mercury is another big one. Interestingly, at the heart of Alzheimer's, this APP, amyloid precursor protein, which is the parent of the amyloid that we associate with Alzheimer's, it's amazing because it is at a nodal site for toxicity. It interacts with multiple metals, for example. It interacts with copper and zinc and iron and things like that. And actually, Professor Ashley Bush from Australia has done beautiful work over the years looking at the relationship between APP and amyloid and metals. Then you've got also things like the second group, which is of the three here.

50:33So the toxins are inorganics, organics. And this is toluene, benzene, glyphosate, things like that. And of course, the big one everyone's concerned about currently is microplastics. And there's no question now from the data that microplastics accumulate in the brain more so than the liver or kidney, that they are associated. People who have high degrees of microplastics in their brain have an increased risk for cognitive decline. What's not yet clear is what's cause and effect, whether it's associated but not causal or whether it's actually causal or both. So that's the organic set. And then the third group within the toxins is the biotoxins.

51:19So things like trichothecines, I mentioned ocratoxin A earlier, and gliotoxin and things like this that we're getting typically from mold species. So again, people will say, oh, come on, molds are everywhere. Yes, they are. But there are some people who are particularly sensitive to them who get this chronic inflammatory state and have damage from their mycotoxins. It's a common contributor to cognitive decline. Yeah, thank you. So it's funny hearing that, I imagine, is going to be quite scary for a lot of people. Because what you basically just outlined is the bulk of the problems in the modern world when it comes to health, right?

52:05And we know from the data just how many people are sick these days and are struggling with a variety of these sort of conditions that you just mentioned. And although you're mentioning them through the lens of brain health and cognition and Alzheimer's, I mean, the truth is, if you address those three big buckets, you're not just going to improve your brain. you're going to improve virtually every other aspect of your health as well, right? It seems like the brain is almost the end organ, you know, the sort of final organ to fall. You know, we get those, we used to get those diagnoses in our 70s, our 80s, maybe, and I know that's coming back to 60s and 50s now, right?

52:51It's as if the rest of the body can just about tolerate it and put up with it. the brain's just about holding on until it can no longer hold on. You know, inflammation, sleep problems, mitochondrial damage, oral microbiome issues, leaky gut and gut health issues, mold, air pollution. These are all things that many of us are being exposed to or struggle with. This is going to get very empowering because you're going to show us shortly just how much there is that we can do to help with these things, right? But I just want to tie in genetics just for a minute here. You mentioned the genetics of APOE before.

53:37Yes. And how important it is in your view that people understand it so they can take appropriate action early. But let's just say toxins, for example. You just mentioned mold, right? Or even things like air pollution and microplastics. Genetics plays a role here as well, because I think we are living in an increasingly toxic world. But the truth is some people genetically, I think, are better able to deal with these toxins than others. Some of us just aren't very good with detoxifying these toxins from our environment. So are there any, first of all, do you agree with that? And secondly, if you do, are there any specific genetic tests that you recommend where we can actually determine what is our detoxification status?

54:24and do we need extra work here compared to someone who perhaps doesn't have the same genetics as we do?

54:43There's no question we see it again and again and again. For example, you'll often see a husband and wife living together in a home that turns out to have a high degree of mycotoxins, and the husband or wife will become demented. The other one will not. And so they'll say, well, how can this be something that's in our home? Because we both live here. Well, it turns out that genetically, for example, the one who's got the dementia has a null mutation in the GST1 gene, as an example. So this is one of your detoxifying genes related to glutathione, which is a major detoxifier in your body. And so, okay, this person, we need to boost that up.

55:25We need to recognize that. And by the way, the other person may end up getting a cancer. So they still have something that could potentially be related to the toxins, but they're not developing dementia. So there are differences in detoxing. And absolutely, as far as what to look at, very soon we'll all have our whole microbiome sequence. I think that's coming. It's becoming less and less. The very first genome that was sequenced took about something like$20 billion because so much had to be set up, so much had to be done. You can now get your entire genome sequenced for about$600. So you can see how far this has come, just like when we first had cordless phones.

56:11I mean, look how far things have come there. And so this is going to happen soon. But for now, you can get pieces of it very simply. And for example, IntellX DNA is one of the ones that does it. 3X4 genomics is another one that comes. DNA life is another one. There are multiple of these that will look at these and look at the key pieces. We want to look at, do you have a hypercoagulable state? Do you have a poor detoxifying state? Do you have a pro-inflammatory state? These sorts of things. Where do you stand with your trophic factors and hormones and things like that? So yes, you're absolutely right.

56:55There are people who are predisposed. And this is what we're looking for when we're trying to understand how to get best outcomes for each person. Yeah. Thank you for that overview. I mean, part of me really wants to go deeper into endogestics, inflammation, and toxins. but I think we just hold it there at the moment and move into treatment. If we've got time, we'll go a bit deeper into each one of those three or we'll save it for a part two conversation because I want to make sure in this conversation, Dale, that everyone listening understands, first of all, that Alzheimer's can... There is something you can do about Alzheimer's that earlier you start picking this stuff up, the more you can do, But even if you've already got a diagnosis, there may well be things that you can do.

57:45I don't know what's really interesting. You've written multiple books. This new one, The Ageless Brain, How to Sharpen and Protect Your Mind for a Lifetime, is absolutely fantastic, Dale. And what I love about it the most is that... And A, it's really clear. It's very well written. But I think for someone like me in my 40s, I can read that and go, I know exactly what I need to do, what I need to test and what I need to do if I want to ensure as much as I possibly can that in a few decades time, my brain is still functioning as well as it could do. right it's it's it's that it's not a doom and gloom book it's a book that's saying hey listen i don't care how old you are these are the core things you need to do if you want your brain to function as well as it can for the duration of your life which i'm pretty sure everyone listening to this once right so thank you for writing it dale i think it's a it's it's a gift to people who take the time to read it.

58:48In that book, you go through the kind of seven basics, and then the two specifics that you want everyone to be thinking about. So would it be okay for you to sort of take us through all that? So yes, this works, I think. Is it fair to say before you do this that if you're in stage three or stage four, so stage four being you have dementia, you want to be doing these things but you may need to do extra as well whereas if you're in stage one or stage two if you get dialed in on these seven things you can make sure you never end up at three or four is that a way of framing it before you go through it?

59:28Yeah, exactly so this is what the book is about having a brain span that is as long as your lifespan so, you know, it is so sad as you well know someone may live to 80 or 90 or beyond, but their brain span may only be until they're 50 or 60. And you mentioned earlier, we used to think of this as an old timers disease, you know, 60s, 70s, 80s, 90s. Now that we know what to look for biochemically, you can see changes in the 20s. That's the surprise. This is not a disease of old people. It's a disease that is diagnosed when you're old often, but it can start in your 20s and 30s. And so we want to look early.

