Expert insights on preventing & reversing cognitive decline
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Welcome to the My Buddy Green podcast. I'm Jason Wachub, founder and co-CEO of My Buddy Green, and your host. Oikos presents 15 Seconds of Strength. Here we go. Steve's got a trunk full of groceries and no one to help him. Oh, that's tough, Jim. Looks like a five-trip load at least. He grabs the first bag, the second. Bob, it looks like he's trying to do it all one trip. He shimmies the door open, steps over the dog. Oh,

And he stumbles. Oh, right into the kitchen without missing a beat. Jim, now that's a man who eats his protein-packed Oikos. With 15 grams of complete protein in each cup, Oikos Triple Zero can help build strength for every day. Oikos, stronger makes everything better.

Welcome to a brand new series we're testing here on the MyBodyGreen podcast. Every Thursday in May, we're dropping a special best of compilation episode focused on some of our most popular topics like brain health, strength training, hormone replacement therapy, VO2 max, and more. In each episode, you'll hear expert insights pulled together from some of our listeners' favorite conversations, giving you a quick, powerful look into the topics that matter most for your health and longevity.

Let us know what you think of this new format. You just may end up seeing more of them. Now let's dive in. For years, we've been told that cognitive decline is just a normal part of aging, that once memory loss begins, there's nothing we can do. But today's compilation episode is here to change that narrative and offer real hope. You'll hear from leading voices in neurology, investigative journalism, and women's brain health, including Dr. Dale Bredesen, Charles Piller, and Dr. Lisa Moscone.

Together, they'll uncover why Alzheimer's may be more preventable and even reversible than we've been led to believe. We'll explore the overlooked factors that drive brain aging, where the research went wrong, and what you can do starting today to protect your brain for decades to come.

From the impact of hormones to the truth about your genes, this show is full of empowering insights and practical tools to help your brain thrive. To kick things off, we're hearing from someone who's truly reshaped the way we think about Alzheimer's, Dr. Dale Bredesen. Dr. Bredesen is a renowned neurologist and the chief science officer at Apollo Health. He's spent decades studying neurodegenerative diseases, and his research has led to a bold, hopeful discovery—

cognitive decline is not inevitable. He'll explain why memory loss doesn't have to be a life sentence and how simple tests can now detect brain changes before symptoms start. Now, the first thing that people are missing is that cognitive decline is inevitable. We have been told over the years repeatedly, there is nothing that you can do to prevent, reverse or delay cognitive decline. If it's coming for you, it's coming for you.

And our research and our studies over the years indicate just the opposite, that there is a tremendous amount you can do. There is what you can do to prevent it. You can do to reverse it. We've published Reversal of Cognitive Decline. We were the first to do that way back in 2014.

We're now in the midst of a six-site randomized controlled trial that shows unequivocally that you can reverse cognitive decline. Well, now we have some wonderful brain markers as well. There are epigenetic markers that look at brain aging. And then there are also markers that look at where your brain stands with respect to cognitive decline. And what I mean by that is,

Years ago, we would know when people had diabetes, but people didn't know that you could measure prediabetes and then pre-prediabetes, in other words, insulin resistance. Now, of course, you can measure fasting insulin. You can measure HOMA-IR. You can measure hemoglobin A1C. So if you're paying attention, nobody needs to get to the point of having full-on type 2 diabetes with vision loss and renal failure and vascular disease.

Well, Alzheimer's has now gone the same route. We can now look ahead of time. We can look at your P-tau-217, which is now a simple blood test. Number one, P-tau-217,

changes, goes up in your blood when you're headed for Alzheimer's disease. So you can see it coming and you can do something about it. You can correct the energetic insufficiency, correct the pro-inflammatory effect, correct the toxicity effect. So with this, you can really look and say what is going on inside the brain of each person so that we can prevent problems. So I think people need to be aware of this.

Practitioners need to be aware of this. Most practitioners, you know, mainstream medicine is not reversing cognitive decline, has no idea what to do about that, and really is not aware that it even exists. So there's tremendous change. We really are in a time of great progress with respect to the brain.

From the silent early stages to full-blown dementia, understanding where you fall on the spectrum can be the most important first step to protecting your brain health. I was fascinated to hear this breakdown.

You go through four phases. So you have a pre-symptomatic phase where you don't even know you've got problems, but you're already beginning to have biochemical changes. The second phase is called SCI. And that's what people are so aware of. So subjective cognitive impairment. And this is so common. People in their 40s and 50s, even in their 30s,

will notice, wait a minute, you know, I don't remember phone numbers the way I used to, or I don't remember some of the names of my friends the way I used to, or names of new colleagues the way I used to. And so the doctors keep telling us, oh, that's just normal aging. No, that's telling you that things are suboptimal. By the way, a very, very common reason now, of course, is COVID.

