Dr. Tommy Wood: Enhancing Brain Performance & Preventing Dementia

The science and practice of enhancing human performance for sport, play, and life. Welcome to Perform. I'm doctor Andy Galpin. I'm a professor and scientist and the executive director of the Human Performance Center at Parker University. In today's conversation, I'm going to be talking to my friend Dr. Tommy Wood. Tommy has an undergraduate degree in biochemistry from Cambridge University, a medical degree from Oxford, as well as a PhD in physiology and neuroscience.

Tommy is now running his neonatal neuroscience lab at the University of Washington. In addition to all that, he is a well-versed rower and strongman, and has worked with athletes across every sport, and in particular, more recently, focusing a lot on Formula One drivers.

And I say all this to help you understand that Tommy's ability to run back and forth between physiology and science and application into human performance is really unparalleled in the areas of brain health and cognitive function. So in our discussions today, we talk a lot about those areas. We talk about how to enhance, understand, identify short-term cognitive performance, what that even means, what that looks like. From an exercise and supplementation and technology perspective.

And then we talk about how that looks in the long term. So how do we prevent And even deter or eliminate things like dementia and brain aging. And Tommy, over the course of our discussion, will bring up at least five points. that I feel like are quite counterintuitive or in other words are going to surprise or potentially even aggravate some folks out there.

The reality of it is, I don't think a lot of us truly understand the current state of the literature on both short and long term cognitive function. And Tommy does a wonderful job in this conversation of bringing that to the forefront. So we really are more understanding of of what the literature says.

and how that transfers into practical application. Another thing I think worth mentioning here that we get into that I get asked about all the time is how things like exercise have a causal effect on brain health. Of course there's a correlation between You know, f strong muscle and physical performance and how well you age.

But how is it directly impacting and how is that i causal if it is at all? Tom Lee wonderfully walks us through all that in a way that I think everyone can comprehend and get a great grasp on. So with all that in mind, I hope you thoroughly enjoy this conversation today with Dr. Tommy Wood. Dr. Tommy Wood, welcome to Perform. Thanks so much for having me. I'm uh really excited to be here with you. There's a lot of things I want to get into today.

Um things that you and I have chatted about before, but most of the things that I actually don't know the answer to. Um hopefully I can probably some information out of you about enhancing brain performance. Uh things that we can do now in the short term as well as long term brain health. Um but I think before we can get to that, for my own personal sake, I know I say some of these things are wrong. So I'm hoping you can kind of fix this.

But maybe it would be best for us to just start off with what is cognitive performance? How do you define that? How should we think about it? And what are the aspects of cognitive performance? I think that One issue that's come up a lot recently in this in this field is that some of these things are actually very hard to define. So, when we think about cognitive function more broadly, the way that we've traditionally thought about it is: how do you perform on some standard cognitive function?

Uh like an IQ test. Um and then there are tests for a whole uh bunch of other functions. Executive function or response inhabitants. trying to uh suppress the desire to to make a response, uh which is an important part of planning and the prefrontal cortex is a plays a big role there. Um also testing working memory and all these Or our you know our ability to learn and remember and short.

And that's kind of what we've had because that's what we've got. We have standardized tests. We know how you score compared to other people. We think we understand which parts of the brain are involved in those functions. But the the real problem is that.

while they do relate slightly to the different functions you and I would want to do from day to day, it's that's an imperfect association. And beyond that, there are a whole uh suite of cognitive functions or things that we do with our brain that you can't really measure with the So part of the problem is um defining what is it that you want your brain to do, um, and you almost have to become sort of your own baseline because

I can test your executive function and I can test your working memory. But if you're an artist, Those things don't relate to that at all. Um, and there are, you know, you can do some standardized uh tests of creativity and stuff like that, but it it's just not the same. So I think uh cognitive function in reality is very personal. And it depends on what you want your brain to do and when you want your brain to do it. But I think that if we're trying to define

Brain health, for want of a better word, it is having a brain that does those things. So, some understanding of what you want to do, when you want to do it, and how can you support your brain. Okay, so the way that I pun intended my brain puts this together is I think about when I say brain health, I'm referring to do I have lesions in my brain? Do I have brain damage?

And then when I think of cognitive function, I'm usually thinking about performance, right? So uh reaction time, memory, word recall, executive function. Is that a fair way to characterize it or should I add a third part there or? I think about brain health more holistically and in reality we know that structure and function in the brain are directly linked.

Um the the brain has quite a lot of redundancy. So you can lose function in an area and either recover it or maybe you don't even notice that that function is lost. Um, so I wouldn't even necessarily separate them out i in that way. I think it would depend on what you're measuring. So we can measure brain health based on an EEG signal, like different electrical activity in different regions of the brain, how those different networks are connected.

We can also measure brain health in terms of, well, how do you how do you feel today? Because that's essentially an integrated output of all the different things that your brain is experiencing. So That's why I think about brain health more broadly. Um and that relates both to um minute to minute performance and enhancing that, as well as what's your long term t trajectory of function and, you know, are you then at risk of significant detriments of function?

