Preventing and Reversing Cognitive Decline with Dr. Dale Bredesen and Kayla Barnes

Today I am speaking with Dale. Bredesen, MD, is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer's disease. He graduated from Caltech and then earned his MD from Duke University Medical Center in Durham, North Carolina.

Dr. Bredesen’s research explores previously uncharted territory in explaining the physical mechanism behind the erosion of memory seen in Alzheimer’s disease, and has opened the door to new approaches to treatment. This work has led to the identification of several new therapeutic processes that are showing remarkable early results. Dr. Bredesen is a prodigious innovator in medicine, with over thirty patents to his name. Notably, he put much of his findings and research into the 2017 New York Times‘ Best-Seller, The End of Alzheimer’s.

We are diving deep into neurodegenerative diseases. How to protect yourself from developing neurodegenerative diseases, why Dr. Bredesen believes we develop neurodegenerative diseases, and more.

Learn more about Dr. Bredesen and explore his programs here: https://www.apollohealthco.com

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Oura ring for sleep measurement and oxygen saturation: https://ouraring.com

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TRANSCRIPT

[00:00:00.250] - Kayla Barnes

Okay, wonderful. So, Dr. Bredesen, it's such a pleasure to have you here with me today.

[00:00:05.030] - Dr. Dale Bredesen

Great to have you, Kayla. Please, call me Dale.

[00:00:08.450] - Kayla Barnes

Okay. Alright. I'll call you. Dale. So, Dale, let's preface for the listeners. How did you get so interested in the brain? Can you walk us through some of your story?

[00:00:17.690] - Dr. Dale Bredesen

Absolutely. Actually, when I was a little kid, I was interested in computers. And when I got to college a freshman year, I read a book called The Machinery of the Brain by Dean Wooldridge and just talking about relationships between computers and the human brain and the areas of dissimilarity as well. And I got hooked on this for the rest of my life. And just the interest of how do you form memories? What happens when things go wrong in your brain? What is neuroplasticity all about? How does it work at the molecular level? So we spent 30 years in the lab, my laboratory colleagues and I, looking at what is the fundamental nature of neuro degeneration? What are the molecules involved? What triggers it? Why is Alzheimer's, for example, so incredibly common? Why has it been so hard to treat? And as you know, this has been the area of greatest biomedical therapeutic failure. As people say. Everyone knows a cancer survivor, no one knows an Alzheimer's survivor. So we wanted to understand the fundamental nature of the neuro degenerative process.

[00:01:31.250] - Kayla Barnes

It's incredibly fascinating. And as we both know, there's still a lot of unknowns with the brain, right?

[00:01:39.290] - Dr. Dale Bredesen

So many, yeah. There's a tremendous amount of people are still arguing about the so called mind brain problem. When I was studying, when I was going through medical school and then post doc, et cetera, I always thought, hey, of course the mind is just the brain. Of course, isn't that obvious to everybody? But so many of the studies have suggested it's not quite that simple. And so I think that the brain is such a great mystery. And we've got even people talking about the various observations of people who literally have flat EEGs, who are under deep anesthesia, even situations where blood has been removed as part of the overall program and part of the overall procedure and still able to say, okay, here's what happened. So actually, to have sentience at a time when there is no brain activity, it's really remarkable. And as you indicated, still so many mysteries about brain function.

[00:02:44.270] - Kayla Barnes

Yeah. And it's a super exciting time because I feel like we're identifying more and more about the brain and learning more and I'm sure we will over the next ten or 20 years. So what kind of camp are you in when it comes to the mind and the brain? Will you kind of break that down for our listeners?

[00:03:01.550] - Dr. Dale Bredesen

I have really changed. Reading the literature, looking at what's happened, what has been not explained, you just cannot explain everything that the mind has been capable of doing in the various reports that people have been able to give by saying this is just neurons firing. As much as it's clear that that's incredibly important and that's part of making our memories, et cetera, I have to say I have been surprised. But I've had to come to the conclusion that we literally are like a person driving a car. Our bodies, including our brains, are the car, but there's a mind in there that is literally separable. Again, I'm surprised that that's what it's come to, but I think you can't ignore the various phenomena that have been repeatedly reported. And so I'm of the mind that you literally have a mind that interacts with your body and brain and literally, ultimately your mind is a repository. You're a little bit like a thumb drive. Your mind is a repository for information. And it's very interesting because I thought we've always heard about E equals MC squared. Energy and mass are related, as Einstein showed. But what's interesting is, okay, there's a third piece here which is information.

[00:04:29.210] - Dr. Dale Bredesen

And I was so excited to see recently a theoretical physicist said the exact same thing, that, yes, he's now trying to show that not only our energy and mass have an equivalence, but in fact, information is another part of that equivalence. So our minds are collecting information that leads to behavioral changes. And unfortunately, as you know, when people develop neurodegenerative disease, essentially the car part of that, the physical part of that that is helping to change that energetic. Those parameters unfortunately, is breaking down. And it's been so surprising to me to see that doctors and pharmaceutical companies have just kept pushing and pushing and pushing on. We're going to find one drug that completely cures a problem that is really a network insufficiency. It's like taking every car that has stopped working and just filling it with gas and saying, okay, that should be good enough. Yeah, for a couple of cars that's going to work fine, but for the majority of cars, that is not going to be the fix. And so we've been very interested in larger data sets, in understanding. I mean, look at all the things that are going on with Google and with Facebook and all these where you have very sophisticated programs looking at where you shop and what you do and what your behavior is.

[00:05:53.860] - Dr. Dale Bredesen

We need to use these same sorts of approaches to get the understanding of these complex networks that are critical for keeping our synapses going, critical for keeping our brain structure supported. And when we do that, it changes the way you look at Alzheimer's and pre Alzheimer's. And we've gotten by far the best results of anyone in terms of reversing cognitive decline, which we've published repeatedly and actually just published in the Journal of Alzheimer's Disease, a new study in which we showed that 84% of the patients actually improve their cognition, whereas with drugs, what you see is no improvement. And you see no stability, but in fact, the best they do is just slowing the decline slightly.