And people will say, gee, since my COVID, I'm really not remembering things quite as well. Okay, time to get in, find out whether you've got some continued inflammation and what to do about that. So SCI lasts on average 10 years before giving way to MCI. Oh my gosh, please don't wait beyond that. We get virtually 100% of people with SCI to reverse their decline. That's an easy time.

The third of the four phases is called MCI, mild cognitive impairment. And that's when the drug trials are done. Our trial was done on people with MCI and early dementia. Dementia is the fourth phase.

And so these people typically, MCI, you typically have your MOCA scores are coming in anywhere from 20 or 21 up to 27 or so. And that's telling you something is not right. By definition, what MCI means is you are no longer able to score normally on cognitive tests.

but you're still able to do your activities of daily living. Whereas SCI, you're saying something's wrong, you know that things are not right, but you're still able to score normally on cognitive tests. Then the fourth and final phase is called dementia. That's dementia of Alzheimer's. Alzheimer's is the most common, but there are others like Lewy body dementia and vascular dementia, things like that. And by definition, that means that you're now losing your activities of daily living.

While researchers like Dr. Bredesen are pioneering new ways to treat and even reverse cognitive decline, investigative journalist Charles Piller has been digging into why progress in Alzheimer's research has been slow, despite decades of funding and attention.

Charles is a contributor to Science Magazine and helped uncover the possible scientific fraud at the heart of a widely accepted Alzheimer's theory. During our conversation, he explained the two major issues that have held the field back and why it may be time to rethink everything we thought we knew about the disease.

So what is the big lie as it relates to Alzheimer's research? Well, that is indeed the question. Jason, thank you for asking it. I would say there isn't one maybe single big lie, but there is a confluence of things.

that has caused Alzheimer's research to have disappointingly slow, disappointingly meager results for patients and for their family members who are caring for them. Let me put it in two parts. One is that Alzheimer's research has been dominated for decades by a one big idea, and that is something called the amyloid

And very briefly for listeners, this hypothesis is based on the idea that something called amyloid proteins, and these are what people may remember as the sticky plaques that emulate the brain.

and other forms of amyloid protein that are a little bit different, over time, cause a cascade of biochemical effects that lead to Alzheimer's dementia. That idea, that central idea, has been in force for a very long time and has been dominating scientists' minds and research and funding and drug development, but unfortunately has yielded

very meager, if any, really substantial results for patients. So that's one part of it. The other part of the big lie, if you want to call it that, is the very unfortunate set of circumstances that in Alzheimer's research, we have seen an enormous amount of

apparent image doctoring in seminal papers and many other papers that have influenced thinking in the field. And when I say image doctoring, what I mean is that scientific images that purport to support the premises of experiments that

Steer thinking in the field have been improperly altered or apparently improperly altered to support a false premise. And these two factors, the combination of

the dominance of a single hypothesis and apparently wrong thinking in the field influenced by important work that may have been based on false pretenses. These combination of things has resulted in, I think, unfortunately, a lot of disappointment in the field of Alzheimer's. There are other factors, of course, but those are pretty clearly part of the puzzle. In 2006, a seminal experiment was done by

researchers at the University of Minnesota. And this experiment, with collaborators, I might add, from other institutions, and this experiment was very clever. And what it did was it took genetically engineered mice that were programmed to produce copious amounts of amyloid proteins in the mice's brains. And the proteins were extracted from mice brains and then purified a certain compound

kind of protein, certain kind of amyloid protein was purified out of the sample. And this is something they dubbed amyloid beta star 56, kind of a catchy name, the star protein.

And this protein was then injected into rats. And the rats were said to develop symptoms of memory loss that they compared to the memory loss that people experience in Alzheimer's disease. So what you had was, for the first time, kind of cause and effect experiment that suggested that a particular substance, in this case the star protein, amylase beta-star 56, could cause dementia.

And so the field pounced on this. It became one of the most cited, revered studies in history.

Alzheimer's science for many years. And people started to say, okay, this revives our confidence that we're on the right path. This really made the field realize that maybe we haven't gotten the right drug yet. Maybe we haven't gotten the precisely right target of the certain kind of amyloid protein in the brain that we need to be removing in order to improve the experience of patients.

