Dr. Tommy Wood: Can Cognitive Decline Be Reversed?

Alzheimer's often we assume it's related to memory, but it's also executive function. Numbers, decision-making, one of the best sort of early predictors of later Alzheimer's disease was people losing the ability to keep track of their finances. If the human condition is to choose the path of least resistance, then we have these computers thinking and doing work for us. We lose these tactical skills of thinking and processing. Either you can use these tools to augment what you're currently capable of, or you can allow them to drive atrophy of those skills. But it still requires us to engage our brain in that process. Or do we just let it take over and do the work for us? I don't think we have any data because we've never been in this position and I can't imagine the brain volume would decrease exponentially, but who knows? They say that Alzheimer's is not reversible, that prevention is the best metric versus once you have problems, you're in trouble. Fully reversible right now is controversial. When you start to lose brain volume, the first thing that happens is not that you're losing cells, what they're doing is they're shrinking down. What must they do? Sleep is important. We know that people who consistently sleep for less than six hours a night have an increased risk of dementia. If you wanted to say, if you want to multiply your risk of dementia, here's what I would have you do. The biggest risk factors that we know exist are... Dr. Tommy Boyd, welcome to the show. Thanks so much for having me. I'm super excited to be here. I am so excited about your new book, The Stimulated Mind, really. And also, we share a mutual agent. Shout out to Joy Tattala and David Black Agency. This book is, I think, going to really put a lot of things in perspective, especially about brain aging. Thank you. That was my hope, of course. And I have to say thank you to you. I think partly it exists because of you because you introduced me to Joy and really helped me get my butt and gear to put a book together. So, yeah, so thankful for your help there. And you have been in research for quite some time. You're an MDP sheep. And instead of practicing medicine, you really have created a way and a structure of thinking about the brain. We are going to talk about dementia. We're going to talk all about Alzheimer's, which, again, you do speak a lot on, but I have my own questions. The first thing is, I was thinking about the elite athlete. You've taken care of many elite athletes, a lot of formula one drivers. And also, we share in common interest in operators, tier one operators, seals, green rays, whatever, people can fight about whatever that means. And it seems like they do two things very, they do things both very differently in the way that the athlete has their rituals. Their brain is this prediction machine. They do, they put on the right sock, they dance around through times and then throw salt over their shoulder. But when things become chaotic, that's not necessarily their strike zone. Whereas the operator functions with a high level of chaos and uncertainty. And not, there must be something with the brain and ways to improve performance and really merge the two. It's a very interesting set of problems that they deal with in many ways are very similar. They need to be able to switch it on at the right time, stay focused, pay attention for extended periods, then use these incredible complex skills that they've learned. It's interesting that when you think about the different scenarios that they exist in, they've then trained themselves in order to be able to thrive in that environment. Whenever you think about operators, there's a guy I talked about in the book, a very good friend of mine called Pauli Dottoro, who worked in that environment for a long period of time. And he once told me that the most stressful environment for him is standing in the line at target. Nothing going on, just like, you sat there like unable to do anything, unable to control your environment. You're sort of like, the line is the line and there's nothing you can do about it. But he has performed under just unimaginable scenarios, many of which he probably couldn't tell anybody about. And I think that what he has done really well is learned how to regulate emotions in the moment. And those are the sort of the tools that he brings. And those are the tools, his tools that I talk about in the book. And I think there are parallels to elite athletes, because we know that one of the most important predictors of prolonged performance in athletes is emotional regulation. And so the skills might be slightly different, or the ways that they use them might be slightly different. But there is a commonality there that two things are required. One is being able to regulate your emotions in the moment. And so that requires some mindfulness, introspection, right? You need to be able to know what you're feeling, to understand it, and then use whatever strategies you have to manage that. But then you also need to understand what happens when you fail and how to overcome that. And I think again, in both scenarios, that's something that they do very well. So the best athletes are the ones that have the most self-compassion, which is not necessarily what we think about. I never thought about that. I always thought of winning as actually a risk. Because you win and then you become accustomed to winning, and that becomes a normal, and you almost expect to win, as opposed to fail, being able to face failure and be able to detach from that and then move on. Yeah. And you're right that the best athletes become accustomed to winning. But I don't think that they let that change their thought processes. And the most successful athletes over long periods of time are very process-oriented, right? You can't always guarantee a specific outcome, but you can focus on how am I doing everything to make sure that I'm most likely to perform in the right moment. And then acknowledge that sometimes that doesn't work out. And so I think the best athletes are those that exhibit these tendencies of mindfulness, common humanity, treating yourself as you would other people, like knowing, like people make mistakes, people fail. And then how do you come back from it? That's how you're successful in the long run. And when you think about regulating emotions, and you do talk about the autonomic nervous system, how does one, when stresses are high and it's almost like a visceral response? The best way that I think we know to be able to do it is to leverage our physiology from like a bottom-up perspective. So everybody's probably experienced being stressed in the moment. And it's very hard to think yourself down from that. I would say it's almost impossible. It's almost impossible. Yeah. Your brain is too busy being dunked in adrenaline to know what's going on. But you can leverage your physiology and senses to downregulate the autonomic nervous system. So some of the easiest ways to do that include breath work, so slow-paced breathing, anything that results in you exhaling for longer than you inhale. There's a ton of different ways to do that. Physiological size, three, seven breathing. But that's essentially it. You spend more time exhaling than you spend inhaling that activates the vagus nerve, slows the heart rate, brings down blood pressure, and then you can sort of manage yourself. It feels subtle though, as opposed to some of the other tools that you mentioned in the book. The breathing feels more subtle. Yeah. I think that it still requires you to have some active engagement in that process where you still have to think, oh, hang on a second, I have to like, you know, get on top of my breathing. Other things that you can do, one of the most powerful ones is actually just like, it's just closing your eyes. So when you close your eyes, you shut down some of these stress-related networks in the brain. And a lot of that is because the thing that's stressful is something that you're looking at. So it's actually just very simple that you can just switch that off. Not that you've heard. Pardon? Yeah. So like, for example, you've heard bad news or there's always, it seems as often that there's this auditory component. So there could be an auditory component. And maybe the stressor has come through the auditory system. But if you decrease the number of inputs that you're getting at any given time, you're better able to process it. So vision is one that's easy to do, but that's not always something you can do, right? If you're a Formula One driver and you're stressed in the car, close your eyes. It's not going to help anybody. Time is dropping. Yeah. So then there are things like, you can still manage what you look at. So there's this idea of something called the quiet eye that's very common, using athletes, basketball players, but also surgeons and operators as well. So it's very purposefully focusing on your target for the first few seconds right before you do the action that you need to do. Because when you become stressed, your eye movements become more erratic. So just purposefully focusing on the thing you're trying to do, which sounds like intuitive. Like, of course, why wouldn't we do that? But because we're stressed in the moment, we kind of forget to do it. Then other things include like, yeah, changing what you hear, right? There's a lot that we can do in terms of music or other sounds that can relax us in the moment. But it's really just thinking about what can I do to change what I'm experiencing, what I'm sensing, that then allows you to sort of like, take a breath, take a beat, and then you can start to bring those stress responses down. The sort of final important thing, there's a bigger picture thing actually, going into stressful environments, is how you think about stress and being stressed. That's very cognitive. It's not, you know, managing the fight or flight or time of the friend. So you need this, this is something that happens before you go into the scenario, right? So yes, you can have these set of tools to manage your response in the moment. But before you go into that kind of scenario, be it, you know, jumping in the car, whatever match it is you're trying to play, or, you know, giving a presentation, like something that the rest of us might be doing on a day-to-day basis. These things are exactly completely relevant, knowing that the stress response is there to divert your attention so that you can perform in the moment and to divert resources to adapt to the thing that you're being exposed