← The Dr. Gabrielle Lyon Show
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- [00:00]
A
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.
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B
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.
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A
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?
- [00:37]
B
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.
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A
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.
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B
What must they do?
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A
Sleep is important. We know that people who consistently sleep for less than six hours a night have an increased risk of dementia.
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B
If you wanted to say, if you want to multiply your risk of dementia, here's what I would have you do.
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A
The biggest risk factors that we know exist are.
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B
Doctor Tommy Wood, welcome to the show.
- [01:32]
A
Thanks so much for having me. I'm super excited to be here.
- [01:35]
B
I am so excited about your new book, the Stimulated Mind. Really. And also we share a mutual agent.
- [01:41]
A
Yeah.
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B
Shout out to Joy Tutela at David Black Agency. This book is, I think, going to really put a lot of things in perspective, especially about brain aging.
- [01:51]
A
Thank you. That was my hope, of course. And, you know, I have to say, you know, thank you to you. I think partly it exists because of you, because you introduced me to Joy and really helped me sort of get my button gear to put a book together. So, so thankful for your help there.
- [02:08]
B
And, you know, you have been in research for quite some time. You're MD, PhD, 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 about Alzheimer's, which again, you do speak a lot on. But I have my own questions.
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A
Right.
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B
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 1 operators, seals, green Berets, whatever, you know, 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, you know, dance around three times and then, you know, 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.
- [03:21]
A
Yeah, it's a very interesting set of problems that they deal with. In many ways are very similar. Right. They need to be able to switch it on at the right time, stay focused, pay attention for extended periods. Then you 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. Right. Whenever you think about operators. So there's a guy I talk about in the book, a very good friend of mine called Pauli Detoro, 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, right? Nothing going on, just like, just sat there, like, unable to do anything, unable to control your environment. Right. You're sort of like the line is the line and there's nothing you could 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 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 prolongs performance in athletes is emotional regulation. And so the. 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 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 that they do very well. So the, the best, the best athletes are the ones that have the most self compassion, which is not necessarily what
- [05:49]
B
we think about that. I always thought of winning is actually a risk.
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A
Yeah.
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B
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.
- [06:08]
A
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, 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 like sometimes that doesn't, 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, that's, that's how you're successful in the long run.
- [07:00]
B
And when you think about regulating emotions and you know, you do talk about the autonomic nervous system, how does one, you know when stresses are high and it's almost like a visceral response.
- [07:13]
A
The, 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.
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B
I would say it's almost impossible.
- [07:34]
A
It's almost impossible. Yeah. Like your brain is too busy being dunked in adrenaline to like know what's going on. But you can leverage your physiology and senses to down regulate the autonomic nervous system. So some of the easiest ways to do that include breath work. Right. So slow paced breathing. Any, anything that results in you exhaling for longer than you inhale. There's a ton of different ways to do that. Physiological size 3, 7 breathing. But that's essentially it. Right. 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.
- [08:12]
B
It feels subtle though.
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A
Yeah.
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B
As opposed to some of the other tools that you mentioned in the book, the breathing feels more subtle.
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A
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, is 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, you can just switch that off.
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B
Not that you've heard.
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A
Pardon? Yeah.
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B
So like for example, you've heard bad news or there's always, it seems as often that there is this auditory component.
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A
So, 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, closing Right. Isn't going to help anybody. 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, that's very common using athletes, basketball players and, but also surgeons and you know, operators as well. So it's very purposefully focusing on, 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, like 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, changing what you hear. Right. There's a lot that we can do in terms of music or other sounds that can, 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. That the sort of, the final important thing, there's a bigger picture thing actually going into stressful environments is how you think about stress and being stressed.
- [10:36]
B
That's very cognitive. It's not managing the fight or flight or time with a friend or.
- [10:41]
A
But 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 jumping in the car, whatever match it is you're trying to play, or 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 gotten to this point where everybody's just saying that stress is bad. Anything that raises your cortisol, anything that raises adrenaline, right, Is 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.
- [11:36]
B
Talk to me about that. Yes.