1:00:13We want to treat early. And then just as you said, you start early. It's very easy. You know, this is an easy thing to do. It's the way, you know, imagine that your oncologist said to you, well, Rangan, you know, don't bother to get a chest x-ray. Don't bother to, don't bother to get a colonoscopy. We only look at things when you've got widely metastatic cancer. You would fire your oncologist. Why are we insisting on this in Alzheimer's disease? Well, let's do the same thing that's been done with cancer and with diabetes and prediabetes. Let's look early on. Let's make sure that you never have to progress to get that final stage.

1:00:53That's been one of the biggest problems. So as you said, when we do this, there are the seven basics that everybody can do. This is optimizing your systemic function so that you have a brain span that is equal to your lifespan, which is hopefully a nice, long, and happy lifespan. So those are diet, exercise, sleep, stress, brain training, detox, and some targeted supplements. Those are the simple, basic things we can all do. We want to optimize those things because, again, we're dealing with a network insufficiency. We're going to bring that network up to snuff. We're going to quit putting so much drag on it with all the inflammation and the toxicity.

1:01:35So for the diet, the one that has worked best, as you mentioned earlier, is called KetoFlex 12.3. It is a plant-rich, plants are critical for detox and critical for better lipid profiles and better glycemic profiles, phytonutrient, on and on and on, as you well know. And so plant-rich, mildly ketogenic diet. We want metabolic flexibility. As you know, the brain is like a Prius. It can either function, just two things, it functions on glucose, it functions on ketones. You should be able to go seamlessly back and forth. For most of the people that we see who have cognitive complaints, they've lost both.

1:02:19They are now insulin resistant and they're not capable of making ketones. Because when your insulin is high, you have insulin resistance, it prevents you from making the ketones. So you've got the worst of both worlds. You know, your brain is sputtering. We want to return both of those. So you're able to utilize glucose, you're able to utilize ketones, and you can go back and forth. The second one is exercise. It's amazing how functional, how helpful exercise is. And probably the best data on so-called HIIT, high intensity. But if you just combine strength training with aerobics, you get the better blood flow, you get a better insulin sensitivity, you do much better overall.

1:03:00And people will even tell me, when I do my exercise, I notice I'm sharper than the days when I'm skipping the exercise. Very interesting. And of course, people support that. Even some people have gotten very interested, as you know, in creatine, which supports those energetics, supports the exercise that you're doing, the strength training that you're doing, and has been helpful for cognition. And then the third one is sleep, and it's really underappreciated. So I check my sleep every morning. How much total sleep? We want to target at least seven hours. How much REM sleep? We want to target at least 90 minutes.

1:03:39How much deep sleep? We want to target at least 60 minutes. And by the way, that's particularly important for people who are detoxing. And then what is your SpO2? you want to make sure that you're 94 % oxygen saturated or above. And with these wearables that everyone's using today, it's simple. You can check and see your status, check and see how you did. Wearables are going to help us for these chronic complex diseases. So that was the third one, sleep. And make sure you don't have sleep apnea. Sleep apnea is a very common contributor to cognitive decline. And then the fourth one is stress. And you mentioned this earlier.

1:04:20You can trace the molecular pathways from stress to Alzheimer's disease. It is a common contributor. And by the way, one of the things that switches you from connection to protection is stress. So just having that chronic on, it's not the people who have acute stress with resolution are not at the increased risk that the people who have the chronic unremitting stress, that's the big problem. We were not meant evolutionarily to handle that. The fifth one then is brain training. And of course, Professor Mike Merzenich, the father of brain training and the one who started Posit Neuroscience and Brain HQ, has done a great job with that.

1:05:03They've done numerous things. And recently, by the way, they have shown, that team has shown, that you can even see improvements in neurochemistry in cholinergic markers in the brain through PET scanning. just by doing brain training. So the brain training, very helpful, no question about it. But you don't want to stimulate that brain if you're not supporting it. So we always recommend start by supporting the brain, then start stimulating it. And there are other stimulations, not just brain training. There are things like light stimulation, sound stimulation, microcurrent, all these sorts of things, magnetic stimulation.

1:05:42These are all ways to get your brain stimulated when you're already in a good support system, that's great. Then the next one is detox. And we talked a little bit about the toxicity before. So important. So just some basic detox things. Saunas, the famous study out of Finland that showed that people who were doing five or six saunas per week had a much lower likelihood of developing Alzheimer's than people that were just doing one or two. And interestingly, in Finland, not too many people are doing zero saunas per week. So, whereas, of course, in the U.S., that's the most common. So, again, detoxing, getting out there, sweating, getting rid of the toxins in the sweat, breathing these out with exercise, having optimal gut function, high fiber diet, which is one of the reasons fiber is actually so incredibly important, both soluble and insoluble, optimizing your gut microbiome, so important.

1:06:43these things. And of course, filter, you know, good, healthy water. All of these things are critical for optimal detox. And that does definitely make a difference. And then the final one is some targeted supplements. And yeah, if you are low in vitamin B12, if you are high, in fact, the best studies on homocysteine came out of the UK showing that there was literally a linear correlation. As your homocysteine goes up higher and higher, your risk for loss of brain volume goes up. And in fact, that they could show that they could stop that dead in its tracks just by giving support with B12, folate, and B6.

1:07:26And we typically use active, typically methyl folate, methyl B12, and P5P, paradoxal 5-phosphate. And some people will need to add some trimethyl glycine, but for most people, they don't. As shown in these beautiful UK studies, you want to see your homocysteine down at below 7. So many people are walking around 13, 14, 15, 20, things like that, this is associated with atrophy of your brain. And so we want to do... So there's one example of supplements. I'm sure you've seen the recent paper out of Harvard on lithium. And now those were only animal studies, but people have known for years that lithium is important for optimal mental function.

1:08:13And so taking some typically five or 10 milligrams of lithium orotate has been helpful for many people. Knowing your vitamin D level, very important. And again, multiple studies showing both low vitamin D associated with more cognitive decline and mutations in the vitamin D receptor associated with cognitive decline. So there are many of these things. I happen to like the resolvins as an example. Also, this came from Charles Sirhan's, Professor Charles Sirhan's work, which again, reduces inflammation, helps you to resolve the inflammation. So the armamentarium to prevent and reverse cognitive decline has grown by leaps and bounds in the last decade.