Right. Like clearly if I have some physical structure damaged in my brain, I won't have the acute performance either. Yeah. Right. I'm gonna have some however that may manifest itself, could be any of the examples you said. But does that work backwards as well? In other words, uh because I'm maybe having a hard time with some form of cognitive function, does that indicate some likelihood of actually having some structural damage as well? Or are those is that street one way?

Because of the redundancy in the structural systems, you don't necessarily um have a direct one to one connection. Um, and you'll probably lose Or for some people you lose some functions or the the functions decline before you can see, say on brain imaging, oh yes, here's a uh some atrophy, here's some loss of volume or here's damage in in a certain area.

So I think that may just be partly because of the uh the resolution of the things that we can measure. So maybe we get to a point where you have. know, a really, really uh strong MRI and we can see in very fine detail all the little blood vessels and all the d you know small parts of all the regions of the brain and then you could get a more direct connection. So I think they are very closely connected. And if you if you're losing a function

you're there's probably going to be a structural correlate of that. But in all likelihood, because function is also going to be driven by, you know, nutrient status, mitochondrial function, some of these other things, you might start to have issues with function before you see structural um issue on uh brain scan or something like that.

If then that is true, if I improve some sort of, I'll just keep calling these short-term acute functionalities, how likely is that then to carry over into long-term brain health? the way that I think about the brain is uh because I'm a I'm I'm a bit of a meathead, as you know. Yeah. I I enjoy lifting weights and the more time I spend studying the brain, uh, the more The brain

could uh be be thought to respond similarly to say skeletal muscle in response to exercise. So all the things that you've spent decades researching, these processes are very similar in the brain. And what that really means is that function is driven by stimulus. Just like if you're trying to get uh strong and jacked. You need to apply uh mechanical tension to the skeletal muscle, right? Regardless of everything.

And you can improve you can improve that response with sleep and nutrition and things like that, but no stimulus, no And the brain is essentially the same. And what you see is that when you stimulate certain networks or areas of the brain with certain activities. In response, you then see an improvement in structure because structure comes from that stimulus and then the way that the brain responds to it. And the brain is capable of that pretty much throughout the entire life.

That's really interesting because almost always when we hear this stuff talked about, we hear it in the sense of neuroplasticity. Yeah. Right. So you have a capacity issue, some neurological adaptation, which You know, s it is structural, but for the most time, we don't think about that as a structural change. We just think it as a functional. Yeah. Right. So you have a new capacity, your reaction time is faster, your word wreck.

Whatever, right? But what you're actually saying is there's also a uh as noticeable physical change. Akin to muscle, right? So when I get my when I train my muscle, I have neurological adaptations that make me stronger. I also have larger biceps. I'm not assuming I don't have a larger brain, right? Well, you obviously the the the space within the skull i is limited, but to some extent you do have a larger brain. And we know that with um

Aging in particular, and as you follow a trajectory, say into dementia, your brain gets smaller, right? You get atrophy of the You can then see increases in the volume of the brain in response to certain stimuli. So you can get, particularly once. the the volume of the brain has started to to decline as you get older, you can see then a response in terms of volume with certain stimuli. So

That's not just neuronal connections. Um, but it part of it is so you have uh, you know, greater density of connections, right? That's the new neuroplasticity, you know, new neurons talking to each other. Early on in the the loss of volume of the brain. Um people think about neurons dying. But actually that happens quite late.

What's happening is those neurons themselves are just shrinking up. So they're still there. They still have the capacity for function. But if you're not using them, right, they will then follow that trajectory. But they that can be recovered. Plus, neurons make up less than fifty percent of the cells in the brain. You have multiple other cell types, you have a huge vascular network in the brain.

And so when you're improving volume, you're also improving other cell types. Uh you know, the extracellular matrix is really important in terms of all the proteins that that sort of regulate how the cells are. So yes, you can improve volume. It's not just neurons though. And I think often we focus on neurons, but really there's so much else. Man, I'm totally guilty of that. Like I just I know certain aspects of the brain change physically in a good or bad way.

in response to, you know, perturbations. But I just always give it the the neuroplasticity twist. So uh I'd love to come back to that. Um I wanna know more about it. But w I I gotta ask w since we're right here

I don't think there's any more debate, at least in my understanding of the literature, anymore, about whether or not exercise and things like that are good for long-term brain health. What there is considerable debate on though is can you actually improve cognitive function right now? You said this earlier. If you want to do an IQ test, and then I coach you on that IQ test, you will improve. You could probably pick about every metric in the brain possible.

But that doesn't necessarily mean you're getting better cognitive function. It just means the brain is is uh neuroplastic and achieves an adaptation response to stimulus. So I'm more interested in in where you stand on that global

argument. Um, first of all, is is there even an argument? Is it pretty well scientifically established? Where does that field lie? And then, you know, overall tell me, can we actually improve cognitive function? And then for sure, if we can, I want to know So Again, it really depends who you ask and how you're measuring.