But we're on that path and we're going to do drug development that heads in that direction. Enormous sums of money were poured into the field to target these special kinds of proteins. They're called oligomers. It's kind of a wonky term, but it means a kind of amyloid protein that is soluble in the spinal fluid that bathes the brain, not sticky plaques that is sort of the classic understanding of what amyloids look like in the brain.

And so a lot of drug development was done, etc. And unfortunately, you still continue to have failure after failure, experiment after experiment. These drugs became excellent at removing amyloid proteins from the brain, but not good at making people's experience better. All right, so...

And that's the background. In 2022, a scientist by the name of Matthew Schrag at Vanderbilt University, working in his spare time on integrity issues in science, which is a subject that he became an expert in, he and I had been talking about another case, but we didn't.

He sort of stumbled on this experiment, this 2006 experiment that was published in the very important scholarly journal Nature. And what he found was that there were a number of images within this seminal 2006 paper that looked just wrong. They looked like they had been digitally manipulated to produce a result that was not actually found in the experiment. ♪

But it's not all doom and gloom. While the field has faced serious setbacks, there's also a growing wave of promising research that's moving in entirely new directions. Charles shares three emerging areas of Alzheimer's research, from surprising connections to infections to the potential of GLP-1 medications to new work on tau proteins. That might finally shift the tide.

There's no magic bullet for Alzheimer's disease, whether you already have it or if you are afraid of getting it or you might have a genetic predisposition in your family that make it more likely that you might eventually get Alzheimer's disease. But I want to mention three kinds of experiments that are going on right now that are different from the amyloid hypothesis approach to Alzheimer's disease that could bear fruit. One is

the so-called infection hypothesis that latent infections from things like herpes virus might be hanging out in the brain many years after the person who had things like cold sores from herpes have subsided and long forgotten might be an influence on Alzheimer's disease. And there's actually clinical trials. These are experiments with people for safety and efficacy studies

drugs that could attack that in the brain and maybe have an influence on Alzheimer's dementia. That's one. Another one that is fascinating to me is the use of these GLP-1 inhibitors. This is the sort of magical weight loss drugs for obesity and diabetes, etc., that have been sweeping through society in the last few years that are also being tested as a possible remedy for Alzheimer's dementia, early stage Alzheimer's dementia. And I

I think within probably by the end of 2026 we're going to have some results from a big trial that's going on that would give us some answers about whether that might be a useful intervention.

There's really fascinating studies going on about the so-called tau proteins. These are the companion to amyloid plaques that are actually inside the nerve cells of the brain. And, you know, that work needs some years to develop, but it's somewhat hopeful that it could be a tack on the problem that we'll see some benefits down the line.

Now let's shift gears to talk about women's brain health, specifically what happens during menopause. Women have a higher risk of dementia and Alzheimer's, and menopause can be a catalyst for the start of cognitive issues. Dr. Lisa Mosconi is a neuroscientist, nutritionist, and author of The Menopause Brain.

Her research focuses on how hormonal changes impact the brain and why menopause is as much as a neurological transition as it is a hormonal one. Hormonal changes don't just happen overnight, but rather years before your period stops and why so many of the symptoms, from hot flashes to brain fog, start in the brain, not the ovaries. ♪

So in the book, you say that most women spend 40% of their life in menopause. And by 2030, 1 billion, 1 billion with a capital B, 1 billion women will have entered or about to enter menopause. So what do we know about women and what's going on in their brain during menopause? This is such a fascinating question and a question that I think we should all be really mindful of.

About in part for the reasons you mentioned that women are half of the world's population and menopause does not happen overnight. So it's really important to realize that menopause, number one, does not happen when you're old. That's a misconception. The average age globally is 49. So that strains at the definition of old age by any standards.

And most importantly, you don't just happen to go through menopause. It's not like when you have your period that just one day hits you and that's the end of the process. Menopause can take years. Transitioning to menopause and the absence of a menstrual cycle can take anywhere between two and 14 years. And what we know about those years is

is that they can be easy, but they can also be hard and demanding, especially on women's brains. And that is really the big part of my work. It's a key component of my work to study the menopause brain, what it means, what it does, why it happens.

and how to feel better as you navigate those important years. - So what are some of the things that are happening if this starts years before '49,

Maybe we start in our 30s. Can you walk us through what's happening in the brain in 30s, 40s, 50s, 60s and beyond? What should women be aware of? What should they be looking out for? Are there labs they should be demanding that their doctors give them? So they should think about this as a process that actually starts as soon as we're born.

Because the truth for women's brains and women's bodies is that we are born with a system, the neuroendocrine system that connects the brain to the ovaries. We're born with it.