- [11:38]
A
So there's this a ton of really interesting work, a lot of it done by Alia Crumb 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 triasocial 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 like a panel of judges and they just sit and look at you impassively. Like no facial responses whatsoever. Is incredibly stressful.
- [12:17]
B
Sounds like graduate school.
- [12:18]
A
Yeah, exactly. And you know, there's a few other ways that you can, 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, 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 Sullenberger 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 stresses 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 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 as 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.
- [13:58]
B
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.
- [14:11]
A
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, to remind yourself, but you can see benefits almost immediately. So I think that just allows us to remember that anytime we're going into a stressful situation, think about the fact a the stress is there to, 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 stresses 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 effect to improve your performance in the moment.
- [15:31]
B
And is it fair to say that the more you push yourself, midlife or youth, the more we say future proof your brain. 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?
- [16:02]
A
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 you absolutely can through lifestyle and the environment. But the other one is knowing that the future is unknowable. What does the work environment or AI or technology look like in 5 years time? How does that affect how we engage with the world on a day to day basis? We have no idea. Right.
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B
Are you concerned?
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A
Potentially, but it all depends on how we engage with those, with those technologies. And I think there's a lot of frameworks that we can build around that. So it could end up being a boon, but could also be disastrous.
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B
Well, but 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.
- [17:08]
A
Yeah. So the way that I think about it, and I think a framework is important because again, I don't know what these are 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. 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 technology, no Google, no LLM, just 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
- [18:18]
B
is a cognitive prosthetic.
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A
Prosthetic.
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B
Prosthetic.
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A
Right. So you, you use, you, you have a prosthetic leg.
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B
I've never heard that term.
- [18:27]
A
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 a 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, the, the sort of the, where the thought process goes. So you 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 deskill in real time. So it's really just going to depend 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.
- [19:27]
B
And also if the body atrophies and decreases in size, I mean, at what speed? 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?
- [19:45]
A
So, so like you say, 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.
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B
Is that based on volume?
- [20:04]
A
That's based on volume 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, you drive, a new stimulus to the brain, any kind of new cognitive stimulus, a 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, it's several years, but there was one study, one of the most classic studies of this. They had people in their 20s and 30s and they taught them how to 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 visual motor, like changing how you move your hands based on the visual inputs of the. 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 where all our brains shrink, but it also
- [22:02]
B
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 had to have been people that thought, okay, well, you know, people are getting bigger.
- [22:22]
A
Yeah.
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B
People aren't moving that. Here's the train going off the track.
- [22:26]
A
Yeah.
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B
I mean, if we have transparent conversations about it, then it becomes a choice.
- [22:32]
A
Yeah, Most of it, like, so you're right, we know that. So we have much better evidence for something like physical activity. Right. We know that physical activity is essentially a physiological imperative. Like your body requires movement in order to work at its best. It's kind of like baked into our evolutionary history.
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B
And will that also maintain similar brain volume as the counterpart cognitive skills like juggling or the more complex tasks?
- [22:59]
A
So some. 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. You and I have published a paper on this.
- [23:50]
B
We should link to that paper.
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A
So we know that because aerobic type exercise, particularly if you increase intensity that drives production of things like brain derived neurotrophic factor. That seems to help the gray matter, seems to help memory. Resistance training seems to release things like insulin, like growth factor one, IGF1, 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, 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 hyperpalatable foods in animals and humans is, I mean, it's a life shortening scenario. And that's a, that's a quote from Charles Brenner, who's a, 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 risk of some of the same, some of the same things because like, 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 or even the accumulation of knowledge, right? 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, that becomes potentially really concerning.