I'm asking you. Yeah, you're asking me. But if you were to ask if you were to sample uh a large number of cognitive neuroscientists, um, and even some of the people that I work with, some will say, Yes, you can improve cognitive function, and some will say, No, you can't. Um, and

This is partly driven by how we're testing it, right? Which we which we've kind of covered. And y yes, we know that um people who Spend longer in education, they have uh improved cognitive function, but part of it is just because they get better at taking tests. And when any study does longitudinal testing of cognitive function, everybody gets better, even the control group, because they just get better at taking.

So then when you're thinking about when you're thinking long term, which we'll come back to Uh I think there is a a good amount of evidence that we can improve cognitive function when when it's when you're in a period of decline. But then if you're thinking right now, how can I improve my cognitive function? the way that I think about it is again related to skill development and what it is that we actually want our our brains to do.

And the human brain, um, more so than any other species, is evolved to adapt to the environment so that it can optimally perform within that. That means that whatever you want your brain to do, and if you train it in the right way. You will improve function, any skill learning, language, sports. Um, and then beyond then when you've done that. You have improved cognitive function, right? You're using your brain to perform some skill. You have improved

at that over time and your cognitive function has therefore improved. We also know that there's then carryover from specific skill learning to more broader cognitive function, particularly longer term. But if you define it that way, I think that We know that the process of skill development is the process of enhancing cognitive function. And then it's just a case of how do I maximize that adaptation and how do I maximize the expression of that skill once I

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If I want to improve creativity. Just do more creative tasks. Yes. If I want to improve memory, practice memory. Yes. And this probably expands to any way we would define cognitive function. For a normal young healthy person, right? So actionable step number one would be simply that. If you want to get better at writing, write. I I that wasn't one of my favorite. I had a a friend, several friends who were writers.

And it's stunning how low energy l last minute that they can pull up, smash out three thousand words and you're like, that would have taken me months. Months to write, right? This is what they do. Naturally. That makes a ton of sense. Where is the broader applicability? Are there any

maybe specific domains of cognitive function that have better transferability to others? Uh are there any particular types, whether this is maybe exercise or nutrition or brain training devices or tactics that have a a more wide ranging again, broader applicability, or is it all pretty much they're going to be good on the individual one and then have very little transfer.

So this is the principle of near transfer versus far transfer. So near transfer means that you learn to get good at the thing that you want to get good at and then it doesn't really translate elsewhere. It's it's been the problem with brain training, uh as has typically been done for the past few decades. And that's one of the reasons why people think you can't enhance cognitive function is because when you do brain training, what you get better at is just some version of the test.

That doesn't then make you a a a better functioning person out in the But if your near transfer is relevant to you, say it's writing or some other kind of specific skill or language, right, then near transfer can be enough. But we also know that if you're trying to think about So far transfer, so improving some cognitive function that then translates to other cognitive functions.

Then activities that um train certain aspects of decision making in the prefrontal in the prefrontal cortex, they seem to be associated with some uh some fire transfer, just you get you get better at regulating your own internal thought and decision making processes. And that relates to a wide variety of scenarios. Um, some of the other things that you mentioned, like exercise is one that

supports what and it's it's exercise specific. So resistance training and aerobic training have effects on different areas of the brain and both good but different. Yeah, both good but different. Um but then that applies to to functions more broadly, right? You're going for a run and that's you know, aerobic exercise is particularly good at

Improving certain aspects of memory. And so it doesn't matter what you're memorizing, right? Memory is brought is broadly enhanced. So some of the lifestyle factors that we know are important are critical for brain health and chromatic. They broadly support cognitive function as well as um skill learning in the first place. Um but then some specific skills may be you know just just related to to that skill.

Okay, I'm gonna give you a couple of avatars here. And uh I'm asking this personally. Imagine uh'cause you've worked with athletes across I mean, geez, every sport. Imaginable. You've worked with uh industry folks, you've worked with non athletes. You've done concussion stuff, you've done aging stuff. So you're you're all over the map in terms of your skill set. So with this, uh somebody comes to you and says, Hey, look, my brain's healthy. Um, I'm 40 years old.

I'm not super worried about dementia, Alzheimer's, things like that. I'm I'm my lifestyle factors are I exercise. I do all, you know, I sleep well, I don't drink, I don't smoke, so on and so forth. I don't have a thing I'm looking for. I don't know what I'm looking for. I maybe run a company, I have kids, something like that.

What should I do to enhance my brain function right now? And I can't define that. I don't know if that means I need to be creative. I don't know if that means I need to have more, you know, uh reaction time. What do Like where would you start with that individual in terms of

What y you said at the beginning, I you should make your own baseline test. Like what should I be thinking about? And are there some tactics where you say, okay, I need all the information. I would really need all I but maybe two or three things here that start off that generally work pretty well. So generally I think about When somebody like that comes to me and they say, I'm healthy, my brain works great. I'm I'd like to improve it as much as I can or maintain it for as long as possible.

