The Brain Doctor That Figured Out The Cause Of Dementia - Dr. David Perlmutter

Dr. David Perlmutter 0:00 In America, Alzheimer's is the, 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 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.

Steven Bartlett 0:31 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.

Dr. David Perlmutter 0:38 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.

Steven Bartlett 0:55 And I've got a few things here.

Dr. David Perlmutter 0:57 This is a big problem because if [beep] wow, that's scary. That's worrisome. So what we really understand now is genetics loads the gun, lifestyle pulls the trigger.

Steven Bartlett 1:06 You know, we often hear from the family what it was like to essentially lose the person they loved.

Dr. David Perlmutter 1:10 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, uh, difficult. And I don't want people to go through that.

Steven Bartlett 1:21 Well, you're a dad yourself now, and you have this wonderful son called Austin. Austin wrote a letter for you.

Dr. David Perlmutter 1:27 You know, uh, I'm thinking of my dad right now, and I'm doing my best so that people don't have to experience what I'm feeling right now.

Steven Bartlett 1:34 So what does that mean for us?

Dr. David Perlmutter 1:35 My hope is that a lot of people get this message that-

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Steven Bartlett 2:06 Dr. David Perlmutter, what is the mission you are on, and why does that mission personally matter to you?

Dr. David Perlmutter 2:13 Well, the mission I'm on is to let as many people know that the, the destiny of their brains, uh, 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, uh, 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.

Steven Bartlett 2:51 And who are you, Dr. David? What is your experience, and what is the, the education that you've had?

Dr. David Perlmutter 2:56 I went to medical school, got my MD, then became, uh, enrolled in a neurosurgery residency and became a board-certified neurologist.

Steven Bartlett 3:05 And why does this all matter so much to you personally?

Dr. David Perlmutter 3:08 Personally, I've been through this, uh, with... You just played that card, didn't you? I've been through this with my father, and, uh, and it's rough. It's rough for, in my country, the 7.6 million, uh, 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.

Steven Bartlett 3:45 What happened to your father? Got a wonderful portrait of him here as well. What a suave man.

Dr. David Perlmutter 3:51 So, uh, he was a brilliant brain surgeon, compassionate, skilled, wonderfully compassionate, uh, individual, and in his later years, he developed Alzheimer's. And you know, 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, uh, I missed it.

Steven Bartlett 4:17 How did you know he had Alzheimer's? What is the-- How do you diagnose it?

Dr. David Perlmutter 4:22 It's what I do. I mean, I, I diagnose Parkinson's in the airport when I'm coming to see you. I mean, I, that's what I do. It's my skill set. You know, just the, the type of memory issues that he was experiencing, losing things, walking into the room, forgetting where he was. It, it was very obvious. I mean, it, it was at least dementia, and generally, that means Alzheimer's.

Steven Bartlett 4:46 And just for my knowledge, what is the difference? 'Cause we-- I hear these words dementia, Alzheimer's, Parkinson's.

Dr. David Perlmutter 4:51 Well, most of dementia is Alzheimer's. You can be cognitively impaired because of, 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, uh, medications that they may be taking or, uh, other types of medical problems.

Steven Bartlett 5:15 So dementia is the sort of umbrella term.

Dr. David Perlmutter 5:17 Exactly. Dementia means, you know, this failure of cognitive function across multiple domains.

Steven Bartlett 5:22 Okay. So Alzheimer's disease, vascular dementia, Lewy body dementia, and-

Dr. David Perlmutter 5:27 Frontotemporal dementia.

Steven Bartlett 5:28 Okay. So everything underneath dementia, it's a general term for a group of symptoms.

Dr. David Perlmutter 5:33 That's right.

Steven Bartlett 5:33 Okay.

Dr. David Perlmutter 5:35 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, the huge aha in neuroscience right now, that disruption o- of the brain's immune system is a central feature across this incredible panorama of what makes a good brain go bad.

Steven Bartlett 6:03 What is it the current medical profession believes that you no longer believe?

Dr. David Perlmutter 6:09 I think that by and large, at least relating to Alzheimer's, and I th- I think we can flesh this out a- a- 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.

Steven Bartlett 6:38 And how many people are likely to get a form of dementia in their life? Like, how, how many people are gonna be affected by these neurodegenerative diseases that you have studied and worked on and can diagnose?

Dr. David Perlmutter 6:49 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, you know, high 40%, and that is, uh, it's very worrisome. In America, Alzheimer's is the, uh, 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, Steven, is hugely influential in terms of charting your brain's destiny.

Steven Bartlett 7:26 When does dementia start?

Dr. David Perlmutter 7:29 Typically, we discuss the idea that, you know, 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, it's like, um, 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 and happened in your country, uh, this past week. There is a new trial being started right here in England called the AD SMART trial, and the government has, uh, 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 Strattera. And this is a trial of about 1,000 people. It's gonna take 18 months to treat Alzheimer's patients. Why I bring it up? Now, as a matter of fact, your prime minister is very much in favor of it in that, um, his father died of dementia. Uh, that said, the reason I'm bringing 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.

Steven Bartlett 9:21 Explain this to me like I'm 16 years old. So beta amyloid are these, these brown sort of plaques they found on the brain with people that had Alzheimer's dementia. Um, so they thought that it was part of the cause of the dementia.

Dr. David Perlmutter 9:33 Right.

Steven Bartlett 9:34 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.

Dr. David Perlmutter 9:42 And you can have the plaques, a, a, a, a brain load of plaques and not be demented.

Steven Bartlett 9:48 So now the working hypothesis is that it's something else that's causing it and you're positing that it's largely based on metabolism.

Dr. David Perlmutter 9:55 Yes.

Steven Bartlett 9:56 And metabolism, as I understand it, is what we eat, what we do, like our activity in our life, our, our lifestyle decisions?

Dr. David Perlmutter 10:04 It's a great question, and I think that, you know, the strict definition is metabolism is the way that our cells, uh, create energy and make things. They make proteins, they make things. So really, uh, 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, let's say that in the context of where the research is going. For example, uh, 10 years ago, about a, a third of Alzheimer's research was really focused on what we talked about, this beta amyloid protein. That number's 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, uh, 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.

Steven Bartlett 11:47 I'm gonna set you a slightly tricky task.

Dr. David Perlmutter 11:50 Okay. [laughs]

Steven Bartlett 11:51 I, I've got some cards here, and I want you to write in order of, um, severity and consequence the top five things that you think from lifestyle perspective are contributing to Alzheimer's and dementia.

Dr. David Perlmutter 12:10 Okay.

Steven Bartlett 12:12 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?

Dr. David Perlmutter 12:21 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. 'Cause 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 were 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 all hugely important mechanisms in keeping the brain healthy.

Steven Bartlett 13:42 Are

Steven Bartlett 13:43 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?

Dr. David Perlmutter 13:54 It does.

Steven Bartlett 13:55 It does.

Dr. David Perlmutter 13:55 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 f- familiar with that?

Steven Bartlett 14:10 No.

Dr. David Perlmutter 14:10 Or can I walk through it?

Steven Bartlett 14:11 Yeah.

Dr. David Perlmutter 14:11 Okay, so we have the, the APOE alleles, and we can have a two, a three, or a four.

Steven Bartlett 14:18 Mm-hmm.

Dr. David Perlmutter 14:18 And you get two chances.

Steven Bartlett 14:20 What do you mean you get two chances?

Dr. David Perlmutter 14:21 Well, you carry two of them.

Steven Bartlett 14:22 Okay.

Dr. David Perlmutter 14:22 So you can have a two two, you can have a two three, a three three, a three four, a four four, and a two four. I guess those are all the permutations that, uh, can, 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 fivefold-

Steven Bartlett 14:54 Five- five hundred percent?

Dr. David Perlmutter 14:54 Five hundred percent, fivefold. And if you carry two, in other words, you're APOE4 four, the risk may be as high as twelvefold increase.

Steven Bartlett 15:05 One thousand two hundred percent. And you're saying Chris Hemsworth has-

Dr. David Perlmutter 15:08 And he's been very f- uh, public about it. But here's what is so valuable and, uh, on the list of things that you and I have not covered yet, and incredibly valuable. Why? 'Cause people are getting their genome sequenced now, you know, left, right, and center. Everybody knows. And a quarter of people who get their genome sequenced 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 shouldn't 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.