[00:06:40.670] - Kayla Barnes

Yeah, absolutely. And I believe that I've always been in a school of this very holistic kind of precision type way of addressing any issue in the body. And that's what I love about the way that you're approaching this so much is it's not just one thing. Right? Well, first of all, there's multiple types of Alzheimer's. Can you talk about that a little bit?

[00:07:02.030] - Dr. Dale Bredesen

Yeah, great point. So, of course, in the standard of care, people say, oh, you have Alzheimer's. Well, why? Well, we don't know. It's just this unknown entity. And there are all sorts of theories, as you know. It's about misfolded proteins, it's about amyloid, it's about tau, it's about herpes, it's about type three diabetes, on and on and on. And none of those theories has ever led to a successful treatment. So when we started now looking at larger data sets and saying, okay, what is changing? We know that the fundamental signaling that occurs in the brain changes with Alzheimer's. You are changing. For example, just looking at one molecule, ATP amyloid precursor protein, which is of course, the parent of the amyloid that has been vilified in this disease. You see, really interestingly that this molecule is a molecular switch. So when things are good, it is actually cut and signaling in one direction, which says to the rest of your brain, okay, grow, make new synapses, make new connections, memories. On the other hand, when things are bad, too much inflammation, not enough support, not enough blood flow, mitochondrial function, oxygenation, on and on and on, it literally goes into a protective downsizing mode.

[00:08:20.550] - Dr. Dale Bredesen

And there's a direct analogy with what happened to our country with covid 19. Of course, in early 2020, we were all told there's an insult in that case, SARS COVID two, and we should now respond to that insult by going into a protective mode. And we, of course, entered a recession. The brain is doing very much the same thing when things are good, it is growing and making new synapses. And it recognizes when you have, for example, oral bacteria make their way into your brain. That's been found repeatedly. Pgingvalis is a great example of that. One specific bacterium in the brain which gets into the brain from the mouth, and there are many others, of course, herpes simplex, another good example. These have all been associated with Alzheimer's. And so your brain literally makes a decision, I'm going to go into a protective downsizing mode. And in fact, when it secretes that amyloid, the amyloid, actually surrounds these pathogens and kills them. So the amyloid is not something there to give you Alzheimer's. It is something there to protect your brain against various pathogens and insults. And it is quite a good antimicrobial peptide, as Professor Robert Moyer and Professor Rudy Tanzi from Harvard showed several years ago.

[00:09:44.730] - Dr. Dale Bredesen

And that fits beautifully with what we're seeing. This is part of the signaling that leads to, unfortunately, downsizing. Now it's trying to protect you and say, okay, you can still do quite well with fewer synapses, but if you don't identify what's causing that response and address what's causing that response, just what you said, a precision medicine approach and there are dozens and dozens of things that can contribute to that, then what happens? Your brain just keeps signaling downsize, downsides, downsize, until you cannot take care of yourself and you die from Alzheimer's disease. So this actually tells you much more about what Alzheimer's actually is and how we can prevent it and how can we reverse the decline. So, as you indicated, when you look at those larger data sets, guess what? You see that there are six different types of Alzheimer's. So there's type one, which is inflammatory, and these people look quite different than the type twos. The type twos are atrophic. They tend to be older, they don't have a lot of inflammation, but they just don't have the hormones and the trophic support and the nutrients to keep all of those synapses.

[00:10:56.970] - Dr. Dale Bredesen

You have almost 1 quadrillion synapses in your brain. It's amazing. Then what we call type one five, because it has a little of both, is glycotoxic so common that the sugar we are exposed to, as you know, both non enzymatically glycates, many proteins. We measure it as hemoglobin a onec, of course, but there are hundreds of proteins that are not enzymatically glycated and so they cause inflammation. So you get a little type one, but they also cause insulin resistance with these chronically high levels of insulin. So you now lose that. When we used to grow brain cells in a dish, you'd always have to include some insulin in the dish to keep the brain cells alive. So when you lose that insulin signaling, you lose the growth factor effect of the insulin. So that's type 1.5, then type three toxic and that's three different types of toxins. The inorganics, like air pollution, like mercury, the organics like formaldehyde, benzene toluene, glyphosate, and then it's the biotoxins like trichothies, like various mycotoxins gliotoxin. Okratoxin, a type four is vascular. You don't have blood flow to your brain. You're not going to be able to support that brain and guess what?

[00:12:13.940] - Dr. Dale Bredesen

It will then downsize. And then type five, which is traumatic, and years ago shown that if you have significant head injury, you make amyloid as part of the reorganization after the trauma. So we can now see that different people have Alzheimer's for different reasons. Most people get it for more than one reason and therefore we need to go after those things and preferably as early as possible to get the best outcomes.

[00:12:42.590] - Kayla Barnes

Wow, there's so many amazing things to break down from that list. And I think it's really good for people to know that there's all these different types and the insults, as you're saying, can come from many different areas. But let's talk about, first of all, how early does Alzheimer's or neurodegenerative diseases start developing? Because I feel like people think they need to prioritize brain health later in life, because that's when they think something's going to happen.

[00:13:09.410] - Dr. Dale Bredesen

This is maybe the most important question to discuss, because when I was training way back in, the whole idea was that Alzheimer's was a disease of aging, and you get it in your sixty s, seventy s, eighty s, ninety s. Now we know that the process starts in your brain at least 20 years before a diagnosis. We know this from longitudinal Pet scans and from spinal fluid analysis. It may start even earlier than that. So people, even in their twenty s and thirty s, you can begin to see changes where an interesting thing, one of the hallmarks is decreased glucose utilization in the temporal and parietal regions of the brain. And people who are APOE four positive can even have that in their late 20s, even though they may not get a diagnosis until their fifty s, sixty s, or seventy s. And so, yes, you're absolutely right, the process begins early, and therefore there's a lot we can do about it. You have to remember, you go through four stages when you get Alzheimer's and what we call Alzheimer's, where you actually beginning to lose activities of daily living. That is the fourth and final stage.

