Top Neurologist: The Weekend Habit That Could Raise Your Dementia Risk!

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Finally we have a partner who can enable us in a simple way for those people that are both left brain or right brain and enable our dreams. At the time of recording, Xero has an offer for 90% off for six months through referrals.xero.com slash DOAC. Terms and conditions apply. Thank you to Xero. Thank you for sponsoring this podcast but also thank you for helping me to scale my business as somebody that quite frankly has never loved finances that much. In America, Alzheimer's is the third leading cause of death. If you live to be age 85, your risk of developing dementia and generally Alzheimer's, it's close to a high 40% or a flip of a coin and women have twice the risk of Alzheimer's in comparison to men. But what people may not be aware of is it is significantly preventable and that's the message that I've got to get out. I'm a board certified neurologist and I've seen a lot of brains and thousands of scans. Alzheimer's is primarily a metabolic condition of the brain. So I've got some cards here and I want you to write the top five things that you think are contributing to Alzheimer's and dementia. Number one, we have offloaded agency of our brains to the pharmaceutical industry. So I'm putting forth to you the most important things people can be doing in keeping the brain healthy. And number two, being sedentary. This is huge. Exercise and movement is a multi-tool for the brain. Then there's food choices. You know, I've got a few things here. This is a big problem because if... Wow, that's scary. That's worrisome. So what we really understand now is genetics loads the gun. Lifestyle pulls the trigger. You know, we often hear from the family what it was like to essentially lose the person they loved. And I've been through this with my father. And when you see your parent like that and you think back to who he was and what he was, it's difficult. And I don't want people to go through that. Well, you're a dad yourself now and you have this wonderful son called Austin. Austin wrote a letter for you. You know, I'm thinking of my dad right now. And I'm doing my best so people don't have to experience what I'm feeling right now. So what does that mean for us? My hope is that a lot of people get this message that... Guys, I've got a favor to ask before this episode begins. The algorithm, if you follow a show, will deliver you the best episodes from that show very prominently in your feed. So when we have our best episodes on the show, the most shared episodes, the most rated episodes, I would love you to know. And the simple way for you to know that is to hit that follow button. But also, it's the simple, easy, free thing that you can do to help us make the show better. I would be hugely grateful if you could take a minute on the app you're listening to this on right now and hit that follow button. Thank you so, so, so much. Dr. David Perlmutter, what is the mission you are on? And why does that mission personally matter to you? Well, the mission I'm on is to let as many people know that the destiny of their brains is really based upon how they are choosing to live their lives today. So we live in a world where we're sort of messaged to really live your life come what may, however you like. And there'll be some magic development in the world of neuroscience that will save you when your brain isn't working like it should. We aren't there yet. I welcome that day, but we aren't there yet. What we really understand now, in fact, the greatest development in neuroscience is that our lifestyle choices are really the architects of our brain's destiny. And who are you, Dr. David? What is your experience? And what is the education that you've had? I went to medical school, got my MD, then became enrolled in a neurosurgery residency and became a board-certified neurologist. And why does this all matter so much to you personally? Personally, I've been through this. He just played that card, didn't you? I've been through this with my father, and it's rough. It's rough for, in my country, the 7.6 million Alzheimer's patients. Not so rough for them as it is for their families, the truth be known. And it is significantly preventable. That's the message that I've got to get out. We don't have a treatment. Would I welcome a treatment? You bet. Would I have used a medication and prescribed it for my own father? Of course I would have. We aren't there yet. What happened to your father? Got a wonderful portrait of him here as well. What a suave man. So he was a brilliant brain surgeon, compassionate, skilled, wonderfully compassionate individual. And in his later years, he developed Alzheimer's. And it's interesting because I diagnosed him late in the game. I remember the moment that I finally realized, my gosh, he's demented. And I missed it. How did you know he had Alzheimer's? How do you diagnose it? It's what I do. I mean, I diagnose Parkinson's in the airport when I'm coming to see you. I mean, that's what I do. It's my skill set. Just the type of memory issues that he was experiencing, losing things, walking into the room, forgetting where he was. It was very obvious. I mean, it was at least dementia. And generally, that means Alzheimer's. And just my knowledge, what is the difference? Because I hear these words, dementia, Alzheimer's, Parkinson's. Most of dementia is Alzheimer's. You can be cognitively impaired because of poor blood supply to your brain. We call that vascular dementia. There is dementia that goes along with the accumulation of something called Lewy bodies in the brain. People can be cognitively impaired with reversible issues, like as a consequence of medications that they may be taking or other types of medical problems. So dementia is the sort of umbrella term. Exactly. Dementia means this failure of cognitive function across multiple domains. Okay. So Alzheimer's disease, vascular dementia, Lewy body dementia, and- Frontotemporal dementia. Okay. So everything underneath dementia, it's a general term for a group of symptoms. That's right. Okay. What has become so fascinating for me, as you look at those seemingly very disparate diagnoses, and they are, but they're all united by one common mechanism, and that is disruption of the brain's immune system. That's the fundamental. That is the huge aha in neuroscience right now. That disruption of the brain's immune system is a central feature across this incredible panorama of what makes a good brain go bad. What is it the current medical profession believes that you no longer believe? I think that by and large, at least relating to Alzheimer's, and I think we can flesh this out across more neurodegenerative conditions as we speak, but I think still the party line is one that believes that the central player in Alzheimer's disease is the accumulation of a protein called beta amyloid in the brain. Get rid of the beta amyloid and problem solved. That is not reality, and it's unfair. And how many people are likely to get a form of dementia in their life? Like how many people are going to be affected by these neurodegenerative diseases that you have studied and worked on and can diagnose? Lots. I mean, if you live to be age 85, your risk of developing dementia and generally Alzheimer's is close to a flip of a coin. It's close to high 40%, and that's very worrisome. In America, Alzheimer's is the third leading cause of death. People don't realize that, and it is largely preventable. That gets back to our first question. Why am I here? What do I do? And my mission is to message people that what you're doing at your age, Stephen, is hugely influential in terms of charting your brain's destiny. When does dementia start? Typically, we discuss the idea that a patient becomes, not even a patient yet, but somebody is having issues, forgetful of names, going into the room forgetting why, losing things. That's when they go to the doctor, and that's when the process begins of evaluation and ultimately choosing some form of treatment. And the reality is it's like a heart attack. We don't wait for you to have a heart attack to begin looking at your blood lipids, looking at your blood pressure, asking you, are you active? How are you sleeping? What's your physical activity like? And we should be doing the same thing as it relates to dementia. We should be talking to people in their 30s and in their 40s and asking those very same questions. Alzheimer's is primarily a metabolic condition of the brain. Let me tell you something that's really interesting. It happened in your country this past week. There is a new trial being started right here in England called the AD-SMART trial. And the government has put up £33 million, $44 million, to begin a study of two medicines in the treatment of Alzheimer's disease. One is called metformin, which is a diabetes pill, and the other is actually an ADHD drug called Stratera. And this is a trial of about a thousand people. It's going to take 18 months to treat Alzheimer's patients. Why I bring it up, as a matter of fact, your prime minister is very much in favor of it, in that his father died of dementia. That said, the reason I bring it up is metformin is a metabolic drug. It's a diabetes drug. Think about that. They've moved away from targeting beta amyloid to finally recognizing that metabolism is a central player here. Explain this to me like I'm 16 years old. So beta amyloid are these brown sort of plaques they found on the brain with people that had Alzheimer's dementia. So they thought that it was part of the cause of the dementia. Subsequently, they found out that you can have those plaques and still not have the dementia symptoms. So we now know it must be something else. And you can have the plaques, a brain load of plaques and not be demented. So now the working hypothesis is that it's something else is causing it. And you're positing that it's largely based on metabolism. Yes. And metabolism, as I understand it, is what we eat, what we do, like our activity in our life, our lifestyle decisions. It's a great question. And I think that the strict definition is metabolism is the way that our cells create energy and make things. They make proteins. They make things. So really, upstream of what makes a good brain go bad are changes in metabolism. The metabolic markers, our blood sugar, our blood pressure, our body fat, our blood lipids. These are the metrics of metabolism that are so important for the brain. And the heart. And in fact, your entire body. So when we say that Alzheimer's is fundamentally a metabolic condition, let's say that in the context of where the research is going. For example, 10 years ago, about a third of Alzheimer's research was really focused on what we talked about, this beta amyloid protein. That number is down to about 14% now in favor of looking at things like metabolism and looking at the brain's immune system. These microglial cells that are really the upstream issue as it relates to not just Alzheimer's, but all manner of neurodegenerative condition. So when we understand metabolism and its effect on the microglial cells, we're throwing a very wide net indeed. Meaning that if we can target our metabolism earlier in life, keep our blood sugar under control, exercise, get enough sleep, have relationships with other people who knew that was such a powerful tool for brain health. We really are creating an environment that helps us reduce the risk across the spectrum of brain degenerative issues, not just Alzheimer's. I'm going to set you a slightly tricky task. Okay. I've got some cards here and I want you to write in order of severity and consequence, the top five things that you think from lifestyle perspective are contributing to Alzheimer's and dementia. Okay. If you've got more that you want to add, you can add more. Just tell me how many you've got, you've done. Okay. So how many have you got there? I have five. And again, let's restate what I'm doing here. I'm putting forth to you what I think are the most important things people can be doing as relates to being in charge of their brain. And that is in fact, number one. And that is the biggest issue is not embracing the fact that you are the architect of your brain's destiny. Because if we don't do this, nothing here will matter. Nothing here will take place. You've got to embrace that. And you've got to recognize that we have offloaded agency of our brains to the pharmaceutical industry, if you will, and other forms of technology. And again, that's great. If there was something that were effective, there is not anything meaningfully effective right now. John Kennedy said that the time to fix the roof is when the sun is shining. And that's why I'm here today. So, number two. Sedentarity, meaning being sedentary. This is huge. This exercise and movement is a multi-tool for the brain. It targets the function of insulin. It targets inflammation. It targets mitochondrial function. It targets blood flow. These are are all hugely important mechanisms in keeping the brain healthy. Are you somewhat very focused on brain health in part because of your father? And does that statistically give you a predisposition to the same disease? It does. It does. I think, you know, when we talk about what we inherit in terms of risk, I think a lot of people these days are focused on the Chris Hemsworth story that he carries two of what are called the ApoE4 genetic alleles. Are you familiar with that or can I walk through it? Okay. So we have the ApoE alleles. We can have a 2, a 3, or a 4. And you get two chances. What do you mean you get two chances? Well, you carry two of them. So you can have a 2-2, you can have a 2-3, a 3-3, a 3-4, a 4-4, and a 2-4. I guess those are all the permutations that can happen. Carrying more of the ApoE2s is associated with a pretty dramatic risk reduction. ApoE3 is neutral. But carrying the ApoE4 allele, like about 25% of people, is associated with an increased risk of Alzheimer's. If you carry one by about five-fold, 500%, five-fold, and if you carry two, in other words, your ApoE4-4, the risk may be as high as 12-fold increase. 