Dr. David Perlmutter 16:17 There's an interesting study that came out in the Journal of the American Medical Association in November of 2025. The, the author was named Marino. And what he did was looked at people from the, the Framingham Heart Study, and he divided the group of, uh, individuals, uh, there were about 1,000 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, uh, individuals, uh, 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, 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 APOE4, they had about a 67% reduced risk of becoming an Alzheimer's patient.

Steven Bartlett 17:33 If they exercised.

Dr. David Perlmutter 17:35 If they were in the, the group that exercised the most in comparison to the group that exercised the least. Again, the exercise is the multi-tool here. It is a, a huge and readily available tool for each and every one of us. That's what doctors should be, should be teaching patients. Not, "Well, it looks like you're cognitively impaired. We're gonna put you on an IV, a therapy, uh, every two weeks and hope for the best."

Steven Bartlett 18:00 What is the exercise doing physiologically? How is it helping the brain?

Dr. David Perlmutter 18:03 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, to work when you move. Uh, and as it turns out, you may not know this, but your muscles are an endocrine gland.

Steven Bartlett 18:17 What does that mean?

Dr. David Perlmutter 18:19 Great question, and, and I'm glad 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, uh, improve how insulin works so our blood sugar can remain, uh, 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 gonna certainly look at that in great detail. And exercise improves the blood going to your brain. That's got to be a good thing.

Steven Bartlett 19:32 Any particular type of exercise or all exercises?

Dr. David Perlmutter 19:35 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, 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, uh, aerobic activity 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, when you're my age, uh, 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.

Steven Bartlett 20:19 What's the next card? I think, I mean, we've got a toolbox here as well-

Dr. David Perlmutter 20:22 Yes

Steven Bartlett 20:22 ... which has got some things in it. [laughs]

Dr. David Perlmutter 20:24 The goodie box.

Steven Bartlett 20:26 You're aware that some of these are relevant to things you've just said, right?

Dr. David Perlmutter 20:28 They are. And I'm going to pull out a-

Steven Bartlett 20:30 Okay

Dr. David Perlmutter 20:30 ... something, a very, very high-tech device that I think people should get-

Steven Bartlett 20:36 Okay

Dr. David Perlmutter 20:36 ... that might be their most powerful tool that they can, um, save up for and get so that they can improve their brains. Ready?

Steven Bartlett 20:45 Yeah.

Dr. David Perlmutter 20:45 And here's one. [laughs]

Steven Bartlett 20:47 Mm-hmm.

Dr. David Perlmutter 20:48 And here is the other. Get moving. Movement moves all the needles. Movement moves everything.

Steven Bartlett 20:55 So if I use these-

Dr. David Perlmutter 20:57 You're not gonna use those. They're too small for you.

Steven Bartlett 20:58 [laughs] This is better than any drugs or medicine that I could possibly buy.

Dr. David Perlmutter 21:03 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, uh, used in the Alzheimer's trial right here in, in, uh, in England. Think about that, that metformin. Metformin does many things that exercise does. Exercise does more.

Steven Bartlett 21:23 Sold.

Dr. David Perlmutter 21:24 You're sold?

Steven Bartlett 21:24 I'm sold.

Dr. David Perlmutter 21:25 [laughs] Mission accomplished.

Dr. David Perlmutter 21:30 Lack of social connection. Who knew?

Steven Bartlett 21:33 Really? That's the third thing.

Dr. David Perlmutter 21:35 Who knew? From here on out, these are all equally ranked.

Steven Bartlett 21:38 Okay, so this is the t- in the top five.

Dr. David Perlmutter 21:40 In the top five.

Steven Bartlett 21:41 Lack of social connection. What evidence is there that relationships and social connection is-- correlates to dementia?

Dr. David Perlmutter 21:46 It's a tough metric, isn't it? How does one measure that? And we, we first got an inkling that social connectivity was good for health, good for the body, and good for the brain, uh, from the Blue Zones information that looked at, uh, people who lived long and had lower risk of dementia. And these are individuals who ate a certain diet, which we can talk about, and, uh, lived in, 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 s- is good for the brain. It's good for inflammation. It's good for metabolism. Now, you would, 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? 'Cause until I can see a mechanism, I'm not gonna-- I'm not buying in. And what we know when we connect to people and when we develop a relationship, our bodies, our brains, uh, increase the, uh, 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, uh, secreted when we're, uh, feeling trust for another individual, when we're feeling connected to another. We're feeling-- I'm getting oxytocin from p- my time spent with you today.

Steven Bartlett 23:14 Mm-hmm.

Dr. David Perlmutter 23:15 And I'm grateful. Thank you for that. And hopefully, I'm giving some back to you. And th-this oxytocin, um, 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, uh, the Evil Twin, increasing inflammation, increasing the destruction of our synapses.

Dr. David Perlmutter 23:42 Let me set that up a little bit more because I think we're gonna rely on that, uh, 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.

Steven Bartlett 24:01 What is a microglial cells?

Dr. David Perlmutter 24:03 So a microglial cell is an immune cell that lives within your brain.

Steven Bartlett 24:06 Okay.

Dr. David Perlmutter 24:06 Makes up about 10% of your brain cells. You know, when people say, "Well, brain cells, those are neurons," I mean, 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, you know, that are involved in, 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. Uh, 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, 'cause our synapses connections are lost, and we lose connection at a macroscopic level whereby we no longer are able to, uh, 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 mi- uh, mitochondria. It contains a host of mitochondria that are producing this currency of energy called, uh, ATP. This cell uses a totally different energy, uh, 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 M- 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, uh, to our metabolism, to insulin, to exercise on the positive side, to metformin on the medication side.

Steven Bartlett 27:12 We're damaging our mitochondria, and that's causing it to malfunction and then change from the M1 to the evil twin?

Dr. David Perlmutter 27:18 That's exactly right. There are two inputs. These, uh, 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.

Steven Bartlett 27:45 So is that the symptom? Like, is that the effect?

Dr. David Perlmutter 27:49 The effect is the shift from M2 to M1.

Steven Bartlett 27:53 From the normal twin to the evil twin.

Dr. David Perlmutter 27:54 Right.

Steven Bartlett 27:55 Okay, because something goes wrong with my energy production system, i.e. my metabolism.

Dr. David Perlmutter 28:00 Yes, but again, there, there are two inputs here. Uh, and it goes both ways. When these microglia shift to being more destructive, they down-regulate or reduce the function of their mitochondria.

Steven Bartlett 28:12 Okay, so it goes back upstream.

Dr. David Perlmutter 28:14 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.

Steven Bartlett 28:43 How do we know that these microglial cells are anything to do with Alzheimer's and dementia?

Dr. David Perlmutter 28:48 We can actually see that on a special scan called a TSPO scan. And what we're looking at right now, uh, this is the, uh, healthy control, uh, 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, uh, 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.

Steven Bartlett 29:35 I've seen this kind of photo a few times. Um, is that really what an Alzheimer's brain looks like?

Dr. David Perlmutter 29:42 It is.

Steven Bartlett 29:43 And you've seen a lot of brains.

Dr. David Perlmutter 29:44 I've seen a lot of brains.

Steven Bartlett 29:45 How many brains do you think you've seen?

Dr. David Perlmutter 29:47 Well, uh, real brains, um, 100. I-

Steven Bartlett 29:50 And, and now that's real human brains in your hands?

Dr. David Perlmutter 29:53 Brains in my hands, in my laboratory. That's right.

Steven Bartlett 29:56 And then scans?

Dr. David Perlmutter 29:57 Thousands of scans.

Steven Bartlett 29:58 And have you seen an Alzheimer's brain?

Dr. David Perlmutter 30:00 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, are wider because the mountains have, uh, 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, uh, and, and don't look at the, the whole picture in, in 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.

Steven Bartlett 30:39 Okay, so, and the brain could be shrinking for any number of reasons.

Dr. David Perlmutter 30:42 Yes, but, uh, you know, keep in mind that your brain will shrink as you age, but the extent that you're seeing in, in, in these images is really extensive. And so this, this is a characteristic macroscopically of an Alzheimer's brain. You know, you, you-- there are microscopic characterizations as well, and there are blood characterizations as well

Steven Bartlett 31:02 My sister-in-law just had a baby. I vaguely remembered some stat that some neuroscientist on this 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, uh, in part, I was trying to figure out if this explains why kids have terrible twos.