1:09:02Yeah. Thank you. It's incredible because what's really interesting is that the first four out of the seven are, I guess what I've called the four pillars of health for many years, food, movement, sleep, and relaxation. Okay. So everyone listening, especially regular listeners to my podcast, will be hearing about those four pillars from a variety of different experts around a variety of different diseases, around a variety of different health outcomes, right? it is going to be very hard for you to live a vibrant energetic disease-free life if you don't pay attention to food movement sleep and relaxation okay so i never get tired of hammering home that point those four pillars are really really important and of course with reset to the brain you've added on three things brain training regular detoxification and finally targeted is supplementation.

1:10:03Okay, so those are the seven, which I think, frankly, whether we're worried about dementia or not, paying attention to those seven things is going to be good for your overall health anyway. But let's just go through them sequentially. You have put a bit of detail there for us. But number one, it's a plant rich, you know, mild ketogenic diets, okay, which you call Ketoflex 12 slash 3. So you said the plants are really important because they help with gut health, they help you with detoxification. All the phytochemicals in those plants can be very helpful for your brain. I think in the book, I was reading The Age of Spraying this morning, I'm pretty sure you were talking about one of the benefits of plants is the fact that our brain is very susceptible to oxidation because of how many lipids, how much fat is in the brain.

1:11:01And I think you made the case that plants are antioxidants and they help reduce this. Am I recalling it correctly from your book, Dale? Yeah, and that's one of the many benefits, as you indicated. So as you know, just polyphenols alone, one of the many, many, many phytonutrients, has turned out to enhance cognition. And yes, there's antioxidant effects of these. So there are multiple mechanisms by which plants, and by the way, they improve your glycemic status as well. So they are gonna help you prevent yourself from getting type two diabetes. They increase your glutathione, your ability to detoxify.

1:11:46Sulforaphanes have really emerged as being very helpful. So there's no question, for many reasons, these plant-rich, mildly ketogenic diets have done the best when it comes to cognitive decline and supporting cognition. And what does it mean, Ketoflex 12-stroke 3? What does the 12-stroke 3 mean? Yeah, the 12-stroke 3 means that you want to have at least 12 hours between finishing the last meal at the end of the day and beginning the next one. So in other words, you don't want to eat right up until bedtime, then sleep for, you know, heaven forbid, four or five hours, although we hear it all the time, wake up and then down a high carb meal.

1:12:25That is not good for your brain. You want to finish, you know, if you finish eating at 7 p.m., you don't want to start eating again before 7 a.m. You want to give your time, your brain some chance to cleanse itself. And of course, there's been a lot of work over the last several years on that whole process, the so-called glymphatic system. You want to be able to cleanse these various damaged molecular species that occur during the day that occur with the various insults. And then you want to pick up in the morning. And so give yourself some time. Now, some people will go even longer. Be careful.

1:13:01We don't want for what we see is there are people who are very frail at the beginning. They don't have much of it. They cannot get into ketosis very easily. They don't have any fat to burn. Going for too much fasting makes them worse, not better. We have other people where they're overweight. They've got plenty of adipose to burn. They can get into ketosis pretty easily. Having some fasting really helps them, and it reduces their inflammation. So again, it's not one size fits all. You have to look at what's optimal for each person. So 12 hours of fasting, and then slash three, because you don't want to eat for three hours before going to bed.

1:13:39You don't want to go to bed with a full stomach, especially a high carb. One thing that happens, of course, your insulin will stay high. Your growth hormone will stay low as long as you've got that. And then you'll wake up often. We see this all the time. When people check their glucose, for example, with the CGMs that have become so popular, continuous glucose monitoring, they'll say, oh, I finally understand. I wake up at 3.30 or 4 in the morning, and my heart's pounding. I might be sweaty. It's like, yes, you're hypoglycemic. And they'll come and they'll look, and their glucose will be 42. So they're way down.

1:14:16So you want to have a smooth, you want to smoothen that curve. And that's why this plant-rich, mildly ketogenic diet, to smooth that glucose curve and to help you to sleep through the night. Yeah. When you say mildly ketogenic, that's obviously, you know, mildly is quite a subjective term, isn't it? Are we talking low carb here, basically? Once someone has got to the point where their brain energetics are not working so well, where they're displaying symptoms, have you found, you know, low carb is an interesting term because to someone, 150 grams of carbs a day is low carb to someone else that's 25 grams a day, right?

1:15:03So it's very hard to know what someone means when they say that. But have you found, for example, with some patients, you have to actually give carb limits, like no more than 50 grams a day to make sure that you are hitting ketosis? Help us understand that. Let's put some numbers on it. So when I say mildly ketogenic. With people who already have any symptoms, we see the best results when they get to at least to 1.0 millimolar beta-hydroxybutyrate. So you can check it on your finger, check your ketones, and there will be continuous ketone monitoring, I'm told, within the next few years, which will be exciting.

1:15:44But meanwhile, you can check your ketones and you can also, as a first-order approximation, do it with a breathalyzer or look in the urine, although the blood's always more accurate and is the best way to do it. We want to see you at 1.0 to 2.0 in that range. That's mildly ketogenic. For people who, hey, when they're looking at neonatal seizures, they're looking at 6 to 8 millimolar beta-hydroxybutyrate for this truly ketogenic diet. This is mildly ketogenic diet. One, two. We see people who get to two and a half or three even. That's mildly ketogenic. If you're asymptomatic, you have no symptoms and you're just looking at prevention, no problem.

1:16:23Get to 0.7, 0.8, 0.9. You don't need to get quite as high. But once you get the symptoms you want to get, and we see the best results. Now, Professor Stephen Kinane from Canada has done studies where he's just taken people with MCI, so they're already in that third stage, just giving them exogenous ketones. That alone has improved those. And of course, as you You know, Dr. Mary Newport has done some beautiful work with just using coconut oil, showing that you can get some improvements, a way to give yourself exogenous ketones. So those are the numbers we're looking for. And as you said, some people will, you're going to need to get down in that 20 to 50 gram range to get that.

1:17:05So again, you got to get some follow-up. You got to look to see how you get that system into a mildly ketogenic state. Yeah. Thank you, Dale. That's super helpful. CGMs, you know, as I've said many times on this podcast, continuous glucose monitors, I don't think I've seen a more powerful behavior change tool than CGMs since I became a doctor. There's something about seeing your own data, seeing your own sugar go ridiculously high, that immediately starts to change behavior, right? Can some people get stressed out by this? Yes. Is it for everyone? Perhaps not. But for many people, it can be truly game-changing.

1:17:47You mentioned exogenous ketones there. And a few weeks ago, I spoke to Ben Bickman. You probably know Ben's, you know, a real expert in metabolic health. And he was talking about the incredible benefits of exogenous ketones and even studies in polycystic ovarian syndrome where people don't even change their diets, but take exogenous ketones and getting some quite profound results. We also discussed Stephen Kinane and some of this incredible work that he's been doing out of Canada. What's your take on exogenous ketones when someone has got a cognitive issue? And I guess there's two or three ways to look at this.

