Rethinking Cognitive Decline: Stimulus, Exercise, and the Aging Brain | Dr. Tommy Wood, MD, PhD | The Metabolic Link Ep. 90

Welcome to the Metabolic Link. I'm Dr. Angela Poff, co-founder of Metabolic Health Initiative, and a scientist who studies the role of metabolism in health and disease. Today's episode features a conversation with Dr. Tommy Wood, a physician, neuroscientist, and author of the new book The Stimulated Mind Future Proof Your Brain from Dementia and Stay Sharp at any age.

doctor Wood is an associate professor of pediatrics and neuroscience at the University of Washington, where his lab studies brain health across the lifespan, including brain injury in newborns and adults. and the factors that influence long-term cognitive function and risk of dementia. His academic path spans biochemistry at the University of Cambridge, a medical degree from the University of Oxford, and a PhD in physiology and neuroscience from the University of Oslo.

In addition to his research career, Dr. Wiz has worked for more than a decade as a performance consultant to elite athletes, including Olympians and Formula One drivers. Helping translate neuroscience and physiology into real-world performance strategies. This conversation explores how brain health is shaped across the lifespan, from education and cognitive stimulus to metabolism, exercise, and lifestyle factors that influence resilience and long-term cognitive function.

And if you'd like a chance to ask your own questions directly to Dr. Wood, he's going to be joining us for a live QA on March 25th at 9 a.m. Pacific, 12 p.m. Eastern on our medical education platform, The Metabolic Initiative. It's a great opportunity to ask questions directly and dive deeper into the science around brain health, metabolism, and performance. You can find the link to register for free with a seven day free trial at membership.metabolic initiative dot com slash wood.

All right, let's jump into the conversation with Dr. Tommy Wood. Dr. Tommy Wood, it is great to have you back again. It's been a few years since we last spoke and did a very comprehensive podcast on sort of your expertise, but I am excited to jump into the topic. of uh your book today. I have many questions about the book and also um Work that you're doing on top of that, the book entitled The Stimulated M uh Mind, The Future

future proof your brain from dementia and stay sharp at any age. And I think this book really, really resonated with me. Uh and we're gonna dig into I have many questions. Uh but I would like you to begin. Most people kind of know about your background. I would like to know sort of, you know, what inspired you to write this book and who did you have in mind?

for writing it uh and come to that but maybe we could start off with the Stanford Barn Ow experiments and that would might set the stage to the first question of of sort sort of who and why you're addressing these topics in your book.

Yeah, absolutely. Uh thanks so much for for ha having me back. Uh fantastic to to to be here with you. I'm a huge fan uh of the show and and everything around it. So the The preface to my book opens with this story about um some experiments that were done at Stanford uh with Barnells, you know, now twenty or thirty years ago. where they looked at how the age of the brain determines how um we respond to or adapt to new stimuli. Um and this really gets at this idea or this question of, you know

I I can you teach an old dog new tricks? That you know, that's such it. Like, do you get to a point where the the brain is no longer able to adapt uh and improve? And There were a series of experiments that sort of explored this. But the the the core idea or the core approach was they they took these barn owls.

And they attached prism goggles to their heads. So uh a prism being something that redirects light, um and what that means is and there are these great pictures on you can find them online in the papers of these like Barnows wearing these like funky looking goggles. And what it means is that um

They shifted where things were in the visual field compared to where the owl expected them to be. Um and so like if you put if you put them on when they've done similar experiments with humans, like everything shifted a certain amount to the left or right. And then you can look at how the owl map um in the world around it, both visually and then it also uses its ears um a a lot to write to to direct where where it's looking and and have it sort of like map of of of space around it.

And What they did is they so they put these goggles on. And then they are How does the age of the owl affect whether it can adapt? to this um new stimulus. And the adaptation basically mean can it start to uh behave such that it's uh it's uh corrected for this slight shift in where everything is'cause otherwise, right, you hear uh

Uh like a mouse running around and like you look and you can't see it because everything's sort of shifted. It's not it's you can't see it where you hear it. Um and what they first found was that the young owls could adapt very quickly, but old owls could not. Um and then this, you know, if you kind of stop right there, you're like, well this is we know this, right? The adult brain is fixed and we we can't we can't change it.

But then they did two additional things to show that this isn't actually the case. So the first is that when they housed the older owls socially with other owls, they saw the the age at which the brain could adapt to to the prism goggles. You know, when much later into life. Essentially saying that when you have to then interact with the environment and interact with other individuals, right, that's a stimulus to drive adaptation in the brain.

And then the next experiment was rather than having the um owls just fed dead mice Where they could, you know, they can shuffle over, they can smell where their dead mouse is, they can eat it even though they can't they can't really figure out where they are in 3D space'cause their their sort of visual fields are shifted. They instead forced them to hunt for their dinner by putting live mice in the cage. And then adult owls again could adapt to this vis visual shift.

So saying that, you know, when there's necessity or when you create the um uh an interaction with the environment that's required, like adaptation is needed, the brain could adapt just fine. So The the if we if we compare this to like humans, in one scenario you're just like sat at home, socially isolated, food is just brought to you, you don't have to interact with the world at all. Um Right, that's the first condition and and the brain doesn't do very much, right? But

You go out, um, you socialise, you are like given new challenges that you have to interact with, then the the brain can adapt just fine. So Um just a really interesting um set of experiments to show that the adult brain is capable of adapting, you know, and y we can translate that to improving function, you know, even very late in life. But it requires a specific type of stimulus and engagement in the environment in order to drive those changes.

Mm-hmm. And that stimulus presumably is activating like The sympathetic nervous system, uh, adrenaline, dopamine, things like that. So you need to be like excited and engaged. And I think about, you know, the the hungry hunter has to go out. Actually I was thinking about uh

Bow fishing. I don't know if you know what that is. Like yeah, you know, it's so I grew up like bow hunting and then also like in the summer bow fishing. And you have to um the fish is not where you're shooting. You have to correct. for the depth in the water and some. And when I was reading the preface of your book, it reminded me of uh bow fishing, like how you'd have to like aim at

you know, to correct for that prism effect. So uh but you learn it, you know, over time at first you're like missing everything and then you kind of learn to correct like, you know, where the fish is. But it's also the just that stimulus of having to like catch the mouse and then, you know, uh and that's such a important I mean, that's essentially the theme of your book. You and so many people focus on diet or drugs or supplements or things like that, but it's really the

the the cognitive stimulus that's probably the biggest lever that we can pull, right? I mean, to produce plasticity, adaptation, and ultimately to preserve and maintain brain health and cognitive function, right?

The essence. Yeah. Absolutely. And and I um so so there's other things are important, right? Diet, sleep, all the yeah, supplements supplements, like all all that kind of stuff is important. But the way the way that I think augment that too. Yeah, yeah. Exactly. These are metabolic modulators. Yeah. So absolutely. And and so the way I think about it is actually very similar to how you might respond to

physical physic physical exercise, right? Resistance training for muscle strength or muscle size, cardiovascular training for, you know, aerobic fitness. And We know that if you want um to have bigger biceps you need to do bicep curls, right? The stimulus is the most important thing. You can improve or like get the most out of your training with a proper diet and good sleep and recovery strategies. Right. But without that stimulus, you're not going to drive

those adaptive processes in the first place. And and in many ways the brain is the same. And like you said, One of the ways that we direct that is with focused attention that is required in order to direct neuroplasticity and those adaptive changes. Um and that's where those neurotransmitters you mentioned are really important. You know, dopamine, acylcholine, noradrenaline, right? You need to engage in the task um in order to to drive those processes.

Yeah. Yeah. And you know, another theme like engaging in the task and making sure that you have That the set and setting is important too. Right. So like your brain has the energy. If like your brain is unhealthy, then it's kind of like if you're lifting weights but you don't get enough protein and you don't get the nutrients that you need. Uh, when you lift weights you have a stimulus and it's doing all sorts of damage to your muscle and oxidative stress and everything.

But it's the uh adaptive response to the stimulus that actually creates a stronger muscle. And we're talking about a essentially a stronger, you know, adaptable plastic brain. Right. So That involves brain energy and metabolism and a major theme of your work is that Uh the brain is fundamentally an energy energy hungry organ and

And early in life, uh, so how do factors um that are early in life, uh metabolic factors, begin shaping the long-term brain health? We know that if we're laying down bone, uh, we have to like lift You know, uh what we do early in age impacts our bone health and our bone mineral density. Uh although I think we could start lifting at a late age and our muscles can adapt really. But I think there's I think in your book.

It talks about maybe things that you do early like your education, especially your your education. Um So uh how do we you know How do we sort of view it from that lens, like factors that we do sort of early in life related to long-term brain health? And and how do we know if we're on a trajectory? uh long before the symptoms appear and that could be lifestyle things like we can't, you know, remember people's names, we keep forgetting our keys and things like that. So

So maybe set it up from the context of or maybe explain it from the context of things that we do early in life and we get into certain cognitive patterns. And I think people people like me approach, you know, in the fifties and, you know, going into sixties and stuff. what are some of the early canary and the coal mine sort of things that we need to pay attention to. If you've noticed tiny tells of aging, less energy, more restless nights, unusual blood work, you're not alone.