[00:14:23.270] - Dr. Dale Bredesen

So stage one, you are asymptomatic. You don't have symptoms, but as I said, you can already pick up changes even in your twenty s, thirty s, and forty s on Pet scans. Stage two is called scarlet, and the epidemiologists have shown us that that occurs for about ten years. So you have about a decade, very addressable. We see virtually a hundred percent of the people with STI, if they get treated appropriately, get completely back to normal. And this is what we all have when we say, oh, my memory is not what it used to be. I'm not able to remember phone numbers. I may occasionally, when I'm driving around, forget which way to turn, I've forgotten my keys, things like that. I may have a little trouble organizing things, stuff like that. That's ski. And often your spouse may note, or your partner, but you're still able to score in the normal range on cognitive tests. So that's ski. And of course your doctor just tells you, oh, you're just normal aging. No, please don't listen to that. That's the time to get in and get evaluated, and you can go on the internet for a free CQ test and just see where you stand.

[00:15:41.260] - Dr. Dale Bredesen

Everybody should know where they stand, and everybody also should know their basic genetics and what their risk factors are. So the third phase, unfortunately, is called Mild Cognitive Impairment. And unfortunately, so many doctors say, oh yeah, you got MCI Mild Cognitive Impairment, go home and come back in a year. And this is like telling someone they have mildly metastatic cancer because it is a late stage of Alzheimer's disease. And so we should absolutely be doing something. And by definition, that simply means that now you are also not scoring in the normal range on your cognitive tests. And then the fourth and final stage is what we call Alzheimer's. And by definition, that means that you're now having trouble with your activities of daily living. You may be having trouble doing bills now, or a common one, I hear is I couldn't calculate a tip the other day. I can't come up with names. And then ultimately, of course, it gets to the point where things like, you can't take care of yourself, unfortunately. So that's the tragedy of this illness. It should be a much less common disease. We should not be allowing anyone to get to that fourth and final stage.

[00:16:55.890] - Dr. Dale Bredesen

Everybody should either be on active prevention if they've turned 45 or over please get on active prevention. Or earliest reversals. There's so much that can be done. Part of the problem is that so many of these groups and foundations have told us there is nothing to be done to delay, prevent or reverse Alzheimer's disease and nothing could be further from the truth. And we've published that repeatedly. There is a tremendous amount to be done. The armamentarium is large, and so the earlier you start, the better.

[00:17:29.870] - Kayla Barnes

I love it, and that's why I'm prioritizing my brain health now. And it's exciting that other people are everything that I do, I'm like, is this hurting? Is this helping or harming my brain? Because our brain is our most important organ. We can't replace it. It's the most expensive real estate in the body. So I love that you're promoting to start earlier. So let's talk about some of the things that we can actually do. If you are in your 20s or late or early 30s, what are some of the things that you can start doing to help promote better brain health or protect your brain?

[00:18:08.840] - Dr. Dale Bredesen

Great point. And of course, the most important thing of all is just get evaluated, get what we call a cognoscopy. So it'll tell you just like you want to know what your cholesterol is and what your lipids are. Although, as you know, the cholesterol itself has not turned out to be the villain. That was one thought either. We're very much like Amyloid, so what you want to do is find out your number. So here's the thing. There are four major groups of things that get you into trouble with your brain as you age. Number one, anything that is pro inflammatory. So you want to know if you have leaky gut. You want to know if you're eating inflammatory foods. You want to know if you have a chronic infection. This is relatively common. We come across people all the time that didn't know that they were harboring babies or tickborne illness, for example, or they had chronic Lyme disease that they didn't realize. Things like that second one, toxicity. If you're exposed to toxins, and again, most of us don't know it until it really bubbles over the top. Find out there are some simple ways to do that.

[00:19:13.980] - Dr. Dale Bredesen

Third thing, energetics. And that's four pieces your brain. As you said, this is the real estate that's critical. And so, of course, 20% of your blood flow goes to this relatively small organ of about £3. It's amazing. And so the energetics, that's blood flow, that's oxygenation. And we run into people all the time that didn't realize when they go to sleep at night, they drop their oxygen very low. Easy to check. You can do it on an Apple Watch. Pretty soon, the aura rings will have it. You can do it on a fitbit. You can do it with a little oximeter, inexpensive, or you can just ask your doctor to do it. It's blood flow, oxygenation, mitochondrial function, and then the ability to get into ketosis, because your brain has to use either ketones or glucose to power it. And the problem is, you lose both of those when you're getting cognitive decline. You lose the ability to use glucose because of your insulin resistance, and you lose the ability to make ketones because you're not keto adapted. And if you've got insulin resistance, the high insulin actually prevents you from getting into ketosis. So that's the third piece, energetics.

[00:20:28.940] - Dr. Dale Bredesen

And then the fourth piece is trophic support for your brain. Your brain needs nourishment, and that's three things. It's nutrients, it's hormones, and it's growth factors like nerve growth factor and BDNF. So those are the four big areas. So again, you can get a simple cogniscopy and see that's some blood tests, simple online cognitive assessment. And then if you're having problems, include an MRI. If you're not having problems and you're just there for prevention, you don't need an MRI. But if you do an MRI, make sure to include volumetrics. You want to know if you have any brain atrophy. So then simple things that we can all do. Please check your oxygenation at night. Easy to do. Please see if you've got please see if you're developing insulin resistance. You want to know your home IR. If you're sitting up there, two or three. If you've got a fasting glucose of 100 and fasting insulin of ten, your home IR is going to be over two, which says that you really have some significant insulin resistance. So you want to keep your home IR down around 1.0. So you want to know what that is.