1:18:25One is that, as you mentioned, some people are really quite frail. And actually to not eat sufficient amounts and to go for long periods of time without eating or low carb to get into ketosis can be problematic if they're frail. So that's one potential issue. And then of course, there's the issue where some people won't change their diets and will go, no way. Or family members won't permit you to change their diets. And they'll be like, no, no, no. They love their biscuits. They love their sweet cakes. It's almost deemed, you know, let's be honest, like some people would deem that not giving their grandma their favorite cupcake with their sweet cup of tea in the afternoon, they would say, well, this is ridiculous.

1:19:09You know, they're in the final stages of their life. Why can't they enjoy their sweet cup of tea and their cupcake, right? So, and I understand that sentiment. I just feel if you only knew what a sustained approach could do for potentially for your grandma's cognition, you might think about it differently. But there are at least two examples there where I can think of exogenous ketones being potentially very useful. Yeah. Yeah. Such a great point. So imagine that someone said, you know, but Dr. Chatterjee, she loves to smoke a pack of cigarettes each day. So why should she stop? Well, because smoking cigarettes is not helpful for you.

1:19:46And by the way, it's not helpful for your cognition or your cardiovascular system or your lung function or the risk of cancer, all those things. So it's the same sort of thing here. And of course, as our colleague Mark Hyman has pointed out, you know, we should be thinking of these poor diets much the way we think of smoking. They do have negative impacts on our health. Now, the great news is as people realize this, they're getting better and better at making better and better food that is actually healthy. It's just that it's cheaper and easier to make that fast food that's not good for your health.

1:20:23And by the way, you know, years ago, I was on the National Institute of Aging Council, and one of my council colleagues did a study showing that in the UK, you develop on average your first chronic illness in your 50s, whereas in the US, you develop your first chronic illness on average in your 40s. So the UK is already doing about a decade better than the U.S. in terms of developing chronic illnesses. But as you said, now that we understand these things more, okay, we're just trying to get your supply up and your demand down. So there are a couple ways to do this. If you're able to get into ketosis on your own, that's actually got some benefits that exogenous ketones don't have.

1:21:14But for most people, It takes a month or two to slowly get yourself into this. So my argument is, look, you've come in. You're telling us that you're in the protection side. We want to bring you back to the connection side. Let's boost that. So just go ahead and use the exogenous ketones for the first couple of months. Then you can slowly wean off them. We need to get you that supply, especially for the people who are frail. Now, there's a wonderful assisted living place here in California called The Vineyards. And I just visited there recently. They're the first one here now to be adopting this after Marama, which Heather Sanderson started years ago and was the first place to do this.

1:21:55This is now the second one. So excited about this. They have brought in a couple of chefs that will make you things that you will say are just as good as your afternoon cakes and teas and everything that are extremely healthy, fit with Ketoflex 12-3. I mean, it's fantastic. We just need to have more people have access to those things so that you won't feel that you're giving up something. So yes, we want exogenous ketone at the beginning, and then on the long haul for many people, we'll be able to do it just with endogenously generated ketones, but not all. Yeah, that's really interesting. And I just want to highlight a cost issue.

1:22:35You mentioned before about the genome, the human genome, how expensive it was initially, and how rapidly costs have come down, where it can be a couple of hundred bucks now to actually get... and I'm sure the cost will come even lower over the next few years. Unfortunately, exogenous ketones are pretty pricey at the moment, depending on which company you go for. And I say that to acknowledge that. I still think we should be having this conversation and saying what's available, because some people will be able to afford it and have access to it and can get those improvements. But of course, there's more knowledge around exogenous ketones as more people start buying exogenous ketones, of course, the costs are going to start coming down again.

1:23:21So I anticipate, I would certainly hope in two or three years, it's way cheaper than it is now. Yeah, exactly. What about red light therapy? Do we know what that can do for the brain? Oh, absolutely. And that's been used. V-Lite is one of the ones, for example, Neuronic is another group that is getting very good results with this. V-Lite's done a number of - Is V-Light a company that uses red lights or is it a specific type of light? V-I-E-L-I-G-H-T, yeah, V-Light. It's a company, and this work came out of MIT originally with Professor Li Wei-Sai and has been adapted for this. So typically this driving at a gamma frequency, which is about 40 cycles per second, seems to be what helps to stimulate the brain to do best in terms of its memory.

1:24:09Again, you don't want to stimulate it too much until you've supported it. I mean, that just makes sense. Again, it's like before you put oil in your car trying to drive it 100 miles an hour. You don't want to do that. You want to make sure that other things are set first, and then you want to drive it. Yeah, that's a key point. In the chapter on brain training, which is one of my favorite chapters actually in the book, you specifically mentioned that. I think it's a really key point. The order sometimes matters. and you were hypothesizing that sometimes brain training doesn't show an effect certain types don't show an effect in the research but others do and you were hypothesizing that and in fact I wrote it down you said you know you believe that once neurodegeneration has begun the added cognitive demand from brain training may further tax a distressed brain unless the support is increased or the demand reduced.

1:25:11And I really love that nuance there, this idea that brain training is going to be really good for your brain, but it depends on where your brain is at, right? So let's get the brain as good as we can with nutrients, with diets, with supplements, and then let's add in the brain training. I thought that was a really interesting point. So imagine that you said, hey, you know, I've been malnourished for two years now, so I've got very little muscle left. So I'm going to go out and start working out with weights like crazy while I'm still malnourished. It makes no sense. So you've got to have that supply side to slowly increase that.

1:25:50And the other thing it means there is don't go crazy with the demand. Don't make it so that you're stressed out. As you know, it's been found that more and more people who are overtaxing their muscles, people who are running too many marathons can really have some joint problems over the years. So make it so that it's physiologically appropriate. it. Yeah. You mentioned when you were talking about stimulation there, you mentioned light and music. And I don't know if it's your work or was it Rudy Tanzi's work? I can't remember. What is, where are we up to with the impacts of music on our brains?

1:26:32Yeah, this is such an interesting point. And there was a wonderful film, documentary film a few years ago called Alive Inside, where they were showing that specifically music from your era, when you've got memories in there from music of when you were in your teens and 20s and a youth and enjoying and out partying and dancing and all these sorts of things, and playing that music would activate the nucleus accumbens and give some joy and give some dopamine and that sort of thing. Now, interestingly, at that time, that alone did not seem to improve cognition. Since then, there's been another study that suggests that, yes, you even get some cognitive benefit.