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this idea of stimulus being the primary determinant of function in the brain, you know, how you use your brain ultimately determines how it functions, does start with the process of of brain development. And we also see across all these different stages of life, um, early childhood, midlife, late life, that things like um nutrient availability, uh, metabolic health, right? These are critical um sort of modulators of uh brain function.

But sort of overarching through that is this idea of of of stimulus. So you mentioned education and

That's probably some of the best evidence that we have that that stimulus drives function uh in the brain just because it's something that we can look at at the whole population level. It's very easy to to measure and then we can you know, we can do cognitive function tests. Um But even before that, one of the things that really brought my attention to this is, you know, I I study newborn brain injury.

And there are several um studies now, some of which that I've I've been involved with and or you know, did some statistical analyses for. where in the setting of an imperfect start to life, you have some kind of early life brain injury. What happens in the hospital, you know, some you know, kids born very you know, very preterm or extremely preterm, they might spend months in the in the nitcube in the hospital before, you know, th they can go home.

What happens there is obviously very important. Um, they have brain injuries, they're exposed to drugs and painful procedures and all these things that can affect brain development. But the biggest predictor of how that kid then does in childhood is the home that it goes home to, more so than all the things that happened in hospital. Um This is usually measured by proxies of socioeconomic status or p parental education. Um, but you can imagine how that determines

um the opportunities that kids get to play sports and read books and the food that they get and you know the education that they get and all that kind of stuff. And those things have a a b a bigger impact. on how that kid develops compared to you know maybe some of the things that that happened earlier, even though some of them could be very, very serious. So it shows that environment and how you interact with it is really driving a lot of cognitive functions.

And so then as we go through childhood and into early adulthood, you see in multiple studies that the peak of cognitive function, you know, if you measure sort of like a battery of lots of different cognitive functions, happens around the time that you leave formal education.

So the higher your level of educational attainment, the higher your average the higher the average peak of um uh cognitive function and the later it happens. Right. So um because it has to happen later because you're spending more time uh in school.

And attainment is a better predictor than time in education because attainment shows that you know you're engaging with the material, you're passing your exams, you're kind of you're you're learning how to learn, you're learning how to focus, right? These are critical components uh sort of of driving function.

And and then so so we know that that period is critical to kind of it sets like some aspect of our maximum capacity. So how are you defining I just want to be clear how you're defining maximum capacity. I do remember taking uh IQ tests through college thinking like what's my I am I smart enough to do like a neuroscience program? Yeah. And I took it several times and towards the end of my PhD, uh, I took it again and

It went up like twenty points after doing from s from the first time I took it. I I didn't get I didn't feel like I got twenty points smarter, but I I was better at taking the test and that was an I you know, an IQ test and it was like it was higher than I expected, like towards the end of my academic, you know, really intense studying.

you know, the physics, the calculus and all that stuff. And I think my my brain was just trained to sit down and have the attention span to do these kinds of tests. Right. So so when you're when you're talking about people get their maximum c th is that a battery of cognitive tests or are we talking just like IQ? Yeah. That that that's a fantastic question because it's it does this gut gets down to some of the issues that we have in examining cognitive function at you know

more broadly, because say compared to exercise training, right? I know how to test your function.

for a specific that's going to be related to a specific performance. I also know how to measure the stimuli in the gym, say that are driving that function. It's much harder to do that in the brain and we're only just starting to develop some of the technologies to do that. So You're right that part of the reason why people who spend more time in education um ha you know have higher cognitive function or cog cognitive function tests is because we get better at taking

That's absolutely part of it. But that's not necessarily a bad thing because if we're thinking about the processes of engaging with skills and challenges and that that drive function in the brain, right, that requires focused attention. So one of the reasons why education helps to support cognitive development is through a process of le what we call learning to learn. Right? You learn how to engage in these things such that they can start to to to drive adaptation. So

Some of it is messy because of that. Um, but I I think that still tells us something about whatever what we need and the the skills that we need in order to to kind of uh improve brain function. Um when we when these tests are done sometimes it's like a like a Wexler full scale IQ. That's like a a very standard uh IQ test. Some IQ tests do have their issues because they tend to be biased towards certain um demographics. That was like part of the inception of of the IQ test.

Um, was basically supposed to show that white men are smarter than everybody else. Um, unfortunately. Um, and we're still sort of unpicking some of that. Um, but Bye. What the you would generally test a whole range of domains. So you might test uh processing speed uh with something like a digit simple substitution test. You might uh test uh response inhibition or certain aspects of uh executive function with like a go, uh go no go test.

uh working memory with something like an NBAC. Um and so you can kind of stack all of these up together and then often when they talk about global cognition it's like a an average across all these different uh across all these different areas. Um although some things uh do support uh different cognitive functions in different ways. So different types of exercise um drive different changes in in different cognitive functions, for instance. But usually you're kind of looking at an overall battery.

Then um to kind of finish that trajectory, so so we have some kind of idea of our maximum capacity driven by education, but we also know that it doesn't have to be that way. We're talking about at the population level, right? because what you see is that um depending on your educational attainment

your risk of dementia is lower. And if you do get dementia, it happens later because you've come from a higher peak. So you need to lose more function before you get to the point at which we might, you know, w which might be diagnosed as dementia. There's plenty of evidence now to show that what you do after education changes the slope of that decline. So you can do that based on

uh cognitively stimulating or complex jobs. That's again one of the easiest ways to track this stuff because your work is usually something that you do Every day for for for decades. Um, but you can see signatures in um late life music learning, in uh skill learning, in dance in dancing, in learning uh Duolingo.

Right. We n um when you look at people's hobbies and they spend more time reading and going to lectures, you see d uh you see differences in terms of the the the slope of cognitive uh cognitive decline over time. So yes. Some aspect of your function is shaped early in life, but you can still have control over um that that function even if you didn't get some level of educational attainment early in life. So it's like um it's like a combination of

that bone and that muscle picture that that you mentioned, like both seem to be part of the the the picture of cognitive function. We all know how important the quality of our food and our environment are for our health. So we're intentional about what we feed our families. Good meat, homegrown produce, clean water. Yet for years I wasn't paying attention to the products I used on my skin, our body's largest organ system.

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is essentially a downward slope, like say if you graduate with your M D and your PhD, I don't know when you graduate, but um do you feel that You know, even in the case of your I mean,'cause you're in intense learning situations where you have to learn new things all the time, new content, new New research and things like that, that the slope is essentially down. So that's not the case like with muscle. If a like a 70-year-old picks up.

You know, a resistance training protocol, they they could they could add five, ten, fifteen pounds of muscle if they aggressively go at it. uh from the context of cognitive function, maybe even IQ and things like that, that is unlikely to happen, but we can dramatically shift that slope and uh but you have more headspace, right? Like Uh if you if you get, you know, if you basically build cognitive

bank, like I think about I think of the analogy that you use quite frequently with building muscle. So you're basically building like metabolic currency. Like if you're saving your four oh one K financial, you know, Currency and uh metabolic like currency over time and you're depositing into the bank. So can we think about it like that too with cognitive function just uh we're depositing into the bank, but we will have a negative slope over time. That's just

But we can delay that. But there's no way that we can like reverse that. You know, there are case reports where people have reversed, you know, symptom dementia and Alzheimer's and things like that. But I guess they're kind of one-offs, maybe, from your context.

So there's there's a few parts that I'm unpicking. I threw a lot of c I threw a lot of like random kind of questions at you, but but I'm just approaching it from the context of Some people may say, well, this person reversed their Alzheimer's disease and now their clock test or mini mental status exam or whatever has improved and they're they're sort of uh improving upon that.

But the general population we have to accept that it's a downward slope, but we can dramatically alter that slope. So so y so y yes and no. Um because I I think that Um th there's two parts to that. One is Yes, ultimately we cannot prevent the processes of aging. And at some point, cognitive function, just like all bodily functions, will decline, right? Like even if we continue to train and we're very diligent there, like we're never gonna be you're never gonna be as as

uh strong at 90 as you are right now. Like that's we just right we that's the case overall until something dramatically changes in science. So there will be some element of decline, but when you think about cognitive function declining, say more broadly, often we like look at these uh curves where like yes, cognitive function uh increases um up to a sort of like our mid uh twenties to early thirties, right? That's when

the prefrontal cortex uh sort of finishes developing, that's when we finish a formal education. Then after that it sort of dec d declines fairly linearly and maybe there's a drop off later on. Those data are population data. So there right, this is what happens on average. So yes, there's always gonna be somebody as you get older or people as you get older whose function is dropping. Therefore that drags the population average down.

But when you look at studies that follow the same individual for several decades, and there are um there was one sort of like this one of the seminal studies on this was was actually done at the University of Washington by uh Warner Shaye, it was called the Seattle Longitudinal Study.