[00:21:39.420] - Dr. Dale Bredesen

And of course, healing your gut. So many of us have leaky gut. I wasn't even taught about leaky gut in medical school. And unfortunately, medical school way back then was all about make a diagnosis, what is it? And then write a prescription or send people to surgery. And really, 21st century medicine is now about why it is not just what it is and this is a huge issue. Unfortunately we've heard so much about all these failed Alzheimer's trials and unfortunately very much of that field has been more about incomes than outcomes. People have put $28 billion into one drug which unfortunately failed. So and you've I'm sure heard about all the fraud recently associated with Alzheimer's research. So we really need to get back to the basics here and as you indicated simple things you can do like making sure you're insulin sensitive. I'm getting on a plant rich mildly ketogenic diet with appropriate periods of fasting typically twelve to 16 hours at night of a fast which really will help you and as you know just the fasting part alone so huge and with that appropriate diet it helps with your detox it helps heal your gut it helps keep your glycemic load down.

[00:23:04.530] - Dr. Dale Bredesen

I mean on and on and on so many things that diet and then basic simple things exercise and there's so much with these for example these Katsu bands the restrictive bands that some of the Olympic athletes use they actually help you to do better with your insulin sensitivity by building some muscle and then sleep. Sleep you could go on for hours just about sleep. And of course Matthew Walker has written a wonderful book matthew is a professor right over here at Berkeley has written a wonderful book called Why We Sleep goes into all the issues and why that's so important for your brain and for your immune system and for stress levels on and on stress and then some brain training some targeted supplements and detox and these are kind of what we call the basic seven things that are so important just to keep your brain health. If everybody did the right thing we could really keep people sharp to 100 pretty much everybody and that's the way it should be.

[00:24:10.670] - Kayla Barnes

I love that and those are all principles that I really appreciate. Doring actually did roll out the oxygen sensing fantastic. Yeah that's live. Now you want to keep it between about like 95 and 100 every night. Is that what you would aim for?

[00:24:25.990] - Dr. Dale Bredesen

Yes a normal SPO two is 96 to 98 and I don't worry too much if people are down to 93 what I worry about is when I see them coming in 82 we've seen people dropped 70. It's really concerning. And there is an interesting publication from a few years ago where people simply correlated your mean SPO two. So average SPO two through the night where you sit in that average was 95 was it 88, was it 79? Where was it? And then they showed that correlated beautifully with the size of various regions of the brain including the hippocampus. So literally as your SPO two is going down at night the size of your hippocampus is going down which is really concerning because the hippocampus shrinks associated with cognitive decline as you know it's a critical part of our brain for memory formation and consolidation.

[00:25:28.610] - Kayla Barnes

Absolutely. What do you think about meditation? I've read some studies that long term meditators can have thicker hippocampal volume and also more gray matter. Are you a fan of meditation?

[00:25:42.230] - Dr. Dale Bredesen

You know, it's so interesting. As a scientist, I always used to think all this stuff is just a bunch of who. It's not important. What we really want to do is get to the chemistry. But I have to say, I've really been converted. You cannot deny the published data, as you indicated, changes in brain structure, changes in brain performance, better neuroplasticity, better blood pressure control, on and on and on. So you can't help being a fan of meditation. And again, my bottom line is always the same. Can we improve outcomes? Can we get people to prevent cognitive decline and reverse cognitive decline? And in the paper we just published, in the trial, 84% of people, these were people in late stages because it was MCI and early Alzheimer's that we picked. We didn't have anyone who was an SEI patient. These people, 84% of them, showed documented improvement in their cognition. And by the way, they included things like meditation and biofeedback and things like that. So again, this is very clear that this is one of the things that's associated with better outcomes.

[00:26:52.910] - Kayla Barnes

Absolutely. Can you walk us through some of the other methods of this new clinical study? Because I think it would be super interesting to know kind of what you guys had the patients do, because that's an incredible result. I mean, 84% of people getting better and starting to reverse that cognitive decline is so incredibly impressive.

[00:27:13.810] - Dr. Dale Bredesen

Yeah, it's unprecedented. And actually, we have people who started on this sort of approach ten years ago. We have now follow up where people are sustaining their improvement for ten years, which you never see with the drug. You just go right back to declining again. And so that's the whole idea. And again, in the long run, I think drugs plus the personalized, these precision medicine protocols are going to be the best way to go. But what was done? The bottom line from this is very straightforward. For each person, we determined what was causing the decline. And most people have 510, 15 different contributors. So people would have some degree of toxicity, they would have some degree of insulin resistance, they may have had some head trauma in the past, they may have a little vascular disease. And these things are all contributing. They may have a leaky gut, poor oral microbiome, chronic sinusitis. All of these things contribute to cognitive decline that ultimately we call Alzheimer's disease. So the bottom line was we addressed those, and we would start with everybody would get. So there was a core piece that everybody would get, and then there was a personalized piece that depended.

[00:28:23.050] - Dr. Dale Bredesen

We would find people, for example, who had chronic lyme that they were unaware of or who had some tickborne infections or mycotoxin exposure, and they were treated specifically for those things. But in addition, everybody got a core that included a plant rich, mildly ketogenic diet. We try to get them into the 10 to 40 millimolar betahydroxybutyrate range, which is where people seem to do best. And if people like to use breathalyzer, for example, the Biosens, you want to get up to the ten to 40, what they call aces first, because they're measuring acetone, of course, instead of BHB. And then we had everybody do exercise, both aerobic and strength training, typically five to seven times a week. So good idea. If you got an Apple Watch, close your rings every day. It really does help to have some significant exercise. And then going back to what we just talked about, sleep, stress, brain training, we had everyone use Brain HQ because that's the one that's actually been published the most. Professor Mike Merznik was the one who invented brain training and developed Brain HQ. Again, there are other ones. If you like to use those, fine.

[00:29:40.810] - Dr. Dale Bredesen

But whatever you do stimulate your brain, it's so critical and interestingly. Speaking of stimulating your brain, physical stimulation turns out to be helpful as well. So whether you do light, people use V light, for example, or some people, like Dr. Robert Hidaya, use laser, which is, again, mild, gentle stimulation of your brain. Even things like magnetic stimulation, which Dr. Geraldine Brosfield has used so successfully in Southern California. Any of these things, once you're doing the right things and you don't want to do it without doing the right things, but once you're supporting your brain to now produce some stimulation both on the brain training side and on the light or magnetic or even sound, the 40 Hz sound has been another 140. Hertz seems to be, again, the sweet spot for many people. So all of those things were parts. And then again, as I said, some people had to be treated for specific pathogens or specific detox. People used, for example, dental siding to improve their oral microbiomes. Again, oral microbiome abnormalities, things like pigeon gillallis that we mentioned earlier, t denticola, prevotella, intermediate, these are all pathogens that can get into your brain.