1,200%. And you're saying Chris Hemsworth has... He's been very public about it. But here's what is so valuable and on the list of things that you and I have not covered yet and incredibly valuable. Why? Because people are getting their genome sequence now, you know, left, right, and center. Everybody knows. And a quarter of people who get their genome sequence are getting their results back. And seeing that they might carry an ApoE4 allele, and then you read the little printout from AI that says, this puts you at increased risk for Alzheimer's. That's scary. That's worrisome. Early in the day, we as neurologists were told, well, when we know the ApoE status of our patients, if they carry ApoE4, we shouldn't tell them. Well, why should we tell them? Because they're on the road to Alzheimer's. Nothing is further from the truth. If you carry an ApoE4 allele or two, you are not necessarily destined to get Alzheimer's. So incredibly important. Your lifestyle issues can offset this issue of a genetic predisposition. It's a genetic predisposition. I won't deny that. It is not a genetic determinant. There's an interesting study that came out in the Journal of the American Medical Association. In November of 2025, the author was named Marino. And what he did was looked at people from the Framingham Heart Study, and he divided the group of individuals, there were about a thousand in each group, 4,000 total, into younger people, 25 to 44 years, middle-aged people, 45 to 64, and older, 65 to 88. That's my age group. And he followed these individuals for a number of years and determined who got dementia and who did not. And he compared that to their level of physical activity. And what he found was really quite remarkable, that in middle-aged people, those who were the most active compared to those who were the least active, had about a 45% risk reduction for this disease, Alzheimer's, for which there is no meaningful treatment. That's huge. Similar results in the older age group, those who were most active and carried APOE-4, they had about a 67% reduced risk of becoming an Alzheimer's patient. If they exercised it. If they were in the group that exercised the most in comparison to the group that exercised the least. Again, exercise is the multi-tool here. Again, exercise is the multi-tool here. It is a huge and readily available tool for each and every one of us. That's what doctors should be teaching patients, not, well, it looks like you're cognitively impaired, we're going to put you on an IV therapy every two weeks and hope for the best. What is the exercise doing physiologically? How is it helping the brain? Well, it's doing a lot of things. Exercise means you're basically activating muscle, right? That's how you move. You need your muscle to work when you move. And as it turns out, you may not know this, but your muscles are an endocrine gland. What does that mean? Well, great question. And we teed it up. We know our endocrine glands are, you know, the adrenals, the thyroid, the pituitary. And why are they called endocrine glands? Because they make chemicals that go elsewhere and do something. Your muscles create a suite of chemicals called myokines. Myo, muscle, kine, means they move around. And they do things at a distance and they make their way to the brain, for example. They help stimulate the brain to produce something called BDNF, so it'll grow new brain cells and nurture your neurons and nurture the connections between neurons, which are the synapses. When we activate our muscles, we improve how insulin works. So our blood sugar can remain where it needs to be. Elevated blood sugar is a powerful risk for brain degeneration. A simple blood test like the A1c, measuring your average blood sugar, is a powerful indicator, if it's elevated, of risk for Alzheimer's. When we exercise, we reduce inflammation. Inflammation is a key mechanism that changes our brain's immune cells from being supportive to being destructive. And we're going to certainly look at that in great detail. And exercise improves the blood going to your brain. That's got to be a good thing. Any particular type of exercise or all exercises? I think all exercise is great. The big discussion is, well, what's best for my brain? Is it aerobics or is it strength training, resistance training? And it turns out that a recent meta-analysis asked that question and came to the conclusion that it's both. That we want to strengthen our muscles and we want to engage in aerobic activities such that we can gain the metabolic benefits. But, you know, think about it. If these chemicals that your muscles are making are good for your brain, that the more you have of these chemicals, the better. So build muscle. When you're my age, it's harder. It's much more challenging to keep your muscle mass and to build muscle. So it's something that you really want to start at a younger age. What's the next card? I think, I mean, we've got a toolbox here as well, which has got some things in it. The goodie box. You're aware that some of these are relevant to things you've just said. They are. And I'm going to pull out something, a very, very high tech device that I think people should get. Okay. That might be their most powerful tool that they can save up for and get so that they can improve their brains. Ready? Yeah. And here's one. And here is the other. Get moving. Movement moves all the needles. Movement moves everything. So if I use these. You're not going to use those. They're too small for you. This is better than any drugs or medicine that I could possibly buy. It is. It's interesting because what I've just described to you in terms of the activity of muscle activation is very similar to the drug that's now being used in the Alzheimer's trial right here in England. Think about that. That metformin. Metformin does many things that exercise does. Exercise does more. Sold. You're sold. I'm sold. Mission accomplished. Lack of social connection. Who knew? Really? That's the third thing. From here on out, these are all equally ranked. Okay. So this is just in the top five. In the top five. Lack of social connection. What evidence is there that relationships and social connection correlates to dementia? It's a tough metric, isn't it? How does one measure that? We first got an inkling that social connectivity was good for health, good for the body, and good for the brain from the Blue Zones information that looked at people who lived long and had lower risk of dementia. These are individuals who ate a certain diet, which we can talk about, and lived in areas that had a lot of verticality, meaning they were going up and down steps. But I think importantly, what we learned from the Blue Zone data is that these are people who are connected to other people. They've insinuated themselves into community. And that is good for the brain. It's good for inflammation. It's good for metabolism. Now, you would ask, as I have asked, well, what is the mechanism here? Right? You want to understand that as a scientist, right? What's the mechanism? Because until I can see a mechanism, I'm not buying in. And what we know when we connect to people and when we develop a relationship, our bodies, our brains increase its output of a chemical called oxytocin. You've heard of oxytocin. It's called the love hormone. But it's more than that. This oxytocin is secreted when we're feeling trust for another individual, when we're feeling connected to another. We're feeling, I'm getting oxytocin from my time spent with you today, and I'm grateful. Thank you for that. And hopefully, I'm giving some back to you. And this oxytocin stimulates our good brain immune cells, these microglial cells, and helps keep them in their supportive, loving, nurturing role, as opposed to letting them drift to becoming what I call the evil twin. Increasing inflammation, increasing the destruction of our synapses. Let me set that up a little bit more, because I think we're going to rely on that moving forward. Our brain's microglial cells can exist in a supportive, loving, we call this the M2 configuration. We have long arms that are able to reach out and be effective and do good things. What is a microglial cell? A microglial cell is an immune cell that lives within your brain. It makes up about 10% of your brain cells. People say, well, brain cells, those are neurons. They used to say, well, if you drink a beer, you're losing 50,000 brain cells. Well, there are other cells in your brain aside from the neurons. There are immune cells. There are cells that are involved in the structure of the brain. So these wonderful, loving, nurturing microglial cells, M2, are going around. They're shoring up our synapses, the connection of one neuron to the next. They are making sure that our very valuable blood-brain barrier is working and keeping the bad things out. They are making sure that our neurons are functioning appropriately and are healthy. They're basically doing good things. But they can shift. They can become what I call the evil twin. And this is the evil twin, the M1 microglial cell. The reason I call it an evil twin is because they're genetically the same, like twins. But this is the cell that is destructive. These are the cells that destroy our synapses. And when our synapses are destroyed, we lose connection. We lose connection at a microscopic level, of course, because our synapses connections are lost. And we lose connection at a macroscopic level, whereby we no longer are able to connect to other people, to ourselves, to the world around us. That's what's going on. This shift from M2 to M1 is the fundamental upstream event in Alzheimer's disease. These cells are sensitive to our metabolism. These cells are sensitive to inflammation. When our blood sugar is elevated, it shifts them to being destructive. When there's inflammation in the body making its way to the brain from any source, it shifts the M2 supportive microglia to being destructive. Any metabolic issue, and most importantly, most importantly, the energetics of these cells is playing a fundamental role. This is a cell that gets its energy from active function of the mitochondria. It contains a host of mitochondria that are producing this currency of energy called ATP. This cell uses a totally different energy production facility called glycolysis. So, upstream of this shift are changes in the mitochondria. This is what's upstream. This is the fundamental here. Mitochondrial energy production is what dictates the shift between M2 and M1. Now, I fully recognize that there are countless transitional states between M2 and M1. It isn't a binary issue. It's an analog issue going from M2 supportive to M1. But again, upstream of all of this is the energetics. It's the mitochondrial function. And this is what is so sensitive to our metabolism, to insulin, to exercise on the positive side, to metformin on the medication side. We're damaging our mitochondria and that's causing it to malfunction and then change from the M1 to the evil twin. That's exactly right. There are two inputs. These M2 microglial cells and M1 for that matter, have receptors that are receiving information. Inflammatory chemicals from anywhere in the body, like a leaky gut, you've talked about that before on your program, creates increased inflammation in the body. Those