to. So stress isn't bad, right? We keep, like, we've gone to this point where everybody's just saying that stress is bad, anything that raises your cortisol, anything that raises adrenaline might as bad for you. But it's actually there to divert resources so that you can become better and stronger and adapt, right? So the mindset that you take into any stressful scenario actually changes your hormonal responses to that stress. Talk to me about that. Yes. So there's this, a ton of really interesting work, a lot of it done by Ali Akram at Stanford, talking about this idea of stress being enhancing. So they take, she's done a ton of studies where they take people and before they put them in a stressful situation, and often what they do is something called the tri-social stress test, which if anybody hasn't heard of that, it's you sort of like walk into a room and you get five minutes to talk on a topic that you haven't prepared and you're standing in front of a, like a panel of judges and they just sit and look at you impassively, like no facial responses, whatsoever. Is it incredibly stressful? Sounds like graduate school. Yeah, exactly. And, you know, there's a few other ways that you can sort of stress people. But what you see is that before they go into that scenario, they randomize them to two groups. One group says, stress is so bad for you, right? It's bad for your health. It sort of helps drive failure and choking and all these kinds of things. And the other group, they say, well, do you know what stress is actually there to make you perform? And think of all the amazing people who've performed under stress, right? All the military generals, all the world leaders, Sully Sullenberg, landing the, like his plane in the Hudson, like all that, all that kind of stuff. You know, stress is a good thing, right? That allows you to respond. And then you stress those people and you see cortisol increases the same in both of them. Like it's still stressful. But you also see increases in other hormones that drive adaptation and recovery, like DHEA in the group that have this stress is enhancing mindset. And they've also shown that the stress is enhancing mindset, like how much you believe that stress builds you up rather than breaks you down predicts like how, you know, whether you're likely to survive seal training. So knowing that these, this can be a good thing, at least in the short term, then changes your response to it. And people who where this does have an effect in the moment, there are other studies that show that people who have more of this stress is enhancing mindset and release more things like DHEA when they're stressed, they make better decisions when under stress. So it's a mindset going in, but it also changes how you respond in the moment. How long do you think it takes to really encode that kind of a thing? I know that it's variable for everybody, but, you know, we've all had these aha moments where we hear something and then all of a sudden, you know, we like get it. Yeah, it can happen essentially immediately. Because if you look at some of these studies, they just frame stress differently right before the stressor, right? So just thinking about it immediately before you end up in that scenario is enough to start changing things. That doesn't mean that you will always remember that every time you're stressed, right? You're like, you're going to need to remind yourself, but you can see benefits almost immediately. So I think that's just allows us to remember that any time we're going into a stressful situation, think about the fact A, that stress is there to improve your responses, allow you to adapt. Also remember that you're usually stressed because you're doing something important or something cool, right? So like in many ways, stress is like a privilege. Like there are chronic stressors that are separate here. We're talking about in the moment when you have to perform saving lives or on, you know, whatever athletic field you're playing on or, you know, out in the, you know, as an operator out in the field. But just remember that it's usually you're asking something more of yourself and that's often a good thing. And then again, that sort of gives you this knock on effects to improve your performance in the moment. And is it fair to say that the more you push yourself midlife or youth, the more, you know, we say future proof your brain, you know, in your title, it says future proof your brain from dementia and stay sharp at any age. And, you know, in the book, you talk about nutrition and training and tactics. Is there a way that we become very good at managing this autonomic arousal, this embrace challenge that then future proofs our brain? That's what I think we see from a number of different perspectives. So I talk about future proofing your brain primarily in two different ways. So one is can we decrease our risk of dementia in the future? And we know that that you absolutely can through lifestyle and the environment. But the other one is knowing that the future is unknowable, right? What does the work environment or AI or technology look like in five years time? How does that affect how we, how we engage with the world on a day to day basis? We have no idea, right? Are you concerned? Potentially, but it all depends on how we engage with those with those technologies. And there's, I think there's a lot of frameworks that we can build around that that could, so it could end up being a boon, but could also be disastrous. Well, but if you, if the human condition is to choose the path of least resistance, then we have these computers thinking and doing work for us. We lose these tactical skills of thinking and processing. Yeah. So, so the way that I think about it, and I think a framework is important because again, I don't know what these going to look like in even two years time is that you essentially have two options. One is that you can use it as cognitive orthotic. This is a phrase I've stolen from my friend, Ken Ford, who runs the Institute for Human and Machine Cognition. So an orthotic helps you build on your current capacities to do something you wouldn't normally be able to do, right? And we see this in studies that have used things like large language models in students writing essays. If you try and do the work yourself first with no, no technology, no Google, no LLM, just like whatever you've got, you work as hard as you can to write this essay first. And then afterwards you say, Hey, Claude, what could I have done differently? What didn't I think about? What am I missing here? That gives you an orthosis because it allows you to kind of build on your current capacity and it requires you to still think and engage in that process. The alternative is a cognitive prosthetic, which is a cognitive prosthetic prosthetic, right? So you you use you have a prosthetic leg. I've never heard that term. So again, I've taken this from Ken. I take I take I take no I take no credit. A prosthetic you use because you don't have that because you don't have that thing, right? You have a prosthetic leg because you've you've lost the leg or you never have a leg. And so if you use AI as a prosthetic, then you're using it instead of your brain, as if you didn't have a brain, right? That's that's essentially the sort of the where the thought process goes. So either you can use these tools to augment what you're currently capable of, or you can allow them to drive atrophy of those skills, or maybe you never develop those skills in the first place. And that's what I'm really worried about. Like even in my own fields, like I see colleagues using these tools to essentially do their science for them. And then you can almost see them de skill in real time. So it's really just going to pan on do we want to use it to extend our capabilities, which could be amazing. But it still requires us to engage our brain in that process. Or do we just let it take over and do the work for us. And also, if the body atrophies and decreases in size, yeah, I mean, what's the I don't again, I don't think we have any data, because we've never been in this position. And I can't imagine the brain volume would decrease exponentially. But who knows. So, so, so like you say, one of the, one of the most important things about the brain in terms of its long term function, is something you would call brain reserve, which is a fancy way of saying how much brain you have in your skull, right? And is that based on volume? That's great. That's based on volume. So it's, and it's adjusted to the size of your skull, right? What percentage of your skull is filled with brain? And we know that when you build, when you build skills, or you drive a new stimulus to the brain, and you any kind of new cognitive stimulus or complex cognitive stimulus, and they've seen this with taxi drivers in London memorizing maps, and they've seen it with people learning how to juggle, and they've seen it with people learning new languages, or your musical instrument skills. You can see the shape and structure of the brain change. How fast? Usually, within months. Some of the studies, it's like, so I give the taxi driver study at several years. But there was one study, like one of the most classic studies of this, they had people in their sort of 20s and 30s in the Torban House of Juggle. And within three months of learning how to juggle, you could see in particular volume changes in the visual cortex. So like in the back of the brain, which is because juggling is mainly a sort of a visual motor, like changing how you move your hands based on the visual inputs of the balls moving. That's like the primary stimulus. And so you can see that change. And the bigger the improvement in skills, the bigger in change on an MRI scan. And then when they stop, when they stop juggling, those changes recede. So the brain in those areas starts to shrink and change change again. So this then I think tells us that we know the brain can expand and change structure and respond to specific stimuli and skills. But just as when you stop training, your muscles shrink and you lose performance, the brain is going to potentially do the same. So you're right that, you know, I don't want to like suggest it's going to be this doomsday scenario where we're all our brains shrink. But it also brings up a really good point. And just kind of like the obesity epidemic that I imagine in the moment people saw coming, you've got highly palatable food and you have spam, you've got all of this stuff. There have you been people that thought, okay, well, you know, people are