The first thing is just to make sure if that first statement is true. And the easiest way to do that is with some simple blood test. determine some like nutritional status becomes really critical for the brain. We can um we can deal with poor nutritional status and the brain works just fine early in life, but if you're trying to, you know, maximize everything

We know uh vitamin D, iron status, magnesium, uh, B vitamins, omega 3s, some of these and uh glucose glucose regulation or at least just making sure you don't have pre diabetes. You know, some of the basics I would just make sure that all of that is sort of buttoned up and that's and that's easy.

Would you mainly say those are energy metabolism markers? As long as your energy metabolism's fine, you're probably okay. So there's an interesting thing uh about energy metabolism in the brain and as it relates to brain structure as well, which is that it kind of follows a U-shaped curve.

So at low levels of energy availability, we start to lose brain structure and brain function just because we don't have the energy to support it. And then we see a very clear energy toxicity effect as well. So if we have, you know Pre diabetes, diabetes, um lipid dysregulation, you know, all the markers of energy toxicity, which are very, very common, right? Two-thirds, if not more, adults in the US have some bone.

then you start to see uh a decline in cognitive function and brain volume as well. So yes, energy regulation is really important. Some of those nutrients have their own um effects in terms of brain structure as well. So if you think about the relationship between B vitamins and omega-3s, This has been shown again and again and again that they interact. So if you have good status of one but not the other, you see no effect and vice versa.

And this is where we've had trials that say we give omega threes but they don't work or we give B vitamins but they don't work but they haven't taken the the the other interaction. And it makes perfect sense because if you want DHA, the long chain omega three fasci acid to sit in the synapse where you want it c you know to help communication between two neurons.

It needs to first get into the brain and that requires usually healthy uh instant sensitivity and energy regulation. And then it needs to go down the path of being attached to some kind of phospholipid, right? So choline or serine or ethanolamine.

Uh so you need that to be available and then you need methylation to work so that these things get attached together and that's where the B vis has become important. So some of these things are directly structural, uh, as well as being, you know, functional, thinking about energy and I don't want to lose the plot. I'll come back to our avatar here in a second. I have a many follow-ups to that. I'll ask just one though.

I don't think people would have assumed you can get a reasonable assessment of short term immediate acute cognitive function from blood. Hm. So Uh Right now, you probably can't. Um, you and I are in the process of uh uh developing what should be a a fairly simple uh blood test that relates directly to cognitive function, dementia risk, also mortality risk. But like I said, critically cognitive function right now. It's not going to be perfect.

But it does relate generally to nutritional status and energy status, which which makes perfect sense. So on top of that I think you could um, you know, really button up the details with making sure that all you have all your nutrient ducts uh in a row. But

In reality, if you're gonna try at the population level at least, try and predict somebody's cognitive function, you could see or if they have pre diabetes or any kind of um nutrient deficiency, they're gonna have lower cognitive function and there's there's you know dozens, hundreds of such Do they need to necessarily be at a critical

technical deficiency there or or if they're, you know, say bottom tenth percentile, they should pay attention. Do we have any insights into where those cutoffs start to lie for these metrics? Yeah, it it it probably You're you're right that in general what we consider to be a a deficiency nowadays is usually you're below the normal range, right? You're in the bottom two point five percent of some nutrient marker and right, you're like you're gonna have some

Your day to day cognitive function is not your ma your main issue, right? There's gonna be even bigger problems than that. But there are some cutoffs. for for all of these things. Uh well in j in general, say blood sugar regulation, you want to make sure that normal fasting blood sugar, not prediabetic. Beyond that, there's probably not that much benefit from from from being lower than that.

But something like homocysteine is a marker of methylation status. Um, generally, if you went to a lab, the normal range is 13, 15. Um five to fifty five to thirty like bottom end, five, high end, thirteen, fourteen, fifteen. And most people will say you sort of like target below fifty. In terms of cognitive function, it probably needs to be less than 11. Uh, some people would go a little bit lower than that for things like cardiovascular disease, risk.

Um but then uh similarly for omega-3 fatty acids, if you do something like the omega-3 index, you probably want to be like ideally over six percent, maybe close to eight percent or higher. Um and that like I said, those those two. Yeah, I would say that in our experience. If you are above nine to ten for home assistine, we're we're looking very seriously at other things. Yeah. And an omega on you'd be surprised how many are under five. Yeah. Like very, very, very, very commonly.

This is why you see in those folks a little bit of basic multivitamin and omega-3 support. And all of a sudden the brain fog is gone. The the decline like it's just it just disappears from these people really quickly, which is is really of no surprise. So um coming back to us then we check those blood markers, uh then what for that?

So then you can make sure that the other lifestyle factors are sort of all in a row and when we think about long term cognitive function, there's kind of a a framework for thinking about So sleep and all these other things, stress mitigation. Um, I'd I'd definitely, you know, look at all these other lifestyle factors. But if you're thinking about enhancing cognitive function, like I said earlier, I think stimulus is really the most important.

Your avatar probably has quite a cognitively stimulating job, which we know uh increases long-term cognitive function and decreases the risk of dementia long-term. So then I would think about a a lifelong plan of ongoing broad cognitive stimuli. So if he's never played a musical instrument. He learns to play a musical instrument. If he um all his exercise is in the gym and it's unimodal, then he picks up an open skill sport, he goes to play.