chemicals can make their way to the brain. And there are receptors on the microglial cell that will shift it to becoming more destructive. So, is that the symptom? Like, is that the effect? The effect is the shift from M2 to M1. From the normal twin to the evil twin. Right. Okay. Because something goes wrong with my energy production system, i.e. my metabolism. Yes. But again, there are two inputs here. And it goes both ways. When these microglia shift to being more destructive, they downregulate or reduce the function of their mitochondria. Okay. So, it goes back upstream. It goes back upstream. Creates a feed-forward process. And importantly, very importantly, these cells are pro-inflammatory. Meaning that they are, once they become activated, they're secreting chemicals of inflammation throughout their environment, their local environment in the brain. And those chemicals come back and target the healthy microglial cells. and further shift them over to the dark side, like zombies. How do we know that these microglial cells are anything to do with Alzheimer's and dementia? We can actually see that on a special scan called a TSPO scan. And what we're looking at right now, this is the healthy control right here. And when we image on this PET scan for TSPO, in the Alzheimer's brain, you can see it is absolutely just lit up. And what is so incredibly empowering that takes this story to a very wide net that it throws is that we see positive TSPO imaging, meaning activation of the brain's immune cells across a wide variety of neurodegenerative issues. Here's the empowering part. These cells can shift back and become supportive again. And the influence that directs them back to being supportive is under our control. I've seen this kind of photo a few times. Is that really what an Alzheimer's brain looks like? It is. And you've seen a lot of brains. I've seen a lot of brains. How many brains do you think you've seen? Well, real brains, a hundred. That's real human brains in your hands? Brains in my hands, in my laboratory. That's right. And then scans? Thousands of scans. And have you seen an Alzheimer's brain? Oh, countless times. Well, I think this is an extreme example. But what we're seeing here is we call it atrophy. The valleys between the mountains are wider because the mountains have shrunken. And then the inside of the brain here, these are called the ventricles, they are filled with spinal fluid, are expanding to take up the empty space. Now, we always have to be careful. We only look at this image and don't look at the whole picture in an aggregate. This could be an indication of something called hydrocephalus, where fluid is increasing in the brain and makes these ventricles larger. It's just expanding because the brain is basically shrinking. OK, and the brain could be shrinking for any number of reasons. Yes, but keep in mind that your brain will shrink as you age. But the extent that you're seeing in these images is really extensive. So this is a characteristic macroscopically of an Alzheimer's brain. There are microscopic characterizations as well. And there are blood characterizations as well. My sister-in-law just had a baby. I vaguely remembered some stat that some neuroscientist on the show had told me, so I googled it. And it said that we have more brain connections at two years old than we do when we're an adult. And the brain basically, up until two, sort of has all these incredible connections, which probably explains why kids are so bloody good at learning stuff. And then the brain kind of loses the connections so it can reinforce the ones that matter. And in part, I was trying to figure out if this explains why kids have terrible twos. We are going to go to a really cool place right now. OK. And let me set it up first of all. So what you're describing is something called synaptic pruning. And it is where the brain becomes much more adept at what it's ultimately going to need to do. The rate of synapse or connection formation at age one year is about one million synapses being formed every second. So what does that mean? That means that in this brain, nerves are wiring up. They're wiring up, connecting to each other at the rate of a million connections per second in the one-year-old. Now, this idea of synaptic pruning, the refinement part is happening at about 20%. Means that while these connections are being made, about 20% of them of those connections or others are actually being destroyed. So the brain is refining itself. We're losing connections very rapidly. What is the mechanism whereby this synaptic pruning, this refinement takes place? The microglial cells. The microglial cells are the ones that are appropriately destroying or taking away these synapses, which is a normal activity. It's what we want to happen. There are situations when there's not enough synaptic pruning and there are consequences. Autism spectrum disorder being one of them. Fragile X syndrome is another. These are situations where the brain doesn't adequately synaptic prune, and they're called hyperconnection syndromes, where the brain is actually overconnected. Think about it, though. These same microglial cells that are involved in appropriate synaptic pruning when we are growing up, when we're children, are the same microglial cells that inappropriately digest away or destroy our synapses when we are older, and that can manifest as Alzheimer's disease. So there's a thinking now in neuroscience that Alzheimer's is the reactivation of a normal developmental event. How cool is that? That Alzheimer's, the loss of our synapses, which is what's characteristic of this disease, is a reactivation of what would have been normal when we were children. So the brain is pruning itself? Inappropriately. Why might it be doing that? That is the million-dollar question. It's doing that for a number of reasons. First, because of the activation of these microglial cells, which is not appropriate. I mean, to be fair, the biggest input that relates to the shift of the microglial cell from supportive to destructive is our chronological age. And I say that because that's what the data says, but I believe it should be our biological age. And the reason I say it could be our biological age is because it opens the door then for us to target our biological age, like exercise and diet. But that said, it is, you know, a consequence of aging and helps us understand why the number one risk factor for Alzheimer's is the number of birthdays we've had. We can't really change that, but we can change the other inputs, that's for sure. So what is number, is it four? Let's see. Non-restorative sleep. Non-restorative sleep. Non-restorative sleep. So sleep has, you know, a lot of things we talk about when we're talking about sleep, how we metricize our sleep. But it's non-restorative when we don't get enough and it's not high quality. How would you know? Hashtag add. I don't know. Well, you'd wear a wearable device, right? I mean, you could subject yourself to a formal polysomnogram, which means you're going into a lab and it's creepy, I've done it. And you wear all kinds of things, measuring your heart rate, your brain waves, your blood oxygenation, and somebody's watching you and recording you all night long when you're sleeping. I found it very creepy. But you have access to an Oura Ring, an Apple Watch, a Whoop, and you can measure your sleep and with pretty good reliability, get a sense as to its quality and its quantity. That's what restorative sleep is all about. Restorative sleep is so important. It allows us to consolidate our memories, our experiences in REM sleep. It allows activation, as you know, of the glymphatic system that allows us to take out the garbage, basically, which new research indicates happens when we move as well. Yet another part of the motion multi-tool. But sleep helps us reduce inflammation as well. It improves insulin functionality. These are key players that relate to brain function and brain health function preservation. So, you know, even one night's poor sleep dramatically changes the function of insulin, has a significant effect upon our blood sugar control, and really does set the stage for degeneration. Not only that, but it significantly affects our decision-making ability after just one night of poor sleep. I've heard about this glymphatic thing, and ever since I heard about the glymphatic drainage system, I have slept significantly better, but I've also become a little bit of an arsehole with my friends because I've told them about it many times. And the way that I kind of describe it, which I'm sure is being scientifically butchered when I say it, is that at nighttime, it's almost like the street cleaners come out in our brain. That is a perfect metaphor. And they come out and sweep up the streets. But they're only coming out if you're in deep sleep. Okay. And how long does it take to get into deep sleep? To get into it? Well, it's something that typically happens later on in your sleep cycle. So for me, it's around hour five and a half. Hour five and a half. Okay. So you have more deep sleep further into the night. That's right. And you sleep in these cycles, right? You do sleep in cycles. Okay. And the cycles are like 90-minute cycles or 60 to 90? Depends on the person, of course. But the fact is we cycle through various aspects as the orchestra is getting ready to play its music, each area gets to practice a little bit. And it all converges on ultimately salubrious sleep. Salubrious means it's an adjective. It means health providing. I used to really think of sleep as non-negotiable. But now I really do prioritize it. And I used to think in my earlier years that if I slept, I was being unproductive. And now I've kind of inverted that where I feel like I'm being unproductive if I haven't slept. You know, the other thing I think that fleshed this out a little bit is the idea that sleep dramatically affects your decision-making ability the next day. There are two areas of the brain that are fundamental for how we make our decisions. The prefrontal cortex, which is here is the frontal lobe. And the prefrontal cortex involves this part of the cortex. It takes up about one third of the entire cortex or outside of the brain. And another area for decision-making is deep within the temporal lobes. These are the temporal lobes. And it's shaped like an almond. It's called the amygdala. Some people call it the fear center. But these areas are, oh, here we go. Okay, so within the temporal lobe, which is here, the temporal lobe, inside of it is this almond-shaped organ, or rather, this almond-shaped area that's called the amygdala. And both of these areas play important roles in decision-making. The amygdala is an impulsive, self-centered area that makes rapid decisions. When I'm tired. Well, we'll get there. I'm leaning up to that. I just can relate to the description. I know you can. We all can. The prefrontal cortex, again, this area behind your forehead, is the adult in the room, basically. And what happens as we reach our teenage years is this prefrontal cortex sort of takes control. The adult in the room, hopefully, becomes more and more influential and exerts what we call top-down control over the amygdala. So we're less impulsive. We understand the consequences of our actions. We can plan for the future. We can do things that we can think about how it's going to affect not just me, but how it's going to affect you, how it's going to affect the planet. That's the prefrontal cortex. We depend highly upon this top-down control of the prefrontal cortex reigning in the amygdala. The problem is things can threaten that connection. And one of the things is inflammation. Inflammation can dramatically reduce the functionality, the ability of the adult in the room to be in charge. And if you are chronically inflamed, then your decision-making is suffering day in and day out. Let me take this a little bit further because it's an interesting concept here that food has a role in inflammation. We used to call it the standard American diet. I think kind of blaming America for the crappy diet of the world today. But it was the standard American diet then became the Western diet. And now it's pretty much the global diet that so aggressively features these ultra-processed foods that are pro-inflammatory. Now think about what I just said. The world is eating foods that are increasing inflammation. And inflammation separates the connection between the adult in the room and the impulsive, we're the best. I want it for me. That's it. It's going to be my way. Globally. This allows us to relate the change in global nutrition to some of the things we're seeing happening in our world today. And is this linked to card number five of your top five? Poor diet. I've got a few things here in terms of food. Let's see what I have. Some orange juice. Can of beer. Big tray of food because we're doing great. We want to do our best to avoid sugar. So how much, let's say this is 12 ounces. Why don't you tell me, Stephen, how much sugar, I'll put it in this glass here. Tell me when to stop. How much sugar is in here? Do you know the answer? Do you know what? I probably am closer to the answer now I've done this podcast. If you'd asked me when I was younger, I would have said one. Okay, one. Before I did this podcast, I would have thought, yeah, there's one sugar. No, there's a little bit more than that. You tell me when to stop. That's two. All right, here we go. All right. Now, three. Oh, three. Can I stop? I mean, four. Okay, here we go. Five. Six. Look at this. Seven. Eight. And if this were a can of soda, just two more. There are eight teaspoons of sugar in your wonderful glass of oranges. Oh, but what about the vitamin C? What about the fiber? It doesn't offset what this is doing to your body. Isn't it crazy that, you know, we wake up in the morning and then we drink eight teaspoons of sugar? And there was a narrative at one point that it was healthy for you. So like back in the Sunny D days, I thought if I drank orange juice. Yeah, Sunny D days, that's not necessarily juice. I mean, what is Sunny D? I thought it was like one of my five a day fruit and veg. Yeah, yeah. I thought it was healthy. Yeah, it's crazy. How old are you? 34? 