And it started in the fifties, nineteen fifties, and they took people, waves of people every seven years. So the same people came back every seven years, and then they added new people every seven years as well. Um and some of the first studies that came out of that showed that um the average change from like people as they go into their fifties, sixties and seventies was no change. So yes, the overall population

Um d d declined because some people were losing function. That drags the average down. But the majority of people, sort of like fifty to sixty percent, actually maintained most of their function f in their fifties into their fifties, sixties and seventies. So There's a difference between what's happening to the individual versus what's happening at the at the population level. So I think that's important because it says that actually it's not unusual.

to maintain function for several decades uh in into late life. And that's a completely different way to think about it compared to how we might normally think about it. So I don't think decline is inevitable, particularly in that age period, you know, fifties to sixties, seventies, eighties. Right now we think it's unusual. We call them super ages. But actually I think that this this could be um something that most people would expect uh to experience.

So that decline or at least significant decline that then affects quality of life isn't um sort of predestined. And even then, I think there are studies that show that we can move the needle in the opposite direction, right? We we can increase function. So Some of this is um You especially if previously we had uh some significant risk factors for for cognitive decline, because that's where most of these studies have been done. Either individuals with a a high risk

Of cognitive decline, or they've already experienced some some some cognitive decline and we're trying to sort of reverse some of that. So there's the pointer and finger studies, for example, where they did. big lifestyle interfa like multi component lifestyle interventions. Finger was done in in Finland about a decade ago. Pointer was the US version that that was just r um published uh last year.

where they did um cognitive training, um, they uh some dietary changes. My favorite point of the pointer trial is they sent everybody uh vouchers to buy blueberries every month, which I thought was really cool. Um uh so physical activity, diet changes, um, they did cardiovascular risk monitoring. And and c and cognitive training. Um, and they showed that those who did that compared to a an active control group saw greater improvements in cognitive function.

Um especially those who started from a lower level of cognitive function to begin with. That was very similar to what was found in in in Finger. Um but because you're testing these people regularly, you do see the t the tests improve overall. So you're kind of looking for changes in that upward slope due to the due to the intervention. But it does seem that they that they can improve cognitive function rather than just

prevent decline. Um and then yeah, there there are then they're they're small studies and some of them are quite intensive, but there there are examples where you can at least improve quality of life and potentially some aspects of cognitive function, even in in early

in the early stages of cognitive decline, maldognitive impairment or early Alzheimer's. I think there's a a lot of promise and a lot more to be done there, but it certainly looks like you can um improve some aspects of function rather than just preventing d decline. What do you need right now on your path to health optimization? More energy, more focus, better sleep, a stronger immune system?

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Do you think that you know that Cerebral brain energy metabolism is A key factor or a key lever that we have the ability to change through dietary manipulation, through exercise, of course, too, affects cerebral blood flow. things like that or supplementation or or drugs um that could potentially work in this capacity, maybe like stimulants like caffeine or uh modafinil or other other things. Uh Do you uh do you think and just getting to the point of brain energy and metabolism, uh,'cause

And and you discuss metabolic stress a lot as like a common thread in your book. Uh so and maybe so metabolic stress, we'll talk about it from the context of like uh Pathological situation or a as we age. So we get a cognitive decline. Our mental health becomes uh more fragile, I think, or less resilient over time. And and we tend to get like and I see this in older patients, they get

situationally overwhelmed and where they didn't maybe ten, twenty years ago. And uh the same situation, just navigating something if they're lost in traffic or something like that. and neural regeneration. So uh so you have metabolic stress can impact cognition. mood and mental health and also neurodegeneration.

So there's like a couple different metrics there. Uh so what are the early what are the earliest warning signs that people should kind of pay attention to? And we talk about like situational cognitive decline. I guess people call that brain fog, but I don't know if that's like a term in use. But I guess the important like people listening to this that are maybe 50s, 60s, 70s.

What are their earliest sort of warning signs that people should pay attention to? Cognitive, mood, mental state, like uh, or maybe things that we should measure too. Like So I know that's a that's also a loaded question, but uh but yeah, just the early warning signs because I think uh whether people listening or their parents or their loved ones

uh will tell them certain things like I feel older and saying that you feel older too can make you advance any so uh like as parents age or whatever, you know, they're they they say things and there's sort of that's probably not a good thing to say. But uh but I think Like when these situational subjective uh you hear subjective comments. Uh, when is when should we be concerned? And what are their early warning signs that we should pay attention to to then really?

do an intervention. And we'll talk about sort of, you know, your interventions and things like that that you have. Yeah. So thinking about some of the things that people m might notice. Um so that kind of th those situational changes, I think they fit into um

these changes that we we we might see over time um in terms of like total total capacity. So in uh the book I have this idea of headroom, which is essentially a combination of br uh uh resilience and reserve, which are sort of like measurable scientific things that account for like how like what can your brain take over your lifetime and still maintain function, right?

Um and they technically measure different things but they're they're they're very similar and some of the same uh And so Headroom as as I uh propose it, is it is the difference between what you need for just like

day to day like we're having a conversation versus what are you totally cap what what's like the maximum you're capable of. And I've stolen this directly from Art Devaney, who people may know. Um he talks he talks about uh physiological headroom, right? So it's the difference between Um the leg strength required to get up out of a chair versus what's your maximum back squat, right?

That's your headroom. Is that the difference? And you want that to be as big as it can be for as for as long as possible. Because once you're under significant strain, you need to be able to tap. uh into greater capacity in order to maintain a given level of of function. So as your headroom declines, which is largely driven by sort of environmental and lifestyle factors.

um, those situations become more stressful, right?'Cause you you you don't have additional headroom to to to tap into. So that's one thing that people could think about. You mentioned brain fog and subjective cognitive decline.

Those are not technically the same thing, but they have very similar um criteria and similar symptoms. So subjective cognitive decline has now actually been included in the sort of spectrum of cognitive change where at one end we have cognitively normal and the other end we have uh you know dementia and The so like subjective quality of decline is now included as like the the first Warning warning signs of the yeah.

Uh, because you couldn't measure it on a cognitive function test, right? If you had normal you're right, you were on the in in the normal bell curve for a some cognitive function.

Before, now you feel like something's not quite the same. If I tested you, you'd still be in the normal range. So I'd say like there's there's nothing, there's no issues here. But you might notice something, your family members might notice something. So I think it's important that these are now included in diagnostic criteria'cause'cause that allows researchers and doctors to start taking it more seriously.

Um the the symptoms overlap with brain fog, which we might think more in relation to long COVID and other post viral symptoms and other things where we you know we just can't really define what's going on, but it could be Changes in memory, could be changes in um could be changes in mood.

Um, could be like, you know, changes in uh verbal fluency, all these things kind of c come together. And actually when you look at what gets lumped into subjective cognitive decline and brain fog, those are you know, they have those symptoms in in common. Um And there are different ways to sort of quantify them. So I I kind of um step back a bit and say, if you've noticed any of these things recently,

That's not necessarily something you need to worry about, but it's it's like the the check engine light goes on. Maybe it's time to like think about, you know, where are my risk factors? Are there any changes I can make? That kind of stuff. Because for for two reasons. Those who have subjective cognitive decline have an increased risk of later dementia. That doesn't mean that having subjective cognitive decline will mean you'll get dementia, right? Because

We think that the changes associated with subjective cognitive decline are reversible. So if you had significant risk factors, you notice something, you change something, you can change that trajectory. Um so that's kind of where um I think people can can can focus. Well you start to notice something, that's the point to just think about, hey, where could I maybe make some changes?

Because it's not it's it's it's early enough, we're not too late at all. Thinking about um sort of the the energy metabolism side. We know that um One of the best sort of metabolic predictors of cognitive decline dementia is uh pre diabetes, and then risk has increased even further in those with type two diabetes.

Um, blood pressure is another one. Um and so one of the reasons why I talk about um metabolic stress, um, I have that a sort of lump it into this big broader category of excess energy availability. Which essentially in a at a doctor you'd you'd measure the components of metabolic syndrome, right? So blood sugar, blood pressure, waist circumference, lipids.

The reason why I call it that is because at the other end of energy availability we see the same thing, right? So low energy availability, very common in athletes, but also common in, you know, areas where access to to food is is uh less abundant. Compared to say the US. And again, we see um lower uh brain reserve, so lower brain volume, we see mood changes, we see cognitive function changes, right? So we see those at o uh both ends of the energy spectrum, um, either too high or too low.

So that so we can kind of following that full spectrum, that's why I call it excess energy availability. And so We know that blood sugar issues uh are significant predictors of chromosome decline. We also know that um one of the

The pathonimotic, which basically means if we see this, we think we we know what it is, right? So is a a pathnemonic of Alzheimer's disease is decreased glucose uptake into certain areas of the brain. Um And so there's obviously an issue with energy availability or energy production.

um in those areas of the brain that are affected by um Alzheimer's disease or dementia. So the hippocampus is is one that people talk about a lot, very important for memory um production or um encoding and consolidation. And what's interesting, um, and i is that we've sort of focused on the access of energy to the brain as being important, right? This is where alternative fuels could become important, right? We know that the work of Stephen Canaan shows that if you give

M C T oil, you can increase um uh ketone uh access into the brain. That seems to overcome some of the energy deficits. Not the glucose deficits, but you're just you're providing an alternative fuel. seems to be associated with improved cognitive function in those who've experienced some cognitive decline. But some very early studies. Showed that Some of this change in glucose uptake into the brain is demand driven.