Or learns to skateboard. God forbid, no more people playing pickleballs. Don't do that, Tommy. Um, if he uh has never spoken another language, then he then he learns. Um some of these things uh uh w it's interesting when you look across the literature, the one activity that probably ticks a lot of these boxes and seems to uh really support cognitive function as well as mental health is dance.

And because that brings in play, uh like it's it's an open skill, there's music, it's social. Um so he so a dance class with his partner, right, would be a great a great way to sort of integrate a bunch of. Cognitive demanding. What does that actually mean? That's a that's a question that I actually can't answer. I talk about cognitive demand a bunch, but in reality, we don't know. Like it's a the it's a theoretical concept because

Why we could put you on an MRI scanner and we could see which areas of your brain become active, or we could do the same thing with EEG. But in reality, like how do I quantify the stimulus that's being put on you um compared to somebody else. I mean, we can't. Like, what's the equivalent of volume in the brain if like compared to say lifting weights? Where I can quantify how many bicep curls did I do?

Um, what was the weight? Um yeah, you could look at velocity and all these other things. We can't do that. So yeah. And so I kind of hope that one day we'll be able to quantify that. So then we could say this is the cognitive demand that you're getting. This is the stimulus, and this is the adaptation that we expect to see. But right now, it's some of it is still a bit theoretical. Um and when you think about cognitive stimulus and cognitive enhancement.

One of the reasons why there's so much controversy is because it's actually quite a young field. Like we're where exercise, like cognitive enhanced the cognitive enhanced field, is where exercise science was decades ago, four or five decades ago. The principles all make sense. You can see it happen in animal models. You can measure the fact that these neurons were active.

Um, but how you truly dig down and quantify the networks being activated uh and the level of that activation or maybe what's required in order to see um a response, that's something that still needs to be. Dance makes sense to me because You didn't say these words, but sensory input is a huge impact here, right? So proception. In the case of dance it is hearing.

Uh you're feeling you're feeling the other person probably. You're feeling the ground. You don't want to step on toes. It is rhythmic. Uh different, these are all different parts. Of the brain, if that's a fair way to say it. And now you also have memory. It's this step and this step and this step, right? Plus improv improvisation. All the four or five different areas immediately make sense.

When you think about something like let's just say pickleball, you said earlier If you are a skilled pickleball player then the act of playing pickleball is not as cognitively demanding, I'm assuming, as it was the first week you played, right? Now there's still some because you're reacting to the external environment, change of direction. This is proception. Where am I at in space?

What shot am I gonna make? What's the score? All those things, right? But it's not as high as it used to be the last time because parts of that experience now. of where to put your hands, how to swing your technique, have been now pushed to we'll just call it subconscious, right? This is learning. This is how you get better better at sports, right? Yeah. Where the cognitive demand piece

To me, sets a little bit differently. I again I don't know if I'm actually thinking about this correctly, because if I think about a day-to-day work experience for me, the dance thing makes sense because of all those different sensory inputs. When I think cognitive demand, I'm thinking some sort of difficult mental task. I'm not thinking like a physical body movement, right? So I'm thinking if I'm reading a scientific paper. That to me feels like a high cognitive value. Demanding tab.

I can do that scrolling my phone like pretty quickly. Um and hubris aside here, like it does not take me long to scroll through a paper anymore and get the gist of do I buy it, do I not buy it, shoddy paper. Where other folks, I certainly know, say my just self as a graduate student, like it's the whole day reading every word, right, to get the gist of it.

Is it just something that is a generally hard task? If I'm doing, if I'm writing, is that always gonna be a high cognitive demand? If I'm sending an email, is that always gonna be low? Um I know, for example, just speaking from my relationship. If my wife gives me information about something hang with the kids in school, that's the highest cognitive demanding effort I will have in my whole damn like, Wait, who? What's the kid's name again? Like I just have

Like I'm I have to drop everything and complete pay attention or else it goes to zero. The next day she'll remind me and I have zero recollection. She's probably if she listens to this, she's gonna die in anger. Listen'cause she's like, Yeah, it's infuriating. She does the same by the way. So to the point of saying, like, how is it the task itself? Is it novelty? As long as I'm doing something different? Where where do we know that something is cognizant? Or where can we get closer to guessing?

So Novelty plays a big role. And it's probably because novelty drives attention and focus. And if you're actually going to respond to a stimulus, you need to direct attentional resources to it. So then difficulty becomes important as well. So it should be challenging and you should be Giving it your full attention and focus, whatever it is. And then those are probably some of the prerequisites in order to see some kind of adaptation in the brain.

How you subjectively feel about a task being difficult. Although I'm a big fan of the subjective for a lot of things, in this uh case it it doesn't really work. Really. And it's probably because of the way that we use our brains nowadays. What you s mentioned earlier

listening to to your wives talk about something to do with the kids. And he said the only reason the only way that you can actually internalize it if you like, if you give her your attention. So what that tells me is what you're tr what you're doing is multitask. Um, and you're not actually multitasking. What you're doing is task switching. So you're trying to pay attention to this thing in front of you right here, and then you're trying to pay attention to her.