getting bigger. People aren't moving. That here's the train going off the track. I mean, if we have transparent conversations about it, then it becomes a choice. Yeah. Most of it like, so you're right, we know that. So we have a much better evidence for something like physical activity, right? We know the physical activity is essentially a physiological imperative. Like your body requires movement in order to work it as best. It's kind of like baked into our evolutionary history. And will that also maintain similar brain volume as the counterpart cognitive skills like juggling or the more complex tasks? So some of it, yes. So we know that some of the things released during physical activity support brain structure and function. So there are studies in older adults where you have them do a brisk walking paradigm. So they like for a year, three times a week, 40 minutes of brisk walking, that improves the size of the hippocampus, which is really important for memory, as well as fitness and some aspects of memory, which makes sense because the hippocampus is associated with memory. You also see in similar age groups, if you have them do a resistance training program, rather than aerobic exercise, which affects the structure and function of the gray matter. So like the outside of the brain and the hippocampus inside resistance training is particularly beneficial for the structure of the white matter. And this is, we, you and I have published a paper on this. We should link to that paper. So we know that because aerobic type exercise, particularly if you increase intensity, that drives production of things like brain drive neurotrophic factor, that seems to help the gray matter, seems to help memory. Resistance training seems to release things like insulin life, pro-factor one, IGF one, which is really important for white matter, which is kind of like in the middle of the brain, really important for fast connections between different parts of the brain and the brain and the body. And so resistance training improves the structure and function of the white matter again, like even in older adults. So yes, some aspect of physical movement is going to help drive brain structure and function. But similarly, we know that the food environment, the sort of unrestricted access to high-valuable foods in animals and humans is a life-shortening scenario. And that's a quote from Charles Brenner, who's one of the great sort of longevity scientists. And so I think like coming now down to cognitive stimuli, I think we're now at a risk of some of the same things because what is it that drives brain development in the first place? It's the development of motor skills, social skills, language. But then it's also these core complex skills that humans have been doing for millennia, like dancing and moving and then teaching and music. These kinds of things are the primary determinants of how our brains, even the accumulation of knowledge, whether that's in a formal education system or not. These are the things that drive development of the brain. And we know that if we continue to engage in these later in life, that helps to maintain the structure and function of the brain and slows the rate of decline. So if we end up in a scenario where we're not having to develop these skills, we're not having to use our brains in the same way, of course, like that becomes potentially really concerning. Thank you to Timeline for sponsoring this episode. If you're a frequent listener to the show, you know I believe that muscle is the organ of longevity. It regulates metabolism, protects independence and supports long-term health. But muscle health, surprisingly, isn't just about protein and resistance, training. It also depends on mitochondrial health, the energy-producing engines inside your muscle cells. And as we age, mitochondrial function declines, which affects strength, recovery, and of course metabolic health. One of the ways the body maintains mitochondrial health is through mitophagy, the process of clearing out damaged mitochondria and renewing healthier ones. 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He was super fit and he had a really bad Alzheimer's dementia. It kind of blew my mind at the moment because it wasn't like it was just EpoE4 or genetics. It just seemed to happen. This is one of the issues that I've certainly faced. I know a number of people have faced when, when we talk about this idea that Alzheimer's and dementias in general are potentially preventable. So right now, depending on which analysis- Do you believe that? I do believe that. And depending- Hence the book. Hence the book. Even though actually a lot of the, a lot of the book is about cognitive performance today, right? So- Which is actually what I loved about it and why I started with this idea of friction. I didn't call it friction, but this idea of being able to operate in this austere environment as opposed to predictable planning to win. Yeah. And we can definitely come back to that even more. I think there's a tons of unpack there. But knowing that depending on which analysis you read, somewhere between 45 and maybe 70 plus percent of dementias may be preventable. If we think about those different types of dementia, right? So you already mentioned Alzheimer's disease, that makes up something like 60 to 80 percent of dementias. The next most common is vascular dementia, which makes up 10 to 20 percent. And they actually have a ton of overlap. So the majority of cases of Alzheimer's disease have some evidence of vascular disease with like issues, disease in the blood vessels in the brain. So- Which there's probably component of that, which is a natural part of aging. Do you think those microvascular- Yeah. changes? Yeah. So, yeah, one of the reasons why white matter is actually really interesting when it comes to cognitive function and cognitive decline is it's most susceptible to issues with blood flow because there isn't as much blood flow in those parts of the brain than in the gray matter. So if you have any issues with blood vessels, the white matter becomes particularly susceptible. The blood vessels are also thought to be one of the tissues in the body that age earliest and fastest. But we know a number of things that can help to at least slow that aging process, right? Many of which we've talked about already, like exercise. So between those two, they make up like 70 to 90 percent of dementias. There are other types, frontal temporal dementia, lube-body dementia, dementia with Parkinson's disease. But when we talk about preventable dementias, they're probably in those two buckets, right? Because we know they're related to lifestyle and the environment. Genetics as well. But genetics is largely a risk multiplier in most scenarios. So when we talk about that, then understandably, well, people will give me examples of that. Well, you're telling me exercise decreases the risk of dementia, but I know this guy who exercise tiny was super fit and he's still got Alzheimer's. And this then like allows us to maybe think about the fact that this is not a single variable problem, right? And there are tons of different risk factors that kind of interact and they interact differently within each of us based on our genetics, our environment and other things. And so there's this well known quote in urology, which says that once you've seen one case of Alzheimer's, you've seen one case of Alzheimer's, right? Because that's so true. Each of each person experiences a very differently, different trajectory, different changes in cognitive functions, right? When we think about Alzheimer's, often we assume it's related to memory, but it's also executive function and our ability to make decisions. Numbers. Yeah. So numbers, decision making. There was a paper that came out recently that showed that one of the best sort of early predictors of later Alzheimer's disease was people losing the ability to keep track of their finances, right? That kind of like complex overview of things. Those are some of the things that you lose earliest. But each of us experience that differently. So then we need to think about like, what are all the different risk factors that could be involved? And how might they each of them be relevant to me? Right. So somebody who's very fit exercises a lot, that's unlikely to be the primary lever or their primary risk factor. So then you might have to look elsewhere. But like, sometimes people struggle with this, right? Because they know people who've had dementia. And if I say dementia is potentially preventable, that could be interpreted as me saying, well, somebody got dementia, it's their fault, which of course is not the case. Because we're each doing the best that we can at any given moment in time. What must they do? If you wanted to say, if you want to multiply your risk of dementia, here's what I would have you do. Yeah. Struggle with obesity. Yeah. We have a body fat percentage over, I don't know, 35%, whatever it is. Drugs and alcohol. Don't say sleep. I'm not a great sleeper. I'm trying. It's like my one clip tonight. Yeah. If you were to say, okay, here is what I don't want you to do. Yeah. So I think that the biggest risk factors that we know exist are, yes, being sedentary. I'm not particularly concerned about as much about a specific body fat percentage. It's actually it's interesting when you look at population data sets, like for men, the like the best metabolic health on average seems to be like 20 to 30% body fat and women, it's like 35 to 45%. I don't think that that has to be the target. But what I really care about is how that's affecting your metabolic health. Right. So we know that the two biggest risk factors, the metabolic risk factors for dementia are hypertension and pre-diabetes or type 2 diabetes. And how would you define hypertension? People define it differently. Also in an aging population, sometimes they'll say you want your blood pressure higher for cerebral profusion. Yeah. So the best sort of meta-analyses of all the data we have suggest that if you're above 130 over 80, so systolic over dynecology, some might say 130 over 85, depending on the criteria, then you have a significantly increased risk of dementia. Essentially, anything over 120 over 80 seems like risk starts to increase. And then by the same token, pretty much the only pharmaceutical therapy that we know significantly decreases the risk of dementia from large randomized control trials is blood pressure medications for people with high blood pressure. Have you seen any data with things like C. allus or T. d'Alaffil for