Dr. David Perlmutter 31:33 We are gonna go to a really cool place right now.

Steven Bartlett 31:36 Okay.

Dr. David Perlmutter 31:36 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, uh, you know, becomes much more adept at what it's ultimately going to need to do. The, the rate of synapse or connection formation at age one year is about one million synapses being formed every second.

Steven Bartlett 31:58 So what does that mean?

Dr. David Perlmutter 31:59 That means that in this brain, nerves are wiring up. They're wiring up, connecting to each other, uh, 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% that rate, 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 over-connected. Think about it, though. These same microglial cells that are involved in appropriate synaptic pruning when we are growing up, when our, when we're children, are the same microglial cells that inappropriately digest away or destroy our synapses, uh, when we are older, and that can manifest as Alzheimer's disease. So the, 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.

Steven Bartlett 33:56 So the brain is pruning itself.

Dr. David Perlmutter 33:58 Inappropriately.

Steven Bartlett 34:00 Why might it be doing that?

Dr. David Perlmutter 34:02 That is the million-dollar question. It's doing that, uh, for a number of reasons. Uh, first, because of the activation of these microglial cells, which is not appropriate. I mean, you know, to be fair, w- 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 it should-- I, I believe it should be our biological age. And the reason I say it's our biolo- 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, um, it is, you know, a consequence of aging and, uh, helps us understand why the number one risk factor for Alzheimer's is the number of birthdays we've had. Can't really change that, but we can change the other inputs, that's for sure.

Steven Bartlett 34:54 So what is number... Is it four?

Dr. David Perlmutter 34:57 Uh, let's see. Non-restorative sleep.

Steven Bartlett 35:00 Non-restorative sleep.

Dr. David Perlmutter 35:02 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?

Steven Bartlett 35:15 Whoop. Hashtag ad. [laughs] I don't know.

Dr. David Perlmutter 35:19 Well, you'd wear a, a wearable device, right? I mean, you could subject yourself to a formal, uh, 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, your blood oxygenation, and somebody's watching you and recording you all night long when you're sleeping. I found it very creepy.

Steven Bartlett 35:41 Hmm.

Dr. David Perlmutter 35:41 But you, 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 m- uh, motion multi-tool. But sleep helps us reduce, uh, inflammation as well. It improves insulin functionality. These are key players that relate to brain function and, uh, brain health function preservation. So, you know, uh, e- 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.

Steven Bartlett 36:49 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 asshole with my friends 'cause I, I've told them about it many times. And the way that I kind of describe it, which I'm sure is, um, being scientifically butchered when I say it, is that at nighttime, it's almost like the street cleaners come out in our brain.

Dr. David Perlmutter 37:07 That is a perfect metaphor.

Steven Bartlett 37:09 And they come out and sweep up the streets

Dr. David Perlmutter 37:11 But they're only coming out if you're in deep sleep.

Steven Bartlett 37:13 Okay. And how long it, does it take to get into deep sleep?

Dr. David Perlmutter 37:17 To get into it? Well, it's something that typically happens later on in your sleep cycle.

Steven Bartlett 37:20 Okay.

Dr. David Perlmutter 37:20 So for me, it's around hour five and a half.

Steven Bartlett 37:24 Hour five and a half. Okay. So you have more deep sleep further into the night?

Dr. David Perlmutter 37:28 That's right.

Steven Bartlett 37:29 And you sleep in these cycles, right? Like the-

Dr. David Perlmutter 37:30 You do sleep in cycles.

Steven Bartlett 37:31 Okay. And the cycles are like 90-minute cycles or 60 to 90?

Dr. David Perlmutter 37:36 Depends on peop-

Steven Bartlett 37:36 Okay

Dr. David Perlmutter 37:37 ... uh, on the person, of course. But, you know, the fact is we cycle through various aspects as, you know, as the orchestra is, is getting ready to play its music, each, each area gets to practice a little bit, and it all converges on, you know, ultimately salubrious, uh, sleep. Salubrious means, uh, it's an adjective. It means health providing.

Steven Bartlett 37:58 I used to really think of sleep as non-negotiable, but now I, you know, I really do prioritize it. And, um, you know, 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.

Dr. David Perlmutter 38:12 You know, the other thing I think that, uh, fleshes this out a little bit is the, 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, uh, prefrontal cortex, which is here, is the frontal lobe.

Steven Bartlett 38:32 Mm-hmm.

Dr. David Perlmutter 38:33 And the prefrontal cortex involves this part of the cortex. It's, uh, 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, uh, 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, uh, which is here, the temporal lobe, inside of it is this almond-shaped, uh, 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 v- rapid decisions.

Steven Bartlett 39:21 When I'm tired.

Dr. David Perlmutter 39:22 Well, we'll get there in a moment.

Steven Bartlett 39:23 [laughs] Yeah.

Dr. David Perlmutter 39:24 I'm leading up to that. We're gonna [laughs]

Steven Bartlett 39:25 I just, I just can relate to the description.

Dr. David Perlmutter 39:27 You bet. 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, uh, things that we can think about how it's going to affect not just me, but how it's gonna affect you, how it's gonna affect the planet. That's the prefrontal cortex. We depend highly upon this top-down control of the prefrontal cortex reining 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. Now, let me take this a little bit further because it's, it's an interesting, uh, 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 gonna 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, uh, in our world today.

Steven Bartlett 41:24 And is this linked to card number five of your top five?

Dr. David Perlmutter 41:28 Poor diet.

Steven Bartlett 41:29 I've got a few, uh, a few things here in terms of food. Let's see what I have. Some orange juice. Can of beer. Big tray of food.

Dr. David Perlmutter 41:43 We're close. We're doing great. We wanna do our best to avoid sugar. So how much-- Let's say this is 12 ounces. Why don't you tell me, Steven, 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?

Steven Bartlett 41:58 Do you know what? I probably am closer to the answer now I've done this podcast. I-- If you'd asked me when I was younger, I would've said one.

Dr. David Perlmutter 42:07 Okay, one.

Steven Bartlett 42:07 Before I did this podcast, I would've thought, yeah, there's one sugar.

Dr. David Perlmutter 42:10 No, just a little bit more than that. You tell me when to stop. That's two. All right, here we go. All right, now... Whoop. Three. Can I stop?

Steven Bartlett 42:21 I mean...

Dr. David Perlmutter 42:22 Four. Okay, here we go. Five. Six. Look at this. Seven. Eight. And if this were a, 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.

Steven Bartlett 42:50 Isn't it crazy that w- you know, we wake up in the morning, and then we, 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 th- I thought if I drank orange juice-

Dr. David Perlmutter 43:02 I th-- Yeah, Sunny D days, that's not necessarily juice. I mean, what is Sunny D?

Steven Bartlett 43:08 I thought it was, like, one of my five-a-day fruit and veg.

Dr. David Perlmutter 43:10 Yeah, yeah

Steven Bartlett 43:12 I feel healthier. Yeah. It's crazy

Dr. David Perlmutter 43:14 How old are you? 34?

Steven Bartlett 43:15 34.

Dr. David Perlmutter 43:16 34. Okay. You are the perfect population that needs to get this message, because right now, you know, your metabolism is, is being formed. If we can get this message to your age group, uh, it will have a huge, uh, outcome. And, you know, when you get to be my age, and you will get to be my age, you, you will wish you had, had known this.

Steven Bartlett 43:39 Why?

Dr. David Perlmutter 43:41 Because you'll s- have set yourself up for a good brain. I gave a talk the other day in, uh, 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 that you're 85 years of age." I said, "Now open your eyes. Now look around the room, and I'm gonna 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 gonna be in?" And what we're talking about right now allows you to be the arbiter, allows you to be the architect, uh, and, and the decision maker in terms of which half of that room are you gonna 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.

Steven Bartlett 44:44 I think this is probably one of the most important things that I-

Dr. David Perlmutter 44:47 Good for you

Steven Bartlett 44:47 ... did in terms of figuring out the truth about the foods that I loved. Why do you think this is, um, so useful and-

Dr. David Perlmutter 44:56 For, for the reason that you just described, and that is, we're talking about a continuous glucose monitor. So, uh, I don't know if there's really one in here, but this is-

Steven Bartlett 45:04 There probably is.