1:27:14But overall, as part of improving your physiology, music and joy, joy has turned out to be much more important than I ever thought as a scientist I ever thought it was going to be. There really is a biochemistry to joy. And so for people to get out and enjoy their social interactions and, of course, social interactions are shown again and again and again to be important. We've had a couple of people mentioned recently that it's a woman and man. When the man leaves and goes on trips, the woman actually declines. When they come back and they have good time together, the woman gets better again. And she goes up and down depending on whether the travel is on or whether they're happy together.

1:27:59Music is a classic one, of course. Dancing, hiking, all the things that people love really do make a difference. Again, and of course, reducing your stress. It's basically giving positive feedback to your neural network to say, yes, we are on the right track. It's the reason you have negatives with the nocebo effect. You're constantly getting that feedback. Is this something that's good for me, supporting what I'm doing or not. One of the things you also talk about, Dale, is the importance of addressing when our senses start to go. So, you know, your hearing, for example, right? So once you start to lose hearing, it's important you address that.

1:28:44But I'm fascinated, yes, for the audience, what that means, but also on a personal level, I've got a bit of sensory neurodeafness in my right ear. from essentially being a music fanatic in my teenage years and my 20s and playing in rock bands and watching a lot of gigs and wanting to get closer. I can still remember at university, there was a band playing every Wednesday night. We'd go for the entire six years at medical school. We rarely missed a Wednesday night. And I would stand in the bar, literally with my right ear next to the speaker. So I was as close as you could get. But, you know, if I was coming to you as a patient and saying, Dale, this is what I've got.

1:29:28I don't want to increase my chances of cognitive issues when I get older. Is there anything I can do? What would you say to me? Well, first of all, I would say, because this is a network, and you've still got your left ear, presumably. I do. Great. Okay. And you've still got activity. You've got all the other pieces. So you've got 35 holes in the roof that are doing well. That extra one is probably not going to give you a problem. I'm going to call it a half hole as well. I'm not even calling it a full hole because the left is working. Okay, it's a half. It's a half there. And in fact, as I've mentioned before, these things shut when you now switch over, you're doing all the good things.

1:30:11Now, if you get significant symptoms, let's revisit that. And in fact, there are people now doing things like cochlear implants that are showing improvement, which is very interesting. But of course, we just had two days ago, one of the patients actually came by the house here and she's doing very well. Single copy of ApoE4 really was there more because her mother had passed away and she's been involved with us in our trials. Just a remarkable woman. And she was putting off getting hearing aids. She clearly needed them. And she said, you know, I found out these things work so well and they are so small now, you can't even see them on her.

1:30:53She's got them sitting behind her. You can't even tell. And she's got her hair over them. So you would never know that this person happens to be using hearing aids. And she said, my gosh, the difference is huge. Well, hold on. The difference is really interesting. The difference is huge. So that difference can be short-term immediate in terms of, oh, wow, I can hear more now. I don't need to ask everyone to raise their voice or whatever it might be. but you're also saying the difference is huge in terms of the input now coming into the brain, right? So the quality is amazing on two different levels.

1:31:28And I guess that's the point, isn't it? You're saying that all of our senses have the ability to offer inputs into our brain. We don't want to dull that down. We want as many of those inputs to be active for as long as possible. So if your hearing's going and it is hearing loss that is amenable to a hearing aid, you're saying actually that is going to massively or it's going to have a significant effect on reducing your chances of cognitive impairment when you get older. Yes, so it's been shown people who have hearing loss are at increased risk for cognitive decline. It's a common one actually.

1:32:05So as you said, the senses are stimulating you through your smell, through your vision, through your hearing, through your taste, through your touch. All of these things are important. And by the way, one of the earliest patients I treated who had Lewy body disease had lost his sense of smell. As he got on the treatment, his wife said, well, wait a minute, he can smell again. So, you know, this is part of the neurodegenerative part itself. So it's not just they increase your risk. It's also that they are a manifestation of the reduction in synaptic efficacy. So as you're improving this physiological system, you are improving the senses.

1:32:47Yeah, no, I love that. Dale, you mentioned before about biomarkers that we can check. I want to go into that in just a moment. But something I've been thinking about recently is what are the key biomarkers that people need to look at throughout their life? This goes beyond brain health, okay? Brain health is a part of it, but I was looking at it through the lens of metabolic health, because of course, if you have exceptional metabolic health throughout your life, you are going to dramatically reduce the likelihood of getting any chronic disease, let alone dementia, any chronic disease, right? So I guess my question to you, as one of the world's leading experts in Alzheimer's dementia, is if there were some biomarkers, let's say, for example, let's just pick five.

1:33:37So HbA1c, which is your average blood sugar. Insulin, which, you know, fasting insulin, which, you know, is a very, very important biomarker, which unfortunately, you know, people in the UK don't have easy access to on the NHS. Homocysteine, which you mentioned before and how you want that under seven. High sensitivity CRP, a marker of inflammation. I don't know, you know, I mean, there's all kinds of different ones. like ApoB or triglycerides, right? Let's say those five or six biomarkers that you could identify which we can, what is optimal. And if someone from the age of 20 all the way to 80 made sure they checked them regularly and they stayed in the optimal range for decades, what do you think that would do to their risk of getting dementia?

1:34:35There's no question, and it's been shown repeatedly, it would reduce their risk. However, it would not reduce it to zero. As we talked about earlier, they may have some genetic mutations that they're unaware of. They may have a pro-inflammatory state. They may have exposure to mycotoxins, for example. All these things are important. They may develop sleep apnea. So it will heal their biochemical status. So we think in terms of two different sets of tests. There's one that says, where do I stand today? And you alluded to that earlier. That's the P-tau and the GFAP. And now where do I stand today with my brain status?

1:35:16And then there's another that says, where am I headed? And these are the ones you were just talking about. Where am I headed? What does my future look like? And you do want to know your inflammatory status. You do want to know your glycemic status. And we're getting better and better, of course, with earlier and earlier and more and more sensitive tests. And by the way, this is where P-Tau is headed. There is a super P-Tau 217 coming out around the end of this year that will give us even earlier looks so that we can really help people early on, even earlier, and make sure that they don't progress.

1:35:53But to reply to your point, it will reduce their risk. Absolutely. That's clear. but it will not reduce it to zero. So therefore, you still want to see where you stand every five years, and you want to make sure that if you start having problems, okay, something different than what you're addressing has come up. So go in and get those things evaluated. We find this all the time, and I mentioned Dr. Toops earlier. She had a patient just recently. She'd done all the basics. She said, hmm, somehow this patient's not responding yet, so I need to look further. she did a cone beam CT to look at oral abscesses and found an occult abscess when she treated that the person got better so again you got to look you got to find what's driving the problem and you've got to address it yeah in terms of then someone who's been listening to this podcast or they just stumbled across this video on youtube dale and still watching right and is thinking wow, I didn't know any of this.