vasodilation? Yeah. So again, the best studies are less on C. allus and T. d'Alaffil and more on S. d'Alaffil. So Viagra. There is a study done looking at some big sort of insurance databases here in the US. And there was a similar study looking at this in the UK until recently in the UK, they changed it so you could buy Viagra over the counter. But they found that in both those large studies, those men who had Viagra prescriptions, and they mainly focus on Viagra because that was just the most common, you would think that inhibiting that pathway, improving blood flow, would probably work for all of those drugs. But actually, S. d'Alaffil is being tested as a neuro protective agent separate from its effect on blood flow because it might affect inflammation and neurogenesis and other things. So maybe having other effects in the brain as well. And that seems to be associated with a lower risk of dementia in the men who, particularly those who had, you were getting regular prescriptions. So you knew you were using it regularly. Now, I would argue that it's not purely an effect of the medication. If that effect is true, right, this is not a randomized control trial compared to like the blood pressure medications, which are some high quality. And you could say this is the mechanism of action as to why this would potentially work. Yeah. But if you think about the things that are important for long term brain health, physical activity, and when you see physical activity, both a combination of resistance and zone to high intensity, where are we at? Yeah. So, well, let's let's finish the Viagra conversation. And then we can come back to the next. So yeah, so all the men actually on female listeners are now listening as a random aside, the guy who helped to invent Viagra was knighted by the Queen for services to chemistry. This is one of my favorite phrases. Anyway, so when you think about the things that are important for long term brain health and dementia risk, we know physical activity is important. We know that social connection is important. When you are a man with a rectile dysfunction, who goes to a doctor to ask for a prescription, you need multiple things where you need the likelihood of an active sex life. You probably have your own kind of supportive partner, like the act of having sex counts as physical activity. And so we focus very much. How much sex counts as physical activity? Any sex counts as any physical activity. Right. Of course, more is better if that's your primary source of physical activity. But the reason why I'm saying this is that it's not just the fact that the drug changes blood flow that might be improving brain health. It's all these other things are required in a scenario where somebody is regularly using Viagra. So I think that's where some of that benefit is potentially coming from. Right. You're having a partner or partners having active sex life, which counts as physical activity, having some kind of social connection, all that kind of good stuff that we know is also beneficial for the brain. So that doesn't mean that everybody needs to go out and get a Viagra prescription. I think that it's the context of where it's being used that is important as well. So like going back to the metabolic health thing and the things that we would think that would amplify our risk, right? So high blood pressure. Which we define as anything over 120 over 80. Which is unusual for people because that is easily tolerated. Yes. Yeah. You wouldn't notice it. I'm also tolerated by physicians. They would say 120 over 80. This is perfect when potentially lower maybe a little bit better for a good function. Yeah. So it kind of looks like it's kind of the risk is kind of flat until 120 over 80. And then it starts to increase. And then it's like significantly increased somewhere around 100. So it's just sort of a systolic of 130 over a diastolic of 85. And then high blood sugar as well, we know is really important. Like so if you have pre-diabetes, your rate of cognitive decline is faster than somebody with normal blood sugar, right? So a fast blood sugar under 100 versus over. Do you think that that number is accurate? This is just a hypothetical question. You mean like is lower better? Yeah. Is lower better because I think we tolerate what we're seeing in the landscape in general is we have a tendency to tolerate these higher numbers. So we say pre-diabetes, but by the time they're diabetic, they have retinal pathology. They have microvascular disease. So probably if I was looking at a fasting blood sugar, you know, maybe again, we'd be lower would be better. It's a great question. And when you look at like meta-aggressions, right? So you get like a big data set numbers and you kind of look at this as like a continuous factor. The risk really does start to increase somewhere around there. So if somebody's like high 90s versus 100, that's probably pretty similar. I think once you're into the low 90s, high 80s, that's probably that's probably just fine. Really the strongest evidence is for like surprisingly, even though we might consider them or some people might consider them not ideal, really the biggest evidence is for just avoiding the components of metabolic syndrome, right? Which is actually which is a potentially fairly low bar, but is also incredibly rare, like less than 10% of the adult population can say that they don't have any of the components of metabolic syndrome. Which would be elevated triglycerides, elevated blood glucose, elevated blood pressure, wide waistline and a low HDL. So below 50 in females and below 40 in males. And so like if you tick those boxes, right, then I would say that metabolic health is not going to be your primary risk factor, right? So then other things where we already talked about being sedentary, low cognitive stimulus and cognitive engagement, low social support, low social connection. How big of a percentage does that play? It will depend from person to person and study to study. When I, so a couple of years ago, maybe it's three years ago now, my colleague, Josh Turk, Netanyah, he's a neurologist. We wrote a paper together, sort of hypothesizing that the primary driver of cognitive decline in sort of modernized societies was the way, changing the way we use our brains, right? As we get older, we stop doing the things that we know helps develop and maintain cognitive function, like learning new skills, social interaction, that kind of stuff. And then I spoke to a friend of mine who's a retired palliative care physician called Juhi Mabel. That's tough. That's a very tough field. Very tough, very tough field, very tough job. For those who don't know what that is, it's end of life. I did that for a couple of months on rotations and you're seeing 30 patients that are getting ready to die a day. A lot of Julian's work is really important because it talks about dying with dignity, like death isn't death isn't failure, which is often what we kind of assume as physicians, where I need to keep this person alive as long as possible when that's not even necessarily best for them, let alone for other people in their lives. But what he, work that he's done has focused on the building of what he calls compassionate communities. And so the first example of this was in Frume in the UK, where they around the primary care practice, they built this network of people so that every patient coming in with a chronic disease had a social network built around them. That's amazing. They sort of interviewed them like, what do you need? What do you want? What do you want to do? And what they found was that in that scenario, they significantly decreased emergency room admissions, whilst all around it, the counties around it, they significantly increased over a period of time. This has now been repeated in multiple cities and places around the world. And so when I spoke to him about this idea, he was like, yes, this is true. But basically, all of this is driven by the human need for social connection. Like his idea is that our connection to others is the primary driver of this idea of cognitive stimulation and cognitive skills and how they build and maintain the brain. And that doesn't make sense, right? You don't usually learn a skill or a language so that you can do it at home by yourself, right? You're usually using it so that you can go out into the world and express it with other people, be that music, sport. And we know that of all the different types of social connection, something that seems to be particularly beneficial is pro-social behavior. So it's not just like interacting with other people. It's having the opportunity to do things for others. And that actually activates the Navas Vegas nerve, like downregulations, a bunch of stress responses. Like, you know, like, it just feels good. Isn't there a stress response, tendon befriended? So we talk about fight or flight as if it's the only stress response. There's other documented stress responses like the courage response. Many people that are able to modulate that initial, oh my gosh, and then go right into action. And then there's also tendon befriended, which is very much about community. What can I do? There's a stress or what can I do for you? Yeah. And so that's when you look at, so not all of this is related, not all of these data related to dementia risk, but also just like overall mortality risk. But we don't necessarily know that because, again, a cognitively impaired brain could be one in isolation, doesn't do things for other people, isn't moving, isn't, is maybe only connecting on Zoom. Those nervous system connections are probably not as dynamic or real as the human pro-social connection. Oh, yeah, definitely. So just to say that there's a ton of evidence that suggests that one of the primary reasons or one of the primary drivers of the benefit of social connection is pro-social behavior. So it's not just like interacting with other people, but it's taking those opportunities or having those opportunities to care or help others. And that, and we know that the way that we connect with people or are disconnected from people, changes inflammatory responses, changes baseline stress responses. There are some super interesting... Are you convinced by that? I mean, have you seen convincing data? So for example, there was this scientist and he was talking about rheumatology related disease, so rheumatological related disease, elevated levels of ANA and these markers. And basically what they saw was as interpersonal, I don't know if it was just trauma, but really stressful, just thinking of shame would increase the actual thought, the cognitive tap down process of feeling shamed increases or would increase these autoimmune biomarkers. Do you... So I think the way I think about this and that this like the shame... But doesn't that sound a little crazy? It does. It sounds completely insolent. For those that are physicians or just they're like, I'm evidence-based. What do you mean if I shamed you in some way in that moment and then took your blood? Would you have that immediate response of beyond cortisol, but increase in autoimmune markers and I don't know. So there was a recent study that actually looked at something very similar in terms of weight shaming and saw a similar thing. So in individuals who are obese, if you put them in a scenario where you increased the sort of shame around their body weight, they saw inflammatory responses in the short term. And so all of this fits into this idea of how our body responds to changes in social status and social rank. So all of these are social stresses, humans are social beings. Our complex social structure is one of the primal drivers of human brain evolution. Meaning what do you mean? So when... A truncated version. Yeah. Now I'm going to go back to Darwin because you are. So when Darwin first wrote On the Origin of Species, that's where we think we got a lot of this idea of evolution and we also came up with this idea of survival of the fittest, right? 