34. Okay, you are the perfect population that needs to get this message. Because right now, you know, your metabolism is being formed. If we can get this message to your age group, it will have a huge outcome. And, you know, when you get to be my age, and you will get to be my age. You will wish you had known this. Why? Because you'll have set yourself up for a good brain. I gave a talk the other day in Vancouver, British Columbia, and I started off by asking everybody in the audience to close their eyes. I said, I want you to imagine when you open your eyes, you're 85 years of age. I said, now open your eyes. Now look around the room, and I'm going to draw a line right down the middle of the room. Half of you have now been diagnosed with dementia. Which half of the room are you going to be in? And what we're talking about right now allows you to be the arbiter, allows you to be the architect and the decision maker in terms of which half of that room are you going to be in. Now, you know, these issues can happen in your 60s. They can happen in your 70s, which is not to say that there are not some very promising things in development right now that if we have time, we can talk about. The future looks bright from that perspective. But again, you know, Benjamin Franklin said that an ounce of prevention is worth a pound of cure. And it makes all the sense in the world. I think this is probably one of the most important things that I did in terms of figuring out the truth about the foods that I loved. Why do you think this is so useful? For the reason that you just described. And that is, we're talking about a continuous glucose monitor. So I don't know if there's really one in here, but this is probably is. Yeah, it's personalized medicine. How do your food choices affect your blood sugar and your blood sugar affects your brain's destiny and your heart and your body for that matter? But this is how you will know. For me, it was cashews. I had no clue that cashews, nuts would raise my blood sugar the way they did. And I had the glucose monitor on and it lit up when I ate cashews. I had a tendency to overeat cashews. I thought they were safe. I was also very surprised at the degree of my blood sugar elevation with exercise, though it was transient, while I was beginning to exercise. That's a normal response. And I knew it. I kind of expected it. But when I finally saw it play out on my smartphone while I was running, it was impressive. But, you know, and I'm not saying you need to wear a CGM at all times, but I think it's extremely valuable and now available without a prescription. It was a big pushback in America about making CGMs, continuous glucose monitors, available to people without a prescription. You know, there were editorials written in journals saying, oh, my gosh, people are going to be neurotic. They shouldn't know this information. This is the purview of the doctor. And my argument was, well, if that's the case, if people shouldn't have their data, then we shouldn't allow people to buy a bathroom scale. I mean, that's a crazy, crazy thing to say, but the continuous, yeah, there is one in here. These little devices, they don't cost a lot of money. They're $20, $30. You can get them on Amazon and lots of other places. You stick it to your arm or you, this one, you prick your finger. But I think the best ones are the continuous ones where you stick to them, stick it to your arm. Yeah, then you can record your data and you can upload it to, uh, you know, It puts on your phone, directly to your phone. But you can do a lot with that data. And, you know, the main thing is, how do you know what your changes are doing unless you're able to measure them? I mean, if you want to lose weight, you can, you go in the bathroom scale, uh, frequently and see if it, if it's working, you want to get your blood sugar under control and you should, how would you know? I mean, to go to the doctor once a year and have a fasting blood sugar measurement, uh, I'm not going to say it's useless. I mean, it'll give you a clue, but it's, we can do so much better. A few things that I've discovered from looking at my own continuous glucose monitor that surprised me and things that I liked, but I am now, you know, I'm a little bit more conscious of. One of them is barbecue sauce, which I loved. It's 40 to 50% sugar, which shocked me. Balsamic glaze, 40 to 50% sugar. Had this commercial fat free French dressing, which was turned out to be 35% sugar. Why fat free? It said fat free on it. I thought it was healthy. Yeah. They do a lot of those sort of tricks on labels. That's really worrisome that you gravitated towards something that was fat free. I mean, you know, fat free cookies, fat free. And the other one's gluten free. I mean, there's crap on the gluten free aisle in the grocery store. Yeah. There's another thing I learned from this podcast is, um, I learned that roughly 1% of the world are truly like gluten intolerant. Yeah. 20% of us, including me, buy gluten free stuff. I actually used to go around saying I was gluten free, but having learned a few things on this podcast, I think I might actually be fructane intolerant. Well, I would say respectfully that the number of people who are gluten sensitive is probably more than that. Uh, there is an entity, a defined entity now called non-celiac gluten sensitivity. So, you know, the classic gluten issue is of course, celiac disease, which is an autoimmune condition. There are blood markers for it. There are, um, diagnoses made by looking at the small bowel with an endoscope. And the reality is that, uh, a lot more people have non-celiac gluten sensitivity than have a full on celiac disease. So I think it's, it's a big number. I was very taken by the work many years ago of a Dr. Marius Hadjivassilou, who's actually here in England at Sheffield Hospital as well, who described issues related to the brain that weren't related to celiac disease, but were related to gluten consumption. That got me launched in a big way to looking at gluten as it relates to the neurological consequences in some people of, of consumption of gluten. I remember one time as I was beginning to learn this and reading his work and he was describing how some people have headaches from consuming gluten. Who knew? And I had a patient with lifelong headaches, was on narcotics for her headaches. And I said, Hey, what the heck? Let's give it a shot. Let's go gluten free. See what happens. Come back in six weeks. She came back in six weeks and remarkably she was headache free. She was just over the top happy. She was headache free. She was off narcotics. So she went to, she had a gastroenterologist because she had gluten issues probably related to GI symptoms as well. And she said, I saw Dr. Perlmutter and he put me on a gluten free diet. Now my headaches are gone. And the doctor said to her that's preposterous. And to prove it to you, I'm going to do an endoscopy. I'm going to look at your small intestine and prove that you don't have celiac disease. He does an endoscopy. She doesn't have the hallmarks of celiac disease. And he says to her, go back on gluten. And she said, but, but, but, okay. She goes back on gluten. What happens? Headaches returned with a vengeance. And so she returned to the office, you know, bashfully and explained that story to me. What I read was that roughly 0.5% of the general population have non celiac gluten sensitivity. In terms of celiac disease, it affects roughly 1% of people. And then 0.1% of people have a wheat allergy. But when you ask people, the general population, if you survey them around being gluten free, up to 20% of adults report feeling much better on a gluten free diet. However, double blind placebo controlled food challenge trials show that only a fraction of self-diagnosed individuals react specifically to gluten. And generally, I think the, um, in this report, it says that the misunderstandings are a lot of people are allergic to fructans and fructans and gluten always appear at the same time. And I think this also explains why when you go to certain countries and have really good ingredients, I often citing Italy for like the pasta and things like that, where they don't have fructans, you don't have the same response, but also it could just be the total net carbohydrates that's causing you to feel shit. It could be the calorie reduction that's causing you to feel shit. Um, or many other things like, you know, so like placebo is one of the things they think it might be. I'll give you one other thing not mentioned. And that is that in America, um, though we don't have GMO wheat, GMO genetically modified crops are created such that glyphosate or Roundup can be sprayed to kill the weeds, but the plant is resistant and will survive. So they've not really done the GMO wheat thing yet. So therefore you would think there wouldn't be any glyphosate on the wheat. That's a wrong assumption. Glyphosate in America is sprayed on the wheat to desiccate it, to dry it out so they can get more wheat to market more quickly. And that might be another factor. Why? Because glyphosate is residual in these foods that we eat and glyphosate has a significant effect on the gut microbiome. Okay. So it could be the chemicals they're spraying on the food as well. That's right. And you know, we were told, uh, that the science was that the glyphosate only affects plants. And since you're a human, you shouldn't worry about it. Well, it affects plants and it affects bacteria. But again, we humans, why should we care? Well, we've got billions and billions of bacteria that live within us. We depend upon to be healthy. So here we are now consuming a chemical and it's in all of us that can affect the bacteria that live within us. And here's another bit of a stretch, but I think really fascinating. Mitochondria were originally bacteria and these, uh, mitochondria are very much still like bacteria. They have a circular DNA like bacteria and they are sensitive to glyphosate. Glyphosate is a mitochondrial toxin. So that's what we are consuming when we are consuming foods that have been sprayed with this herbicide. I, um, have a stat here that genuinely shocked me. It says that sales teams spend about 50% of their time on admin and manual CRM updates rather than selling. That is deadly for their bottom line. And that is part of the reason why a decade ago at my previous company, I switched to using pipe drive who are our sponsor. 