1:36:53This is brand new information for me. Let's say that, you know, they don't have symptoms. Maybe they're in their 20s, their 30s, their 40s, their 50s, whatever it might be. And they're like, okay, I want to now do something straight after this podcast. I want to take action to see where I'm currently at. I think I've heard you talk about three things to do. Is it my CQ test, bloods and a cognoscopy, you know, or for that person who wants to do something immediately to assess things, what can they do basically? Yeah, the easiest thing to do is buy the original book, The End of Alzheimer's. Just take a look at why we're doing what we're doing.

1:37:36And then, yes, the simple thing, there's a free online test. Go to, just go online, mycqtest.com. That will give you a free, it's about a 20-minute or so simple cognitive assessment. And you can see where you stand because we all know this does sneak up on us. There are so many people where they say, well, I think I'm okay. I mentioned one of these in the book, but then it turns out, wait a minute, no, things are farther along than I thought they were. Okay, well, let's get to work and let's make sure that things improve. That's different from the MoCA, right? It's not the same as the MoCA. It's more sensitive than the MoCA.

1:38:15It's more sensitive. So anyone listening can literally go to mycqtest.com and spend 20 minutes on it, and they will get a score. Yes, absolutely. And then from that score, they can see, am I still at a point where it's just about prevention? I really don't. I'm doing well. Or am I already starting down, and I really need to get serious about this earlier? I really need to get... So we've developed, that's why we have a prevention program and a treatment program. Prevention is called precode. Treatment is called recode for reversing cognitive decline. So just, I would say to everyone, please, you know, recognize that these things can sneak up on us.

1:38:54Just as it happens with all chronic illnesses, cardiovascular disease, cancers, et cetera, we now have the way to look earlier, see where you stand, and then find out why. You can then get some laboratory studies pretty easily. We can actually, here in the States, you can do it. You know, even we don't need a doctor because there's a doctor who oversees the tests so that you can get this done. It's easy to do, and everyone should know their status going forward. Okay, so one thing they can do is MyCQ test to get a score that assess their current cognitive status. Okay. Right. The next thing I think they can do is there are these super sensitive blood tests.

1:39:35You mentioned P-Tau217. And I think you said above the age of 35, do it every five years. Above the age of 60, do it every two years. There's a few there, PTAO, GFAP, NFL. Maybe just explain what PTAO is. I mean, why is that a useful test? And if we have an elevated level, what does that mean for us? You know, should we be scared or should we feel empowered, basically? Yeah, great point. And I think it's important for, and just, you know, we've heard about cholesterol for so many years and what it means. And now everyone's saying, no, you really need to look at ApoB instead. That's more important.

1:40:18Great. So thankfully, we're now in a new era in which you can look at your brain biochemistry because of its reflection in the blood. I think this is a wonderful advance. And this is why I just, as I mentioned, had my mind checked recently. So there are four tests that you can get pretty easily. And the first one is, as you mentioned, P-tau. So this means phospho-tau. This is a remarkable molecule. So in that connection side, tau is a molecule that stabilizes microtubules. So it's just like if you're going to put out, you know, the neurons putting out a new part, you're putting out a new part on your house, you got to have the bolts to bolt down those rafters to make to steady them.

1:41:07And that's what tau does. Now, when you switch to protection mode, oh my gosh, now there are bacteria, now there's insults, now there are toxins, now there are problems. You literally switch your, you phosphorylate your tau at numerous different sites, but the 217 is the one most associated with Alzheimer's. That does a number of things. It changes the charge on the tau. It changes the shape of the tau and it pops the tau off the microtubule so that you can now collapse that connection. And now you're using your phospho tau to kill microbes. It becomes an antimicrobial protein. It's truly remarkable.

1:41:48So this thing pops back and forth between being a stabilizing feature and now off to fight the bacteria. And so you wanna know your level. If your level is high, It means that process is going on in your brain. Your tau is off fighting things. It's been phosphorylated to do so. And therefore, you're in that early, early process. Don't worry about it. Thankfully, the tests are available. Now let's start to work with you. As we see, as we improve people, their phospho-taus start to come down, come down, come down, which is really wonderful. So now you've got a way to track it. And I'm working with a number of people right now.

1:42:28who are exactly in that situation. They have only minimal symptoms, but they have high phosphotaus. And so we're now looking at why that is, bringing that down. So it's a great way to treat things early. Now, the second test is A-beta 42 to 40 ratio. That tells you, again, whether you're on that connection or protection side, as the 42 is going down, it's telling you, uh-oh, you're keeping your 42 to fight bacteria in your brain. you're not seeing it in the blood. And so that's a second marker. The third one is GFAP. That's telling you if there's ongoing inflammation, which is an important thing to know.

1:43:08And then the final one is NFL, neurofilament light. That's telling you if you have damage to neurons. So for example, if you've got a high P-tau and a low NFL, you've got a relatively quiescent activity of your Alzheimer's. It's very early. You're not damaging a lot of neurons too quickly. If you've got both high, it's saying this is a more active process and you really need to get on it. And, you know, people are going to listen to this and watch this all over the world. In America, is it quite easy to get these tests? Yes. In America, you can get them right over the internet. You literally go on and go getabrainscan.com.

1:43:54Just get a brain scan. And you go, there's a local draw station. You can do it on your own. and you can get this and they'll have a report. So it's very simple. And do you know, have you heard in the UK, if it's easy to get, I mean, I'll look into this after this conversation, but at the top of your head, have you heard that it's relatively simple here? Well, certainly doctors are starting to order P-Tau more. Again, we're stuck in a kind of outdated era where people will say, well, you don't really need this. Why would we look at this? There's not a lot you can do for it. That's going to change over the years.

1:44:26there, you know, again, this will become just like looking at ApoB or your cholesterol. It's kind of interesting. You mentioned do the P-Tau test once you hit 35. But I think I've also heard you say that some people in their 20s have got elevated P-Tau. Why do you not say do it in your 20s? Yeah, that's a great point. What I was mentioning is, or was trying to describe is, the tests that have been very sensitive, not P-TAL. These have been other things where they've looked at, for example, some very, very demanding cognitive tests. Here's one study that was published as an example. They looked at people from 18 to 25, and they're trying to see whether exercise enhanced memory.

1:45:17And what they found was there was already a difference between the ApoE4 positive and ApoE4 negative in the teens and early 20s. Really striking. So those are the sorts of things. P-tau tends to come up a little bit later than that, which is why we recommend 35. And even to be fair, most people at 35 are still going to have a normal P-tau, although this new super P-tau, I think is going to be even more helpful. So you catch things, again, it's like getting fasting insulins. You're going to catch it, for example, with an oral GTT with insulin, you're going to catch things earlier than looking at hemoglobin A1c.