And there's a cost every time you do that because you have to refocus. And what happens is if is essentially you're not doing either or you're doing both or three things very, very poorly. I think I set the world record for highest.

Task switching cost ever. If I have to task switch like that, like it takes I have to literally sit down, I'm like, shake my head. I'm like, okay, hold on, give me a minute. Okay, what? Like it takes m the m the lag. It's like a bad video game. It's so long on me when I switch tasks, I'm just like I I like I

focus my whole day on not doing that because it is so catastrophic for me to have to do that. Yeah. I'll I'll I'll I can do the task, but I'll have no memory of it. Yeah. It'll be gone for forever. I'm actually very similar. Like I am a terrible task switch, and like my wife always jokes, I'm a terrible multitasker. And

Recently I've you know I've leaned into it. Like the human brain cannot task switch like that efficiently. People just can't do it. Um you may have to be able to navigate that for for your job, but in reality, like work by Gloria Mark shows how um constant task switching is very stressful. Um and every time you switch a task, you have that the that cost of time, as well as the fact that if you're distracted from a task

It's it may be a long period of time before you ever return to it. And during that whole period of time, while you're not doing the task that you actually want to be doing right now, there's this sort of underlying simmering stress, because you know it's there, but you're not, but you're not doing it. So I think a big part of this is that multitasking, as we call it, or task switching, which is very common now, email to this document you're writing to social media.

It's what uh a friend of mine, James Hewitt, calls the cognitive middle. And you kind of imagine it. I so it I'll I'll I'll keep going over to to my terrible exercise analogies, but it's kind of like spending all your time at threshold. It's incredibly f like physically tiring.

But the adaptation you get from it is kind of disproportionate to how much it drains you. Yeah. Right. Yep. Yep. This is the last couple of sets that you did where you got nothing different, uh-huh, but you got high fatigue. Yes, exactly. And you're doing that with your brain all day.

So what you really want to do is to try and periodize that as much as you can, right? So you have your periods of intense focus, intense cognitive performance, and that's your deep work, the time when you really need to get stuff. And then the rest of the time you're sort of a uh uh you you're doing your sort of like your z your zone two brain work. And that can be

answering emails, like some of the basic stuff. As soon as you start to do mo you know, a ton of those things at the same time, you start to to sort of head back into middle gear. But that's you kind of have to think about almost polarizing your your brain use just like a lot of people might polarize their training.

Your lab does mostly neonatal stuff. Right. So your actual scientific time is mostly spent in young developing brain. Yeah. Right. You've clearly done work across the entire lifespan. Does that task switching energy increase?

as you get older. Cause I feel like when I was a kid, I could test switch immediately. I don't actually have a recollection of it being a problem as like a grad student. Yeah. But now I'm like, oh my gosh, just detrimental. And I'm why I'm asking that is I'm wondering if that is the case. Could that be explaining some part of people feeling like they have cognitive decline, feeling like their energy is lower throughout the day, feeling like their brain fog is hitting now, when in reality

They're just burning more gas and they had no idea. Yeah. Particularly early on in life. I think the brain interacts with the environment in the way that we should be doing as adults and we're not doing. If you watch a kid learning how to walk, that is all their focus on. Um and essentially for the first thirty years of life.

the brain is continuing to adapt and mature. And it can still respond to stimuli after that, but it takes almost half our lifetime for the brain to fit to you know finish adapting. And that adaptation is driven by learning these skills, social interaction, language, motor skills. But particularly early on. That's all the brain is is focused on doing, right? I'm gonna spend this next

10 minutes trying to stand up and then I'm gonna take a nap. And you know, you know, my brain is gonna start to figure out all the inputs that it received during that period of time. I've had some days like that. No doubt. Yeah, even now. Yeah. And So then as you get into the teenage years, I think that you're right, kids seem to be able to to jump back and forth continuously. And that that probably is that they are better at

focusing their attention very quickly. And I think that's partly because All the other things that we have to deal with when we're older aren't in place. So a lot of what happens as we get older and we think that our cognitive function is diminishing. is actually just um a product of of the environment, as well as the fact that we're not focusing on tasks in the way that we should in order to to maximize the benefit from them. So

When you're trying to learn a new skill in your forties, you obviously have less time to do it. You have kids to worry about. You probably didn't sleep very well. You know, you're stressed about your job and all these other things. And then you say, Oh, I just can't learn a language like I could when I was a kid. But when when you're a kid, you have nothing else to do. Yeah. Right. You have your French class. Three times a week and all you're doing in that class is learning French.

And you're dedicating, I mean, whether or not you enjoy it or you actually paid attention at the time right, but you have these focused periods to just work on learning this skill. Whereas you're learning French as an adult. It's like, well, I'll do ten minutes of Duolinga while I'm sat in traffic. And then you wonder why you're not learning French as well as you could when you were younger. Right.

And some of the right, some of these adaptations do slow over time, but it's not that the adult brain can't do it. It's that we're not actually applying the principles that we did when we're younger in order to learn these skills.