So it's not supply driven, it's demand driven. So we've we've been thinking a lot about the supply, but not necessarily as much about the demand, because they took individuals with a range of cognitive functions, cognitively healthy and then different stages of Alzheimer's disease. And then they gave them cognitively stimulating tasks and they found that even in the early stages of Alzheimer's disease.

Uh glucose uptake could be increased into the normal range with the right amount of cognitive stimulation. So I I think about this again very similar to glucose uptake into muscles. where we know that's largely demand driven, right? If if you don't move at all, those muscles aren't going to take up any glucose, but you start to move them and they'll start to draw glucose in. So

There's the component of overall metabolic health, um energy access, energy substrates, right? We know that hyperglycemia and those things also affect uh vascular function. So even just like getting the blood flow to the brain in the first place.

But we can also think about how we're using those parts of the brain so that we can increase demand for those substrates. I think that's important as well. So we need to think about both. Finding a doctor you actually like feels like discovering a diamond in the rut.

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So I I think my mind goes off into like mechanisms and I think about like neurovascular coupling that that's associated also um From the context of skeletal muscle uh like exercise, you have the translocation of the the glute four receptor. And in the brain, uh well, neurons we have the GLUT three res the GLUT three transporter and also pyruvate dihydrogenase complex or PDH. And I know like in TBI and and Alzheimer's disease.

There's a deficiency in PDH and then there's an internalization of the the GLUT three. Like recep so maybe I'm thinking about it from like a vascular neurovascular coupling that that could be maybe reversing some of the sluggishness or activation of the PDH complex or maybe translocation of the GLUT three. Uh so mechanistic I think of like pharmacologic like mechanisms amenable to pharmacological intervention or supplement intervention too, we know that ketones can bypass

the GLUT three and also bypass PDH. It's actually the standard of care for PDH deficiency syndrome. And um maybe I'll pivot a little bit like we're talking about brain energy and you talk a lot about fuel flexibility. Two in the brain, especially like in the aging brain and insulin resistant.

So do you think in that context of The stimulus can create the demand and that can overcome some of it, but a hallmark characteristic of Alzheimer's and maybe other dementias like Lewy body dementia is that glucose hypometabolism. So can we do maybe instead of like one intervention, can we do a stimulus, like a learning stimulus, and then couple that. with a metabolic based intervention that could be a dietary pattern like a ketogenic, you know, modified ketogenic diet.

And then also supplementation. And you talk quite a lot about creatine, monohydrate, and maybe ketones and lactate too. So maybe delve into that. You've sort of defined the problem, but maybe talk about sort of

uh operationally how we can sort of address uh that. Yeah. So I think that all of those things um are on the table and and are are very, very interesting in terms of potential um interventions. There's clearly um you know, finding what we could whatever we can do to either support the the metabolic machinery that exists or, you know, pro you know, make sure that the ener your required energy substrate is getting where we want it to go. Um and so I I have this

My model for how I think about all these different risk factors fit together. It's called the three S model, which is sort of like in in the in the book I go through all these different areas, right? I go through exercise, I go through nutrition, I go through sleep and stress and all this stuff. And then sort of like

So that it's not this overwhelming list of things we need to fix. I kind of boiled it down to this model. So one of the S's is stimulus that we've kind of covered, and then the next S is is supply. And relevant to this is um the supply of

blood and oxygen, right? So you n we need a healthy vascular system, particularly because of that idea of neurovascular coupling, which if if people um aren't familiar with it, it's essentially when an area of the brain becomes more active the neurons and astrocytes release factors that essentially dilate local blood vessels so you get more blood flow, you get more oxygen, you get more glucose or ketones or lactate or whatever your um

substrate of choices. So that's why risk factors for heart disease and risk factors for dementia overlap so significantly. Uh and it's also why most cases of Alzheimer's disease also display um vascular disease in the brain. Um and so that's that's where right blood pressure, blood lipids, those those become uh important as part of this because they're gonna affect uh vascular health.

Um so so that's gonna be part of it. Can those vessels dilate to to to provide the blood to the areas of of the brain that that that are demanding um you know a additional blood flow oxygen substrate. Um and I and I do think Well I haven't seen specific studies on this, um in the

in the in the muscle tissue at least, PDH expression at least is partly demand driven, right? So that might suggest if it's similar in the brain, then more stimulus is going to help to support some of those uptake mechanisms.

those other things that that we that we could consider. We know that, you know, every multi component um Therapy that's been shown to improve cognitive function, either in those at high risk or those who've already had some degree of cognitive decline, includes a dietary component and most of them include dramatic improvements in diet quality.

And so in um so that one trial was done by Dean Ornish's group, so it was a whole food plant based trial, although they also did a ton of m like mineral and and vitamin supplements uh on on top of that. Um And some some have used the Evan Theater trial, uh, which is run by Dale Bredison. That's not been published yet, but the preprint just came out.

They used um it's like a a modified intermittent fasting, more ketogenic type diet. Um, but then the pointer and finger trials just did much more, just like improving overall diet quality, something more like a Mediterranean diet. So

ketogenesis maybe didn't seem to be n necessary. Um so I think something around improving glucose metabolism, improving you know it improving um access of other substrates, so so ketones definitely um very interesting, particularly once you get further down the line of Cognitive decline, I think they're gonna become more important, right? Because we know there are papers that show that they overcome some of those deficits, like you said.

Um I'm not sure that's I'm not sure that's necessarily in the prevention stage, right? So we might never need to get to that point. Um but creatine is also uh particularly interesting because it sort of acts to distribute the energy throughout the cell after it's been uh generated. Right. So um studies showing that it overcomes some of the m um

cerebral uh energetic deficits in the setting of um sleep deprivation. And then there was one recent study where they it was but it was a pilot where they gave it to individuals with early Alzheimer's and saw some improvements in cognitive function.

It was an uncontrolled pilots, right? So they didn't have a control group and that kind of stuff. But um certainly there are randomized control trials and meta-analyses that show creating supplementation improves particularly memory and particularly in older adults.

So again, all of that kind of coming together to say that supporting um those energy production uh pathways seems to be a critical part of maintaining or if we can get to that point, potentially reversing some aspects of COVID decline.

Mm-hmm. Yeah. So with the progressive glucose hypometabolism, which is a hallmark of Alzheimer's and maybe other dementias like Louis body or just dementia in general, that's not defined as either one, uh, you're creating more head space and cognitive reserve. with just supplying potentially supply well, dietary pattern, that overall diet's probably the biggest lever because that's going to influence.

so many cardiovascular parameters, but uh alternative energy fuels like M C T, which can turn into ketones but also cross the blood brain barrier and can be used directly as fuel. And then ketones, exogenous ketones, and then lactate. You know, there's a supplement, alpha L polylactate. I remember I took that like like thirty years ago, uh Cytomax. I don't know if they still they're still around. But uh so there's that potential and then uh

W we like a lot of things are often studied as scientists in isolation. So there's like a monotherapy of like, you know This and that. Even like in the world of exogenous ketones, which I'm a big proponent of formulation, like all these things have drawbacks, but when you formulate them together, it overcomes a lot of the side effects and potential toxicity. Uh so in regard to cognitive function and aging, uh, I want to kind of pivot a little bit more towards exercise and stress adaptation and

You're really thoughtful about on the context of like exercise is a stressor. So it creates a stress and it's a stimulus. And uh and I just gonna like any amount of exercise is gonna have a beneficial effect. Like you don't have to go in and do crazy amounts of like exercise. So I think I think maybe you can harp on that a little bit. But how do people get the brain benefits of exercise without tipping into chronic stress or burnout?

So there's like elite physical fitness where you have to do like a zone two and then hit and then this whole crazy protocol that could be intimidating to some people versus like just general long-term brain health, which is just get out and walk, like you know, maybe three times a week or something like that.

So uh I want you to like kind of maybe talk your your opinion and I and uh we align very much on your the opinion here in regards to exercise and stress, but would love to hear your thoughts.

Yeah, so one of the reasons why I kind of I I talk about stress in the book is this General adaptation to a stimulus that tells our body that we need to adapt, right? That's what stresses are. And the reason why I think it's important to frame it in that way is because. Right now, right, you say stress and I'm like, Oh, stress is a bad thing. Right. It's just a thing I need to avoid. But but actually

Stress responses are what drive focus and attention, right? A low level of stress response, but it's the same thing. And stress responses are what drive adaptation in exercise. And and it's what drives um, you know, injury recovery after trauma and all these other things. And it also gets you in the zone to perform at whatever it is that you're trying to perform at in a given moment. Right. So stress is actually really

uh important. And so the Well what we see with exercise in particular Up to a and you're absolutely right, it's up to a point. Um and I think um there are certainly people who go too too far o over the other side of this and I've seen several of them uh throughout my career. Um but up to a point exercise seems to increase our buff uh our buffer to like uh tolerate stress. Right. So there's this idea called the cross stressor adaptation hypothesis, which says that

Getting better at dealing with one stress makes you better at dealing with another stress and exercise is the is the way that they've best uh shown that. So Um, people who regularly exercise um or who do a an exercise training program in a in a randomized controlled trial, they then handle psychological stresses better. Just like the the body is capable of handling uh stress better. But

That obviously requires that you've spent time adapting to that stress, which is so you've given your body time to rest, relax, recover, sleep, all those things that we know that are required for adaptation. Whereas

you know, it's very common for amateur athletes to sort of push into overtraining because they assume that the thing that's holding them back in terms of their performance is they're not doing enough training. Whereas so they're like often they just do more and more and more and more and that's that's counterproductive. Um, so people do often end up in that scenario, but for the vast majority of the population, what they need is just more exercise and and more movement.