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The company paying for it really, really, really have changed my business. They reached out to me about three weeks after I posted this particular Slack message to my team saying how obsessed I was with this product. I almost feel like I'm letting the cat out the bag by telling you guys about it, but I'm going to because I like them. Grokbot now sponsors this show and I've already invested in SpaceX, which is the company that owns Grokbot. Grokbot is an app on my phone, but it's also on my computer. And basically I have all of these different agents. You can think of them like team members that are working with me to do work right now. Like this graph here is a graph showing my usage and my team's usage. In four weeks, daily use rose from a hundred requests by one person to about 63,000 requests. It has taken hold. It's freed me up again to do the things that only I should be doing as a creative, as an entrepreneur, as an investor, which is the sort of higher level things around taste, creativity, judgment. You will get more done with Grokbot today, and you can get 50% off your first month by heading to x.ai slash DOAC. x.ai slash DOAC. What about these other things? What's your take on some of these other foods here? What I'm seeing here are wonderful foods. This looks like chocolate, onions, blackberries. I think this is supposed to be Himalayan tartary buckwheat. So these are foods that are rich in, we'll leave the alcohol here off the plate for just a moment. These are foods that are rich in what are called polyphenols. That's what gives them their colors. That's why the blackberry is black. It's why the onions are colored. We have blueberries and I guess raspberries as well. Do they contain sugar? Yes, they do, but they contain sugar in a way that it's released more slowly into the body. And again, coupled with the polyphenols, these are chemicals that are read by our gut bacteria. In other words, these are signaling our gut bacteria to do good things, to increase their antioxidant production, to create chemicals that are good for the entire body. So we're in a sense nurturing ourselves, but we're also nurturing our gut bacteria. This Himalayan tartary buckwheat is probably one of the richest sources of these polyphenols on the planet. What's a polyphenol and how does that help my brain? So again, a polyphenol is a targeting molecule that activates pathways to create antioxidants in the body. They activate a pathway called the NRF2 pathway and that increases our detoxification. It increases our production of antioxidants and it reduces inflammation. So all the good things. What I'm not seeing here is the number one source of polyphenols on the planet, at least in terms of consumption, that is coffee. So there's a vote for coffee, but there's very little polyphenols in these highly processed or what we call ultra-processed foods. In America, 60% of the calories that adults consume are derived from ultra-processed foods. They're processed such that these polyphenols are processed out of the foods and what we're getting are foods that by and large have added sweetener and have all kinds of issues related to even just the processing of them. I'll put up all the foods with strong levels of polyphenols on the screen now so everyone can see and I'll rank them by how much polyphenols they contain per 100 grams in order so you can see if you eat some of those. Extra virgin olive oil is one of them that I love. I mean a lot of because I had it contains lots of polyphenols. It does and you know it's really one of the keys we've now come to understand of the so-called Mediterranean diet. You know unfortunately now if you travel the Mediterranean you'll see that they're eating not the Mediterranean diet anymore and I like that you have chocolate on the plate by the way. way. Chocolate's good? Chocolate's good. Polyphenols. Dark chocolate, though, I'm guessing. Dark chocolate. So the number that you look for, you want to go north of 80. 80 percent. 80 percent, yes, because the higher that is, the lower, generally, is going to be the sugar content. I had the opportunity to make some chocolate in Peru, and I'll never forget the day. Wow. Tell me about it. I've said this story before, but they gave me this massive tub that was like this big, and he was like, we're going to make white chocolate first, and there was a big bowl of sugar like this, and he goes, pour in 60 percent, or it might have been 70 percent of the white sugar into the bowl, and I was like, what? He was like, pour 70 percent of the sugar, and I filled it up to here with sugar, and then there was this liquid we poured in, and I was like, wow, the white chocolate I eat is 70 percent sugar. I used to love white chocolate. Really? Absolutely. Why wouldn't you? Of course it is. Your brain is programmed to find sweet. That's your survival mechanism. It tells you that the food in nature is not poisonous, and it helps your body store fat for the winter. That's what our genetics do for us. That's through the activation of uric acid. And then milk chocolate was like half the size, it was about 50 percent, and then obviously dark chocolate is ... Right. And you know, you could go overboard on any of this, and certainly go overboard on the chocolate, but you know, the traditional diet that humans and protohumans consumed was one that was rich in fiber, which these foods are, rich in polyphenols, as demonstrated by the different colors that you see here, and had very good levels of fat, the castigated fat, the low-fat this, the low-fat that, that we were so programmed to gravitate towards. And you know, it gets, I think, to the broader theme. We'll do some alcohol in a moment. Broader theme of really the central issue here, in terms of what's making us sick, is this mismatch between what our genetics expect and what our genetics are seeing. In other words, our genome that we are gifted from all generations who've come before us, it's been refined generation after generation, our genome. Right now, we are experiencing this incredible mismatch between our evolution, meaning our genes, and our environment. I mean, I think that's a central issue related to modern ailments, that we are living a life that just doesn't send the appropriate signals to our genome. And I've been interested in this for, since I was 15. I've heard you say that people with type 2 diabetes have a 300 to 400 percent higher risk of Alzheimer's. Some studies have shown that. I think a number that we can absolutely support by more recent data is at least 75 to 85 percent increased risk. Wow. That's a big number. But what people may not be aware of is that even Parkinson's disease has increased in the type 2 diabetic by about 85 percent. Why would that be? Because when you look at the Parkinson's brain, and this data became evident in the late 1980s, you see activation of the microglial cells destroying that part of the brain called the substantia nigra, the black substance that makes dopamine. It's an activation of the microglial cells. The original work was fascinating. It was seen at Stanford University when suddenly people started showing up in the emergency room who developed Parkinson's in one day from shooting an IV designer drug that was contaminated with something called MPTP. And that was a mitochondrial toxin and it basically fried those cells in their brains that made dopamine and became a powerful research tool. I was at a conference last week where MPTP was used in laboratory mice to damage that part of the brain, create Parkinson's. And now they've developed an offset for that. They're giving the mice MPTP, but giving them something else called RNS-60 that was able to keep these mice from having that damage occur by activation of their microglial cells. So what is this? Well, it looks like a brain of a very long animal, like an alligator, but I think it's body fat, or I think it's fat. Not that pleasant. That's a pound of fat. And you don't want it here. You do not want it here. You don't want it on your belly? No, you don't want it on your belly. You don't want it around your organs. That's called visceral fat. So when you're 30 pounds overweight, over ideal body weight, that's 30 of these. Think about that. And that's common. I mean, it's so incredibly common. So this is an organ. It looks like just stuff we used to consider fat as being pretty inert, but as a resource for calories, we could tap into body fat if we needed calories, if we were starving. That's what its intent is. But it is creating chemicals that have functioned throughout the body, and by and large, these are chemicals that are damaging. They're pro-inflammatory chemicals called cytokines. We think of fat as just being the byproduct of its storage for the food we ate. Right. And we don't think of it as an organ, or that it's secreting or doing anything, but you're telling me there's chemicals coming off this. You bet there are. There are pro-inflammatory chemicals that are secreted by body fat, and they're not necessarily always bad. I mean, even the notion of inflammation always being bad, we challenge. We need inflammation. If we suddenly were able to reduce all the inflammation in your body immediately, you would perish. You need to have the inflammatory response. It's a life-saving activity. It's the excessive inflammation that gets us into trouble, or lower levels of inflammation over a longer period of time. You know, people talked about the cytokine storm in COVID. The cytokine storm in COVID was this sudden explosion of cytokines, inflammation throughout the body, damaging everything. And I think that we should consider things like Alzheimer's as not a cytokine storm, but as a cytokine drizzle. This is still an uptick of inflammation, though slight, but it happens over a long period of time. And we've got alcohol there as well on the table. What is your point of view of alcohol? I mean, they used to say that a little bit of alcohol is contributing. Well, there was a lot of data that showed that there was what we call a U-shaped curve in terms of dementia risk. What is a U-shaped curve? The very lowest level, i.e. no consumption of alcohol, there was a certain risk for dementia. With consumption, then the risk went down a bit. One glass of wine per day for women, two glasses of wine per day for men. But then the U comes back up. So we thought there was a sweet spot. And it turns out that reassessing that indicates that really any alcohol consumption is probably not good for the brain. And I think context is important. The argument was, well, red wine has polyphenols, vis-a-vis our previous discussion. You know, have a glass of red wine. We know that many people in the blue zones, for example, will drink some wine, as do I from time to time. But I find it threatening. Alcohol itself is a neurotoxin. And I think it's, let's get our polyphenols from what you just described, what you just showed from coffee and extra virgin olive oil. I think I'll tread lightly here at risk of becoming an internet meme, but how does alcohol harm the brain? It is directly toxic to neurons. And from my perspective, I think you've probably guessed through the lens through which I see brain science these days, it helps polarize our microglial cells away from being supportive. These things? Yep. The bad twin and the good twin? That's the good. That's the bad. The good twin and the bad twin? Yep. So it turns these into these? That's right. Are these all over the brain? They're all over the brain. And they move around. They move around? Yeah. And that was what was so exciting, that discovery that, you know, originally when they were first discovered, you would see these little cells interspersed between the neurons on a slide, you know, of a dead slide. And it was thought that they are small, they're called micro, and they're glia, meaning glue. It was thought that they glued the brain together, glued the brain cells together. Then technology evolved that allowed the observation in living tissue and noted that they're moving all around. They're swimming around looking for something to do, looking for something to repair, or conversely looking for something to destroy. And let's be clear, that is something over which we have control. So this good microglial cell is the M2? That's right. And then the bad one, the evil twin, is the M1? That's right. And alcohol flips the M2 into the M1? Alcohol, high blood sugar, inflammation, stress, sedentarity, lack of restorative sleep, all the things, even social isolation. And then when we have the M1, the evil twin, how does this then directly increase our probability of getting dementia? What's the mechanism? Those microglial cells create havoc in the brain. They destabilize our neurons. They destabilize the blood-brain barrier. So now we're letting things in that can make the problem even worse. Most fundamentally, they destroy synapses. So neuroscience is now looking at Alzheimer's as what a new term, a synaptopathy, a disease of the synapses, a loss of the synapses. And interestingly, I'll connect this segue for you. What is our answer for the question? Why do women have twice the risk of Alzheimer's in comparison to men? Is it because they live longer? Not really. What's going on in the female brain and what has recently been identified is this sudden drop of estrogen, particularly one estrogen called estradiol at menopause, causes the synapses to be labeled with signaling molecules called complement that