[00:30:59.940] - Dr. Dale Bredesen

It's been surprising what the neuropathologists have shown us. So this was a precision medicine protocol for people with cognitive decline. That worked, as I said, unprecedented improvements in patients.

[00:31:13.790] - Kayla Barnes

I love that. And I love that you bring up oral health, because I talk about oral health, my platform, all the time because of the importance of bacteria in the mouth, can be directly coordinated to brain health. So I think that's super important. There's new companies emerging, too, that are just oral microbiome testing tests, so I think those can be super helpful. And I'll put a couple of those in the show notes going back to the gut and the brain. This is relatively new science, stating that there's. Such an important connection. Can you walk us through why that is?

[00:31:49.970] - Dr. Dale Bredesen

You know, this is a good point and it's still being worked out, but you're absolutely right. Now, for Parkinson's disease, for example, and for Alzheimer's disease, there are these repeated observations that brain health and gut health are related. And it turns out there are multiple mechanisms, and I'm sure we don't know all of them yet, but for example, one obvious one is that poor gut health leads to literally leakage of various peptides, fragments of bacteria and things like that into your bloodstream. Of course, you have a systemic inflammatory response, which increases, unfortunately, your likelihood of developing cognitive decline. Just looking at something as simple as hsCRP, looking at your Creactive protein, it goes up. You are having systemic inflammation and things we use, for example, resolvents, which help you to resolve that inflammation. But then you also want to know why is it there and you want to remove the source of that. Second thing is, of course, the gut connection. So just the enterprise and as they show, there are this bi directional flow of neural encoded information from the gut to your brain. So your gut is literally telling your brain things are not good, and your brain is literally telling your gut you're going to have to change the way you're functioning.

[00:33:13.470] - Dr. Dale Bredesen

So that's a second obvious one. And then thirdly, very interesting, of course there are specific bacterial types that are associated with production of nerve growth factor in BDNF, for example. And so people are all over trying to get specific bacterial species that seem to support production of trophic factors and of course neurotransmitters as well. And even the demonstration that if you take, for example, the gut bacteria and you literally do a gut bacterial transplant into a transgenic mice, transgenic mouse, you get more Alzheimer's produced earlier. So again, there is a direct relationship between the pathophysiology of Alzheimer's in the brain and your gut microbiome, which is kind of amazing. And then interestingly, bacteria make their own amyloids. Now, again, it's turned out that amyloid is not the villain we once thought. It's really a response to these various problems, but it's turning out that you can actually see the gut bacteria amyloids in the brain as well. So there is a much greater connection. And I think we're all realizing this, this idea of a blood brain barrier. Yes, there's a beautiful barrier there, but there are many things that can cross it. And I would mentioned very interesting paper from just a couple of years ago where a group said, we want to see how strong the blood brain barrier is when we introduce a pathogen into the blood.

[00:34:48.680] - Dr. Dale Bredesen

Does it take months to get into the brain? Does it take years? Does it take days? And so they actually took normal rodents. So these weren't ones that had an abnormal blood brain barrier. Normal rodents injected some candida, okay, simple, common pathogen and said, okay, how long is it going to take? And the answer was minutes. These things. So the bottom line is, yes, as great as that blood brain barrier is for many nutrients and things like that. And yes, you want to prevent some of these toxins and things from getting into the brain. There are many pathogens that work their way in and we find them. Things like from your mouth, from your lip, HSV one, for example, from your sinuses, for example, HHV six A and things like that. And so it's a great barrier, but it's not that good at preventing many of these pathogens from getting into your brain. So as you can see, there's just this proliferating understanding, growing understanding of the connections between the gut microbiome and the brain function and ultimately what's driving cognitive decline.

[00:36:01.010] - Kayla Barnes

Absolutely. And correct me if I'm wrong, but the blood brain barrier can sometimes also become a bit more permeable based on our lifestyle habits, right. Similar to how you can get leaky gut, our brains, lack of sleep and neurotoxins and alcohol, things like that, cannot contribute to the blood brain barrier being a little bit less protective.

[00:36:23.330] - Dr. Dale Bredesen

Absolutely. And actually that was a surprising paper from a couple of years ago showing that basically there was a pretty good correlation between the loss of the gut barrier and the decrease in the blood brain barrier. And I should mention that is a hallmark of Alzheimer's disease when people have looked at all the different pathophysiological changes that we see in the brains of Alzheimer's patients, but try to now construct a longitudinal look, what changes first, what changes second? Among the very first things was a decrease in the ability of the blood brain barrier to exclude things that it's supposed to exclude. So that is an early change. Now, some of this may be because you change your blood brain barrier as you're inflamed and you're responding, you literally want more of your immune system to work its way into your brain and get rid of whatever those invaders are. So to some extent, again, that's a response. But one way or another, losses of blood brain barrier integrity are among the first changes in the Alzheimer's and developing Alzheimer's brain. And I should mention, when you look at the many effects of amyloid, we talked about the antimicrobial effects early, by the way, it also binds metals, things like copper and zinc and things like that.

[00:37:48.170] - Dr. Dale Bredesen

One of the things that this amyloid, this little 40 to 42 amino acid peptide does is, as one person called it, a floculent. It literally patches holes in the blood brain barrier. So if you've got problems with your blood brain barrier, unfortunately, again, one of the responses is you're driving the amyloid to patch those holes. Now, in a perfect scenario, what happens is just like patching a tire, in the long run, you now heal that patch. You now slowly get rid of the amyloid. Basically, you get a new tire. But unfortunately, as long as you've got the ongoing pathophysiology, that hole is not going to be fixed perfectly. You're just going to collect more and more amyloid with more and more holes in the blood brain barrier. And of course, we associate this with what's called Congo Philip angiopathy or amyloid angiopathy. Many people actually have their vessels in their brains literally filled with amyloid. And unfortunately, that can lead to strokes and it can lead to hemorrhage within the brain. So, again, we want to remove the causes of the problem so that people don't have to invest their blood vessels with lots of amyloid.