1:45:57So we can start to fix these things. As we catch these earlier and earlier, they are just going to become much less concerning. I mean, that's the key point here. Yeah, I guess the other practical thing is, at what age are people actually thinking about their health, right? I remember myself in my twenties, right? You know, would a blood test at the age of 21 have changed the way I lived in my early twenties? Maybe, maybe not. I don't know. But I guess 35 also is quite nice in another way, because it's probably the kind of age where people are starting to shift from, you know, I'm young, life's going to go on forever.

1:46:40I can do whatever I want and I can still get up the next morning to starting to feel their body a little bit more. So 35 might work on that level as well, where it's kind of like, yeah, if you're elevated, you might actually be motivated to do something about it. So I thought that was quite an interesting point. So going back to what people can do, number one, my CQ test, it's a 20 minute cognitive assessment. Number two, you can do these really sensitive bloods. And would number three be, you know, you've used the term my cognoscopy instead of a colonoscopy later on, we should do a yearly cognoscopy.

1:47:15Is that what you say would be the third thing, or is that already covered in those first two? Yeah, so a cognoscopy is just basically a way of saying, again, every five years or so, check to see where you stand. You want to know your homocysteine, your HSARP, all the sorts of things you talked about. But you know what's been fascinating to me? We have two daughters who are both in their 30s now, and they both now have their first child. And it's been so interesting for me to see they grew up in a world in which there was concern for metabolic health, in which people actually talked about this.

1:47:52And some of the times, you know, my wife and I would go out for dinner and say, well, you know, if you're doing the right things most of the time, you can cheat occasionally. As Dr. Joel Fuhrman has taught us all, you know, if you're doing 90 % of the things, then, you know, 10 % of the time you can kind of take it off, cycle in and out. And our kids would say, you're doing this? Oh, yeah, we don't do that. No, are you kidding me? Oh, we always are going to have organic stuff. So that generation, the millennials, they're better than my generation was at looking at these things. But you're right.

1:48:25In your 20s, you feel indestructible. That's why I say 35 is a great time. You're kind of assessing things. You're thinking about, you know, you might have beginning of a family or maybe you're thinking about it. you're thinking, hmm, maybe I'm not going to live to 500 years old. Maybe I am not indestructible. And maybe I better look at how my body is doing. And great, it's pretty easy and you can do it every five years. It's easy. No, I love that. And really help yourself. Dale, I'm sort of reflecting back to every sort of avenue I opened up in this conversation. I'm making sure that we closed it off.

1:49:02I mentioned before that in terms of what we can do, there are seven basics and two specifics. I know we covered the seven basics, the plant-rich keto diet, exercise, sleep, stress, brain training, detox, and targeted supplementation. Could you just outline those two specifics for us as well, please? Yeah, great point. So the two specifics are infectious agents and anything that's creating inflammation and toxicity. And so we've talked about those a little bit before, but here's an example. Infectious agents play a huge role. In fact, here's what from the laboratory we believe we understand a little bit better now.

1:49:42When you have these initial insults, you have this beautiful system that actually precedes, you know, we think of the innate immune system and then the adaptive immune system. Well, before the innate system, of course, is the barriers, right? It's the skin. It's the cerumen. these have the beautiful advantage that you can deal with pathogens without creating an inflammation that compromises function. So you can cover things with amyloid, synuclein, things like that, without having the inflammation. In fact, there's very good evidence you can have amyloid in your brain for 20 plus years without compromising your cognitive function.

1:50:26So you've got this wonderful opportunity to inactivate these things. But if you now exceed that, if you now start activating your microglia, bringing in your cytokines, activating your mast cells, that's what is now associated with cognitive decline. So we want to know if you have tick-borne illnesses, if you have P. gingivalis or T. denticola or other oral pathogens, if you have leaky gut, of course, If you have various other, influenza is another one, chlamydia pneumoniae is another one. COVID has been a big problem in terms of increasing risk for cognitive decline. So we have a number of people that need to be treated for long COVID to get best outcomes.

1:51:14Can I just say on that? On and on. So one of these two specifics is infection. So as well as the basic seven, you got to make sure you look for these infections and treat them but i just want to before we move on to the second one um what you said about amyloid there was super interesting also in terms of how we viewed alzheimer's for so many years we used to think that this was a pathology you know of amyloid right so a lot of drug therapy was trying to actually remove the amyloid but what I learned from you, maybe almost a decade ago, when I first came out to see you and train with you, is this idea that amyloid isn't the problem.

1:51:55Amyloid is a protective, it's trying to protect the brain like you've just said. It's interesting, isn't it, that we thought amyloid was the problem, but amyloid is not the problem. It's actually trying to be part of the solution. Is that a reasonable way of thinking about it? That's exactly right. Now, the reason everyone got so confused is because, yes, it's just like a cytokine. It's associated with some inflammation down the road. So when you see the AL, you have more amyloid. Yeah, that's a problem. But it's not there because it's trying to give you Alzheimer's. It's there because it's responding to an insult.

1:52:31And in fact, I sent you a few days ago, I sent you a paper. Take a look. We just posted a unifying theory of all of these neurodegenerative diseases. So it's now freely available online to everyone. Take a look at that because I go into detail about what these are. These things are all prions. Of course, my mentor, Dr. Stan Prusiner, won the Nobel Prize in 1997 for discovering prions, which are infectious agents, but they're also turned out to be anti-infectious agents. They actually destroy these various pathogens. And that's what these diseases are all about. Okay, so the two specifics, one is infections, and the second one is toxicity, which again, it's just these extra things to look out for.

1:53:17And I think you did cover this before, organic, inorganic, and biotoxins, which are basically mold, right? Yes, and you've got to detox to get best outcomes. And people, we see it all the time, where they leave that out, and they're not going to do as well. Again, you start early, that's less of an issue, you're going to have some good endogenous detox and just less of an issue. But once you're already in that third and fourth stage, you'd better make sure to look for those and address them. Okay. So we could do a whole two hours just on detox alone, but very simplistically on detox, it's reducing your exposure to certain things to try and reduce mold, reduce how much mercury you're consuming from fish, reduce your exposure to heavy metals, reduce your exposure to plastic and microplastics as much as you can.

1:54:09That's one arm off it. The other arm is to, I guess, enhance your own detoxification pathways. You mentioned sauna before. Do you have a take on a traditional sauna versus infrared sauna, or do you think they both have value? Yeah, actually, infrared is a little better. If you've got a choice, then yeah, the infrared is appropriate. And then there are advantages to near-infrared and far-infrared. I think most people will prefer the far-infrared. But either way, it gets a little better penetration. Yeah, that's what I've heard as well. You know, again, if you're doing any, that's a great step in the right direction.