is basically what is called an eat-me signal. There's a Dr. Beth Stevens at Harvard who's done some amazing work. What do you mean eat-me signals? Destroy-me. The synapse binds a chemical called complement, and complement triggers these microglia. And it says, for you, M1 microglia, come and destroy this synapse. I mean, she's demonstrated this. You can actually see it happening. It's pretty breathtaking. So the evil twin receives a signal to come and destroy parts of the brain. It's directed right to the synapse to destroy that synapse. Why would the brain be doing that? Well, good question. These cells are activated for the reasons we've talked about, these metabolic changes, the inflammation, the exposure to polluted air, breathing these PM2.5 particles from wildfire, all of the things that are known to activate this microglia cell and cause it to do that. But I think, more importantly, this explains why, when we age, we're at higher risk. It's really, I think, the most exciting and fundamental area of neuroscience research right now. So, how does it work? What's the research doing now? Well, all kinds of cool things are happening. There's a Dr. Li-Wei Tsai at MIT, and what has she done? She's demonstrated that the non-Alzheimer's brain has a beautiful background rhythm called gamma oscillation, a beautiful sinusoidal rhythm underlying the brain. The Alzheimer's brain has a disrupted rhythm, doesn't have that beautiful sinusoidal rhythm. And she stumbled upon the idea that brain rhythms change based upon frequencies of light that are put in front of a laboratory animal. And she found in the laboratory rodent that is geared to get Alzheimer's, that is one of the experimental tools that we use, that a light flashing at 40 times per second, 40 Hertz, how do we discover this stuff? Who knows? Restores the background gamma. And she said, well, that's interesting. I wonder what effect that's going to have in humans. And what she found was 40 Hertz light and 40 Hertz sound. She has a device that does this. Reverses gamma oscillation in the brain and reverts microglia cells back to being supportive. The evil twin cells. The evil twin back to being supportive. So she's actually done this technique in humans with Alzheimer's. So what does that mean for us, like for the average person? I have a 40 Hertz light generator on my desk. Oh, really? So you can go and buy? You bet I do. I mean, what does that do for you according to the science? According to the science, it is keeping my microglia doing what they need to do. She's actually done interventional trials in patients with existing Alzheimer's disease and her results are better than any drug that targets beta amyloid. The beta amyloid drugs are the FDA approved treatment for beta amyloid. And I make it very clear in my recent book that these drugs are, for the most part, ineffective and significantly dangerous. And my vote is that they are not to be used. 40 Hertz sensory stimulation, most famously pioneered through strobe lighting, flickering LEDs, or auditory clicks, has emerged as one of the most intriguing non-invasive approaches to recruiting microglia to clean up the brain. Wow. Can you imagine? I mean, that is a why that's fantastic hashtag WTF moment. It's breathtaking. You flash a light and you hear a sound and your microglia cells revert back to being on your side. So I keep a device right by my computer screen and it's passively shining that light into my eyes. Can I prove that it's doing anything wonderful for me? No. But am I a believer in the science? You bet I am. In animal models, just one hour of daily 40 Hertz light stimulation drove significant drops in plaque and tangle burden. Hmm. I mean, it goes on and on and on. I'll put some of that data on the screen. Closing off on this subject of alcohol, you said in your book on page 102 about this study where they found that microglia exposed to binge-level alcohol for 24 hours showed a 15% decrease in their ability to clean out beta-amyloid. Exactly. So, someone binged drinks for 24 hours and the microglia... Uglia drop in their ability by 15% as it relates to their ability to clean out that beta amyloid, which is the plaque associated with Alzheimer's. Yeah, it's the plaque associated. It's not the pivotal player, but it's important. I mean, we need to unpack a little bit more about this kind of misdirection of targeting beta amyloid. It's a player, there's no question, but I can't afford a 15% reduction. I mean, they're already downregulated towards M1 because of my age. So, you know, that's the vote against alcohol. And, you know, even one night of non-restorative sleep does the same thing, even more so. Interesting. One night of not getting a good night's sleep dramatically reduces your ability to clear beta amyloid. Can you recover from that? Because it's going to be a lot of people thinking, fuck, I had, you know, seven bad nights last week. Well, I'll tell you one thing. I mean, I know you travel a lot between LA, New York and London, and I don't know how you do it. Yeah, it's a lot. Yeah, and then fly back to Europe. But I do, this is why I think about all this stuff so much, because I'm like, what I do now at the age of 34 really is going to compound. Yep. It really, really is. And I'm going to figure out the mistakes I made. I mean, you know, in neurology school, they, again, they teach you, well, how do you, what do you do for the Alzheimer's patient once the problem has begun? And great. I'm glad people are looking at doing research, but it's setting, you know, sowing the seeds at your age is when it really begins. Let me take this one interesting study that was just published, and it just blows my mind. It was done looking at women who conceived in the year 1953, right where you and I are sitting right now here in England, and whether they had sugar rationing or they didn't have sugar rationing at that time. Sugar rationing from World War II was still in place in 1953. And it looked at a large cohort of women and followed them for a number of years, when people became, I guess, so it followed at least 50, 60, 70 years. And what it found was the women who had sugar rationing, who weren't able to get sugar while they were pregnant, and for 1,000 days, so through pregnancy, and then the first couple of years of life, the risk of that child, now that that child is 60, 70, 80 years old, developing Alzheimer's was reduced by 40% because mother didn't have access to sugar when she was pregnant. Wow. I mean, you know, people are always saying, well, Dr. Perlmutter, when should the Alzheimer's prevention program begin? You know, my standard response is, well, you know, we had to be paying attention to our 30s and 40s, but this really winds the clock back, doesn't it? What is the mechanism, though? I think there are multiple mechanisms. I think, you know, sugar in and of itself, raising blood sugar compromises brain function and even the genesis of the brain. But I think sugar also changes the milieu, the makeup of the gut bacteria. And the study actually didn't really comment on that, but I'm kind of sensitive to that. Higher levels of dietary sugar change the array, the function, the diversity of the bacteria and other organisms that live within the gut, like yeasts, for example. And the baby has the mom's gut microbiome? Actually, no. The baby does not really have much of a microbiome until such time as it's born. The method of birth is really fundamentally important for the development of that newborn's microbiome. In other words, cesarean section versus a vaginal delivery has a huge impact. When a baby passes through the birth canal, it's being anointed with a special concoction, a special array of organisms in the birth canal. Bacteria. Bacteria and viruses and yeasts, all kinds of organisms that get in the baby's eyes and its nose and its mouth. And I call it an anointment. It's a blessing, right? That this newborn gets his or her microbiome started, seeded at that moment, based on how it's birthed. Being born by cesarean section, that newborn will develop a microbiome based upon what was on the surgeon's glove at the time that baby was delivered. In fact, there is research being done, I think at NYU, many women are probably familiar with this, where if they're going to have a c-section, they take a swab of the vagina. Baby is born by c-section. Then that swab, which still contains those secretions, is placed in the baby's nose and its mouth to help restore that specific type of microbiome. What is the link between the microbiome and Alzheimer's and dementia? Well, I think the link is quite profound. And I think that we've got to understand that these organisms are making things that are good for the brain. They're making many types of short-chain fatty acids, for example, that are important for brain functionality. The microbiome, these organisms are secreting chemicals that are changing gene expression throughout our bodies and, of course, in the brain. I think the biggest issue when we have changes in these microbes that can be brought on, for example, by taking certain medications, oh, we happen to have them here. For example, proton pump inhibiting drugs. These are acid blocking drugs that people take because they think they need to lower their stomach acid based upon what they're seeing on television or elsewhere. And when you change the pH of the gut, you're changing the organisms that live there and their function. And when you do that, it can lead to increased leakiness or permeability of the gut lining that sets the stage for inflammation in the body. Those inflammatory chemicals can then make their way throughout the body and make their way into the brain. What do they do there? They polarize our supportive, loving M2 microglia to being destructive. Remember those TSPO images that show. TSPO? TSPO images that show. What's that? These are the images, the type of receptor, the TSPO receptor that is found on the M1 dangerous microglia that we can actually attach something to and then scan it, PET scan. Remember that that shows activations microglia. Explain it to me like I'm 14. So again, the TSPO is simply a way in living humans to demonstrate activation of their microglial cells. Which are these? Brain immune cells. These evil twin things. Yeah. Let me be a little kinder to our M1 microglia. There is a time and a place. When we have an acute injury, acute infection, we want to have that type of microglial cell to do its job, to destroy or to neutralize. When we have a head injury, for example, we activate our M1 microglia. But we have to be able to revert back to being the supportive microglial cell. The healthy one. When we keep our microglia in their destructive phenotype or configuration after the event has occurred, it leads to delays in improvement or even lack of improvement. Improvement in what? Good question. We know that these football players, for example, get this encephalopathy that when they bang their heads playing football too many times, they experience this progressive neurodegenerative condition that ultimately may kill them. But they're not banging their heads anymore. Why so? Because the microglial cells that appropriately responded don't revert back. I've already talked to new founders. They all carry the same belief that the biggest threat to their small business is having a bad product. It's not. The biggest threat they face is hiring the wrong person for their small team. Because bad hires put the handbrake on growth and rapidly infect company culture. And I get it. When you're starting out, you need A players to grow your company. 