Um, and all the benefits on cognitive function related to physical activity, movement, exercise, particularly as as you get up into like an hour or two a day, the benefits are essentially linear, right? So the more that you do of anything.

Compared to what you're doing already, will be beneficial. Um so If you're currently relatively sedentary There are studies that show this is in older adults, but one of the first studies that um where we saw an increase in size of the adult hippocampus and an improvement in memory function um and cognitive function related to cognitive function related to hippocampus function was in a brisk walking intervention.

Three times a week, 40 minutes of brisk walking. And they even built up to it. They did like 10 minutes and then they built up until they were brisk walking three times a week. Um, and so that is is a great place to start. Um, we do know that for greater benefits, greater intensity is probably required. Um so one of the

And and so like the the basis should just be general movement, regular walking. Once you're doing that regularly, then you can start to, you know, add some add some intensity, add add something more like zone two, zone three, that kind of stuff. Um how many steps, Tommy? Is that like uh I'm thinking like maybe three, four, or five thousand steps per day or something that forty walk or something? Yeah, so um

That's that's something yeah, like three, four thousand um forty minutes. Um that when you look at like the big um sort of population data sets looking at how many steps a day and risk of dementia. The the risk decreases line linearly up to about sort of somewhere between eight and twelve thousand steps and then it sort of starts to level off. So that's like The more steps you do from zero to ten ish thousand, right? The better. Um and if you can add

brisk periods of walking, right? That briskness where some intensity does seem to be beneficial. Um and so in that particular study they saw that um the greater the in improvements in cardiovascular fitness, so b those they measured as VO two max was associated with greater improvements in hippocampal function as well as greater um

Circulating BDNF, brain derived new neurotrophic factor. Um hypocampal function or hypocampal volume? Two. Just on both. Okay. Hypocampal volume. So they measured cognitive they measured memory function and they measured hippocampal volume on an MRI.

A more recent study took people and in a six-month protocol randomized into three different groups. Like you just got a low intensity forty minutes of walking three times a week, moderate intensity kind of jogging three times a week, or Norwegian four by four high intense high uh high intensity interval training three times a week. So that Four minutes.

of um running at eighty five to ninety percent um of maximum heart rate. Heart rate. They had a three minute break. Sometimes it's a four minute break. Three minute break, and you do that four times. They did that three times a week, which is actually a pretty tri crazy training protocol. Um, and three times a week for six months. They showed that the greatest improvements in hippocampal function were in the high intensity group.

And after a six month training period, that benefit was sustained for five years later. Um, right, which is crazy. Um like re like first of all, really well controlled study, and then to like test people five years out, super impressive. So the wait that's four minutes like all out or at a it's not quite all out. You should you it's basically the speed that you can maintain for four minutes.

Four times over. So if you're like getting to your third or fourth minute and you can't maintain the same speed, you've gone too fast. Yeah. Yeah. Um the the kind of the key differentiator here, I think, in what ties a lot of these studies together, because you see it in other like sprint interval and high intensity interval training studies. is lactate production. So that's the real difference between the the jogging and the the HIPAA is is lactate.

And we know that lactate actually has very some very similar effects on the brain as ketones, um, including BNH stack inhibitor and especially in increasing the production of B DNF. Um, because, you know, there's been a lot of talk about exercise and B D and F recently, but um when you measure B D and F in an exercise protocol, you're measuring it in the blood.

B DNF in the blood doesn't cross the blood blood blood brain barrier. There isn't a B DNF transporter in the blood brain barrier. So the B DNF in the brain is made in the brain. And lactate drives BDNF production. We know that lactate gets into the brain really easily. So low level physical activity is fantastic. Cardiovascular function, it's certainly having benefits to the brain. We we see that in people, it's particularly if they were sedentary to start with.

But there is going to be some additional benefit to this higher intensity work, um, and that's probably largely driven by lactate, as well as, you know, other exercise and my uh exokines and myokines that we know get uh released during that kind of high intensity work.

Say I do a set of like squats, right? And then just kind of walk around for like a minute or two, then do another set, you know, and I'm doing resistance training, sets being, you know, could be thirty seconds or a minute. Uh is that analogous in some ways to that like resistance training, you know, stimulating lactate?

and doing a number of sets and I'm just I I don't like I don't like I don't like hit and I and I I like walking. I mean we walk like our dogs like twice a day. Pretty brisk. Uh but it's di cardio. I just cannot, you know. So it's I have a assault bike and everything and I like, you know, I'll sprint with the dogs here and there, but just to like do it, you know, just to schedule it and do it, just yeah, kind of resistance.

I get it. I I'm a hundred percent with you. I I feel it I feel exact having been a rower And and ultra runner previously. I'm like the less I could do of that, the happier I am. Um, although my coach makes me, he does put it in my program. I do I do have to do some cardio. But I'm so glad you asked that question because the answer is yes, I think.

Um and so um there's one study, for example, they didn't do squats, they did leg press. So I I think squats are probably uh uh uh probably maybe gonna have an even bigger effect. But it was it so this was they did it in different in people of different levels of um uh like experience with weight training. But in the weight trained people, they did it was three it was just three sets on the leg press. One set of sixty percent, one set of seventy percent, one set of eighty percent of one rep

with two rest uh with two minutes rest in between and each set was to true failure, like as as many as you can get. So like in the eighty percent they were doing like ten to eleven reps on average. Those guys, if they were experienced with weightlifting, which just means that they know how to push themselves under heavy weight, they were getting um lactate over 10 millimoles per liter, and it was staying elevated for like fifteen, twenty minutes afterwards.

So you can get your lactate as high as if you did HIT by by doing resistance training. I will say that some of the other things that get released might be different. So um we know that uh HIT and aerobic work. seems to have a uh more of an effect on hi the hippocampus and memory, whereas resistance training seems to have more of an effect on the white matter and processing speed and executive function. Um so

if you're doing very high high intensity resistance training work, which is not always done in those studies, it's more sort of like typical bodybuilding type sets. They're not working really people really hard. Um one of the reasons why I uh uh one of the re one of the differences is the other things that get released. So Uh more like VEGF, so vascular endothelial growth factor if you're doing a aerobic work or hip work. Um more um IGF one and osteocalcin if you're doing resistance training.

And IGF one, we know, is really critical for white matter both development and structure. So I think you will get a lot of the same benefits. The exact kind of balance of other things might um might determine, you know, sort of the the end effect. Um but yes, I I think like heavy squats are gonna get you pretty close to the effect that you would see from from some hit work.

Yeah, and I guess you could just do like lighter weight in like sets of like for a minute of squats. Like you just do a high rep and I suppose I would default for that for my hip. Yeah. And you can you can also get similar lactate levels by uh with uh BFR. So if you do blood flow restriction. And the lactate is kind of like the metric that you really want to focus on, at least from a scientific point of view, the elevation of lactate, right? Yeah, yeah. So you know, if you're getting

Into the high single digits, low double digits, right? That's the kind of level of lactate that you're seeing in those HIIT protocols, which is probably it's not going to be everything because a whole bunch of stuff gets released during excise and some of which we just don't know about yet.

But it's probably going to be a good indicator of the the level of work that you've done. Yeah. I have some big picture questions, but before I jump to them, I have some brain injury focused questions associated with that. And you kind of talk about a little bit concussion a few times. Uh it you you describe the brain as a energy limited organ. And so what happens, can you describe what happens to brain energy metabolism immediately after?

a severe traumatic brain injury, like minutes to hours, and then after weeks. of a TBI and how does that factor into recovery? So if we're gonna do like an FTG PET scan, for example, like immediately after, a couple hours after, and then uh a protracted sort of uh following of that person over time. Maybe that person has like CTE or something, or they took a couple uh severe hits. So just Uh, you know, sometimes it's described as an energetic crisis. And do you have any sort of uh

I know you have your like your your fingers on the pulse of kind of what's happening on TBI and and TBI there's a lot of heterogeneity in in TBI too. But generally speaking, not a penetrating TBI, just like but a severe TBI, what's happening in the brain acutely and then chronically.