[00:39:05.210] - Kayla Barnes

Absolutely. And because this is so recent, there's kind of such an awakening but awareness in neuroscience right now with these studies that were obviously they were done in 2006, right. The kind of amyloid studies that have really shaped Alzheimer's research and a lot of these drugs. So it doesn't seem like you've really been operating even under that methodology because you're looking at, let's reduce the insults to the brain. Right. But what do you think that these studies, if they're false, what do you think that's done to Alzheimer's research?

[00:39:43.790] - Dr. Dale Bredesen

It's a very good point. And this goes back to things that people found over the years that just turned out to be wrong and something that was very influential. Now, I have to say, the senior scientist who did this, I know personally, she is a fabulous scientist, MD, PhD, from Harvard. I don't question her work. Did The Postdoc do something wrong in the lab? It's possible. And I don't know that person personally. The Postdoc, I have every confidence that the senior scientist there was doing the right thing, but with what they were looking for was, is there a specific form of amyloid that is going to be, quote, the bad actor in Alzheimer's? And they found one which was called Abeta Star 56. And that did influence a lot of work, although, to be fair, other people were looking at other things, et cetera. But, yes, it led to millions and millions and millions of dollars of grants and maybe for the wrong reasons. We would argue that it's not a big surprise that, sure, there are multiple amyloid formations that have different impacts, and of course, some of them are very good antimicrobials, some not so good antimicrobials.

[00:41:08.730] - Dr. Dale Bredesen

And so it doesn't surprise me at all that there's one form that happens to be particularly good at downsizing your brain, because we know other forms also are doing that to some extent. So I think what was kind of missed here was this idea that this is everything, this is the cause of Alzheimer's, get rid of that, we're going to be good to go, was unfortunately, probably the wrong conclusion. But I think that the work again, I have every confidence in the senior scientist on that study, who's a brilliant scientist. So I think that the conclusion here is, yes, there are different forms of amyloid. Now, it's unfortunate that millions and millions of dollars were given to something that turned out not to be, quote, the answer for Alzheimer's and of course, the drug development. Billions of dollars have been put into drugs to remove amyloid and they simply don't make cognition better. That's been proven again and again and again and again with Baptnese, a map with Solenaezamab, with Adicana MAB, with Gantaneromab Crenase, just go right down the list. These things remove amyloid and they don't make people better. In fact, we've seen where they can make people worse because again, you're responding to something.

[00:42:26.750] - Dr. Dale Bredesen

Getting rid of amyloid is like sending the police home saying, okay, you came out here because something went wrong, just go home, because we're afraid that a stray police bullet could hurt us. Yeah, that's fine, but the underlying problem is going to continue and could even be worse. So again, I think that the problem here is that the whole field is a bit misguided because they focused on what is really a mediator of the problem rather than what is the upstream cause. It's really because the drug world and the NIH world don't understand functional medicine. That's the sad truth.

[00:43:06.950] - Kayla Barnes

I couldn't agree more. And it seems so, I guess, straightforward, but also reasonable that we should protect our brains and treat our brains like the rest of our body if we want other organs to function properly, our heart, things of that nature, we have to check on our blood biomarkers, make sure that things are optimized. And so for me, it seems very straightforward, but hopefully, I guess, maybe not having to focus so intently in some areas on only this one amyloid protein is going to widen the research, which I'm really excited about, but you're already doing that. You're showing in trials that you're actually improving the cognition by just changing the lifestyle factors, which I think is again so exciting because these are things that people have more access to.

[00:43:54.530] - Dr. Dale Bredesen

Yeah, there's so much more that can be done than people realize. We've had people, we had one doctor from France who said, who would ever think that changing your diet would make any difference? That's so silly. Well, this guy is obloviator, has never made anyone better himself. Just keeps giving drug after drug after drug. But the point here is not that diet is a cure for Alzheimer's. That's not the point here. The point here is that you have to address what's causing the problem. I think that's a pretty straightforward thing for all of us to get and unfortunately, a lot of the Alzheimer's experts haven't figured that out yet, despite repeated publications. And so the point here is to address those things. So, yes, as you indicated, for some people, diet alone is going to make a big difference. But if that doesn't do it for you, don't forget you may have undiscovered toxins or undiscovered pathogens. We had as an example one woman who's an APOE 44. Maybe we should touch on APOE just for a moment. Everybody should know their APOE status, please. And again, we're told don't find it out because there's nothing you can do about it.

[00:45:02.820] - Dr. Dale Bredesen

That's absolutely wrong. There's a tremendous amount. Wonderful website, APOE Four info started by Julie G, who is an APOE Four for herself. If you have zero copies of APOE Four, for example, I check myself. I'm an APOE 33, which is just cause like vanilla. It's the most common. Then your chance of Alzheimer's during your lifetime is 9%. It's not zero, but it's not too large. If you have one copy of APOE Four, and that's 75 million Americans, most don't know it, your chance now goes up to 30%. And if you have two copies, and that is 7 million Americans, again, most don't know it, your chance is well over 50% in some studies, up to 90%. Most likely you will develop Alzheimer's during your lifetime. So if you know it, if you start early on active prevention or earliest reversals, you can avoid this problem. You literally can make Alzheimer's optional. So everybody should get that checked out. It's a good thing for everyone to know. And there again, there's a tremendous amount you can do to prevent that problem. Now, Julie found after she went from 30th percentile on her cognitive testing up to 98th percentile, she just did beautifully.