- [25:52]
B
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 blood 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. Timeline's mitopure contains urlithin A backed by over 18 years of research and multiple placebo controlled human trials supporting, get this, mitochondrial health. This isn't a stimulant or a quick energy boost. It works at the cellular level, supporting mitochondrial renewal, which over time may help improve muscle function and recovery. If muscle is the organ of longevity, supporting the engine inside that muscle matters. Go to timeline.comdrlion to get 35% off a mitopure subscription. You know, when I was doing my fellowship in geriatrics, I'll never forget this, and this was really surprising to me. Obviously you do cognitive testing and you do physical testing, and part of the job of a fellow is to run a memory and aging clinic. So you see individuals come in with vascular dementia, with Alzheimer's dementia, and I'd love for you to touch on those. But I will never forget this guy. He was a gym teacher, he was super fit, and he had really bad Alzheimer's dementia. It kind of blew my mind at the moment because it wasn't like it was just APOE4 or genetics. It just seemed to happen.
- [28:03]
A
This is one of the issues that I've certainly faced, and I know a number of people have faced when we talk about this idea that Alzheimer's and dementias in general are potentially preventable. So right now, depending on which analysis,
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B
do you believe that?
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A
I do believe that.
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B
Hence the book.
- [28:18]
A
Hence the book. Even though actually a lot of the. A lot of the book is about cognitive performance today. Right.
- [28:24]
B
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.
- [28:36]
A
Yeah. And we can, we can definitely come back to that even more. I think there's a ton to 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. So you already mentioned Alzheimer's disease. That makes up something like 60 to 80% of dementias. The next most common is vascular dementia, which makes up 10 to 20%. And they actually have a ton of overlap. So the majority of cases of Alzheimer's disease have some evidence of vascular disease, like issues disease in the blood vessels
- [29:13]
B
in the brain, which there's probably a component of that which is a natural part of aging. Do you think those microvascular white matter changes?
- [29:21]
A
Yeah. So, yeah. One of the reasons why white matter is actually really interesting when it comes to cognitive function, 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. Like exercise. So between those two, they make up like 70 to 90% of dementias. There are other types. Frontotemporal dementia, Lewy 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 multip in most. In most scenarios. So when we talk about that, then I understandably. Well, people will give me examples of that. Well, you're telling me exercise decreases risk of dementia. But I know this guy who exercised tiny was super fit and he still got. 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 and 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?
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B
Because that's so true.
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A
Each person experiences 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 be.
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B
Like numbers.
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A
Yeah, so numbers, decision making. There was a. There was a. 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, 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 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 as their fault, which of course is. Which of course is not the case because we're each doing the best that we can at any given moment in time.
- [32:24]
B
What must they do? If. If you wanted to say, if you want to multiply your risk of dementia, here's what I would have you do.
- [32:31]
A
Yeah.
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B
Struggle with obesity.
- [32:33]
A
Yeah.
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B
B, 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 Kryptonite. Yeah. If you were to say, okay, here is what I don't want you to do.
- [32:53]
A
Yeah. So I think that the, the biggest risk factors that we know exist are. Yes. Being sedentary, I'm not particularly concerned about as much about a specific body body fat percentage. Actually. It's interesting when you look at population data sets, like, for. For men, the, like, the, 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 prediabetes or type 2 diabetes.
- [33:36]
B
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 perfusion.
- [33:44]
A
Yeah. So the, the best sort of meta analyses of all the data we have suggest that if you're above 130 over 80, so, so systolic over diastolic, 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 controlled trials is blood pressure medications for people with high blood pressure.
- [34:25]
B
Have you seen any data with things like Cialis or, you know, Tadalafil for vasodilation?
- [34:32]
A
Yeah. So again, the best studies are less on Cialis and Tadalafil, more sildenafil. So Viagra. There is a. There's a study done looking, looking at 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 focused 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. For all of those drugs. But actually, sildenafil is interesting. It's being tested as a neuroprotective 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 the blood pressure medications, which are sort of high quality.
- [35:45]
B
And you can say this is the mechanism of action as to why this would potentially work.
- [35:48]
A
Yeah. But if you think about the things that are important for long term brain health, physical activity.
- [35:59]
B
And when you say physical activity, both a combination of resistance and zone to high intensity, where are we at?
- [36:06]
A
Yeah. So, well, let's. Let's finish the. The Viagra conversation and then we can come back to the next slide. Yeah.