1:54:46And for some people who have large exposures to mycotoxins, for example, you're going to need to be on binders that actually bind these things up. Yeah, and get them out. Go back to the wonderful work of Dr. Neil Nathan. I just had a wonderful discussion with Neil a few days ago. He's really had tremendous results, and he's consulted on a number of our patients to help them get their toxins down in the best possible way. You're going to have, as you said at the beginning, you have to get away from the source. As long as you've got that continued source, you are going to continue to activate your brain to make the amyloid, to make the P-tau, and ultimately to get inflamed and start to downsize, unfortunately.

1:55:27I mean, Dale, look, you said before you were in your mid-70s. You look fantastic. Of course, you're very, very cognitively sharp. Have you changed the way you use plastic or drink out of plastic yourself since you came across the data on microplastics? Oh, absolutely. Yeah, and so we typically try to use glass instead of microplastics, instead of plastics to get exposed. And of course, there are some hard plastics that do a little bit better, but it is an issue. And it's an issue also because as part of improving my diet years ago, of course, I started having more wild caught, smash type fish, low mercury, low toxicity fish.

1:56:11And unfortunately, they've got microplastics in them. So there's no question, we're all exposed to microplastics. We're living in a somewhat toxic world. And so what we have to do is just try to keep that to a minimum and improve our ability to detoxify these things. You can't get 100 % away from it. Yeah. And just for people who don't know that term, you mentioned smash fish there. That's, of course, wild salmon, mackerel, anchovy, sardines, and herring, right? Herring. Those are the five. Because you don't want the big sharks and the big tuna fish and things like that because they're full of mercury.

1:56:47Yeah. These are the five you want to focus on. Okay, so like you, I've changed my own behavior around plastic. Literally, we're recording this, what, end of September. Ten and a half months now, I've rarely, rarely used plastic. And basically, it's because I did a blood test at Next Health in LA when I was there. And my levels were in the red. I mean, again, it goes back to that point about CGMs before. when you see something or you measure it, you have a different level of motivation. So I knew about the research on microplastics. I was aware of it cognitively. And I would try and reduce it as much as I could.

1:57:28But you know what? It wasn't that much. Suddenly, I saw my level in the red range. I'm like, okay, right. I'm done with this. Like I am borrowing exceptional seconds. That says I don't drink out of plastic. I certainly never drink out of hot. You know, I will never, ever now have a hot drink in a takeaway plastic cup because that's even worse, right? Yeah. As you said, feedback is everything. Knowing where you stand so that you can make appropriate adjustments is so helpful. Okay, Dale, just to finish off then, if there's someone who has been listening, right, and they're super interested in what we were talking about, are they thinking...

1:58:08Dale, look, I'm really worried. I've cared for my mother for years. She had Alzheimer's. I'm scared I'm going to go the same way as her. Can you help me? What would you say to her? Yeah. So what I tell everyone, and the same thing for people who come back with a high P-TOW, take a deep breath first. It's going to be okay. We're not living in the caveman era anymore. Now we understand that there are things that can be done. So please, just, you know, we're going to make sure that you get for many, many years to come that you do well. So please get evaluated. Start, as I said, to see where you stand today and then where you're headed.

1:58:53So yes, you'll have to have a few blood tests. You'll have to look to see what's actually going on. If you've already got symptoms, you're also gonna wanna have an MRI. But the bottom line is, this is just like what happened, as I said early, with pap smears and looking at PSAs for prostates and looking at chest X-rays and looking at fasting insulin. We're now in a modern era where we can look at these things, we can tell where you stand and we can do something about it in the vast majority of people. So please don't worry, but also please don't run and hide. Don't stick your head in the sand because getting active is the smartest thing you can do.

1:59:33Yeah. That's lovely advice. Very, very empowering. It's kind of very honest, very direct, but also very empowering. There's something people can do if they get the data. And for people who want to work with doctors who you've trained or use your specific protocol, where would you direct them online? I mean, you mentioned Recode and Precodes. You mentioned Apollo Health. I know you're involved with creating this personalized brain institute in Santa Monica. But for people all around the world who want to learn more, yes, I can get your books, but where are the doctors that they can find to help them?

2:00:11So it's very simple. If you go to mycqtest.com, that will direct you. So if you do well on that, it'll direct you to more on the prevention side. And if you don't do as well, it will direct you to the treatment side. The doctors will be included in there. So if you go on to, you can either go to MyCQTest or you can go to drbredesen.com. And it will give you a list of the people that we have trained that are doing this. Now, it's important to say, as I mentioned earlier, there are some doctors that are getting better results. And there are some doctors that are getting not as good results. So talk to the doctor that you choose.

2:00:49Can you tell me some people? Have you published anything? Have you shown anything? Can you at least give me some examples of people that have improved? Or have me talk to one or two of the people that have improved so that I can get a good idea. Because I think that's an important thing. People will say, well, yeah, we do this, but we do it my way. And I do a little of this and a little of that. And they're not getting particularly good results. So make sure that you have someone who's doing well. Yeah. Dale, I just want to say thank you. I appreciate the time you've given me today. I also appreciate you as a human, honestly.

2:01:25I've been very lucky to know you personally as a friend for many years now. I think the work you are doing is literally incredible. I know you've faced a lot of pushback throughout your career, but what you're offering the world is a paradigm shift in how we look at this debilitating condition that has had such a horrible impact on so many different families. So I want to acknowledge you. I want to say thank you to you. I think it is such important work. Keep going. You are so fit and well in your 70s. I hope we're still podcasting together when you're mid 80s and you're mid 90s, right? So we're going to keep improving.

2:02:07The new book is The Ageless Brain, How to Sharpen and Protect Your Mind for a Lifetime. I would highly recommend it to anyone. Doesn't matter where you are in life. If you want to improve the health of your brain, this book has got something in it for you. And Dale, as I said before, that I see this as a part one and I'm very hopeful in the next few months we can get a part two in and go a little bit deeper. So yeah, thank you so much for coming on the show and I can't wait till next time, Dale. Thanks so much, Rangan. Great to talk to you. I look forward to talking to you again.

2:02:44Really hope you enjoyed that conversation. Do think about one thing that you can take away and apply into your own life. And also have a think about one thing from this conversation that you can teach to somebody else. Remember when you teach someone, it not only helps them, it also helps you learn and retain the information. Now, before you go, just wanted to let you know about Friday Five. It's my free weekly email containing five simple ideas to improve your health and happiness. In that email, I share exclusive insights that I do not share anywhere else, including health advice, how to manage your time better, interesting articles or videos that I've been consuming, and quotes that have caused me to stop and reflect.

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