12 years after he published On the Origin of Species, he published a series of like a collection of thoughts about evolution of the human species in particular called the descent of man. And he did that because he realized that survival of the fittest as an idea didn't explain human evolution. And where he ended up was that the collection of beings that were the most what he called sympathetic towards one other and looked after one another were the group that would survive and dominate the environment. What he called sympathy, we would probably call empathy now. And basically there's now a ton of evidence to suggest that it's our complex social structure, how we look after each other and behave in a group. Plus, you know, changes in nutrient availability and megafruity acids, all that kind of stuff contributed as well. But that seems to be a primary driver of how our brains evolved. And so then the one of the primary determinants of our overall well-being is our social status and our social rank. And like very quickly before I get into that a little bit more, we can see from studies of social isolation, and this has been done experimentally looking at individuals like simulated trips to Mars. So NASA done studies like this, we see looking at the brains of people who do like, our Arctic exploration, like you're on your own at the top of the world for months. The parts of the brain that are most evolutionary recent in humans, humans, part of the prefrontal cortex, parts of the lateral parietal lobe, the temporal lobe, that are responsible for some of our most complex cognitive functions. These areas of the brain are most susceptible to aging and most susceptible to periods of social isolation. And these are the things that explain, you know, us having our human brains. And you can see that in short-term and long-term studies. And they've also done studies looking at prisoners in solitary confinement, and you see the same thing. So the structure and function of our brains seems to be driven by the social environment. Yes, all these like nutrition, physical activity, all critically important as well. But the structure and function are the architecture is really based on the interpersonal connection. That's unusual to think about. Yeah. And you can see it like in very short-term, where you put somebody in socialization for a couple of weeks, cognitive function declines because of the lack of stimulus and sort of connection you're getting from other people. And so in like a bigger picture sense, so anybody who really wants to dig into the research, Julie and I, who I mentioned earlier, we recently edited an edition of a journal, the Journal of Lifestyle Medicine, on compassionate communities and social connection, why it's so important to health. One of the papers was written by George Slavich and Steve Cole, they're at UCLA. They've done a ton of research in this area. And one of the ideas is that any time we experience a social stressor, and that could be social isolation, but it could also be changes in perceived social rank. So that's where shame which now also is happening much more rapidly. Yeah. Getting back to the blood level connection. Now we can with the velocity of the connection, you could be shamed on, I mean, you and I both know someone who was went from status over here and in one second, completely shamed within moments to millions. And we see this all the time. And it happens even in like on a much smaller scale to each of us, like anytime you're on social media and you see people who are richer, more beautiful, more jacked, more successful than you are, right? You're always like, trying to put yourself into place in like the bigger world of society around you. And so these kinds of things can drive social stress. And what social stress does is it triggers an evolutionarily conserved shift in immune function and stress response. So when you take somebody and they're and you socially isolate them. So if I'm in my, you know, one of my ancestral homes of Iceland, 1000 years ago, and I get separated from my group, I'm on like lost on some mossy lava field in the middle of nowhere. What happens is you see a shift in the immune system that you change from more of a like adaptive immune response that's particularly important for like, like handling viruses, flus and colbs and things, because that's what you get, you get exposed to those when you're in a social group. It shifts to become more of like an amplified innate immune response. So you see a bit of wound healing and higher low grades of inflammation, because right, you're no longer going to be exposed to these kinds of things that you get when you're exposed to any group. But if you get injured, and you're by yourself, like your stuff, you have to be able to survive. So you can measure these shifts in the immune system in response to social stress. And so in the short term, that's a good thing, right? It actually improves survival in the short term, because you have this shift in the immune system and the sympathetic nervous system. But if that's activated cryically, you have higher baseline levels of stress, you have higher baseline levels of activation of the sympathetic nervous system, which then seems to contribute to the progression of chronic disease. So all of this, driven by all these potential ways that we can feel socially stressed, which historically was around social isolation. But now there's a ton more ways that we can experience that. This episode is brought to you by Four Sigmaatic. If coffee is what gets you through the morning, but also what leaves you jittery, unfocused, or crashing by mid-afternoon, you're not alone. A lot of people are using coffee to push through. I might be one of them, but not actually support the brain. And that's why Four Sigmaatics focus. Organic dark roast is different. You're getting a premium organic Arabica coffee blend with lion's mane and hey, I'm talking Mufasa style and shaga mushrooms. Lion's mane supports focus and mental clarity. And because it's adaptogenic, it helps smooth out the spike and crash cycle that caffeine alone can cause. If you're thinking, hmm, gross, does it taste like mushrooms? The answer is no. But it's smooth, full-bodied, dark roast with subtle chocolate notes. It tastes like real coffee. And if flavor wasn't enough, Four Sigmaatic third-party tests their coffee from mold, mycotoxin, pesticides, and heavy metals. It's also one of the best-selling functional coffees every retailer is like. Target Whole Foods with over 100,000 five-star reviews. And right now listeners of this podcast can get a free bag of their best-selling dark roast ground coffee. Just pay shipping and handle them. Go to FourSigmaatic.com slash Gabrielle. That's F-O-U-R-S-I-G-M-A-T-I-C dot com slash Gabrielle. Would you say if you were kind of circling back to what you wouldn't want people to do, what would you not want them to do? Yeah, so be sedentary at home alone. Eat a calorie-dense nutrient-poor diet. Because like we know there's a ton of nutrients that are critical for brain function. Which are, what are your top? So the most of the ones that we have the most important evidence for are Vitamin D, Omega-3-Fatty Acids. The B vitamins associated with methylation. Vitamin D ingested orally, meaning through foods or just the exposure outside? Either. If you need to supplement, I think there's very good evidence for it from a cognitive standpoint. And that's in terms of mood disorders, but also potentially in terms of dementia risk. But then also we know that it's important for like athletic performance, right? So that's something that we're very cognizant of with the athletes we work with. So Vitamin D, Omega-3-Fatty Acids B vitamins related to methylation. So B12, Pholate, B6, Riboflavin, which is B2. And the market that seems to be most important is homocysteine. So elevated homocysteine, we know is associated with significantly increased risk of dementia. And the randomized control trials where if you lower homocysteine, particularly in the context of adequate Omega-3 status, you see slowed brain atrophy, slow cognitive decline. And then iron, particularly critical. I think there is even post growth. Even post growth. So iron is critical for the development of the white matter in babies. And then it's also important for maintaining the structure and function of white matter later in life. So there are several studies that suggest that anemia or low iron status, particularly in women as they enter sort of like the perimenopausal transition, one of the reasons they experience cognitive symptoms is because of issues with iron status. And that is even very common in people eating a sort of vodka and what you might consider an adequate diet. So that's something definitely to take care of or look at. You can see that you see this kind of bell shaped curve between cognitive function and hemoglobin levels. So if you're anemic, you have low hemoglobin, we know that's suggesting poor iron status. That's not going to be helpful for the brain. But at the high end, high hemoglobin is usually the most common causes obstructive sleep apnea. You become hypoxic during the night. The