- [36:12]
B
So all the men, all the male actually, and female listeners are now listening.
- [36:17]
A
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. But 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 erectile dysfunction who goes to a doctor to ask for a prescription, you need multiple things. Right. 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
- [36:58]
B
much sex counts as physical activity?
- [37:03]
A
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. The, you know, having a partner or partners having, you know, active sex life, which counts as physical activity. Having some kind of social connection, like all that, all that kind of good stuff that we know is also beneficial for the brain. So that it 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
- [38:03]
B
is unusual for people because that is easily tolerated.
- [38:07]
A
Yes. Yeah, you wouldn't know, you wouldn't notice it.
- [38:09]
B
And also tolerated by physicians. They would say 120 over 80. This is perfect. Potentially lower, maybe a little bit better for brain function.
- [38:17]
A
Yeah. So it kind of looks like it's kind of like 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 systol, 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 fasting blood sugar under 100 versus over.
- [38:41]
B
Do you think that that number is accurate? This is just a hypothetical question.
- [38:48]
A
You mean, like, is lower better? Yeah.
- [38:49]
B
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, maybe lower would be better.
- [39:11]
A
It's a great question. And when you look at like meta regressions, right. So you get like a big data set of 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 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. 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 metabolism, which
- [40:03]
B
would be elevated triglycerides, elevated blood glucose, elevated blood pressure, wide waistline and a low HDL.
- [40:11]
A
So below 50 in females and below 40 in males. And so like if you tick those boxes, right, then, then I'm. 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. That's.
- [40:33]
B
How big of a percentage does that play?
- [40:36]
A
It will depend from person to person, study to study. When I. So a couple of years ago, maybe it's three years ago now, my colleague Josh Turknett and I, 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, help to 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.
- [41:16]
B
That's tough. That's a very tough field.
- [41:18]
A
Very tough, very tough feel. Very tough job.
- [41:20]
B
For those who don't know what that is, it's end of life. I had to, I did that for a couple months on rotations and It's. You're seeing 30 patients that are getting ready to die a day.
- [41:33]
A
And like a lot of Julian's work is, is really important because it, you know, it talks about like dying with dignity, like death isn't. Death isn't failure, which is often, you know, what we kind of, we kind of assume as physicians, right, I need to keep this person alive as long as possible when that's not even necessarily best for them, let alone for, for other people in their lives. But what he work that he's done is focused on the building of what he calls compassionate communities. And so the first example of this was in Froome in the uk, where they, around the, 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.
- [42:17]
B
Like, amazing.
- [42:18]
A
What they sort of like 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, in that area they significantly decreased emergency room admissions whilst all around the counters 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. His idea is that our connection to others is the primary driver of this idea of cognitive stimulation and, and, and cognitive skills and how they build and maintain the brain. And that does 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, yeah, 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 vagus nerve, like down regulates a bunch of stress responses. Like, you know, like if it just
- [43:35]
B
feels good, isn't there a stress response? Tendon befriend that. So there, you know, we talk about fight or flight as if it's the only stress response. And there's other documented stress responses like the courage response. We know many people that are able to modulate that initial oh my gosh and then go right into action. And then there's also tendon befriend which is very much about community. What can I do? There's a stressor, but what can I do for you?
- [44:00]
A
Yeah, and so that's when you look at. So not all of this is related, not all of the, not all of these data related to dementia risk. But also just like overall mortality, we
- [44:10]
B
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, those nervous system connections are probably not as dynamic or real as the human pro social connection.
- [44:27]
A
Oh yeah, definitely. So just, 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 these opportunities to, to care or help or help others. 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.
- [44:55]
B
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 top down process of feeling shamed increases or would increase these autoimmune biomarkers. Do you.
- [45:35]
A
So I think the way I think about this and that this like the shame.
- [45:40]
B
But doesn't that sound a little crazy?
- [45:41]
A
It does. It sounds completely insane for those that
- [45:43]
B
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.