Dr. David Perlmutter 45:04 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, and, 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. Uh, 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, um, when I finally saw it play out on my smartphone while I was running, it w- it was impressive. But, you know, and I'm not saying you need to wear a, a CGM at all times, but I think it's, uh, it's extremely valuable and, and now available without a prescription. There was a big pushback, uh, 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 gonna 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. Same thing.

Steven Bartlett 46:24 I mean, that's a crazy, crazy thing to say, but the continuous glu- yeah, there is one in here.

Dr. David Perlmutter 46:30 Great.

Steven Bartlett 46:31 These little devices, um, they don't cost a lot of money. They're $20, $30. You can get them on Amazon and lots of other places. Um, you stick it to your arm, um, 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.

Dr. David Perlmutter 46:44 Yeah. Then you can record your data, and you can upload it to, uh, you know, your-

Steven Bartlett 46:48 It puts it on your phone.

Dr. David Perlmutter 46:49 Yep.

Steven Bartlett 46:49 Directly to your phone.

Dr. David Perlmutter 46:50 But you can do a lot with that data.

Steven Bartlett 46:52 Mm-hmm.

Dr. David Perlmutter 46:52 And, you know, the main thing is how do you know what your changes are doing u- unless you're able to measure them? I mean, if you wanna lose weight, you can, you go on the bathroom scale, uh, frequently and see if it, if it's working. You wanna 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 gonna say it's useless. I mean, it'll give you a clue, but it's, we can do so much better.

Steven Bartlett 47:21 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.

Dr. David Perlmutter 47:44 Why fat-free?

Steven Bartlett 47:45 It said fat-free on it. I thought it was healthy.

Dr. David Perlmutter 47:48 Yeah.

Steven Bartlett 47:48 They, they do a lot of those sort of tricks on labels.

Dr. David Perlmutter 47:51 That's really worrisome that, uh, 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.

Steven Bartlett 48:03 Yeah. That's another thing I learned from this podcast is, um, I learned that roughly 1% of the world are truly, like, gluten intolerant, yet 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.

Dr. David Perlmutter 48:21 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, 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 full-on, uh, 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. Marios Hadjivassiliou, who's actually here in England at, uh, Sheffield Hospital as well, who described, uh, issues related to the brain that weren't related to celiac disease but were related to gluten consumption. That got me launched, uh, in a big way to looking at gluten as it relates to the neurological consequences in some people of, of consumption of gluten. Uh, 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 bashfully and explained that story to me.

Steven Bartlett 50:42 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 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, 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. Or many other things. Like, you know, so like placebo is one of the things they think it might be.

Dr. David Perlmutter 51:49 I'll give you one other thing not mentioned, and that is that in America, 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.

Steven Bartlett 52:35 Okay, so it could be the chemicals they're spraying on the food as well.

Dr. David Perlmutter 52:37 That's right. And, you know, we were told 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 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.

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Steven Bartlett 55:48 What about these other things? What's your take on some of these other foods here?

Dr. David Perlmutter 55:51 What I'm, I'm seeing here are wonderful foods. This looks like chocolate on-, uh, onions, uh, blackberries. Uh, 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 rich that are, uh, foods that are rich in what are called polyphenols. That's what gives them their colors. Uh, that's why the blackberry is black. It's why the onions are colored. Uh, we have blueberries and I guess raspberries as well. You know, do they contain sugar? Yes, they do, but they contain sugar in a way that is released more slowly into the body. And again, coupled with the polyphenols, these are, 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, uh, 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 p- uh, polyphenols on the planet.

Steven Bartlett 56:55 What's a polyphenol and how does that help my brain?

Dr. David Perlmutter 56:57 So again, a polyphenol is a, a targeting molecule that, uh, activates pathways to create antioxidants in the body. They activate a, a, a, 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... Oh, there. Well, close enough.

Steven Bartlett 57:30 [laughs] Get some coffee in here.

Dr. David Perlmutter 57:32 Uh, so there's a vote for coffee, but there's very little polyphenols in these, uh, 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, uh, and have all kinds of issues, uh, related to their, even just the processing of them.

Steven Bartlett 58:03 I'll put up all the foods with strong levels of polyphenols on the screen now so everyone can see, um, 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. Um, extra virgin olive oil is one of them that I love and I eat a lot of because I heard it contains lots of polyphenols.

Dr. David Perlmutter 58:21 It does. Uh, and, you know, it's really one of the keys we've now come to understand of the so-called Mediterranean diet. Uh, you know, unfortunately, now if you travel the Mediterranean, you'll see that they're eating not the Mediterranean diet anymore. And I'm, I g- I like that you have chocolate on the plate, by the way.

Steven Bartlett 58:39 Chocolate's good.

Dr. David Perlmutter 58:40 Chocolate's good. Polyphenols.

Steven Bartlett 58:42 Dark chocolate though, I'm guessing.

Dr. David Perlmutter 58:43 Dark chocolate. So the number that you look for is you want to go north of 80.

Steven Bartlett 58:47 80% account.

Dr. David Perlmutter 58:48 80%, yes.

Steven Bartlett 58:49 Yeah.

Dr. David Perlmutter 58:49 Because the higher that is, the lower generally is gonna be the sugar content.

Steven Bartlett 58:54 I had the opportunity to make some chocolate in, uh, Peru, and it, I'll never forget the day.

Dr. David Perlmutter 58:59 Wow. Tell me about it.

Steven Bartlett 59:00 I've said this story before, but they gave me this, like, massive tub that was, like, this big, and he, and he was like, "We're gonna make white chocolate first." And there was a big bowl of sugar like this, and he goes, "Pour in 60%," or it might have been 70%, "of the white sugar into the, into the bowl." And I was like, "What?" He was like, "Pour 70% of the sugar." And I filled it up to here with sugar.

Dr. David Perlmutter 59:23 Wow.

Steven Bartlett 59:23 And then he was like, and then there was this liquid we poured in. And I was like, "Wow, the white chocolate I eat is 70% sugar." Milk chocolate was like-

Dr. David Perlmutter 59:30 I used to love white chocolate.

Steven Bartlett 59:31 Really? [laughs]

Dr. David Perlmutter 59:31 Absol- why wouldn't you?

Steven Bartlett 59:32 Yeah.

Dr. David Perlmutter 59:32 Why wouldn't you?

Steven Bartlett 59:33 I know. It's called curiosity.

Dr. David Perlmutter 59:34 Your brain is programmed to-

Steven Bartlett 59:34 Or sugar

Dr. David Perlmutter 59:35 ... to find sweet.

Steven Bartlett 59:36 Yeah.

Dr. David Perlmutter 59:36 That's your survival mechanism. It tells you that the food in nature is not poisonous, uh, and it helps your body store fat for, for the winter. I mean, it's, that's what our genetics do for us. That's through activation of uric acid.

Steven Bartlett 59:50 And then milk chocolate was, like, half the size. It was about 50%. And then obviously dark chocolate is-

Dr. David Perlmutter 59:55 Right.

Steven Bartlett 59:55 Well, yeah.

Dr. David Perlmutter 59:56 And, and you know, you could go overboard on any of this and certainly go overboard, uh, on the chocolate, but, you know, the traditional diet that humans and protohumans consumed was one that was rich in fiber, uh, which these foods are, rich in polyphenols as demonstrated by the different colors that you see here, and, uh, and had very good levels of fat. The, the castigated fat, the low fat this, the low fat that, that we were so programmed to gravitate towards. And, and, you know, it gets, I think, to the broader theme. We'll do, we'll do some alcohol in a moment. Broader theme of, of really the central issue here, uh, 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, uh, 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.

Steven Bartlett 1:01:14 I've heard you say that people with Type 2 diabetes have a 300% to 400% higher risk of Alzheimer's.

Dr. David Perlmutter 1:01:23 Some studies have shown that. I think a, a number that we can, uh, absolutely support by m- more recent data is at least 75% to 85% increased risk.

Steven Bartlett 1:01:34 Wow.