body makes more red blood cells in response. So it's not then the high hemoglobin that's the problem. It's the fact that you have sleep apnea and you're not sleeping properly and you're becoming hypoxic during periods at night. So that's another reason why that's a useful marker to look at. Then other things that we have some reasonable levels for might include magnesium, zinc, choline in certain scenarios, and then the antioxidant polyphenols that you get from berries, the roasted skins of nuts and seeds, coffee, tea, the sort of yellows and reds, lutein and zeaxanthin from like peppers and carrots and things like that. And then astaxanthin, which you get from is what makes salmon and shrimp pink. Those higher intake of those associated with better cognitive function, lower risk of dementia and over a lifetime or could someone come in because these are all fixable deficiencies if someone is deficient? How over what period of time do you think that there is impact? I think that essentially as soon as you can address that, the better. But something like vitamin D, we know that there are some vitamins, detrials, or studies looking at population intakes of vitamin D, vitamin D supplementation is associated with lower dementia risk once people enter their 60s and beyond. So even later in life, if you're starting to address this, you could potentially change that. And most of the studies that look at vitamin status and dementia risk are again individuals in their 60s and 70s. And there are randomized controlled trials of omega-3 fatty acids and B vitamins again in individuals. I am absolutely sold on that data for omega-3 fatty acids in the brain. The most interesting thing to me though is this interaction between B vitamins and omega-3s. So the original study that looked at this was the Bioticog study run out of Oxford in the UK. And they found that lowering homeocysteine, at least below 30, at least below 30 and ideally below 11, was associated with slow rate of cognitive decline, improved cognitive function, but only in individuals who had adequate omega-3 status. That is, that is, I mean, just interesting. Yeah. Because what food has both omega-3 and B12 naturally? What's the highest natural food in nature? Sardines, small fish have both. And the, this has not been replicated in multiple other trials. So the B-proof trial did the same thing. The omega-AD trial came from the other side. They supplemented with omega-3s, but they found that it mostly benefited those who had low enough homeocysteine. So there's a really interesting interaction there. And this, this is particularly interesting to me because you'll have seen like dozens of trials where you give one nutrient and then it doesn't affect cognitive function. And they're like, oh, it doesn't work. Absolutely. But it also doesn't make sense to supplement with something if you weren't deficient in the first place. And most of these trials don't measure nutrient status initially. And then it's, it's silly to think that there's just like one nutrient that's going to solve. But it also goes back to this whole food matrix. Yes. Yeah, exactly. Using over time. Yeah. The people have estimated that we only really know about 10% of what's in like whole foods, right? And so the other 90% is doing something. And there's a reason why seafood intake is associated with more of an effect on dementia risk than supplementing with the omega-3s. Like from the trials, we know that supplementing with the omega-3s can be beneficial. But seafood has a whole bunch of other stuff in it, right? So if it's salmon, you have astaxanthin, you have selenium, you have a whole bunch of other like salmon has some, has some beavits in it. So there are a whole bunch of other things you're getting at the same time. How often do you recommend eating fish? At least two or three times a week. I think the, the goal is to sort of get something like two to four grams of long chain omega-3s on average per day. But it doesn't have, it actually doesn't have to be daily. I published a paper with a colleague of mine, Rory Heath, a few years ago, looking at how the body handles long chain omega-3s and basically if you overeat them, right? So if you eat like a massive plate of salmon one night, your body will store the extra omega-3s in your adipose and then it will access that later and it gets sent to the brain, say, if it needs it. So you don't have to eat it every day, but just like regular consumption will then make sure you've got a bit of a depot. I mean that, so we had Tom Brunner on, you know, Dr. Tom Brunner. He was responsible for the last three dietary guidelines. His expertise is in fat, saturated fat, long chain fatty acids, and he said that the idea that women, pregnant women should reduce their fish consumption, whether it was tuna or anything else, he said, completely wrong. Yeah, this is really interesting to me because it brings up some of the most counterintuitive studies that you might ever read when it comes to this kind of thing. Firstly, I think it is interesting that women seem to be better at converting short chain omega-3s to longer chain omega-3s because they're so critical to infant development, to the fetus. I mean that maybe upregulates even more during pregnancy. So women may be more likely to be able to get short chain omega-3s like aflilinol and acid from chia seeds and more nuts and things. I still think they should be. Yeah, and Tom would say it's not really bioavailable. The conversion is still off and we're not sure why. Yeah, it's better in women than in men because it's important for the fetus, but that doesn't mean that it's enough to not consume them. But when you look at studies of infant development and then some studies of what's going on in the brain in individuals who experience Alzheimer's disease or not, what you see is that there is a net benefit for seafood consumption, even if that comes with increased mercury consumption. And that's true in terms of... Exactly what Tom said. He said there's no reason. He said those that are eating more omega-3 fatty acids and fish, they're offspring are... they are better off from a cognitive standpoint. Yeah, so the study's done in the UK on this, so it's done in the Seychelles on this because the Seychelles is obviously an island nation that really ate a ton of seafood. And this I think is really important because so often we get caught up in this. We focus on one negative thing in this food and we think that offsets all the benefits. But actually all the evidence suggests the net benefit is much greater than this one thing that we might like to focus on. And we can think about it in terms of lots of things. We can think about it in terms of grass-fed meat. We can think about it in terms of seafood. We can think about it in terms of like microtoxins and coffee, right? All the signal says these foods can be beneficial. And like the net benefit is much greater than to outweigh some of these other things. What about alcohol? Alcohol, drug consumption? So alcohol is important, but I wanted to tell you about this one study in terms of... So there's a study that looked at the mercury content of people's brains. And they found that those who had more mercury in their brains have had a lower risk of dementia. And that it doesn't make any sense. Unless you think about the fact that this mercury is coming from seafood, in seafood you get selenium that helps offset some of the negative effects of the mercury. And you get all these omega-3s and all these other things. So it's not that the mercury is beneficial. It's just this signal for people having consumed more seafood. So all that again to just say that I think that eating the seafood is much more important than worrying about some of the things that come along with it. And of course, yes, if you want to eat more sardines, macaroles, smaller fish, anchovies, great. But we shouldn't be scared of seafood because... Which we have been. And women, pregnant women, even myself, but through my pregnancies I was like, oh, you know, I don't want to have too much fish. I was really concerned. Yeah, whereas the... So when you were pregnant, then your body would have sacrificed your own DHA stores for your fetus. We know that. It's very tightly regulated. You will offload those stores because the baby's brain needs it. So then coming to alcohol, this is another thing that I think is really interesting because whenever anybody asks me about alcohol, it's usually because they want to be able to justify their current level of intake regardless of what that is. You know, everybody wants to think that what they're doing is okay, particularly when it comes to alcohol. I think what the evidence suggests is that I don't agree with some of the more recent studies that say that any alcohol you ever drink is bad and you shouldn't ever drink it. Most of those are based on this really weird methodology where you use reported alcohol intake to generate a polygenic risk score for alcohol intake and then you use the polygenic risk score to predict... That's complicated. It does affect sleep architecture. Absolutely. So I am not saying that alcohol absolutely has downsides. It impairs REM sleep, in particular causes a REM sleep deficit. It messes with thermal regulation during sleep. So we know that it's not great for your sleep, of course. But when you sort of look at overall outcomes, brain volumes, cognitive function, it seems like as long as you're averaging less than half, and the reason why I say half is because in the UK, one standard drink is about half what a US standard drink is. Okay. So in the UK... You'll drink more, you're saying? Yeah. So in the UK, it's eight grams of ethanol. In the US, it's 14 grams of ethanol for a standard unit or drink. So if you're on average consuming less than half a standard US drink per day on average, there seems to be no net effect on the brain. So what that means is you have a beer or two once or twice a week or a glass of wine once or twice a week. That's probably fine. Beyond that, then we start to see changes in brain structure. The use of cognitive function increased risk of dementia. So the occasional drink with friends is fine. Is it the effect on B12 status or the B vitamin status or is it something else? I don't think we know. At least I haven't seen studies that have kind of... They may just look at alcohol intake and then they look at health outcomes. I don't think they've looked at mediators of that effect. I would certainly expect sleep to be a big part of that. Can we talk about that? Okay, sleep is important. I