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How tragic was that, right? That's called pugilistic Parkinsonism. Pugilist means a boxer. But any bump to the head, you know, whether it's playing soccer, there was a study that came out last week that looked at F1 drivers as being at risk. The first F1 driver, I think, that developed the CTE, chronic traumatic encephalopathy, made the news just a week ago. I mean, you know, I guess you're banging your head around when you're in that car going that fast. But you got to protect your head. You really got to protect it against trauma. Your interesting study that shows that if you have head trauma, it's going to happen to all of us, maybe, that your risk of poor outcome is increased if you happen to have been a type 2 diabetic prior to the head trauma. Outcome of head trauma in type 2 diabetics is much worse. Why? Because that type 2 diabetes is shifting their microglia, preventing them from coming back and being helpful, being supportive. Shifting it to the evil twin. The evil twin. Exactly, right. Okay. So one of the big takeaways from this conversation is the decisions I make in my everyday life, what I put in my mouth, the exercise I do or don't do, the alcohol I do or don't drink is all going to impact this. Ultimately, that's the event. And upstream of that are the changes in the mitochondria, the energetics of what is going on here. That is playing a really important role, such that we are now looking at what can we do to enhance mitochondrial function? Because when mitochondrial function is restored, it helps keep our microglia in their supportive role. There are transplant techniques now for transplanting healthy mitochondria into human hearts and very soon into human brains. There are ways that we increase our mitochondria in terms of their numbers, in terms of their function, and in terms of our ability to get rid of defective mitochondria. Exercise does it. And metformin does it as well. This drug that is being used right here in England now is part of a treatment protocol for Alzheimer's. Metformin? Is that a supplement? It's a diabetes drug. It's not targeted beta amyloid. But the average person shouldn't be taking that, should they? That's a great question. I was at a conference dealing with a health span, aging. And it was a very small conference, about 20 people. The question was asked, how many of you are taking metformin? This was about eight years ago. And I think 80% of the scientists raised their hands. What you're not hearing from me right now is that we should all jump on board and take metformin. I prefer to exercise. But there is a big study called the TAME trial. Neil Barzilai at Albert Einstein is trying to get this started, but looking for funding. It's, I think, about a $70 million project. He can't get funding because metformin has gone off patent. So nobody's going to get the brass ring at the end of the day. But it's looking at the intervention of taking this drug, metformin, to see what effect it has on longevity and dementia, for that matter. For generally healthy, non-diabetic people, the current scientific consensus is not to take metformin, because there are some potential consequences. Why routine use in healthy adults is problematic. Number one, it blunts the benefits of exercise, apparently. Exercise is the single most validated, reproducible longevity intervention available. Multiple randomized control trials have demonstrated that metformin actively interferes with exercise's adaptations. Number two is risk of masking lifestyle fundamentals in long-form clinical data. Intensive lifestyle modification consistently outperforms metformin in reducing cardiovascular risk. Relying on a pill to simulate metabolic health cannot replicate the systemic vascular and psychological benefits of movement, sleep, and whole foods. And there's a bunch of other known side effects. Okay, so interesting. It's almost like replicating some of the effects of exercise. Yes, but as you wonderfully point out, look at the potential downsides. And I don't think mentioned in this article was the possibility of B12 deficiency that we see in people taking metformin. You know, Dr. Davis Sinclair, you've had him on the program, on the podcast. He recently put out a paper several months ago that looked at all these kind of cool interventions as it relates to these aging clocks that he talked about. And it ranked them. And metformin was described and rapamycin was described. What led the list, and he's a big NAD guy, as you know, what led the list was exercise in terms of these aging clocks. So, again, it gets back to this, what did our ancestors do? They were active. They didn't suffer from the sedentary, this idea that we're just sitting on our butts all day, flying here and there in front of the computers. To me, this has been the central focus of my understanding as to why we are sick. I wrote a paper about this when I was 15. Fifteen? Fifteen. I think you may even have a picture here of it in one of your photographs. Yeah, I wrote a paper about it, and it was published in the Miami News. I think that is no longer a newspaper in Miami. But I simply concluded that the world in which we live, we are not able to adapt quickly enough, genetically enough, to be able to survive in the world that has suddenly turned the tables on us. We are not able to, there it is, to the editor. So, what is this? This is when you were 15 years old. It is. Perhaps the human will change rapidly in the next centuries to adapt himself to beer cans, concrete, and shattering noise. Our generations are each contributing to the evolution of pollution-resistant lungs, but what about the people of today who are stuck with the outdated machinery? And that was written by this young man? You're about 17 years old there, but nearly. No, yeah, I guess. No, by 17 I had grown long hair. Okay. So, yeah, I was a pudgy little one, wasn't I? That was my bar mitzvah tie, too, as a matter of fact, yeah. Got a picture here of your son as well. Austin? Austin. You look very similar. You look more similar now than Austin. Well, I'm going to take that as a very big compliment. And more than that, I would say he's taught me a lot. He really has. In many ways, he's a mentor. And it's so wonderful watching him become a father. It's changed him in ways he cannot begin to appreciate, I think. Not yet, but he will. And our daughter, watching her blossom as an artist on the world stage, it's just breathtaking to watch the two of them. And again, when you have your children, I'm going to come back or I don't know what we'll do. I want to stay in touch because it's going to be a real game changer for you. Did it change a lot of how you think about the brain and the body and longevity and all the subjects we've talked about today, preserving oneself? Now that you've got a grandson. A granddaughter. I would say that I've doubled down. I have absolutely doubled down on everything that I do to be a grandfather. I mean, I became a grandfather kind of late in life. Here I am, 71, becoming a grandfather. Most of my friends who have grandchildren, their grandchildren are in their late teens already, so I've got to do the best I can. I don't want to be do as I say, not as I do. I don't want to be that person. I want to be as transparent as possible with my foibles and with the things that I think are important. I think fundamentally that what we're talking about today changes the ownership and the responsibility. Perhaps there's a criticism there, but my goal is to give agency. We offload our agency to the hope of the development of cures. James Cameron, the movie director famously said that hope is not a strategy. I want to provide a strategy to improve your odds of not experiencing this cognitive decline that is not just a devastating issue for you, but by that time, who knows, your wife, your children. It's an awful situation and the cost is profound. When I say that the drugs are ineffective in the context of hope that there will be effective drugs, I just saw a powerful study come out of Havana, Cuba, of all places, giving an intranasal treatment of something called erythropoietin, which is something made by the kidneys, that had effects in existing Alzheimer's patients that were mind-blowing. Patients who did decline in the placebo group by four points on a standard scale that we use improved four points, but didn't just stabilize, they got better. For those people that do have Alzheimer's or have a relative that has Alzheimer's now, I imagine there's a lot of them listening. I know that because when I have conversations on this subject matter, the comments typically fill with stories. People who have been diagnosed, loved ones have been diagnosed. A lot of the reasons why they click on these videos is because they've just received a diagnosis or they're living with it and they're in search of answers. What is there that we can offer to people who unfortunately are now dealing with dementia in their family or within their own brain? What do we offer and why should you believe me? Why should you believe some guy that's on your show? I'm swimming upstream here. I am indicating that what, at least in America, the FDA has approved is not the way to go. I'm indicating that when we look at a relatively small study from Harvard University, obviously well-respected by Tansy and Rudolf Tansy, Dean Ornish, where they took a group of 51 individuals who have Alzheimer's disease or mild cognitive impairment, going to have Alzheimer's, and they changed their lifestyle. They increased their exercise, they changed their diets, they reduced their stress, and they had them meditate for an hour a day. So these people didn't just slow their decline in the relatively short intervention of 20 weeks, but 70% of them either stabilized or improved. What did they do to their diet? They put them on a plant-forward, more Mediterranean-type diet. A diet rich in the things that we just looked at. Rich in polyphenols, rich in color. Welcome back to the table fat, but the good fats. And encouraged social interaction. These people improved. So that's what I say to this hypothetical. That's what I say to anyone who's listening. Pay close attention to your blood sugar. Get your weight down. And most importantly, this powerful tool that we looked at, a pair of running shoes. That is the salvation, in my opinion. What did the Cochrane analysis that was just published say about these Alzheimer's drugs? We've got to talk about it. Because I wrote in my last book the idea that I am not in favor of the use of these amyloid targeting drugs. And why would I say such a thing? I mean, after all, they are FDA approved. I said it because they are, for the most part, ineffective and they have a significant risk profile. So this Cochrane analysis looked at 20,342 individuals in 17 different studies, 18 months each study, and asked two simple questions. Do the drugs work in the Alzheimer's patient that target beta amyloid? And are they safe? Right? Those are risk and benefit, right? It found that the drugs basically have no meaningful effect in slowing the progression, much less leading to improvement. What about the ketogenic diet as a way to deal with the symptoms of dementia? Well, I think more than the symptoms. I think when you're talking about a ketogenic diet, you're targeting, as you well know, the mitochondria. Ketogenic diet, along with exercise, we're targeting mitochondrial function. And remember that that is the pivot point for determining supportive versus destructive microglia. And a bi-keto diet, for anyone that doesn't know, we basically mean a very low carb diet, less than maybe 50 grams of carbs per day. A keto diet or ketone supplementation, which you can get through various ketone shots, rescues roughly 10 to 18% of the brain's total energy supply, directly closing up to 80% of the fuel gap left by impaired glucose metabolism. Who knew? When you target mitochondria, it's a good thing for the brain. I mean, it's a metabolic issue. The brain requires glucose. And when we become insulin resistant, certain parts of the brain suffer. Not all of the brain cells require insulin, but some parts do. The hippocampus, the memory center, the hypothalamus that controls our metabolism, the prefrontal cortex, which allows us to make good decisions and helps direct our behavior, and finally, an area called the olfactory bulb, which is involved in smell. When you think about it, everything I just mentioned are issues in Alzheimer's. We become forgetful, our metabolism goes catawampus, we lose executive function, and we lose our sense of smell. So, you are so right to point that out, that this is an upstream energy deficiency. The inability of the brain to use energy, you can bypass that with the ketogenic diet, and also in Parkinson's. There's a researcher in New Zealand named Matthew Phillips who has published papers on each of those, and I wrote a book chapter with him on the use of the ketogenic diet in Parkinson's. It's hard to adhere to the ketogenic diet, though, isn't it? It is, and I'm not saying one needs to do that at all times. I think what you want to try to establish is flexibility, such that when you do decide you're going to fast for a day or two, or one meal and stick to the very low-carb and higher-fat regimen, that you're able to jump into ketosis relatively quickly, as opposed to having to adapt to a ketogenic state, which may take a couple of weeks. Dr. David, what is the most important thing we haven't talked about that we should have talked about as it relates to Alzheimer's, dementia, and generally just having a healthy brain for those that maybe aren't thinking so much about a disorder, but just want to be able to show up in their lives on a daily basis and be their best? I mean, I'm one of those people, because obviously, you