Dr. David Perlmutter 1:01:34 That's a big number. But what people may not be aware of is that even Parkinson's disease is increased in the Type 2 diabetic by about 85%. Why would that be? Because when you look at the, the Parkinson's brain- And this data became, uh, 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, was fascinating. It was, uh, 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, 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 create, uh, to damage that part of the brain, create Parkinson's, and now they've developed a, an offset for that. Th- they are giving the mice MPTP, but giving them something else called RNS-60, uh, that was able to keep these mice from having that damage occur by activation of their microglial cells.

Steven Bartlett 1:02:58 So what is this?

Dr. David Perlmutter 1:03:00 Well, it looks like a brain of a very long animal-

Steven Bartlett 1:03:02 Hmm

Dr. David Perlmutter 1:03:02 ... like an alligator, but I think it's body fat. Uh, 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.

Steven Bartlett 1:03:14 You don't want it on your belly?

Dr. David Perlmutter 1:03:15 No, you don't want it on your belly. You don't want it around your organs. That's called visceral fat. So, um, you know, 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, uh, body fat if we needed calories if we were starving. That's what its intent is. But it is creating chemicals that have function throughout the body, and by and large, these are chemicals that are damaging. They're pro-inflammatory chemicals called cytokines.

Steven Bartlett 1:03:54 We think of fl- fat as just being the byproduct of, it's storage for the food we ate.

Dr. David Perlmutter 1:03:58 Right.

Steven Bartlett 1:03:59 And it, 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.

Dr. David Perlmutter 1:04:04 You bet there are. There are pro-inflammatory chemicals that are secreted by, uh, 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, uh, all the inflammation in your body, uh, 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, uh, everything. And I, I, 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.

Steven Bartlett 1:05:03 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 completely-

Dr. David Perlmutter 1:05:11 Well, there was a lot of data that showed that, uh, 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 glass of wine per day for men. But then the U comes back up. So we thought there was a sweet spot. Uh, and it turns out that reassessing that indicates that really any alcohol consumption is probably not good for the brain. Even, a- 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, uh, many people in the blue zones, for example, will drink some wine, as do I from time to time, but, uh, I find it threatening. Alcohol itself is a neurotoxin, and I think w- it's, let's get our polyphenols from what you just described, what you just showed, from coffee and extra virgin olive oil.

Steven Bartlett 1:06:13 I think I'll tread lightly here at risk of becoming an internet meme, but, um, how does alcohol harm the brain?

Dr. David Perlmutter 1:06:21 It is directly toxic to neurons. And, uh, 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.

Steven Bartlett 1:06:36 These things.

Dr. David Perlmutter 1:06:37 Yep.

Steven Bartlett 1:06:37 The bad twin and the good twin.

Dr. David Perlmutter 1:06:38 That's the good. That's the bad.

Steven Bartlett 1:06:39 The good twin and the bad twin.

Dr. David Perlmutter 1:06:40 Yep.

Steven Bartlett 1:06:41 So it turns these into these.

Dr. David Perlmutter 1:06:42 That's right.

Steven Bartlett 1:06:44 Are these all over the brain?

Dr. David Perlmutter 1:06:45 They're all over the brain, and they move around.

Steven Bartlett 1:06:47 They move around?

Dr. David Perlmutter 1:06:49 Yeah. Uh, that was what was so exciting, that discovery that, you know, originally when, when they were first discovered, you would see these little cells interspersed between the neurons on a slide, you know, that, of a dead slide, and it was thought that, uh, they are small, they're called micro, and they're glia, meaning glue. It was thought that they glued the brain together, glu- glued the brain cells together. Then technology evolved that allowed the observation in living tissue and noted they're s- 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.

Steven Bartlett 1:07:33 So this good microglial cell is the M2.

Dr. David Perlmutter 1:07:38 That's right.

Steven Bartlett 1:07:39 And then the bad one, the evil twin, is the M1.

Dr. David Perlmutter 1:07:42 That's right.

Steven Bartlett 1:07:42 And alcohol flips the M2 into the M1.

Dr. David Perlmutter 1:07:47 Alcohol, high blood sugar, inflammation, stress, sedentarity, um, lack of restorative sleep. All the things, even social isolation

Steven Bartlett 1:07:59 And then when we have the M1, the evil twin,

Steven Bartlett 1:08:05 how does this then directly increase our probability of getting dementia? What's the mechanism?

Dr. David Perlmutter 1:08:11 Those microglia cells create, uh, 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 is-- a new term, a synaptopathy, a disease of the synapses, a loss of the synapses. And, you know, 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, uh, what, what is called an eat me signal. There's a Dr. Beth Stevens at Harvard who's done some amazing work.

Steven Bartlett 1:09:13 What do you mean eat me signals?

Dr. David Perlmutter 1:09:15 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, she's demonstrated this. You can actually see it happening. It's pretty breathtaking.

Steven Bartlett 1:09:34 So the evil twin is-- re- receives a signal to come and destroy parts of the brain?

Dr. David Perlmutter 1:09:37 Yep. It's directed right to the synapse to destroy that synapse.

Steven Bartlett 1:09:41 Why would the brain be doing that?

Dr. David Perlmutter 1:09:43 Well, uh, 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 PM two point five particles from wildfire, all of the things that are known to activate this, uh, microglia cell and cause it to do that. But I think more importantly, you know, this explains why, uh, when we age, we're at higher risk. It's really, I think, the most exciting and fundamental, uh, area of neuroscience research

Dr. David Perlmutter 1:10:15 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-Huei 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. It 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, uh, rodent that is geared to get Alzheimer's, that is one of the experimental tools that we use, that a light flashing at forty times per second, forty hertz. How, how do we f- 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 forty hertz light and forty hertz sound, she has a device that does this, restores this gamma oscillation in the brain and reverts microglia cells back to being supportive.

Steven Bartlett 1:11:31 The evil twin cells?

Dr. David Perlmutter 1:11:33 The evil twin back to being supportive. So she's actually done this technique in humans with Alzheimer's.

Steven Bartlett 1:11:40 So what does that mean for us, like for the average person?

Dr. David Perlmutter 1:11:43 I have a forty hertz light generator on my desk at home.

Steven Bartlett 1:11:46 Oh, really? So you can go and buy-

Dr. David Perlmutter 1:11:47 You bet I do. I mean-

Steven Bartlett 1:11:48 What, what does that do for you according to the science?

Dr. David Perlmutter 1:11:50 Oh, according to the science, it is r- keeping my microglia, uh, 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, uh, 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.

Steven Bartlett 1:12:21 Forty hertz sen- 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.

Dr. David Perlmutter 1:12:38 Can, can you imagine? I mean, that is a why that's fantastic, #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, I keep a device right by my, by my computer screen, and it's passively shining that light into my eyes. Uh, can I prove that it's doing anything wonderful for me? No. But am I a believer in the science? You bet I am.

Steven Bartlett 1:13:03 In animal models, just one hour of daily forty 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. Um, just closing off on this subject of, of alcohol, you said in your book on page one hundred and two about this study, uh, where they found that microglia exposed to binge level alcohol for twenty-four hours showed a fifteen percent decrease in their ability to clean out beta amyloid.

Dr. David Perlmutter 1:13:32 Exactly.

Steven Bartlett 1:13:34 So someone binge drinks for twenty-four hours, and the microglia drop in their ability by fifteen percent, um, as it relates to their ability to clean out that beta amyloid, which is the plaque associated with Alzheimer's.

Dr. David Perlmutter 1:13:49 Yeah. It's the plaque associated. It's not the pivotal player, but it's important. I mean, uh, 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, uh, a fifteen percent reduction. I mean, they're already down-regulated, uh, towards M1 because of my age.

Steven Bartlett 1:14:10 Mm-hmm.

Dr. David Perlmutter 1:14:11 So, you know, uh That's the vote against alcohol. And, you know, even one, uh, night of non-restorative sleep does the same thing even more so.

Steven Bartlett 1:14:20 Interesting.

Dr. David Perlmutter 1:14:21 One night of not getting a, a good night's sleep dramatically reduces your ability to clear beta amyloid.

Steven Bartlett 1:14:28 Can you recover from that? 'Cause there's gonna be a lot of people thinking, "Fuck, I had, you know, seven bad nights last week." Or, or does it compound?

Dr. David Perlmutter 1:14:33 Well, I'll tell you one thing. I mean, I know you travel a lot between LA, New York, and London.

Steven Bartlett 1:14:37 Oh, God, yes.

Dr. David Perlmutter 1:14:37 And I don't know how you do it.