understand. I just think if I do all the other things that are right, then maybe I can offset the fact that I'm not a great sleeper. And then when you have little kids, they sleep in your bed and read all this stuff about how there's a close connection for them and it's important. So tell me how I need to kick my kids out of the bed and sleep more. But don't tell me too much because... I think we've gotten to the point where we now understand sleep is important, right? But in many respects, I'm worried that we've taken it a little bit too far. Because of course sleep is critical. We know the people who consistently sleep for less than six hours a night have an increased risk of dementia, for example. And they probably have other bad habits. Yeah, no. And these things come together. I'm just trying to justify it. To be clear. I'm backing you up here. So we know... We've got residency and graduate school and being pregnant, it's miserable sleeping. Yeah, and there's actually good evidence to support that that's not a net detriment. So there's a ton of evidence that shows that those who are physically active offset some of the negative effects of sleep deprivation. Potentially because there are other... You're doing other beneficial things at the same time. You're offsetting some of the negative effects of sleep deprivation that might be related to blood pressure or blood sugar or inflammation. We know exercise helps with that. If you exercise more, we know your sleep quality tends to be better. So maybe you're getting less sleep, but it's better quality sleep because we're exercising. So exercise seems to be one way to offset inadequate sleep, whatever that is for that individual. We also know that, at least in the short term, how we perform is based on how we think we slept rather than how we actually slept. There are multiple really interesting studies where you manipulate how long somebody thinks they slept or how well they slept by manipulating data on a wearable. And actually, if you think you didn't sleep well... So are you ready for this? Not to interrupt you, but I just want to tell you this story because my husband just found this out. We had our friends over, the Seal Future Foundation had this event, and some of the older seals were over. And one of the guys, Robert, he is... He's like the OG Buds instructor. And so he was sitting with Shane and a couple of the other guys, and he's like, you know, I just want to tell you, we told you, you guys slept four hours. We let you fall asleep for four minutes. And the guys were like, what? You know, in this many days, but they were told they were like, all right, we're going to let you fall asleep for four hours. Anyway, and it just blew everybody's mind, whether it's true or not. I don't know. Well, so they've done this in my lab five hours versus eight hours. And this was done by Ellen Langer and Steve Lockley at Harvard. And people go into the lab to sleep, and they either get to sleep five hours or eight hours, and then the clock gets manipulated. So that when some of the group who slept five hours wake up and they think, oh, eight hours have passed, I've slept for eight hours. And some of the group that slept for eight hours wake up and only five hours have passed. So they think they've only slept for five hours. And so then how they felt and performed the next day was better determined by how well they thought they slept rather than how well they actually slept. And people have done something similar with wearable data. And in the short term, the brain actually adapts the network shifts slightly so you can maintain function when you're sleep deprived. So the thing that is affected more is your mood is affected more than your performance. So like you perform the same, but you're just like a little grumpy about it. Of course, like the more sleep you lose, like hours lost, multiplied by number of days, right, the worse for your cognitive function. But in the short term, actually, we deal with sleep deprivation fairly well. But we get ourselves in trouble when we think we're not going to perform well because we didn't sleep well. And then we don't perform well because we thought it rather than because we didn't sleep well. Is there recovery? Can we recover brain function? Yes. So we know that you can offset some of the effects of like sleep deprivation during the week by sleeping more on the weekends. It's not the best for your circadian rhythm, right, because things get a little bit more out of kilter, but you can get some of that back. Napping can get some of it back. But I think that it's also worth, right, I don't want to downplay the focus on sleep. We know it's critical. But as it comes to like parenthood, there is some, there's a really nice study that was done in the UK Biobank where they looked at parents and later risk of dementia. And they found that the more kids somebody had, the lower their risk of dementia, right? And this was for both mothers and fathers. And I think this is interesting because when you first think about it, like you said, being a parent is terrible for your health, right? You don't sleep, you're stressed, you don't have time to exercise, you don't have time to look after yourself like you're so worried about this. My kids were waking me up at five this morning. It didn't fall asleep till one 30 because I had to put together a talk. And they're waking me up at five in the morning to read a survival book. But this and things like guys. Yeah. But but and this is and this is what happens, right? And but think about all the things that come with having kids, right? Think about the social connection and the pro social behavior and like the love and joy and all these other things that we know are really important. Just like with mercury and seafood, right, the net benefit of having children and actually the similar data on being like a pet owner. I was just thinking about in terms of how it affects cognitive function and dementia risk. But like there's this, the net benefit outweighs the downside. So yes, even if you slept terribly during like when your kids were young, overall, there seems to be this net benefit in terms of long term cognition. So all that to say that you're probably doing a lot of things that are offsetting some of the poor sleep. Even if you know, maybe if there's some point, okay, so what maybe it's important now to mention that you asked about recovery recovery from brain volume recovery from, you know, they say that Alzheimer's is not reversible that cognitive decline prevention is the best metric or the the prevention is the best measure versus once you have problems, you're in trouble. So as it relates to like just asleep, and then we can expand out from there, like there was a nice study done by Matthew Walker's lab where they looked at people and their sleep as it changed over their lifespan. So they asked them, like, did your sleep get better or get worse in different decades of your life? And they found that even if people's sleep was improving, not until they got into their 50s or 60s, if their sleep did improve in that decade, that was then associated with a lower like pathology burden in their brains. And we know that one of the things that sleep is important for is clearing out proteins and metabolic waste and one of those things is amyloid, which is part of the process of developing Alzheimer's disease. So that even suggests that right if you're in your, you know, 30s, 40s, you're not sleeping well, because you're raising a family, like even if you start to then improve your sleep later in life, you will still see benefit from that. Once you've actually experienced some element of cognitive decline, whether that's fully reversible right now is controversial. There's certainly lots of evidence that you can improve some aspects of cognition and quality of life through dietary changes, through physical activity, through social connection, all this kind of stuff. So you can certainly change the trajectory of the disease. This episode is sponsored by Branch Basics. 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You can get 15% off the premium starter kit at branchbasics.com with the code Dr. Lion. Again, that's 15% off branchbasics.com with the code Dr. Lion. The you see that on imaging. For example, you might see again, we image a lot of people's brains. We see microvascular, what do they call white matter changes? Women's hyperintensities? Yes, that is. And it will say in alignment with the natural aging process. And it's like, well, okay, is it and do we see an acceleration of it? We certainly don't see a reversal of it. But is that indicative of brain function getting worse? Things like that. Like clinicians thinking, okay, so we fix these things. They believe they experience some improvement. But do we see the actual imaging change? Not all of the studies that have looked to say cognitive function have then, especially in the setting of like already established cognitive decline, we'll then do imaging as well. But so if we're still like early on in that trajectory, we know that say, so we're talking about white matter hyperintensities, we see some of those resolve in some of the resistance training studies, right? So if you're improving white matter structure and function, you may improve the burden of white matter hyperintensities, which are thought to be part of the, yeah, the sort of the decline in white matter structure as you get older. Some of it, you know, very likely to be related to vascular issues. And the change in white matter structure and decline in white matter structure and function is actually one of the best predictors of future cognitive decline and dementia in some studies, even more so than like amyloid and towel burden, even though, you know, they are related. So yes, some of that, you know, seems to be reversible through lifestyle interventions, because we've seen that, we've seen that in some trials. Until you're at the, until you're at the late stages of dementia, the brain is still capable of experiencing neuroplasticity, which then means that structural changes are possible. So when you start to lose brain volume, the first thing that happens is not that you're losing cells. So neurons aren't dying early on, what they're doing is they're shrinking down. It's kind of like when you stop training, your muscles shrink. But if you start training again, you experience much more rapid recovery of previous functions that you have, like your more muscle satellite cells, and like you're able to, you're able to like, get strength and