- [45:59]
A
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 stressors. Right? Humans are social, social beings. It's our. So our complex social structure is one of the prime. Was one of the primary drivers of human brain evolution.
- [46:43]
B
Meaning. What do you mean?
- [46:46]
A
So when the 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, right. That's this where we think we got a lot of this idea of, 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 this 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 another and looked after one another were, 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 that suggests 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, omega 3 fatty 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, like simulated trips to Mars. So NASA have done studies like this. We, we see looking at the brains of people who do like Arctic exploration while you're on your own at the top of the world for months. The parts of the brain that are most evolutionary, evolutionarily recent in human 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 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 brain seems to be driven by the social environment. Yes, all these like nutrition, physical activity, all critically important as well.
- [49:20]
B
But the structure and function are, the architecture is really based on the interpersonal.
- [49:26]
A
Yes.
- [49:26]
B
Connection. That's unusual to think about.
- [49:28]
A
Yeah. And you can see it like in very short term, like you put somebody in socialization for a couple of weeks, cognitive function declines because of the lack of stimulus and, 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, we recently edited an edition of a journal, the journal Lifestyle Medicine on compassionate communities and social connection, why it's so important to health. One of the papers was written by George Slavic and Steve Cole there 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
- [50:18]
B
is happening much more rapidly. 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 went from status over here and in one second completely shamed within moments to millions. And we see this all the time.
- [50:40]
A
And it happens even 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 trying to put yourself into place in 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, and you socially isolate them. So if I'm in my, you know, and one of my ancestral homes of Iceland a thousand 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, that's particularly important for like, like handling viruses, flus and colds and things, because that's what you get. You get exposed to those. When you're, 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 in a group. But if you get injured and you're by yourself, like you're stuffed, 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 chronically, you have higher baseline levels of stress. You, 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.
- [52:48]
B
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- [54:36]
A
Yeah. So be, 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
- [54:54]
B
function which are what are your top.
- [54:56]
A
So the most, the ones that we have the most important evidence for are vitamin D, omega 3 fatty acids, the B vitamins associated with methylation, which vitamin
- [55:06]
B
D ingested orally or meaning through foods or just the exposure outside either if
- [55:14]
A
you, you know, if you, if you need, if you need to supplement. I think there's, there's, 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, 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, folate, 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 there are randomized controlled trials where if you lower homocysteine, particularly in the context of Adequate Omega 3 status, you see slowed brain atrophy, slowed cognitive decline. And then iron particularly critical. I think there is, even post growth, even post growth, 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 menopausal 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 like 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. If you're anemic, you have low hemoglobin, we know that's suggesting poor ion status, that's not going to be helpful for the brain. But at the high end, high hemoglobin is usually the most common cause is obstructive sleep apnea. You become hypoxic during the night, the body makes more red blood cells in response. It's not then the high hemoglobin that's the problem. It's the fact that you have sleep apnea and you're, you're, you're not, not sleeping properly and you're becoming hypoxic during periods at night. So that's another reason why that's, that's a useful marker to look at. Then other things that we have some reasonable evidence for might include magnesium, zinc, choline in certain scenarios and then like the, the antioxidant polyphenols that you get from berries, the roasted skins of nuts and seeds, coffee, tea, you know, 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, you know, higher intake of those associated with better cognitive function, lower risk of dementia.
- [58:07]
B
And over a lifetime. Or could someone come in? Because these are all fixable.
- [58:11]
A
Yeah.
- [58:12]
B
Deficiencies. If someone is deficient, yeah. How, over what period of time do you think that there's impact?
- [58:18]
A
So I think that essentially as soon as you can address that, the better. But so something like vitamin D, we know that there is some vitamin D trials or like studies looking at like population intakes of vitamin D. Vitamin D supplementation is associated with lower dementia risk once people are into their 60s and beyond. So even later in life, if you're starting to address this, this, you could potentially change that. And most of the studies that look at vitamin status and dementia risk are again sort of like individuals in their 60s and 70s and there are randomized controlled trials of omega 3 fatty acids and B vitamins, again in individuals.