However, this system is activated as we go through puberty, then is over-activated as we get pregnant every time we are pregnant, and then it gets partially turned off after or during the transition to menopause and more so after we are in menopause.

So the way that this process impacts your brain is that everything is fine until you hit one of these very important transition states, which I call the three P's.

Puberty, pregnancy, perimenopause, which is a transition to menopause. Those are neurologically active states. It means that your brain is just as impacted by these processes as much as the ovaries are. We're just not used to thinking about that as a neurological process or something that impacts your brain as well. So that is important to know because a lot of women are really scared about

of menopause. They're really confused. They don't know what's hit them. They don't associate the symptoms with the process of going through menopause, in part because they feel like I'm not old enough to be going through menopause. I'm in my 30s. I'm in my 40s. What is this? It's actually menopause.

It's a process that takes many years that impacts your brain in ways that are subtle but consistent. And you may have seen some of the symptoms as you go through puberty or pregnancy as a woman. They're just stronger, sometimes more severe as we go through menopause. So when women say that they're having hot flashes, nice sweats, insomnia, depression, anxiety,

brain fog. Brain fog is a huge concern. Memory lapses. Those are symptoms of menopause that don't start in the ovaries, they start in the brain. Those are brain symptoms that are triggered by the way that menopause changes the brain.

And here's where it gets more interesting. One of Dr. Moscone's most fascinating studies published in Scientific Reports looked at the brains of both women and men to tease apart what changes are really due to age and what's actually due to menopause. As she explains in the next clip, women's brains go through significantly more change during middle life than men's do, and those changes aren't just about getting older.

Since we last spoke in 2020, like which study are you most proud of? The one that came out in Scientific Reports, which is a nature journal in 2021, where we published the largest scale investigation of menopause, of the menopause brain, by looking at hundreds of women and men. We had men in the study too, thank goodness, because I get this pushback all the time. Whenever

I show that there's a difference between premenopausal women and period and postmenopausal women. The constant pushback is not menopause, it's just age. I get it all the time. And I'm like, well, if it was just age, then men would show exactly the same thing, right? Men of the same age. And they don't.

So that's very helpful to say that when you're premenopausal, depending on what we're looking at, but there's hardly any difference between women who are premenopausal and men who are the same age. We match them. But once the women are perimenopausal, then they show more...

changes in their brains as compared to men of the same age. They show reductions in brain energy, reduced or lower brain energy levels. They show different connectivity patterns. They show increased oxidative stress or reduced ATP production. They show more Alzheimer's plaques, some women, not all women, some women. And when you're postmenopausal, the difference is even more pronounced. So it's not just age. So basically I need to prove that it's just not aging.

And we're also doing longitudinal observations. So over time, women's brains change more after menopause as compared to men of the same age that are imaged at the same intervals.

Now that we understand how menopause uniquely impacts the brain, let's shift to a topic that often sparks fear and confusion. Genetics. Next, Dr. Moscone breaks down the difference between true genetic mutations that cause early-onset Alzheimer's and the much more common genetic risk variants, like the APOE4 gene, and her message, your genes are not your destiny.

We'll hear her science-backed advice for protecting your brain starting in your 30s. From nutrition to movement, these simple lifestyle choices can shape your brain health for decades to come.

Can we talk about this for a minute? Because this comes up so much in our hands. There's so much confusion around what it means to have the bad Alzheimer's gene. And I think something happened on television that may have confused at least a lot of our patients. So there are genetic mutations that cause Alzheimer's disease. Those are the bad Alzheimer's genes.

We know quite a few genetic mutations, but the strongest ones impact three specific genes. And I assume nobody's ever heard about these actual issues, these genetic mutations that cause Alzheimer's disease. They are mutations in the amyloid precursor protein in the pre-synilin 1 and 2 genes.

The running families, and they're highly penetrant, which means that if you have the mutations, your chances of getting dementia are very high. You may develop dementia at a young age, in your 30s, 40s, 50s, early 60s. All right. So these are genetic mutations.

You don't get them from 23andMe. You have to go through a doctor and do a serious CLIA-certified lab work. It's a double copy of the APOE, right? It's a complete different thing. This is what people think is the bad Alzheimer's gene. That is not a mutation. So let's clear this up. So people think that the apolipoprotein E, APOE gene, is the bad gene for Alzheimer's disease.

I would like to clarify that there are genetic mutations where you have an actual issue in your DNA, and then there are genetic risk factors.

variants. So genetic mutations are things that happen to your DNA, where your DNA is structurally changed. There may be one piece missing, maybe one piece has been duplicated. There's something that happened to your DNA that should not have happened, and that happened to you and your family and could trigger Alzheimer's disease at a young age.