know, I have conversations with doctors sometimes. Yeah, but who isn't one of those people? I mean, who could you speak to who would say, you know, I really am not so invested in having my brain perform? Everything that we have talked about today in terms of brain degeneration is equally valuable in terms of brain performance, so that was a wonderful segue. So if you want your brain to perform at its optimal level, these are the exact same keys to the kingdom. You've got some goodies in here. We've got a few other things in your toolbox here. We've touched on some of them. Are you a fan of supplements? I am. You are? I absolutely am. What particular supplements do you take? Well, I have a bit of the personalized medicine part of that answer is I have a little bit of a genetic quirk. It goes by the name of MTHFR, and what that means is I don't handle B vitamins as well as I should, and as such, it's a complicated story, but my homocysteine level was elevated. Homocysteine level, homocysteine itself is an amino acid that is a significant risk factor for heart disease and Alzheimer's. Okay. So because of my unique genetics, I have to take a different type of B vitamin called methylated B vitamins, so that's first and foremost for me. Vitamin B, methylated, yeah? Methylated for me and for probably about 25% of the global population. What else do you take? I take DHEA from fish oil. So is that omega-3? Omega-3, but we want to look at the DHEA content. So my fish oil that I take contains, I'm getting about 1,000 milligrams a day of DHEA. When we talk about people that are living with someone with Alzheimer's, we often hear from the family what it was like to essentially lose the person they loved. Yeah. What is it like for the person that has Alzheimer's? It's a great question. I think early on it's incredibly distressing. When you ask people what disease you fear most, overwhelmingly the answer is Alzheimer's. It's not cancer. It's not heart disease. It's not anything else. It's losing the ability, I think, to make your own decisions and self-care. Do they know that they're losing it? Early on, yes. Early on they do, and it gets to a point where they don't realize. And that's a blessing. I watched that happen in my dad. Really? He ultimately became unaware. When you lose these subtle cognitive functions early on, you know damn well something's going on. How long did that take? In his case? Yeah, between diagnosis to... His death? I should say from when his behavior changed to his passing. It took about five years. Five years. And is it the disease that ends up killing the person, or is it something else? It's the disease. It's the disease. Yeah, everything ultimately just shuts down. He did not, I don't believe, carry ApoE4. I don't know what his genetic profile looked like. I do not, and I don't know my mother, so I can't figure out whether my dad did carry the ApoE4 allele. And to be sure, there are 80 other genetic issues that relate to Alzheimer's risk. But again, genetics loads the gun. Lifestyle pulls the trigger. What were those five years like, in terms of how he changed? Well, you have to start at his baseline. He was a towering human, just in terms of his contribution and his compassion. And to be fair, to others more so than to family, call it out like it was, which is something I've worked through, which I think helps explain why I love him. I've been as driven as I have been throughout my life to get recognition that perhaps I could have gotten earlier in life. I'm not sure I planned on going to this topic in our conversation, but what the heck. But that said, when he was aware of it, he was one to deny and offload blame. I never said that, or you must have misplaced this, and became a bit accusatory of things that were happening. When he couldn't find things, he would accuse people of moving things around. And then as it progressed, his issues became less and less of an issue for him and more and more of an issue for all the rest of us. Was there a moment where he realized he had, his brain was changing? Yes. And so did he shift out of that accusatory state and start understanding that this was- No, I don't think he had the tools at that point. And by circumstance, the nursing home in which he lived, his apartment in the nursing home, was across the parking lot from my clinical neurology Alzheimer's practice, such that I could see his room from my examining room. And I'd be meeting in the examining room with families of patients. And I could see his room while the conversations are going on. And they'd say, doc, you have no idea what we're going through with mom or dad. And I would stop and I would say, let me hold you right there so we can relate as humans. That room that you see across the parking lot, that's where my father lives now and he's dying from this disease. So I get it. So now you know who your team player is. And gradually the decline meant that he didn't know who he was? Oh, beyond that, he was totally unable to function. That's the end game in Alzheimer's. It's a total lack of ability to engage any meaningful interaction with others or any meaningful activity. You're just in bed with a blank stare on your face. It's, and when you see your parent like that and think, sorry, and you think back to who he was and what he was, it's difficult. And I don't want people to go through that. I really don't. And if I'm a pain in the ass by saying the things that I say about, don't put your faith in the drugs and make these changes today because they're hard and I wish medicine would do these things, I'm not gonna apologize because that's what answers your very first question. What am I doing? I'm doing my best so people don't go through to have to experience what I'm feeling right now. And this was a long time ago and I'm a 71 year old man and I'm not over it. And I realized I'm not ever gonna be over it. And that's not a bad thing because it motivates me. It gives me the courage to go before your audience. I know that it is vast and to make these statements because if one person gets this message, then I've done my job. And my hope is that a lot of people get this message that we need to regain agency and not be persuaded to hope that there's a wonder drug out there. That's just inappropriate. It's wrong and it's absolutely cruel. And I object to it. Well, you're a dad yourself now and you have this wonderful son called Austin. I actually spoke to Austin and Austin wrote a little letter for you. Here you go. This is from your son, Austin. Okay. And the winner is you can read it. I will. Dad, for the entirety of my life, you've been an example of passion personified. Whether it was for your patients, your family, or the millions of people, you reach on podcasts like this one. You've always cared so much about helping others. You've always cared so much about helping others and empowering us with tools to make our lives better. I'm so proud to watch as you help people understand and improve their brain health. It matters. I see it in the messages I get from people telling me just how much you did for them and their families. I hear it at conferences when people tell me about the things you did for them decades ago. I'm honored to have you as my father. And most lately, I'm filled with the joy to see you become an exceptional grandfather. You are an incredible continuation of the work of your father. I can't wait to see you soon. Love from all of us across the pond, Austin. Well, Stephen, you really did it here, didn't you? You know, I'm thinking of my dad right now. And we go through our lives trying to do the right thing. And he set a very high bar. He really did. He really did. You know, the Dalai Lama said that if you want others to be happy, be compassionate. And if you wanna be happy, be compassionate. In many ways, these are tears of joy. I am so happy with how it's playing out because I'm in my lane. It feels really good to be in my lane and having identified what my skillset is and exploiting it to the ends of the earth. That's what it's all about. Probably a better answer to your opening question. I think that's enlightenment. I think enlightenment is identifying your skillset and using it to contribute. And there you go. And I guess I will continue. I'll continue as long as my brain holds up and I'm doing all the right things. So hoping that it does. As Austin said, you are a wonderful continuation of your father's work. At his eulogy, I sang, I think it's a Dan Fogelberg song, just a line from a Dan Fogelberg song. I think I got that right, attribution. And it was, my life has been a poor attempt to imitate the man. I'm just a living legacy to the leader of the band. And why not? Why not continue on the legacy and teach by example? Doctor means teacher. It doesn't mean healer. So that's what we do. That's what you do. All the things that go on on this podcast, it's all about teaching, whether it's about, should we take creatine or should we not take creatine? And what's our dosage and what's the research? Or what is the cause of aging? You've asked that question so many times. How do you define aging? It's teaching and it's, it marries curiosity with compassion. And that's a great marriage because curiosity gives you the tools to really be compassionate. And at least in medicine, it sure does. Amen. Everything we've talked about today comes back to this old fella, the brain. What are your closing words for people about their brain? What can we say to them to make sure that they walk away from this conversation and they do everything they can to protect this? And I'm gonna amplify that a bit from a personal perspective, what matters and from a global perspective. In a word, reconnect. We reconnect with others and reconnect with relationships. It will go a long way to improving our lives, improving our brain health and improving the planet. Austin, as you know, and I wrote a book called Brainwash. It's right there on top. And we define in this book something called disconnection syndrome at a microscopic level. And we talked about that, how the brain gets disconnected from its prefrontal cortex, our gift as humans. And at a macroscopic level, how disconnected we're becoming from each other. There's personal benefit. We talked about that through oxytocin, but we've gotta reconnect with each other. We gotta reconnect with the planet and we're all in this together. And that would be, I think, my most important message. Well, you certainly are one for a message. I mean, you've written so many incredible books here. Your most recent book called Brain Defenders is came out, I think, the day after my birthday, August 27th. I'll link it below. Brain Defenders, harness the power of your immune cells to protect your brain for life. And I know there's lots of my audience that are especially keen to avoid dementia and Alzheimer's because it runs in their family. And they've seen the horrific consequences of the disease. And this is a wonderful book to feel, to sort of take back a bit of agency as you described and feel like there is some control over something that feels so helpless. You bet. And you're a good man. You're a sweetheart. And I'm sure grateful to meet you and spend time with you today. I am too. It's wonderful what you've done, you know. The consequence of, I guess, your father is you and the millions and millions of people that you've reached and helped, giving them some information, turn the lights on in their life, which gives them that agency that we describe. And I think agency is most valued at times when we feel hopeless. And that's certainly what you've done for so many is give them both actions that they can take, but a sense of hope. And that's really a truly a wonderful thing. So thank you for doing that work, Dr. David. Thank you, Stephen. It's incredible. We do have a closing tradition where the last guest leaves a question for the next. Oh, wow. Not knowing who they're leaving it for. And the question left for you is. Hmm. Oh no. I usually don't let guests see this, so I'm going to break the tradition in this case. This is the question left for you. Oh my gosh. So it's from Mark Cuban. And we've answered the question. The question is, Mark, to answer your question, what makes you emotional? It's an excellent question, but I think we've answered your question. Dr. David, thank you. Thank you. Thank you. As a founder building a business when I was in my early twenties, I think I always had a deep sense of imposter syndrome because there was something that I wasn't good at. And that thing was finances. Finance and understanding your financial position as a small business is the great enabler of all of your dreams. 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