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Okay, so making sure that we are trying to focus on singular tasks at a time and having potentially a little bit of a buffer when we switch from one to the next in terms of expectations. Yeah. Right. We're not gonna be on the next one quickly. So if we go to our our forty year old And we're we're back on this avatar, he's saying, Okay

I just kinda want to enhance my brain function there. We got we got uh I drove us off track there pretty quick. So kinda coming back to that, what would be again your your recommendations of things to think about, stuff that he could generally try? Um you mentioned Learning a language, uh Duolingo, are there any other specific

uh brain training things. Um, do those things work? I guess we'll even start there. Nutrition, supplementation, nootropics, like what are things we can do? Um in that again, I'm not diseased. I'm not hurting. We'll get to that later. Just feeling pretty good. Yeah. What can I do to make my brain skeins? I think

Most brain training as it currently exists is probably not enough for us to see significant fire transfer and in that person. In in that per in that particular avatar. I think we're now starting To see a revolution in VR, particularly in AR, where that might start to change.

And you have very complex environments that you have to navigate and problem solve within. And these are some of the things that the brain thrives on. And they're delivered via the eyes, which is one of the, you know, the primary stimuli that that drives neur you know. neural organization and then, you know, all the downstream consequences. So you're you know, compared to looking at puzzles on a computer screen.

you know, having some in depth, you know, audio and visual stimulus in a virtual reality environment is much more similar to the way that we norm that we normally uh develop complex skills. Um and in and you know, drive brain development. So I think we're gonna see more and more of that coming online Even in you know, regular adults and actually in kids and and older adults, the current technology for say video games.

when in say a three D uh a complex three D environment, it hasn't necessarily there's been a a bit in VR so far research. I think that's gonna really explode over the next few years with like all the devices that are now available. But even like I think the the game that has the most research is Super Mario World three And people who play Super Mario World 3D for a few weeks compared to something like Tetris or Solitaire see greater improvements in certain standardized coverage.

So even that kind of new complex world, your um a lot of uh orientation, puzzle solving. High effort, high focus. Yeah. And like you're gonna die if you're not actually paying attention. Yeah. Whereas and probably the same in Tetris, but definit but not in solid. And actually with increasing complexity you see increasing improvements in So providing these complex um you know multi dimensional and um multi sensory inputs, I think

we already have some evidence that that can improve cognitive function in healthy adults. And I think we'll only see see more of that in the in the You just gave every sub 50 year old permission to tell their parents, I told you so. I told you the video games were okay for me. Uh Fair characterization or no. If cognitive function is low.

either maybe young or older aging, something like a puzzle, um, brain training, brain HQ is probably the yeah the more um most studied one, many ra many randomized controlled trials. Potentially can help. However, if you are kinda normal to above Going past that.

That's just not cognitively demanding. Yeah. Most likely not, right? So now you have to get into situations where again you care more, or there's a heart rate elevation. There's some other uh functional physiological demand that provides enough of a stimuli to cause. Adaptation. So video games of that will come. I'm sure there are plenty of other ones, but you get the concept, right? It has to be all those things you laid out. Mm-hmm.

Um, this is where something like a dance would also then fit in, right? Learning a new skill, presumably rock climbing or surfing, where your environmental exposures and temperature changes. Are great activities. Um combat sports are of course are like fantastic for this. Just don't get punched in the head too much. Too much. Yeah. Um

What about from a nutrition side, supplementation side? Is there anything you can do or on the inverse of that? Is there anything that you just have to avoid? Are there are there particular nutrients or styles of eating that are

really bad for the the normal non diseased person. Or or what do we know about that side? Outside of energy toxicity, which you talked about long term was a problem. Yeah. So In reality the answer is no, there's nothing that anybody has to avoid. There's some reasonable observ observational epidemiolog epidemiological evidence to say, you know, highly refined ultra pro you know, diets high in ultra processed foods, which

That classification is problematic because it imp includes protein powder, which I would, you know, happily recommend to people, but also Twinkies, right? I don't think look, we can be pedantic about this, but a diet high in you fill in the blank here.

Probably not good. Yeah, exactly. I don't know if we have the direct mechanistic research on that for this question, but it we don't have to stretch our imaginations far to say there's so many other reasons why you should avoid that. Yeah. Like just okay. So outside of that. Yeah. And then that's A lot of the downstream effects of that are driven either by nutrient deficiencies or energy toxicity, right? So things that we've things that we've already covered.

in terms of supplementation, it then probably becomes a case of what is it that you're trying to achieve and when are you trying to achieve it. So I think in you know healthy individuals, in athletes, we see some interesting improvements in co in broad cognitive function with, say, creatine supplementation, uh, particularly in in aspects of memory. Um, so that's that's something that's always hard.