It it it will depend so even if if it if the the skull remains closed during all of these s some of the response will depend a little bit on exactly what's happened. So if you've if you've had a you know fairly significant um uh TBI, then you might get uh what we call axonal shearing, right? So you've you've actually severed some some um axons in in a given area, right? Often when you completely sever neurons like that, those neurons will end up just

dying for want of a better word, right? They undergo programmed cell death or they may undergo uh necrosis. Um if um it's less severe and that will probably happen even around a more severe um Uh where there's shearing you'll get um sort of the like stretching, which can um depolarise and and over activate some of these neurons. So early on, some of it may be inappropriately high uh metabolic activity, but then you're also going to get um

Uh uh changes with uh blood flow. So you you end up with these peaks and troughs over hours where essentially you get hypometabolism. then you might get hypermetabolism in like in like the early recovery period. And that's like um Especially hypermetabolism relative to what you're you're capable of of um providing energy for. So you you get like this energy deficit.

Um and then that so and then you can become hypo metabolic afterwards as you get like mitochondrial dysfunction and some of these other uh things that get triggered by like this this injury cascade. Um long term where you s what you see in terms of energy metabolism of the brain is probably largely driven

by um ongoing inflammatory responses. So there are studies that show um ongoing microglia activation. So the microglia being the the uh resident uh immune cells in the brain, you can see ongoing microglial activation even some like several years after a significant T B I. So so some of those symptoms as well as some of those ongoing changes in

um, you know, sort of metabolic function of the brain are going to be driven by, you know, what does the injury response look like uh over long periods of time. Um, but a lot of you know, early symptoms and some of the kind of injury responses are driven by the um gap between energy demand and your energy supply. Supply being both

um sort of substrate. So we know that, you know, some of George Brooks's work shows that say lactate uptake into the brain is increased after TBI. So so that's why one reason why lactate is a is an interesting potential therapy as our ketones after T B I because Glucose metabolism seems to be deregulated at least early on. So if you have some ongoing symptoms, can you overcome that with alternative substrate?

We've been talking about this for a long time. I don't think we've seen the definitive study yet, but it's certainly very hopeful and those you know, lots of trials of those things are uh are going on. So yeah, it's often that mismatch, which is why creatine is another is another thing that

interesting particularly to have on board if you're at high risk of TBI and then potentially there are some studies that show that you y as a supplement, particularly in pediatric TBI, a supplement uh after um creating supplementation afterwards can can improve symptoms. Um so thoughts on like lactate. Just uh sorry to interrupt, but like I think of you know, I followed the lactate story for a while. I studied that before ketones and was thinking like

The elevation of lactate, I'm familiar with Brooks's work, I think, is like, but could be, you know, in part due to impaired glucose, mitochondrial glucose oxidation. Yeah. And when you do an FDG PET scan of the brain with traumatic brain injury, that measures glucose. uh glucose availability glucose in the area and also glucose trapping. So but not glucose oxidation and not ATP production. So you can measure glucose, but it it's there, it's like not being used in

Acute brain injury, I think of like the high FDG signal can coexist with metabolic fail failure. Yeah. And an FDG, like it you would have to do like an oxygen, like cerebral blood flow. uh with cerebral metabolic rate and that's hard to do, oxygen extraction like studies and stuff like that. But I always thought the lactate always the the lactate is what I studied first as a postdoc in two thousand and four.

And I kind of pivoted towards ketones, but I was thinking like maybe some thoughts And and I I discussed this with other people who study brain injury and they they pointed me to some studies on lactate being like elevated lactate was a sign of things going bad. Like and the elevation and and I I attributed that to like impaired flow through the electron transport chain, like just, you know mit mitochondrial uh damage or mitochondrial inhibition.

And that's where like ketones could also kind of uh you know go around. But then if you bolus ketones, then you have the potential for like reductive stress, right? And we talked about that a little bit. Uh, so that's how my mind was thinking about it. Like the the signature of lactate being there was just because glucose oxidation.

was kind of impaired. But not not to say that, you know, it could be dose dependently therapeutic. I tried it in brain slices and just didn't get the results I was hoping for. So I pivoted the ketones. So so I I think Lactate is is, and you this is probably one of the reasons why it hasn't translated yet, is is super messy because of this, right? Because um If you ha right, if you have some kind of trauma and your lactate level goes up

That's that's a bad thing. Right. That usually means that some amount of tissue is is failing or is or is anaerobic, right? Because it's it like like you say, it's it's glycolytic. That's what's gonna generate lactate. And then If you have significantly impaired, say brain metabolic function

It can't use that lactate, right? So lactate remains elevated. Or, right, if if you have liver injury, uh we see that in in if you have some kind of global hypoxic ischemic event, you get some livery injury as well. That liver then can't convert that lactate to glucose or anything where it's the lactate remains elevated. So I think

for lactate as a fuel to be um beneficial, you need some element of function where that lactate can still be used. But you could get to the point where where where you know function is sign is decreased enough that that's that that's not the case. So it it's it's it's all about like what's the balance of supply versus demand or utilization. And I think there will be some cases where additional lactate could be beneficial.

Um, but you know, there may well be others where, you know, ketones would be would be a better alternative source. But you know, as you know better than me, like trying to sort all of that out uh gets really tricky.

Yeah. And I think it needs to be it's very nuanced approach. It's very uh there's a lot of heterogeneity. And you have to look at You know, the body temperature, brain temperature, blood flow, inflammatory markers, like there's so many other and there's just the status and sometimes maybe just uh An energy deficit with like, you know, small amounts of ketones is kind of kind of what I'm thinking with, you know. DHA, EPA, things like that. Uh so اشتركوا في القناة

For TBI, I wanna just one more question. Exercise is often prescribed uh in TBI recovery, but it's also a metabolic. stressor and some people have been you to typically you just tell people to just like rest, relax, don't do anything. I think we've changed opinions about yeah that and I think but the dosage you don't want someone doing hit like right after they get a TBI and like jacking up the lactate.

So, how should patients be thinking about timing, intensity, and the type of exercise from a brain energy perspective or like a concussion TBI perspective? And I know that you need a multidisciplinary team to manage. That too. So yeah, not giving medical advice but just thinking about.

Yeah, what's what's good is that right, we can v very clearly say this isn't medical advice because luckily nowadays, say if you're getting if you get a sports related concussion, people are much better now, right, teams and doctors are much better at managing this now than they than they have been historically.

But p particularly in uh pediatric or as adolescent TBI, although this is now done in adult TBI as well, but the the better randomized controlled trials have been done in uh youth sports concussions. Um Basically the earlier you can get back to physical activity, the better. Um and generally people say some right, if you can sort of right, the low level activity we've already talked about, walking, that kind of stuff, right? The more you can do of that, the better.

then concerted uh you know periods of exercise say, um, they offer you know often say something like twenty to thirty minutes three to four times a week, um at a level below what might cause symptoms to get worse. So whatever s ongoing symptoms you have, be they you know cognitive, fatigue, headaches, anything like that. If if you're making those symptoms worse during a period of exercise, then the intensity is too high.

Um so you can be you should be guided by symptoms. In the trials what they did is they did a um there's the the the buffalo treadmill test specifically for concussions where you look at what level of intensity starts to trigger symptoms and then you prescribe a level of intensity just below that. So n you know, not everybody's gonna do that as part of a, you know, a concussion uh assessment. Most people aren't. But you know, a a level of physical activity at an intensity Um that

um, doesn't exacerbate symptoms, you know, multiple times a week is kind of the the the current best standard. I think what what you're doing is you're starting to improve cerebral blood flow, you're starting to release some of these, you know, exokines and things that we know can have some some benefit for for neurological uh recovery. Um and then

once once you can do that for a few weeks they start to layer on like sports specific or skill specific uh sessions, you start to add intensity. Uh but at least early on, I think, you know, multiple days a week if you can. some level of activity j just below um the the level that would exacerbate symptoms is is kind of the the the current best practice.

Yeah. Yeah. It reminds me I was uh had a special a few special operations guys that with uh one that had diffuse axonal injury was was pretty bad. And then he was transported to the VA near us and

He got under the wing of a dietitian that was really good, but he was really into exercise and he's like fully recovered now. Like, you know, following diffuse axonal injury and they thought they were gonna lose him essentially. And I think he's like a hundred percent recovered. Like it was just defies You know, logic.

Um, okay, so that's kind of it for my I had more TBI questions, but I think I wanna shoot really quickly to just a few rapid fire questions before we finish up on some of the takeaways. Uh and this could be like a one or two sentence uh thing, but I was listening to your podcast with uh Dr. Andy Galpin, which was fantastic. I would direct people

to that. It was like three hours and you cover a lot of ground on that. So uh yeah, my question to try to it that was such a great resource, but I was trying to do questions that complement that and not like overlap direct people there. But uh

So you you also in your book you talk about uh hacks and you mentioned I think with with Andy uh and maybe in our previous podcast, dance and my wife her eyes lit up because she's like really into dancing, like salsa, bachetta, meringue, all that stuff, uh tango. Trying to get me to dance. But you get the physical component, the social component, and then like the the balance and core i is that like would you say that that's one of the

Have people studied that? We have a tango group down here, and I think they treat Parkinson's disease patients and like amazing results, you know, with that. And maybe some thoughts on on dance. Yeah. Yeah. So um so one one thing that we didn't talk about um in the in the sort of like exercise sphere was uh coordinative or open skill movement, which which kind of dancing fall falls into.