- [58:59]
B
That is absolutely, I am absolutely Sold on that data for omega 3 fatty acids and the brain.
- [59:04]
A
The, the interesting, 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 Vitacog study run out of Oxford in the UK, and they found that lowering homocysteine at least below 30, at least below 13, ideally below 11, was associated with slowed rate of cognitive decline, improved cognitive function, but only in individuals who had adequate omega 3 status.
- [59:33]
B
That is, that is, I mean, it's just interesting because what food has both Omega 3 and B12 naturally? What's the highest natural food in nature?
- [59:43]
A
Sardines. Small, small fish have, have both. And the, this has now been replicated in multiple other trials. So the bee 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 homocysteine. So there's a really interesting interaction there. And this is particularly interesting to me because you'll have seen 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.
- [60:15]
B
Absolutely.
- [60:16]
A
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 like one nutrient is gonna
- [60:29]
B
solve, but it also goes back to this whole food matrix.
- [60:32]
A
Yes. Yeah.
- [60:32]
B
Over time.
- [60:33]
A
Yeah. The people have estimated that we only really know about 10% of what's in like Whole Foods. Right. And so like 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 omega 3s. Like, from the trials, we know that supplementary mega 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 B vitamins in it. So there are a whole bunch of other things you're getting at the same time.
- [61:09]
B
How often do you recommend eating fish?
- [61:12]
A
At least two or three times a week. I think the, the goal is to sort of get something like 2 to 4 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.
- [61:55]
B
I mean that. So we had Tom Branagh on Dr. Tom Brunner. He was responsible for the last three dietary guidelines. His expertise is in fat, saturated fat, long term fatty acids. And he said that the idea that, that women, pregnant women should reduce their fish consumption, whether it was tuna or anything else he said's completely wrong.
- [62:17]
A
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 shorter chain omega 3s to longer chain omega 3s because they're so critical to infant development to the fetus and that may be upregulated even more during, during pregnancy. So you women may be more likely to be able to get short chain omega 3s like alpha acid from chia seeds and walnuts and things I still think they should eat.
- [62:54]
B
Yeah. And Tom would say it's not really bioavailable. The conversion is still off. It might not be.
- [62:59]
A
Yeah, yeah. It's better in women than in men because, because it's important for the fetus. But that doesn't mean that it's enough to like not, not consume them. But when you look at studies of infant development and then some studies of like 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.
- [63:28]
B
He said there's no reason, he said those that are eating more omega 3 fatty acids and fish, their offspring are, they are better off from a cognitive standpoint.
- [63:39]
A
Yeah. So the studies done in the UK on this, studies on the Seychelles on this, because the Seychelles is obviously an island nation that really a ton of seafood. And this I think is really important because so often we get caught up in this, we focus on like one negative thing in, in this food and we think that offsets all of the benefits and actually all the evidence suggests that 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 think about it in terms of seafood, we can think about it in terms of mycotoxins in coffee. All the signal says these foods can be beneficial and the net benefit is much greater than to outweigh some of these other things.
- [64:20]
B
What about alcohol? Alcohol, drug consumption?
- [64:23]
A
So alcohol is important. But I want to tell you about this one study in terms of. So there's a study that looked at mercury, the mercury content of, of people's brains, and they found that those who had more mercury in their brains had a lower risk of dementia. And like that. It doesn't make any sense.
- [64:41]
B
Makes no sense. Right, right.
- [64:42]
A
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. Right. It's just this signal for people having consumed more seafood. So like 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, if you want to eat more sardines, mackerel, smaller fish, anchovies, great, but we shouldn't be scared of seafood because.
- [65:15]
B
Which we have been. And women, pregnant women, even myself, but through my pregnancies I was like, oh, you know, I don't, I don't want to have too much fish. I was really concerned.
- [65:23]
A
Yeah, yeah. Whereas the. So, so when you were pregnant, then your body would have sacrificed your own dhc. That's right, DHA stores for your fetus, that we know that it's very tightly regulated. You, you will offload those stores because the, because the baby's brain needs it. So then like, 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 they're, 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.