[00:46:21.800] - Dr. Dale Bredesen

She's now ten years into this and still doing great. But a couple of years ago, she started having a little bit of backsliding like, wait, what's going on? So I talked to her and said, hey, something is being missed. You're not addressing something. And she kind of put it off for a few months and put it off for a few months. And by the way, she writes about this in the book the First Survivors of Alzheimer's Rights. A beautiful story. In any case, all the things that she did and how she's done better. And so it turned out ultimately that she ended up having babies. So she had been bitten by a tick ten years before that and had treated the Lyme disease. But of course, Lyme often comes with Coinfections, and nobody had ever bothered to check and treat the babysia, which she had for more than ten years. And so she's been treated for that by an outstanding physician, Dr. Schweig, who is an expert in this area. And again, she's doing very well once again. So this has been the problem with standard of care for Alzheimer's. People don't look at what the contributors actually are, and so therefore, the patients just continue to decline.

[00:47:34.550] - Kayla Barnes

Yeah. Wow. So really, the take home messages, diagnostics are really everything. Get everything that could be going wrong toxins, diet, potential infections. Get that under control and your outcome can be much better. When you mentioned diet, you talked about plant forward ketois diet, right? And healthy fats, of course. We want to really load up on those. I always kind of talk about that message, but what are your favorite healthy fats for the brain?

[00:48:08.750] - Dr. Dale Bredesen

Yeah, great point. Of course, everyone loves avocados. My favorite meal is a kitchen sink salad that has some great organic romaine in there, some kale in there, and then so many wonderful things. Some pastured eggs, sometimes even some wild caught salmon, for example. So I love salmon. Great source of fats. Some good Evo. High polyphenol. Of course, everyone's coming to the same conclusion. Polyphenol is really helpful, great for cognition. And even when the pandemic hit, I started using cronometer for myself repeatedly and say, OK, did I do the right thing today? I found out very quickly I'm not getting enough choline intake. Often I wasn't getting enough omega three intake. Of course, nuts and seeds, love those. As sources of fats, you have to be a little careful about going too high. They do have omega six s, of course, so you want to make sure that your three to six ratio is in the right range. But those are all wonderful sources of fats.

[00:49:21.810] - Kayla Barnes

And when it comes to cholesterol, lower isn't always better for the brain, right?

[00:49:28.410] - Dr. Dale Bredesen

You're scaring me to death here. This is so true. We have so many people who come in and say, yeah, my cholesterol, my not great statin, and my cholesterol is 105. Oh my gosh, that is a horrible thing to do for your brain. So, first of all, we like to see people ultimately getting off their statins. And one of the things we found in our trial was that as you do the right things, you don't need a statin. Most people don't need statins. It's because they're doing all the wrong things that they're taking a statin. And of course, statins have their own problems, starting with low Coq and Ubiquinol and muscle problems. It's just a disaster. So, yes, please get it so that you're your lipid count is good. I like to see people with LDL particle numbers in the 800 to 1200 range with triglyceride to HDL ratio. Simple thing to look at, around 1.0. You don't want your Triglycerides to be up too high. You want your HDL to be up there over 60 and fill that ratio to be good. And I like to see total cholesterol. Now. Interestingly. Talk to a biochemist.

[00:50:43.380] - Dr. Dale Bredesen

Dr. Dayn. Goodnow. Superb biochemist. He looks at plasma genes. His discovery in that association with brain health, he says the best brain health he's seeing with people with total cholesterol around the 200 and 2230 range, not sitting down there at 110, 105, that is not good for your brain. And it is associated, by the way, with brain atrophy. So please, I see so many people where their doctors have over corrected over medicated. If you're ever going to use a statin, hopefully you won't have to. But if you're ever going to do that, then remember you're inhibiting an important basic enzyme in your body. Please don't over correct your cholesterol.

[00:51:32.670] - Kayla Barnes

Thank you so much for saying that and clarifying it. I think it's going to help a lot of people because I think we've pounded this idea that your cholesterol can't be high at all because it's going to be just horrible for you. But really it's more so the ratio that's mattering. And you want to, of course, make sure that the cholesterol is coming from good fat sources, not processed foods, things of that nature. But really helpful to hear that. Doctor, why do you think that women are getting Alzheimer's at higher rates?

[00:52:01.470] - Dr. Dale Bredesen

That's a really good point. As Maria Shrivere has said repeatedly, alzheimer's is a woman centric disease. This is very unfortunate. So about two to one ratio. So it's somewhere around 65% of people with Alzheimer's are women and about 60% of the caregivers are women. And of course, caregivers for Alzheimer's that is associated with health decline, more stress, shorter telomeres, very important changes from the caregivers, unfortunately. So please, again, be careful. Take some time for yourself if you're a caregiver. So people have looked at why this is and one possibility, the bottom line is we still don't know all the reasons, but one of the potential contributors is the hormonal change that occurs with menopause. Now, when you go through andropause as you know, so males, they tend to slowly drop their testosterone, whereas when you go through menopause, for some women, it happens much more rapidly. And so you have a more precipitous drop in the estradiol. And we know that when you have these rapid drops that is more associated. We discovered something in the laboratory years ago called dependence receptors. These are receptors for various things that are supportive to your body. And what happens is when these receptors have their ligands taken away, the receptor without the ligand, without the Tropic ligand now induces the death of the cell.

[00:53:36.940] - Dr. Dale Bredesen

It's basically saying, I'm here to addict your cell to that support via estradiol be it testosterone, vitamin D, nerve growth factor BDNF, all of these sorts of things. And so I think one of the reasons is likely to be to this precipitous drop. And as you know, you have this about a seven year window with the socalled osteoclastic burst where you've lowered your hormonal support and so your bones are now changing. You're now undergoing more osteoclastic activity and less osteoblastic activity. And what we've seen repeatedly is that people at that period, this is literally a 52 year old woman again and again and again with the release of those toxins coming in with cognitive decline. When I was training in neurology, we never saw people in their 50s with a diagnosis of Alzheimer's. Now we see it all the time. It's one of the more common presentations. And it even looks different because it's often more of an executive dysfunction sort of presentation. We call this type three or toxic Alzheimer's disease. And in fact, there was a nice epidemiological paper written just a couple of years ago showing that indeed, as a population, we have had a marked increase in our early onset Alzheimer's disease in the last 20 years.