Um and you know, there are several meta-analyses that suggest that coordinative movements, you know, have their own additional benefit in terms of in terms of cognitive function. Um and That's when you say you compare uh some kind of unimodal exercise like running or cycling, you do one thing in the same direction.

versus these sort of like complex movements that require you to, you know, rapidly respond to the environment, uh, maybe strategize, right? You're playing tennis, like where you're gonna put the ball next, right? Sometimes there's a social component as well. So if you compare like cycling

to badminton. Uh both are beneficial for cognitive function, but badminton maybe has an edge. Um and there's uh stu uh there's at least one study where they took older adults and they had them do circuit training versus a dance class. And both improved, but there were greater uh improvements in structure on an MRI scan in the hippocampus in the da in the dance group.

Um, there are uh now several studies that look at this. So we have big meta analyses that show that particularly line dancing and uh ballroom dancing You'll significantly improve multiple aspects of of of cognitive function. Um and I think it's exactly for the reasons that you mentioned, right? So you you have the physical component but you also have a social component. You have complex motor skills, there's music, um that and so like listening and attending to music.

uh has been shown to have have some some benefits, you know, even in in isolation. Plus, you know, maybe have some fun, which sort of like helps you kind of t take part in that process. Yeah, yeah. Um and so when you then there have been other meta-analyses that compare lots of different exercise interventions, save for depression, and dancing has the biggest effect size. It's not that it's

significantly better than aerobic exercise, but like if you look at the effect, it was it was like the biggest in in the in the forest plot. Um so I I think as a broad category, sports that or movements that require a attend to all these different things and you know more interaction with the environment, more social interaction, more like requirement of of of rapid processing, which is something that we don't actually do that much of as adults, really, uh other than maybe like driving and

Trying to avoid accidents, right? That's the one time we have to do it. Um I think all of those play a role and that that's gonna be a great place for you to do some aerobic exercise, right? You don't have to go for a run. You could go to a dance class, right? And you're you're getting those those those same benefits plus uh additional. Um and like one final because you mentioned Tango.

Uh one of my favorite uh recent papers um came out is Nature Medicine, I think it was called uh brain um creative experiences and brain clock. Um and they looked at um you know like uh you have like biological clocks where you can measure in blood and all these different things based on epigenetics or on blood you know, blood test markers.

They did this, uh, but now using EEG metrics looking at different networks in the brain um that are susceptible to aging, things like the frontoparietal network, which is important for like top down attention. Um and they showed that those who were regularly engaged in or had gained expertise in creative in sort of like creative arts and they even did some interventional studies actually using video games.

they found that like consistent across all these different complex skills was uh better or like improved function of these of these like modular networks in the brain that are susceptible to aging. Um Right, regardless of what that stimulus was. But one of the things they studied was tang was tango dancers. So Expert tango dancers have Um, younger looking brains compared to um those who don't dance the tango. And like some of it is because

these complex skills and all these different things we're doing kind of help to maintain the the structure and function of those networks in in the brain. So your wife will hopefully be very happy uh to learn about all the amazing things that Tango could do for your brain.

Yeah. I hesitate to tell her that because theoretically, if I try to learn something and then go to Tango and you mentioned like the different sensory things like the music. So there's also like the senses, like the your hearing, your smell and your eyesight and and things like that. Uh and I want to talk a little bit about sauna too, but so if if I if I want to learn something, should I try to learn that and then go dance or maybe also couple it?

Uh I think I heard you talk about or some recent things on like essential oils or just like hmm. Hearing and music and things like that. And that could help with memory consolidation to sort of solidify those experiences or the the things that you're trying to learn, right? Like coupling it in that way. Yes. So there's the a few uh potential parts of that. So one is that

A variety of stimuli across our senses seem to be really important for maintaining brain structure and function. So like one study kind of that that you mentioned there was um they had um uh again older adults and they were in their sixties and seventies primarily, they uh gave them um Uh an essential oil diffuser. Um they had a different smell that they smelled while they were asleep. Um a so one day so one smell per day of the week. So right, seven smells they rotated through.

Compared to a control group, they saw significant improvements in again, uh I think they looked at hippocampal uh measures on an MRI and um and associated cognitive cognitive functions. Um we know that loss of smell, uh loss of hearing, loss of eyesight

um are are associated with declines in cognitive function, maybe partly because of loss of stimulus, but also partly because it changes how you engage um with the world, right? Because you don't go out and do the things that you would normally do. Um and then that loss of stimulus um because of loss of engagement seems to increase risk. Um some of that is reversible. We've seen with studies of cataract surgery and and and hearing aids uh for age related hearing loss.

So so yes, all of these sort of like multi sensory components seem to be important. Um, coupling these things together you could certain you could certainly do that up to an extent. We know that um uh particularly physical activity is is um particularly beneficial for supporting neuroplasticity and and skill learning and and often often just like general the most of these studies do it just like learning in general usually like learning facts

But, you know, the like the increased arousal that you get from exercise, increased release of all those neuro neurotransmitters we mentioned earlier, that seems to kinda set the brain up. for neuroplasticity so that you would then remember or learn your skill better. So yeah, you could uh go to a dance class and then uh immediately learn some Spanish verbs. Um right like those those things could like nice nicely pair together.

Or vice versa. Or vice versa. And and I think you in your book you also talk about like a dog is like I think of animals as like the ultimate hack. Like we have we have cows and sheep and two dogs and stuff. So uh, but a dog is something too. Maybe an older person who's on the fence of doing that, a dog, it gets you active, it gets you into a routine, but also like the dog's like microbiome, like can change your microbiome and like boost your immune system and things like that.

So I wanted to just like some quick thoughts on sort of a a pet. Uh or I'm biased towards dogs, but uh dog is like a hack. Yeah. Yeah. So I actually I I went to Uh during my PhD I spoke at a health conference in the UK. It was a biohacking conference. This is like ten years ago now. And I actually I proposed the dog as the ultimate biohack. Um and and I I had like this whole

figure like yeah there's actually a figure in the book that I recreate. Yeah, yeah, the the kind of the kinds of sh for f for this reason, right? So Um, we know that like dogs are gonna help with your circadian timing'cause they're gonna get up in the morning, you're gonna have to go outside, uh, maybe you'll get some sunlight if you don't live in Seattle in the winter. Um

Y you uh it's then gonna help the way opportunities for pro social behaviour. We know that pro social behaviour is a signific is a is a predictor of cognitive decline and and dementia risk. it you know pro social behavior activates the vagus nerve, right? Ha can have sort of like um stress reducing and anti inflammatory effect.

We uh also know that if you have a dog you're more likely to meet other humans, right? Because you take your dog outside and and other humans come and talk to your dog and then you talk to them. You talked about microbiome effects, the the the benefits of the physical physical activity that you get from walking your dog.

So like all these different right, that may improve your sleep, right?'Cause you've got some sunlight exposure and you've got some ex uh exercise, so then you might so then you'll sleep better. Like all these kind of things kind of come in this in this like wonderful uh friend friendli friendly package. So yeah. Um it doesn't have to be a dog, but there are there are studies that show that older adults, particularly those that live alone That have a pet.

have a decreased risk of cognitive decline and dementia. And probably for for all of those reasons, at least partly because you know, the pro social behavior and social connection that that you have, we know that's important, but it doesn't necessarily have to be with a human, you can get some of those benefits from a pet as well.

Yeah. And the dog is like the ultimate companion. It just stays by your side. And we have a cow that does that, follows me around a dip, but uh quick like just opinion on hyperbaric oxygen, yay or nay for traumatic brain injury in the context. But I've been sort of in that field for a while and a little bit on the fence on things, but I'm now I'm kind of warming up to the idea of hyperbaric oxygen for cognitive, for yeah TBI, a PTSD.

There's a big twenty-eight million dollar study at my university right now, right in the middle of it. It's all blinded, so I don't know what but just general thoughts on hyperbaric oxygen. Someone asked me to to ask you that question. Yeah. Um I am very hopeful that your st your study w like the the study um w will show will show benefit. I I think that it's gonna depend on timing. So immediate

H bot after uh concussion or T B I I would say nay. Um partly because when when you um put people in in a hyperbaric oxygen chamber, their metabolic rate increases. Um, and I w uh it's I think it's the same issue that we get with high temperature immediately after a brain injury. It's gonna increase the the deficit of of energy production.