Steven Bartlett 1:14:39 Yeah, it's a lot. Yeah, and then flying back to Europe. But I, I, I do-- This is why I think about all this stuff so much 'cause I'm like, "What I do now at the age of 34 really is gonna compound-

Dr. David Perlmutter 1:14:47 Yep, it really, really is

Steven Bartlett 1:14:48 ... and I'm gonna figure out the mistakes I made."

Dr. David Perlmutter 1:14:50 Yeah. 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 the re- at doing research, but it's setting, you know, sowing the seeds at your age is when it really begins.

Dr. David Perlmutter 1:15:10 L- Let me take this, th- there's one interesting study that was just published, and it just blows my mind. It was done, uh, 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. The sugar rationing from World War II was still, uh, in place in 1953. And it, it looked at a large cohort of, uh, women and followed them for a number of years, uh, to when people became, I guess, so it followed p- 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 one, uh, thousand days, so through pregnancy and then the f- first couple 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 in our 30s and 40s." Uh, but this really winds the clock back, doesn't it?

Steven Bartlett 1:16:33 What is the mechanism, though?

Dr. David Perlmutter 1:16:35 I think there are multiple mechanism. I think, you know, sugar in and of itself, raising blood sugar, uh, compromises brain function and even the, 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 kinda 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.

Steven Bartlett 1:17:04 And the baby has the mom's gut microbiome?

Dr. David Perlmutter 1:17:07 Uh, actually, no.

Steven Bartlett 1:17:09 Oh, really?

Dr. David Perlmutter 1:17:09 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, uh, 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 m- a, a special concoction, a special array of organisms in the birth canal.

Steven Bartlett 1:17:36 Bacteria.

Dr. David Perlmutter 1:17:37 Bacteria and viruses and yeasts, all kinds of organisms that get in the baby's eyes and its nose and its mouth, and it-- I call it an anointment. It's, it's a blessing, right? That this, uh, newborn gets his or her microbiome started, seeded at that moment based on how it's birthed, uh, 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 delivery, delivered. In fact, there is research, uh, being done, I think, at NYU, many women are probably familiar with this, where if they're gonna have a C-section, they take a swab of the birth-- 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, um, s- specific type of, of, uh, microbiome.

Steven Bartlett 1:18:33 What is the link between the microbiome and Alzheimer's and dementia?

Dr. David Perlmutter 1:18:37 Well, I think the link is, is, uh, is quite profound, and I think that we've got to understand that these organisms are making things that are good for the brain. Uh, they're making, uh, various types of short-chain fatty acids, for example, that are im- 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, uh, changes in these microbes that can be brought on, for example, by taking certain medications-- Oh, we sim-- 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-

Steven Bartlett 1:19:55 TS- TSPO?

Dr. David Perlmutter 1:19:56 TSPO images that show-

Steven Bartlett 1:19:57 What, what's that?

Dr. David Perlmutter 1:19:58 These are the images, the, the type of receptor, the TSPO receptor that i- is found on the M1 dangerous microglia that we can actually attach something to and then scan it, uh, PET scan. Remember that that shows activation as microglia.

Steven Bartlett 1:20:15 Explain this to me like I'm 14.

Dr. David Perlmutter 1:20:17 So again, the TSPO is simply a way in living humans to demonstrate activation of their microglial cells.

Steven Bartlett 1:20:24 Which are these evil-

Dr. David Perlmutter 1:20:26 Brain immune cells

Steven Bartlett 1:20:27 ... these evil twin things.

Dr. David Perlmutter 1:20:29 Yeah, let me, let me be a little kinder to our M1

Dr. David Perlmutter 1:20:32 microglia. There is a time and a place. When we have an acute injury, acute infection, we wanna 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, our M1 microglia. But we have to be able to revert back to being the supportive microglial cell.

Steven Bartlett 1:20:53 The, the healthy one.

Dr. David Perlmutter 1:20:54 Right. When we keep our microglia in their destructive, um, phenotype or configuration after the event has occurred, it leads to delays in improvement or even lack of improvement. Um-

Steven Bartlett 1:21:08 In improvement in what?

Dr. David Perlmutter 1:21:11 Good question. We know that these, uh, football players, for example, get this, uh, encephalopathy that when they bang their heads playing football too many times, they e-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.

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Steven Bartlett 1:23:38 Oh, so it's kind of like boxers who finish boxing, but then gradually you watch them deteriorate.

Dr. David Perlmutter 1:23:43 Exactly.

Steven Bartlett 1:23:43 You watch their speech slur, memory loss.

Dr. David Perlmutter 1:23:46 We're both right now thinking about Muhammad Ali.

Steven Bartlett 1:23:48 Mm.

Dr. David Perlmutter 1:23:48 How tragic was that, right? That's called pugilistic Parkinsonism. Pugilist means a boxer. But any bump to the head, uh, you know, whether it's, uh, playing soccer. Uh, there was a study that came, uh, out last week that looked at F1 drivers as being at risk. The first, uh, F1 driver, I think, that developed this CTE, chronic traumatic encephalopathy, made the news, uh, just a week ago. I mean, um, you know, I guess you're banging your head around when you're in, in that car going that fast. But you gotta protect your head. You really gotta protect it against trauma. Your-- Interesting study that shows that if you have head trauma, it's gonna happen, you know, 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? 'Cause that Type 2 diabetes is shifting their microglia, preventing them from coming back and being, uh, being helpful, being supportive.

Steven Bartlett 1:24:53 Shifting it to the evil twin.

Dr. David Perlmutter 1:24:54 The evil twin. Exactly right.

Steven Bartlett 1:24:56 Okay.

Steven Bartlett 1:24:57 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-

Dr. David Perlmutter 1:25:05 [laughs]

Steven Bartlett 1:25:06 ... um, is all gonna i-impact this.

Dr. David Perlmutter 1:25:10 Ultimately, that's, 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, you know, we are now looking at what can we do to enhance mitochondrial function? 'Cause when mitofun- mitochondrial function is restored, it helps keep our microglia in their supportive role. There are transplant, uh, techniques now for transplanting healthy mitochondria into human hearts and very soon into human brains. There are ways that we increase our, 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 pro- protocol for Alzheimer's.

Steven Bartlett 1:26:04 Metformin? Is that what-- A supplement you can take?

Dr. David Perlmutter 1:26:05 Metformin. It's, it's a diabetes drug. It's not targeting beta amyloid.

Steven Bartlett 1:26:09 But the average person shouldn't be taking that, should they?

Dr. David Perlmutter 1:26:12 That's a great question. I was at a, um, at a conference, uh- Dealing with, uh, a he- a health span, uh, aging. And it was very small c- uh, 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, a, a big study called the TAME trial. Nir Barzilai at Albert Einstein is trying to get this started, but looking for funding. It's, uh, I think about a $70 million project. He can't get funding because metformin has gone off patent, so nobody's gonna get the, the brass ring at the end of the day. But it's looking at the intervention of taking this drug, metformin, uh, to see what effect it has on longevity and, and dementia for that matter.

Steven Bartlett 1:27:09 For generally healthy non-diabetic people, the current scientific consensus is not t- to take metformin 'cause 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.

Dr. David Perlmutter 1:28:04 Yes, but as you wonderfully point out, look at the potential downsides. And I, I don't think mentioned in this, uh, article was the, uh, possibility of B12 deficiency that we see, uh, in people taking metformin. You know, um, Dr. David Sinclair, you've had him on the program, uh, on the podcast. He recently put out a paper several months ago that looked at all these kinda cool interventions as it relates to these aging clocks that he, he talked about, and, uh, it ranked them. And metformin was described and rapamycin was described. What led the list, and, you know, and he's a big NAD guy, as you know, uh, what led the list was exercise in terms of these age re- aging clocks. So again, it gets back to this, what did our ancestors do? They were active. They didn't suffer from, you know, the sedentarity, this idea that we're just sitting on our butts all day, flying here and there in front of the computers.

Dr. David Perlmutter 1:29:01 And, uh, you know, I, I-- to me, this has been the, the central focus of my understanding as to why we are sick. I wrote a paper about this when I was 15, and-

Steven Bartlett 1:29:13 15?