- [66:21]
B
That's complicated. It does affect sleep architecture.
- [66:24]
A
Absolutely. So, like, I am not saying that, like, alcohol absolutely has downsides. It impairs REM sleep, in particular, causes a REM sleep deficit. It messes with thermoregulation, like, during sleep. So. 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.
- [67:00]
B
Okay, so in the UK, you're saying.
- [67:02]
A
Yeah, so in the UK, it's 8 grams of ethanol. In the US it's 14 grams of ethanol for a standard. For a standard unit or drink. So if you're. If you're on average, consuming less than half 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, decreases in cognitive function, increased risk of dementia. So the occasional drink with friends is fine.
- [67:37]
B
Is it the effect on B12 status or the B vitamin status, or is it something else?
- [67:42]
A
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.
- [67:54]
B
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. So, but don't tell me too much because that.
- [68:26]
A
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.
- [68:45]
B
And they probably have other bad habits.
- [68:47]
A
Yeah. No, and these things come together.
- [68:49]
B
I'm just trying to justify.
- [68:50]
A
Yeah. And so, like, to be clear, I'm. I'm backing you up here. Okay.
- [68:56]
B
So we know residency and graduate school.
- [69:00]
A
Yeah.
- [69:00]
B
And being pregnant, it's miserable sleeping.
- [69:02]
A
Yeah. And. And there's actually good evidence to support that. That's not a net detriment. So the. 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. Right. It's. 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. Right. We know exercise helps with that. If you exercise more, we know your sleep quality tends to be better. Right. So maybe you're getting less sleep, but it's better quality sleep because you'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. Thinks they slept or how well they think they slept by, like, manipulating data on a wearable. And actually you perform if you think you didn't sleep well.
- [70:09]
B
So are you ready for this? Not to interrupt you, but I just want to tell you the 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.
- [70:26]
A
Yeah.
- [70:27]
B
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.
- [70:33]
A
Yeah.
- [70:34]
B
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. For four hours anyway. And it just blew everybody's mind. Whether it's true or not, I don't know.
- [70:49]
A
Well, so they've done this. Well, 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's that? 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. 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 you perform the same, but you're just a little grumpy about it. Of course, the more sleep you lose, hours lost multiplied by number of days. Right. The worst 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.
- [72:01]
B
Is there recovery? Can we recover brain function?
- [72:06]
A
Yes. So we know that you can offset some of the effects of sleep deprivation during the week by sleeping more on the weekend. 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. 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 are 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, 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.
- [73:09]
B
My kids were waking me up at 5 this morning, didn't fall asleep till 1:30 because I had to put together a talk. And they're waking me up at five in the morning to read a survival book.
- [73:18]
A
But this is the thing.
- [73:18]
B
So, like, guys.
- [73:19]
A
Yeah, but, but. And this is. And this is what happens, right? And. But you 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 there's similar data on being like a pet owner. I was just thinking about that in terms of how it affects cognitive function and dementia risk. But like there's this. The net benefit outweighs the downsides. 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 maybe if at some point. Okay, so maybe it's important now to mention that you asked about recovery, meaning
- [74:17]
B
recovery from brain volume. Recovery from. They say that Alzheimer's is not reversible, that cognitive decline prevention is the best metric or the prevention is the best measure versus once you have problems, you're in trouble.
- [74:35]
A
So as it relates to just to sleep, and then we can expand out from there, there was a nice study done by Matthew Walker's lab where they looked at people and their, their sleep as it changed over the, 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 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. That even suggests that 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 there 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.