muscle back faster because you had that, because you had it previously. And so I think there is capacity in the system to respond to these interventions, either right, so that your cell bodies could could increase, you also see changes in like the extra servomectrics and structures around cells. So the brain is capable of neuroplasticity basically until the, until the late stages of dementia. So if you, if you were to engage those processes, you would expect to see improvements in brain structure and function. But, and so you should be able to measure that on an MRI scan, even in, even in older adults, how much of that is like definitely proven because, you know, is, is debatable because they just haven't scanned that, you know, not that many studies that do this kind of large scale interventions, then look, look at brain scans. But some small trials, like Dale, our British and Evan Thea trial was, which is not published yet, but the preprint came out recently. And there's a lot that we need to know about the, the structure of how that trial was run, how the control routes worked, all that kind of stuff. But they did, they did seem to show significant improvements in multiple aspects of cognitive function. I know they're tracking brain structure as well in individuals who are already experiencing some, some cognitive decline and early dementia. So everything that exists so far suggests that early on in the process, at least there's still capacity in the system to respond. Maybe it's only going to result in improvement, like improvements in function and quality of life rather than full reversal. And like whether you can fully reverse Alzheimer's disease, like I said, is very controversial. And I honestly don't know what the answer is. But the brain is still capable of responding to these inputs, which should result in changes in structure, even until sort of like early part of that process. I mean, I'm hopeful because for anyone that's ever seen Alzheimer's or any type of dementia, it's, it is devastating. One of the things that they were giving in the cognitive clinic was something called axona. And it was medium chain triglycerides. There's also been some use of ketones. I don't know if you've looked at that at all. Yeah. So the medium chain triglycerides are actually one of the sources of exogenous ketones that because the MCTs get absorbed in an interesting way and the gut that goes straight to the liver and get converted to ketones. There's probably some of the best evidence for them in the setting of some, some cognitive decline. So the, these studies are done by a large by Stephen Canane. And what they did is they took individuals with early stages of Alzheimer's and they gave them MCTs and saw some improvements in brain metabolism and then also in cognitive function. One of the things that you see in individuals with Alzheimer's disease is a decrease in glucose uptake into the brain. Right. So you, that's what it's like. The fancy worth is pathenomonic. You see this in certain areas of the brain. Like, okay, this is, this is Alzheimer's disease. And you do that with an FDG PET scan. And we'll have like a radio labeled glucose. You make it radioactive and you can see where it goes. And in Stephen Canane's study, they saw right, DQ, DQ's glucose uptake into the brain, but then when they gave MCTs, they saw, they did the same kind of scan, but with ketones with the C2 acetate and saw an increase in the C2 acetate coming into the brain. So more energy was getting into the brain and that was then associated with improvements in cognitive function. So is that just a fuel switch? They were switching fuels. It seems to be a fuel switch. So glucose uptake into the brain didn't change with them to MCTs, but ketone uptake did, did, did increase. We often think about glucose uptake decreasing into the brain in terms of like some kind of insulin resistance or some kind of metabolic disease manifesting in the brain. And some people have called it type three diabetes, which there are many other things that contribute to Alzheimer's disease. So like, I don't think you can just blame it on, on glucose metabolism. But it's interesting to look at what is actually happening when, when you, when you scan somebody's brain looking at glucose getting in, because the glucose getting in, you can say how much is getting in, but it doesn't tell you is that because the glucose can't get in or because the brain isn't asking for it. Right. So the, the parallel is in muscle tissue, right? We know that your skeletal muscle is your best glucose sink, right? But if you want your muscles to take up glucose, you have to move them, right? You have to create that demand for the, for the glucose to be, to be drawn in. And the brain is the same. So there was one fascinating study where they took individuals with a range of different levels of cognition. So healthy controls and then different stages of Alzheimer's disease. And you scan their brains and you see how much glucose is getting in. And as you expect, right, the, the worst, the stage of dementia, the less glucose is getting into the brain. But in the early stages of Alzheimer's, if you stimulated their brains with a cognitively stimulating activity, they asked for more glucose and more glucose came in. So I think that one of the reasons why we see decreased glucose uptake into the brains of, you know, individuals without Alzheimer's disease is because the brain isn't asking for glucose. Those regions of the brain are not being used in the same way. And therefore, it's not asking for it. It's just like your muscles not asking for glucose if you're not moving them. So at least again, like early on in the stages of the disease process, the brain can still respond and ask for more glucose if you, if you stimulate the brain. So this is one of the reasons why my like core idea is something that I present in the book is that I think the health and function of our brains is primarily driven by how we use them. And if we continue to use and stimulate those areas of the brain, they'll keep asking for more, for more glucose and they'll actually, you know, help maintain their structure and function. So we just need to think about both sides of the metabolic health side, but then also about like how are we using our brains and how's that determining what fuel source they're using. And you were, you're a lifelong academic and you're able to assimilate and recall and think and you're constantly improving and engaging in these activities. If someone is listening to this and they're like, I don't know, I sit down to read for 15 minutes and I'm tired. My brain is tired or I'm distracted by something else. How would you advise them? The most important thing that we can do in that scenario is anything that requires us to focus for an extended period of time because focus is a skill in its own right. And we see evidence that people who spend a lot of time focusing on anything then get better at focusing. So there's one study where this is done by Wendy Suzuki where they had people do a mindfulness training. So it was mindfulness, like 30 minutes of mindfulness, like they did like body scans and breath work. And within a few weeks, they saw improvements in the ability to maintain focus and attention because the one of the reasons why people struggle with mindfulness is because like you have to just like sit there and think about the same thing again, right, for a long period of time and like people struggle with that. That sounds great. It's like on my bucket list. But anything that anything that we can do that requires us to pay focus attention on one thing is going to help us build that muscle, right? So one of the best ways to do that is with something that's engaging and fun, right? So if you only struggled to read for 15 minutes at a time, yes, great. Maybe you could like build it out, right? 15, 16, 17 minutes, right? It's very similar to a training program, right? You start where you can and you slowly build capacity. But equally, you could play a sport or learn a language or learn a musical instrument or anything that requires you to just focus on one thing at a time because what we've become really less good at, just because we spend less time doing it, is just focusing on one thing at a time. We know that there's this thing called learning to learn, which is basically anytime you're learning something, it requires your focus attention. And when you do that, you then develop the skill of focus that you can apply elsewhere. So somebody's really struggling with their focus. Pick one thing that you want to do more of that you can only do whilst not doing anything else, right? You can't play badminton while scrolling on Instagram, completely impossible, right? Eliminate those factors because you have to pay focused attention if you want to do well. And if it's something that's fun and engaging and you enjoy, you're much more likely to stick with it. One thing that I've noticed, right, most of my work is on a computer, right? I've got emails, I've got Slack and Teams and people are messaging me all the time, I have to jump back and forth. Of course, like everybody, but very regularly, almost once a week, I have to go into the lab and I have to do one thing for three hours at a time. It could be surgeries. Yesterday, I was extracting brains because I do it faster than the team in my lab, just because I've done it so much. But I just like, you sit there and it's just like one thing, I've got nothing else to think about. I've just got to focus on this one thing, same one we're doing, same one we're doing, surgeries in the lab. So it's having these, whatever it is, something that requires you to pay sustained attention for long periods of time will help you build that skill. Because then I can apply that same skill when I'm doing research or writing my book or having to have a long conversation, right, which some people struggle with because they're constantly reaching for their phone or something else. So that's where I would start. Pick something that you want to get better at that requires you to just like pay focused attention to it and slowly build that skill over time and it will help you in other areas. Well, Dr. Tommy Wood, this book, I encourage everyone to get it, the simulated mind, it's so well written, it has just great action oriented items and congratulations. Thank you, thank you so much. I'm really glad you enjoyed it. Thank you again for your help getting it off the ground and getting it out there. I really, really appreciate it. Well done, sir. Well done.