Dr. David Perlmutter 1:29:14 15. I think y- you may even have a, a... Do you have a picture here of it, uh, in, in one of your photographs? Uh, yeah, I wrote a paper, uh, about it, and it was published in the Miami News. I think that is no longer, uh, a newspaper in Miami. But I, I ha- I, I simply concluded that the world in which we live, we are not able to adapt, uh, quickly enough, genetically enough to be able to survive in the world that has suddenly, you know, turned the tables on us, that we are not able to, uh, there it is, to the editor. Yeah.

Steven Bartlett 1:29:47 So what is, what is this? This is when you were 15 years old.

Dr. David Perlmutter 1:29:50 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?"

Steven Bartlett 1:30:09 And that was written by this young man. You're about 17 years old there, but nearly.

Dr. David Perlmutter 1:30:14 No, uh, yeah, I guess. Uh, pr- I-- no, by 17, I had grown long hair.

Steven Bartlett 1:30:18 Oh, okay.

Dr. David Perlmutter 1:30:18 So yeah, uh, I was a pudgy little one, wasn't I?

Steven Bartlett 1:30:21 [chuckles]

Dr. David Perlmutter 1:30:22 That was my bar mitzvah tie too, as a matter of fact. Yeah.

Steven Bartlett 1:30:25 Got a picture here of your son as well. Austin?

Dr. David Perlmutter 1:30:29 Austin.

Steven Bartlett 1:30:31 You look very similar. You look more similar now than Austin does.

Dr. David Perlmutter 1:30:33 Well, I'm gonna take that as a very big compliment.

Steven Bartlett 1:30:35 Yeah. [chuckles]

Dr. David Perlmutter 1:30:35 Compliment. And, uh, more than that, I would say, uh, uh, he's taught me a lot. He really has. Uh, in many ways, he's a mentor. And it, it's so wonderful watching him become a father.

Steven Bartlett 1:30:50 Mm.

Dr. David Perlmutter 1:30:50 Uh, it has, it's changed him in ways he, you know, he cannot, uh, begin to, to, uh, appreciate, I think. Not yet, but he will. And our daughter, um, watching her blossom as a, a, an artist on the world stage, it's just breathtaking to watch the two of them. And again, when, when you have your children, I'm, I'm gonna come back or I don't know what we'll do. I wanna stay in touch 'cause that's a, it's gonna be a, a real game changer for you.

Steven Bartlett 1:31:16 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, you've got a grandson?

Dr. David Perlmutter 1:31:26 Um, a granddaughter.

Steven Bartlett 1:31:27 Granddaughter.

Dr. David Perlmutter 1:31:27 I would say that, uh, I've doubled down. Uh, I, I have absolutely doubled down on everything that I do, uh, to, to be a grandfather. I mean, I became a grandfather kind of late in life. You know, here I am, 71, becoming a grandfather. Most of, you know, my friends who have grandchildren, you know, their, their grandchildren are, you know, in, in their late teens already, so I gotta do the best I can. And I think, you know, I don't wanna be do as I say, not as I do. I don't wanna be that person. I wanna be as transparent as possible with my foibles and, you know, with the things that I, I'm, I think are important. You know, I think fundamentally that what we're talking about today changes the ownership and the responsibility, and perhaps there's a criticism there, but my, my goal is to give agency. You know, we offload our agency to the hope of the development of cures, right? And, and 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, you know, the, a devastating issue for you, but by that time, who knows? Your wife, your children. And, uh, it's an awful situation, and the cost is profound. So 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. I mean, patients who would have declined, who did decline in the placebo group by four points on a standard scale that we use, improved four points. So, but didn't just stabilize. They, they got better.

Steven Bartlett 1:33:27 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.

Dr. David Perlmutter 1:33:34 Yeah.

Steven Bartlett 1:33:34 I, 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 who've 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, what is there that we can offer to people who unfortunately are now dealing with dementia in their family or within their own brain?

Dr. David Perlmutter 1:33:57 Well, what, what do we offer? And why should you believe me, right? Why should you believe some guy that's on your show that is, you know, 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 Tanzi and, uh, Rudolph Tanzi, Dean Ornish, where they took a group of fifty-one 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 twenty weeks, but 70% of them either stabilized or improved.

Steven Bartlett 1:34:52 What did they do to their diet?

Dr. David Perlmutter 1:34:54 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, that 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. 'Cause 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 twenty thousand three hundred and forty-two individuals in seventeen different studies, eighteen 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.

Steven Bartlett 1:36:28 What about the ketogenic diet as a way to deal with the symptoms of dementia?

Dr. David Perlmutter 1:36:33 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 a, the pivot point for determining supportive versus destructive microglia.

Steven Bartlett 1:36:52 And a keto diet, for anyone that doesn't know, we basically mean a very low-carb diet, less than maybe fifty grams of carbs per day.

Dr. David Perlmutter 1:36:58 Significantly, with the addition of more fat to the diet. Good fat, the extra virgin olive oil, the nuts and seeds.

Steven Bartlett 1:37:06 In clinical trials on mild cognitive impairment and early Alzheimer's, a keto diet or ketone supplementation, which you can get through various ketone shots, rescues roughly ten to eighteen percent of the brain's total energy supply, directly closing up to eighty percent of the fuel gap left by impaired glucose metabolism.

Dr. David Perlmutter 1:37:25 Mm-hmm.

Steven Bartlett 1:37:25 This energetic boost translates to up to fifteen percent improvement in standard memory and test scores, alongside a twenty, up to twenty percent gain in daily functioning, helping patients manage basic self-care and everyday tasks with greater independent, independence, sorry.

Dr. David Perlmutter 1:37:41 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, are issues in Alzheimer's. We become forgetful, our metabolism goes catawampus, we lose executive function, and we lose our sense of smell. So y- 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 keno- uh, ketogenic diet. And also in Parkinson's, there is 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, in Parkinson's.

Steven Bartlett 1:38:54 It's hard to adhere to the ketogenic diet though, isn't it? The system's looking-

Dr. David Perlmutter 1:38:56 It is, and I'm not saying one needs to do that at all times. I think what you wanna try to, to establish is flexibility, such that when you do decide you're gonna fast for a day or two or one meal and, and stick to the very low carb and higher fat regimen, that you're able to jump into ketosis rou- relatively quickly as opposed to having to adapt to a ketogenic state which may take, you know, a couple of weeks.

Steven Bartlett 1:39:22 Dr. David, what is the, 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 wanna 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 and-

Dr. David Perlmutter 1:39:44 Yeah, but who isn't one of those people?

Steven Bartlett 1:39:45 Hmm.

Dr. David Perlmutter 1:39:46 I mean-

Steven Bartlett 1:39:46 True

Dr. David Perlmutter 1:39:46 ... who could you speak to, uh, who would say, "You know, I really am not so invested in, 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 t- to perform at its optimal level, these are the exact same keys to the kingdom.

Steven Bartlett 1:40:13 We've got a few other things.

Dr. David Perlmutter 1:40:14 You've got some goodies in here.

Steven Bartlett 1:40:15 There's other things in your toolbox here. We've touched on some of them. Um, are you a fan of supplements?

Dr. David Perlmutter 1:40:24 I am.

Steven Bartlett 1:40:24 You are?

Dr. David Perlmutter 1:40:25 I absolutely am.

Steven Bartlett 1:40:26 What particular supplements do you take?

Dr. David Perlmutter 1:40:28 Well, I have a bit of a-- First, the personalized medicine part of that answer is I have a little bit of a genetic quirk.

Steven Bartlett 1:40:34 Mm-hmm.

Dr. David Perlmutter 1:40:35 Uh, 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, uh, homocysteine itself is an amino acid that is a significant risk factor for heart disease and Alzheimer's.

Steven Bartlett 1:40:57 Okay.

Dr. David Perlmutter 1:40:58 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.

Steven Bartlett 1:41:05 Vitamin B, methylated, yeah.

Dr. David Perlmutter 1:41:07 Methylated for me, and for probably about twenty-five percent of the global population.

Steven Bartlett 1:41:13 What else do you take?

Dr. David Perlmutter 1:41:14 I take DHA, uh, from fish oil.

Steven Bartlett 1:41:17 So that's, is that omega-3?

Dr. David Perlmutter 1:41:18 Omega-3, but we wanna look at the DHA content. So my fish oil that I take, uh, contains, uh, I'm getting about a thousand milligrams a day of, uh, DHA.