- [75:53]
B
This episode is sponsored by Branch Basics. One thing I've become much more aware of over the years is the impact of the environmental chemicals on Our food and also inside our home. If you're a frequent listener, you know we spend a lot of time talking about nutrition and muscle health, but beyond that, we should be thinking about what we're exposed to every day through things like cleaning products. Now, I started using Branch Basics when I was pregnant to of course limit my exposure to harsh chemicals. Their products are made with plant and mineral based ingredients and their premium starter kit uses a single powerful concentrate that can replace almost everything in your home from laundry detergent to bathroom cleaner and even get this produce wash. I like that it simplifies my cleaning routine and removes any concern of exposure for myself and my little ones. If you are also worried about the chemicals you are using in your home, I suggest you try Branch Basics. You can get 15% off the premium starter kit at branch basics.com with the code Dr. Lyon. Again, that's 15% off branch basic basics.com with the code Dr. Lyon. You see that on imaging, for example. You might see again, we image a lot of people's brains and we see microvascular, what do they call it, white matter changes.
- [77:25]
A
Like hyperintensities.
- [77:26]
B
Yes, that is. And it will say, you know, 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? So things like that, like as conditions thinking, okay, so we fix these things, they believe they experience some improvement. But do we see the actual imaging change?
- [77:54]
A
Not all of the studies that have looked at say cognitive function have then, especially in the setting of like already established cognitive decline, will then we'll then do it. We'll then do imaging as well. But so if we're still like earlier 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 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 amyloid and tower burden, even though they are related. So yes, some of that seems to be, 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, 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, of previous function that you had. Like you have 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 there is capacity in the system to respond to these interventions either. Right. So that cell bodies could increase. You also see changes in the extracellular matrix and structures around cells. So the brain is capable of neuroplasticity basically until the late stages of dementia. So 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. Not that many studies that do this kind of large scale interventions then look, look at brain scans. But some small trials, like Dale Bredesen's event year trial, which is not published yet, but it's the preprint, came out recently. There's a lot that we need to know about the structure of how that trial was run, how the control groups worked, all that kind of stuff. But 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 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 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, you know, even until sort of like early parts of that process.
- [81:39]
B
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.
- [82:01]
A
Yeah. So the medium chain triglycerides are actually one of the sources of exogenous ketones. Because the MCTs get absorbed in an interesting way in the gut, they go straight to the liver and get converted to ketones. There's probably some of the best evidence for them in the setting of some cognitive decline. So these studies were done largely by Stephen Kinane. 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. It's like the fancy word is pathognomonic. You see this in certain areas of the brain. You're like, okay, this is Alzheimer's disease. You do that with an FDG PET scan, with a radio labeled glucose. You make it radioactive and you can see where it goes. And in Stephen Cunning's study, they saw decreased glucose uptake into the brain. But then when they gave mcts, they saw, they did the same kind of scan, but with ketones with acetoacetate, and saw an increase in acetoacetate coming into the brain. So more energy was getting into the brain, and that was then associated with improvements in cognitive function.
- [83:22]
B
So is that just a, a fuel switch? They were switching fuel?
- [83:25]
A
It seems to be a fuel switch. So glucose uptake into the brain didn't change with mcts, but ketone uptake did. It 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 3 diabetes, which, there are many other things that contribute to Alzheimer's disease. So, like, I, 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, 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, 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 worse 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 know individuals with 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, 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 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.
- [86:02]
B
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?
- [86:27]
A
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, 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 mindful. It's 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 one of the reasons why people struggle with mindfulness is because you have to just sit there and think about the same thing again for a long period of time. And people struggle with that.
- [87:12]
B
That sounds great. It's like on my bucket list.
- [87:16]
A
But anything that we can do that requires us to pay focused 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 struggle to read for 15 minutes at a time. Yes. Great. Maybe you could build it out, right? 15, 16, 17 minutes. 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 focused attention. And when you do that, you then develop the skill of focus that you can apply elsewhere. So if 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, you know, 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, like, I just. Like, you sit there and it's just like, one thing I want nothing else to think about. I've just got to focus on this one thing. Same when we're doing. Same when 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, you know, having to, you know, 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. It will help you in other areas.
- [89:54]
B
Well, Dr. Tommy Wood, this book, I encourage everyone to get it the Stimulated Mind. It's so well written. It has just great action oriented items and congratulations.
- [90:05]
A
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.
- [90:14]
B
Well done, sir. Well done.