Then there are genetic risk variants, which means that every person has different versions of the same gene. So this apolipoprotein, this ApoE gene comes in three different forms of variants. They're called epsilon from Greek, right? So there's epsilon 2, epsilon 3, epsilon 4. You get one from the mom, one from the dad.

If you have two copies of the E4, or even just one copy, your risk is higher relative to another person who does not have it. So people have the two or three copies. But it doesn't mean that you are going to develop dementia. There are plenty of people with an ApoE4 gene who do not have dementia. And there are plenty of people who don't have the ApoE4 gene who have dementia. And so for those starting young,

We have a listener in their 30s right now. In your view, what are the most critical things they should focus on to set up

their brain health for success and also like perimenopause, menopause. Because as you pointed out, it just doesn't show up one day. The process is starting. Yes, exactly. It's a very long process and you have control over at least some of the processes involved. And lifestyle, I really believe that lifestyle is key.

And my preference personally is always to optimize my lifestyle before asking for prescriptions if I can. You know, within reason, obviously, there's a disease or an infection is different. But for in this case, I think there's so much that we can do preventatively and proactively.

that we just need to think about. And they talk about all of these things in detail in the book, in the menopause brain. But to summarize, I think exercise is really important for overall health and brain health. It's been shown time and time again that it really supports the health of your neurons at all ages, not just when you're young, but also all stages and walks of life.

Diet, I think, is really important because nutrients are not just nutrients, right? Nutrients are information and they are the kind of information that speaks directly to your genetics.

So when you choose to optimize your diet so that there is antioxidants and omega-3 fatty acids or polyunsaturated fatty acids and lean protein and anti-inflammatory compounds, this is not just something that's good for your skin. You know, the same nutrients will penetrate inside your brain cells and go talk to your DNA and tell your DNA what to do. They carry information that...

at the epigenetic level can really improve your health or the opposite. So diet is important. And I think at least in my field, there is consensus that plant forward diets are important for brain health. You have to eat those fruits and veggies. You have to eat the fiber. I don't care where you get your fiber, but there has to be fiber in your diet. It's really important.

Targeted changes can dramatically impact your brain's ability to function at its best, providing an actionable blueprint for not just prevention, but potential reversal of cognitive decline. Here's your framework for protecting your brain from Alzheimer's, according to Dr. Bredesen.

And for Alzheimer's, it's really, as you know, about neuroplasticity. So when you are trying to improve energetics, reduce inflammation and reduce toxicity, there are seven basics and two specifics. That's it. So the seven basics are largely about lifestyles. Just what you said. It's diet, exercise, sleep, stress, brain training, detox, and some targeted supplements. And the two specifics are diet.

Are there chronic infections, which are remarkably common? People don't know. You've been bitten by a tick, for example. You don't know it. You're carrying around Babesia or Bartonella or Borrelia for years. And or the other thing is toxins, which are things like myocarditis.

mercury or glyphosate or microplastics or air pollution or biotoxins like mold-related toxins. These are incredibly common and they are important contributors. You can address them. You can treat them.

And so no question, having a, just for example, diet as the part of the lifestyle, each of these things you can optimize. Having a plant-rich, mildly ketogenic diet with high fiber, high phytonutrients, optimizing your gut microbiome, high detoxicants, things like crucifers, vitamins.

This is remarkably powerful because you are now changing the brain from not being able to get enough energy and literally downsizing because of its lack of energy into now being able to get enough energy. And as you know, your brain can only metabolize two things for energy. So two energetics, it's glucose or it's ketones. Now,

Now for many, many people and virtually everyone I see who's beginning cognitive decline, they've lost both of those. You lose the ability to optimally use glucose because of insulin resistance. And there are over a hundred million Americans with insulin resistance. It's essentially pre-pre-diabetes. This is why type two diabetes is such an important risk factor for Alzheimer's.

But once you ramp up your insulin, that prevents you from making ketones. So now it's like, imagine you have a Prius,

which has got no charge and no gas. You're literally sputtering, and that's what your brain is doing. And you'll notice it. You'll get tired. You'll have some brain fog. These are telling you you're not getting the support that you need. You can return both of those by having a plant-rich, mildly ketogenic diet, doing some exercise, both aerobic and strength training.

From exercise and nutrition to blood tests and stress management, these are all vital tools for maintaining a healthy brain throughout every stage of life. One of the greatest modern discoveries into brain health and cognition is that we have the power to prevent and sometimes even reverse dementia, even when the odds are stacked against us. It's never too early or too late to get started.