Um, so the first maybe two, three days at least, maybe week or two, I would say nay, at least for now until somebody does a good study that shows that's not the case. In the sort of long term, you know, weeks plus in the setting of chronic symptoms, and this is the same in the setting of um, you know, cognitive decline potentially, I think we're seeing an an increase. um um you know, evidence that HBOT may be beneficial. But

You know, the exact protocol I I'm not I'm not sure I would know yet. But it it's gonna be something like thirty to sixty plus sessions. Yeah, and we're talking two plus atmospheres, right? So so proper hard shell for long periods of time. So I th certainly think there's a lot of promise there. Um but Uh I you know, it it's probably gonna be many sessions over long periods of time in like uh you know, a proper hard shell rather than, you know, the some of the soft shells that that people are um

Yeah. The group in Israel, I've contacted them and had conversations with them. They do the air breaks like every twenty minutes. Yeah. Uh air breaks and that changes rapidly the relative um oxygenation in the brain. I think that's kind of key and Yeah. And uh last rapid fire, just uh spec scans like the Amen Clinic. Uh thoughts on that. Uh I get a lot of questions about this. I've

It looks compelling. It looks like uh there's some some value there. And I know Dr. Daniel Eman has scanned like hundreds of thousands of people, I think. Uh, but I don't have that much experience with it. I get a lot of questions about it and wanted to know if you have any thoughts or experience with it. Yeah, so SPECT scans are not routinely used clinically. They are used um

And I think that like that gives us a clue. Um they they are used in the research setting. Um so they they do measure changes in well it measures uh changes in blood flow. So, you know Kind of some overlap with what you can measure with a functional MRI scan, like with both well with the bold sequence, or what you can measure with a PETS uh PET scan if you've got a s a certain tracer. Um but the So I I think there could be utility there, like

they have certainly published papers on that, that you see certain changes associated with certain c certain conditions. Um However, I think if if if we think about the imaging that's currently available that as we that we know is sort of predictive of Cognitive decline, dementia, right. We I I I think the evidence is much better for you know, MRI volumetrics, it's much better for certain um uh amyloid or tau PET scans.

Um and even those are imperfect, right? Because amyloid and tower are only a part of the picture of of dementia and c and cognitive decline. Um so I think like I wouldn't be able to look at a spectr scan a and I'm not sure anybody can and say, This is definitely what's wrong with your brain, right? it might show relative sh differences in in blood flow.

But we know that blood flow is demand driven, we know that it's pathology driven, we know that it's exposure driven. It's then very difficult to figure out well what is actually going on or is or is this even an issue? Um so and for that reason I think it's not

generally used clinically and and that's that's a bit of a clue maybe in terms of its its general like broad applicability. Yeah, my thoughts are it would require a lot of scans longitudinally over time just to get your own baseline and then compare that, you know, if you're doing any kind of therapy. Uh

Well tell me, I mean you've been super generous with your time. Thank you. So I know we went way over, but um if listeners considering like big takeaways, big picture like big takeaways, uh if listeners only remember like one core principle from your book. Uh, what should it be? And there's no way, I mean, we're just scratching the surface of your book here. There's so much. Your book is so dense and it's got just so much information in it. So uh are you gonna do an audio book?

Yes. Yeah, I have to start recording that. I have to start recording that soon. Yeah. Okay, you're gonna record it with your voice. Okay, great, great. I like when you do that. So uh for this podcast here, so if listeners wanna remember a core principle. from your book when they buy your book, Zah uh before they buy your book when it's out in uh you can talk about when it's going to be launched. Uh what would that core principle be in the essence of your book? So you we covered

you know, multiple parts of like the the the the chapters that are in the book. So the it kind of opens with uh You know, some chapters about this like broader ideas about the brain, how do we think about the brain in neuroscience? How do we then start to like have something that the average person can do to sort of like understand their own brains and improve their brain health? And then there's multiple chapters on all the different things that we've talked about plus plus man uh many more.

Um and then uh towards the end, like the third part is well, how do you start to like apply this uh in in the in the day to day, right? How can we how can we make this really sort of practical? And so then I I present the three S model that I mentioned, and then the third S as I never said was is um support, which includes like sleep. Um managing or preventing chronic stress, avoiding um things that prevent adaptation, you know, excess alcohol, smoking, air pollution, stuff like that. Um and

The the reason why I present it the way that I do in the book is that all of those different things interact, all those different buckets interact, right? So so often, um we're presented with a list of Here's eighty four things to do for your brain in twenty twenty six. It's like, Well, I can't I can't. I can't do I can't like I'm gonna struggle with one. Um, but if you do focus on one thing

Um, like that's that's what I would do and that's the reason why I present it as a network. So we know that when you stimulate the brain um with say learning a new skill and there are studies that show this, you uh improve sleep because sleep is also demand driven. As is right, you simulate a brain, you you simulate the brain, you also start to improve

um right, the the sort of supply of different energy substrates. Right. Um so if you if you change one thing, you change everything. Um or you shift the whole network in your favor. So it it means you don't have to think about eighty four different things. You can think about one thing that you're able to start to make some significant movement on. So, right, we've mentioned physical activity. You start to walk more Then automatically you're going to sleep out.

Your blood pressure is going to improve, right? Your blood sugar is going to improve. Multiple risk factors change at the same time. Same thing if you stop smoking or If you start to sleep better. You sleep better, you're gonna be more social. We know that people who um are sleep deprived are less likely to engage in cognitively stimulating tasks, right? So you sleep better, you're gonna start doing some of these things that we know challenge the brain more.

So that's the main takeaway is that all these things interact, which means that you can start in one place and the whole sort of network shifts in your face.

Yeah. And it requires that stimulus too. So it's gotta take I mean you have some very actionable things and I think The stories and the science that you kinda lay out also are understanding that is a big motivation for actually following through with many of the things that you're

advocating for here. And I think that's important because you could just tell people to do things, but if they understand the science and the rationale and stories that go with it, even the owl story that you're coming at right out of the gate when the preface Oh it is really awesome. So uh well thank you, Tommy, for all the work that you're doing for the information you're putting out. You're really educating people.

uh from the perspective not only like doing the science and the clinical work, the basic science, but you just do so much education outreach and even presenting at Metabolic Health Summit where Uh very thankful for that too. So what's the best way that people can find out more about, you know, in addition to your book that's coming out, learn more about you and your work? Uh do you have like a uh one stop shop for or various things for

people can go to for your information? Yeah. So um I have a website, dr tommywood dot com, drtomywood dot com. Um that has Most of those things including uh a tab for the book. If you go to thestimulated mind dot com That will take you directly uh to information about the book. It's available uh for pre order now anywhere you might uh buy a book.

Um people who buy the book uh now and then go to that website. There's uh there's some pre order goodies that are coming out. So you'll get like an exercise video, you'll get um uh uh a a sample chapter from the book and and a few other things. So um if if people are interested they can get sort of like some extra stuff um on top.

Um, and then uh Instagram is where I I sort of have most of my links um as well as and then podcasts and other information. So uh at Dr. Tommy Wood on Instagram, also links to the book there. And finally, I do have a podcast, a a brain health focused podcast called Better Brain Fitness, um, with uh my friend uh Dr. Josh Turkner, who's a neurologist.

Um that's primarily done through Substack. So if you go to just if you like type into your browser betterbrain.fitness, that will take you there. And you can sign up for the free version. Like Substack offer not like asks for like the paid version, but everything that we do is in the free version. Free content. That's awesome.

Well, thank you, Tommy. I really appreciate, you know, everything you're putting out there. And uh I just went to PubMed and before we jumped on well, a couple of days ago and just pulled your public I'd encourage people to go too to your publications. You have a great

review article on brain injury, I think. Andy Galpin was that you were taking cut yeah, that that's it that that came out yeah, came out in twenty twenty four, uh spearheaded by Federica Conti as a a postdoc that Andy and I work with. But yeah. goes through all the supplement and nutrition evidence that we think we have for for trying to promote recovery after after TBR.

Yeah, that was like probably the most comprehensive sort of review on TBI and actionable things that people could do. So yeah, well, thank you again, Tommy. Appreciate your time. And uh yeah, looking forward to Uh, to when the book comes out, I already read it, but I look forward to the audio I'll get the audio version too and just listen to it. I'll recommend it. Look forward to recommending it to people.

Including my loved ones and parents. So really appreciate your time. Thank you, Tommy. Likewise, thanks so much. This is a fantastic. Thanks for tuning in to this episode of the Metabolic Link. If you've enjoyed this discussion with Dr. Tommy Wood, we'll be continuing the conversation during a live QA on March 25th at 9 a.m. Pacific, 12 p.m. Eastern on our medical education platform, the Metabolic Initiative.

These live sessions are designed for clinicians, researchers, and anyone who wants to dive deeper into the science and ask your questions directly. This is a rare opportunity to speak to one of the leading figures in this space, Dr. Wood. You can learn more and register for free with a seven day trial at membership.metabolic initiative dot com slash wood.

And if you found this episode valuable, please consider subscribing, sharing it with colleagues, and leaving us a review. It really helps us further elevate the science on metabolism Neuroscience and human performance. And if you want to learn more about Dr. Wood, visit drtommywood.com to dive into his work and find his new book. Thanks again for listening and watching. We'll see you next time on the Metabolic Link. Do you love learning about metabolics?

So do we. It's why we create a lot of people. An online educational platform providing. Education on medical health and therapies. For healthcare professionals. By joining the Metabolic Initiative, Metabolic link. CMEs are available. Go to metabolic conditions. started. And as always, thank you for listening. metabolic wink.