[00:55:03.330] - Kayla Barnes

Yeah, I'm sure. Of course, we don't have all the answers, but there's also the data even on women leaving the home with about 168 different chemicals on their bodies, which is about double that of a man. So it's the shampoo and the conditioner and the body lotion and the hairspray and the fragrance and so many chemicals that we're just putting on our body that we quite frankly, I mean, this stuff is all pretty new and we're just really slathered in it. So I think that could be a contributing factor potentially, as well.

[00:55:39.160] - Dr. Dale Bredesen

I think you're right. This is a huge issue. Toxin exposure has turned out to be a surprisingly common cause and contributor to cognitive decline. And so Environmental Working Group a good place to look, and all sorts of places just to look to make sure that the stuff you're putting on your body is not giving you problems with your body, including cognitive decline. So, yeah, that's such a good point. And as I said, the young women we're seeing in their early fifties developing cognitive decline, it is a toxic form of cognitive decline. So, again, you overfill the bucket. You just can't handle any more of that toxic exposure.

[00:56:21.090] - Kayla Barnes

Absolutely, yeah. And then women are also primarily the ones cleaning, for example, and using all of these different toxic chemicals and cleaning. Okay, before we wrap up, are there any supplements that you really love for brain health?

[00:56:36.870] - Dr. Dale Bredesen

And again, I would come back to the idea it depends on what you need yourself. And so people always ask, what's the one best supplement to take? Well, it depends on who you are, but just to lay out a few of the ones that I like myself. But again, they may not be the right ones for everyone. So I like, of course, omega threes and take them myself. And I think it's a great idea. And of course, there are issues about which are the best ones to take. Rhonda patrick has done a great job at looking at what types are the critical things, resolvents, which, of course, are related to the omega threes. So the resolven is very good for, as Dr. Charles Seyerhand from Harvard showed a number of years ago, very good for resolution of ongoing inflammation, of course, magnesium three and eight, another good one. Dr. Guasung Liu from MIT showed this a number of years ago, that this is associated with improved cognition. So magnesium three eight is another good one. And then, of course, people are getting interested in scenarios and things like fiscal and corsetin and things like that.

[00:57:49.550] - Dr. Dale Bredesen

Again, time will tell, but they look very promising because of their synthetic activity and then making sure that your vitamin D is not low. I just saw a report. So we developed something called recode reports that looks at all these different 150 different variables. There's a guy who just has just started, actually a very well known guy who's having some issues, and this guy walking and this is a guy who has the best doctors in the world, and his vitamin D was 18. Now, what are you doing walking around with the vitamin D of 18 and then asking why you have cognitive decline? Please, let's get you where you should be on that scale. So making sure that these things are optimal. Those are all some of my favorites. I also like whole coffee fruit extract because it is an increaser of BDNF. It's interesting when you study the molecular biology of Alzheimer's pathophysiology, the big surprise is that BDNF is actually intricately intertwined with ATP signaling and in fact, it does bind to a dependence receptor. So again, it is looking at are you going to downsize? Are you going to upsize? Are you going to have continued good neuroplasticity?

[00:59:10.650] - Dr. Dale Bredesen

So things like exercise that increase your BDNF, very helpful. And whole coffee fruit extract is another good way to increase your BD and F. So all of those things can be very helpful.

[00:59:24.750] - Kayla Barnes

I love it. Every time I go to the gym, I say it's a brain booster. So I really think of the way it's affecting my brain. And the last thing is, I'm really happy that I feel like the narrative around alcohol is finally starting to change. I think we've tried to find different reasons that alcohol can be considered a health food. People say resveratrol, even though we know you'd have to drink an insane amount of wine to actually get that benefit. But from your perspective, alcohol really doesn't have a good place in a brain healthy lifestyle. Do you agree with that or what do you think about alcohol?

[01:00:02.680] - Dr. Dale Bredesen

Yeah, this is a tough one because one of the things that I think we're all realizing, we need to get some workarounds, we need to get some comfort foods, we need to get people to remember, do the right things for your brain, do the best things, but don't be a masochist. You need to have that time when you're seeing something that you want to see, when you're having something that you want to do without hurting yourself. And the great news is, as we're able to study now that we know so much more about the neurochemistry of cognitive decline, we know what's driving this. We know what you can do to prevent it. Okay, so one of the things that commonly comes up is, what about popcorn? Well, again, have some Evo on there. Do a little bit, use it in moderation. So with alcohol, you're right, you could take the hardcore. Look, all alcohol is bad. Well, okay, but maybe people say, well, I love my wine, okay? It does relax you. If you're going to improve your heart rate variability, small amounts, I think everyone would agree with that small amounts occasionally. So a little bit of red wine, maybe some dry farm so that it's organic, et cetera, that's fine.

[01:01:22.450] - Dr. Dale Bredesen

But please don't go out and hurt your cognition with alcohol. As you indicated, there's just nothing good about it. And the more people look, the more they see the negative effects. It's really more about the other side. Are there things we can do to relax occasionally? Our favorite sorts of things, we've all whether it's chocolate, okay, we can do some dark chocolate in the right situation, which has got some great polyphenols and do pretty well there. So one of the great things coming out of all of this is for us to be better as people who have workarounds and our health coaches and our physicians can help us to get these wonderful workarounds. So we can have our dark chocolate and we can have our popcorn, and yes, we can have a little bit of red wine. And I recognize some doctors say zero. Some doctors say, well, a little bit occasionally is not so bad.

[01:02:17.790] - Kayla Barnes

Absolutely. Yeah. It'll be interesting to see again, where we kind of go with this, but I keep seeing more and more information surrounding the size of brains and alcohol intake, so it's just something for people to be aware of. So, doctor, it's been an absolute pleasure having you here with me today. Thank you so much, kayla, it's so.

[01:02:38.540] - Dr. Dale Bredesen

Great to talk to you. And thanks for all the great work you're doing and making so many people better look forward to a world with less cognitive declines.

[01:02:46.190] - Kayla Barnes

Absolutely, absolutely.