Steven Bartlett 1:41:29 When w- we talk about people that are living with someone with Alzheimer's, w- we know, we often hear from the family what it was like to essentially lose the person they loved.

Dr. David Perlmutter 1:41:39 Yep.

Steven Bartlett 1:41:39 What is it like for the person that has Alzheimer's?

Dr. David Perlmutter 1:41:42 It's a great question. I think early on it's incredibly distressing. And 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, uh, to make your own decisions and self-care.

Steven Bartlett 1:42:02 Do they know that they're losing it?

Dr. David Perlmutter 1:42:04 Early on, yes.

Steven Bartlett 1:42:05 Early on they do, and it gets to a point where they don't realize.

Dr. David Perlmutter 1:42:09 And that's a blessing. I watched that happen to my dad.

Steven Bartlett 1:42:12 Really?

Dr. David Perlmutter 1:42:12 He was, you know, ultimately became unaware. You know, uh, when you lose these subtle cognitive functions early on, you know damn well something's going on.

Steven Bartlett 1:42:23 How long did that take?

Dr. David Perlmutter 1:42:24 In his case?

Steven Bartlett 1:42:25 Yeah, between diagnosis to-

Dr. David Perlmutter 1:42:27 His death?

Steven Bartlett 1:42:28 I should say from when you know, when his behavior changed to his passing.

Dr. David Perlmutter 1:42:33 Took about five years.

Steven Bartlett 1:42:34 Five years. And is it the disease that ends up killing the person or is it something else?

Dr. David Perlmutter 1:42:41 It's the disease.

Steven Bartlett 1:42:42 It's the disease?

Dr. David Perlmutter 1:42:43 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 what, whether my dad did carry the APOE4 allele. And to be sure, there are eighty other genetic issues that relate to Alzheimer's risk. But again, genetics, uh, loads the gun. Lifestyle, lifestyle pulls the trigger.

Steven Bartlett 1:43:10 What were those five years like in terms of how he changed?

Dr. David Perlmutter 1:43:15 [sighs] Well, you have to start at his baseline. He was a, a towering human, uh, just in terms of, you know, 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, I've worked through, which I think helps explain why I've been as driven as I have been throughout my life to, um, get recognition that perhaps I could have gotten earlier in life. I'm not sure I planned on going to this part, uh, this topic in our conversation, but what, what the heck? But that said, um, when he was aware of it, uh, his, uh, he was, uh, one to deny, uh, and off, offload bla- uh, blame. "I never said that," or, "You must have misplaced this," or... And became a bit accusatory of things that were happening. When he couldn't find things, he would accuse people of, of moving things around. And then as, um, as it progressed, you know, his, uh, issues became less and less of an issue for him and more and more, uh, of an issue for all the rest of us.

Steven Bartlett 1:44:26 Was there a moment where he realized he had- His brain was changing?

Dr. David Perlmutter 1:44:31 Yes.

Steven Bartlett 1:44:32 And so did he shift out of that accusatory state and start understanding that this was-

Dr. David Perlmutter 1:44:36 No, I don't think he had the tools at that point. And, and, um, by circumstance, the nursing home in which he lived, his apartment in the nursing home, was across the, uh, 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, um, 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 just 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."

Steven Bartlett 1:45:32 And then gra- gradually the decline meant that he d- didn't know who he was?

Dr. David Perlmutter 1:45:37 Oh, beyond that. I mean, he didn't-- You know, he was totally unable to function. That's the end, end game in, in Alzheimer's. It's, uh, 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, it's, uh-- And when you see your parent like that and think-- Sorry. And you think back, uh, to, uh, to who he was and what he was, it's, uh, 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 'cause they're hard, and I wish medicine would do these things," I'm not gonna apologize 'cause that's what answers your very first question, what am I doing? And I'm doing my best so that people don't go through-- to have to experience what I'm feeling right now. And I, you know, I'm-- This was a long time ago, and I'm a seventy-one-year-old man, and I'm not over it, and I realize I'm not ever gonna be over it. And that's not a bad thing because it's, um, 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, there's a wonder drug out there. That's just inappropriate. It's wrong, and it's absolutely cruel, and I object to it.

Steven Bartlett 1:47:28 Well, you're a dad yourself now, and you have this wonderful son called Austin. I actually spoke to Austin, and Austin wrote a, wrote a little letter for you. Here you go. This is from, uh, your son, Austin.

Dr. David Perlmutter 1:47:44 Okay. [laughs] And the winner is... [laughs]

Steven Bartlett 1:47:56 You can read it.

Dr. David Perlmutter 1:47:57 I will. "Dad, [sighs] for the entirety of my life, [sighs] 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 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. [sighs] Love from all of us across the pond, Austin." Well, uh, Steven, you, you, you really did it here, didn't you? [laughs] Um, you know, uh, I'm thinking of my dad right now, and we go through our lives trying to, um, do the right thing, and he set a very high bar. 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'm so happy with how it's playing out because I'm in my lane. It feels really good to be in my lane and doing-- Having identified what my skill set is and exploiting it to the ends of the earth, that's what it's all about. Probably a better answer to your, uh, opening question. I think that's enlightenment. I think enlightenment is identifying your skill set and using it to contribute. And, uh, and there you go. And I guess, uh- I will continue as, uh, I'll continue as long as my brain holds up and I'm doing all the right things, so hoping that it, it does.

Steven Bartlett 1:50:42 As Austin said, you are a wonderful continuation of your father's work. Um,

Dr. David Perlmutter 1:50:48 At his eulogy, um, I sang, I think it's a Dan Fogelberg song, um, just a line from a Dan Fogelberg song. I think I got that right attribution. And it was, uh, "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? You know, why not, uh, 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. You know, all the things that go on on this podcast, it's all about teaching, whether it's about, you know, um, should we take creatine or, 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's, um, it marries curiosity with compassion, and that's a great marriage because curiosity gives you the tools to really be compassionate in, at least in medicine, it sure does.

Steven Bartlett 1:52:00 Amen.

Steven Bartlett 1:52:03 Everything we've, uh, 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, to make sure that they walk away from this conversation and they do everything they can to protect this?

Dr. David Perlmutter 1:52:23 And I'm gonna amplify that a bit. Uh, from a personal perspective, what matters, and from a global perspective. In a word, reconnect. If 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, uh, called Brainwashed. 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 on a macroscopic level, how disconnected we're becoming from each other. There's personal benefit, and we talked about that through oxytocin, but we've got to reconnect with each other. We got to reconnect with the planet, and we're all in this together. And that would be, I think, my most important message.

Steven Bartlett 1:53:25 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, um, 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, um, and they've seen the horrific consequences of, of, of the disease. And this is a wonderful book to feel, to sort of take back a bit of agency as you describe, and feel like there is some control over something that feels so helpless.

Dr. David Perlmutter 1:54:02 You bet. And, uh, you're a good man. You're a sweetheart. And, uh, I'm sure grateful to, to meet you and spend time with you today.

Steven Bartlett 1:54:13 I am too. It's wonderful what you've done. You know, the consequence of, I guess, your father is, is you, and the millions and millions of people that you've reached and helped, given them some information, turned the lights on in their life, which gives them that agency that we describe. And I think agency's 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.

Dr. David Perlmutter 1:54:40 Thank you, Steven.

Steven Bartlett 1:54:41 It's incredible. We, we do have a closing tradition where the last guest leaves a question for the next-

Dr. David Perlmutter 1:54:46 Oh, wow

Steven Bartlett 1:54:47 ... not knowing who they're leaving it for. And the question left for you is [laughs]

Dr. David Perlmutter 1:54:53 [laughs] Oh, no.

Steven Bartlett 1:54:57 Oh, that's, uh... I usually don't let guests see this, but I'm gonna break the tradition in this case. This is the question left for you. [laughs]

Dr. David Perlmutter 1:55:06 Oh my gosh. So it's from Mark Cuban, and we've answered the question.

Steven Bartlett 1:55:12 [laughs]

Dr. David Perlmutter 1:55:13 The question is, Mark, to answer your question, what makes you emotional? It's an excellent question, but, uh, I think we've answered your question. [laughs]

Steven Bartlett 1:55:23 [laughs] Dr. David, thank you.

Dr. David Perlmutter 1:55:27 Thank you.

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