Um, everything else that I think would would go on the definitely take could also be related to the nutritional piece. So magnesium status, vitamin D, all those other kinds. When you're then thinking about um say supplements or nootropics, Often what you see is that there's a trade

that you enhance one function at the the price of another. And that's fine. But that has to be a choice. You you can't just take these things and think I'm going to be better at everything because the the brain doesn't work like that. Well and nothing in physiology works like that generally. No free passes. No free passes. No biological free lunch. So then um

It just gonna depend on on what you're trying to achieve. So if you've um you know had issues with sleep or stress um long term, then there are interesting things like Theanine, Ashragand, KSM sixty-six, they seem to improve stress and also cognitive function in those. Um if you're thinking about trying to perform in the moment in a given sport, uh so I can y I can use Formula One as an example. We've worked with multiple drivers who

because of their engineers and the teammate they're competing against one of the one of the metrics that you can easily see. They show it on the on on the TV right at the beginning of the race is reaction time. So how quickly did this driver get off the line? You try and increase that or try and decrease or improve reacting speed, decrease reaction speed speed speed speed speed.

then there are some, you know, the the s the supplement that would first come to mind is caffeine. Yep. Right. No doubt. And it works. Right. We know that caffeine improves psychomotor vigilance and improves However, we also know that at higher doses, caffeine decreases uh complex.

Complex scalability, right? And decreases certain aspects of ejective function. Imagine any scenario in which you would you would want to be driving two hundred miles an hour on an a thousand milligrams of caffeine. Yeah, absolutely not. And so this

And but it it's it's been done or it's been tried and you'll see a great reaction time off the line and then you're trying to navigate the first corner at two hundred miles an hour or a hundred and fifty miles an hour with nineteen other cars around you and you'll plow into the first corner. Yeah. So This then comes into the idea of getting into the right window of arousal for some given cognitive task. And we can use supplements to do that. Um but we can also use

breathing techniques, exercise to kind of modulate some of that. So There are some supplements and you know, depending on the task, maybe caffeine is the the right one. For most people who who are rate habitual caffeine users. you're generally just reversing the deficit caused by a caffeine deficiency at the moment rather than enhancing function, which is fine. Like we just had coffees before we came in here, right? Um

But then beyond that it's gonna really depend on on the task. And that's largely gonna be related to arousal. What level of arousal is gonna be ideal for the task that you're trying to perform and each task is probably gonna have a different It's really interesting you say that because with all the athletes we work with.

There is a spectrum of caffeine use. Uh-huh. Not only within the person to person that happens, but I mean I say categorically between sports. If you take, for example, our NFL players, they generally are on a pretty high dose of caffeine. It's a cognitive sport, but our golfers

Absolutely not. Oh yeah. Like you know, maybe a cup in the morning or something like that and that that's it. Maybe fifty Migs or something like that, like some little little top off, but they don't wanna have they can't have that kind of neural control.

on very much caffeine at all. Many of them are just no caffeine, period, right? Um some of our fighting sports, they can be a little bit of a mix depending on what kind of a fighter they are. But they can be on all kinds of different areas of this. I know personally, I'm kind of unlike the golf.

I generally like like one shot of espresso. Yeah. Like that that is like good for the day. Just like kind of m mouldering around a little bit. If I have afternoon, I want like decaf or quarter calf, then I'm like, that's like perfect. Um, I have other friends who are like the opposite, right? It's just like, you know, six, eight, ten servings a day. And they're going, If I use almost any form of nootropic, and I've probably tried a dozen outside of caffeine and nicotine.

I can't get a word out. Yeah. My cognitive function goes to zero. Like if if I do like a tenth of a serving, like I just I just can't use it at all. But I'd say ninety percent of the people we've coached with. alpha GPC or things like that, have a positive experience. So Dr. Wood, why why can't I not think straight? I mean, I I have to think about every word that comes out of my mouth if I do the smallest half dose of alpha GPC.

That's a really great question and the answer is I don't know. What the Uh a a lot of people I know really like I've been wanting to know this for like a decade, by the way. The the reason why I can't answer that question is because there isn't that much re like high quality research on alpha G. There's quite a lot on C D P coding or city coding. So another another form of coding which um

You know, people say that alpha GPC is more likely to get into the brain, more likely to be turned into acylcholine. But there isn't that much really good quality research. So when I talk about choline supplementation, I'll always fall back on cytoline because that's it's it's much better understood. So The reason why I can't answer your question is because I don't think anybody's not going to be able to do I anyone that tells me things like Alpha G P C don't work.

You make you're out of your mind. You're out of your mind'cause if I take a quarter of a dose, I can't think. Yeah. Straight. So it absolutely works. I guess it depends on your point earlier. Yeah, what it means by working. How you're defining sort of work. Yeah. Um, are there any categorical

uh pros and cons to the thing. So you mentioned one earlier, in the example of caffeine, you might get enhanced reaction time, but perhaps you have a decrease in focus or attention if it's overstimulation. Are there any other general

swings like with APA GPC or any other ones like we just generally if you get more I don't know does it even work like that? If you get more focused, does that then take away creativity? Or are there any other kind of like big switches that happen like that? There's been Mae'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n rwy'n

There's there was a little bit uh historically on some of the the Racetams. Yep. Um and and and showed something similar, right? You might have an improvement in in some aspect of um executive function or memory, but then uh you know verbal fluency or some other aspect of cognitive function decreased and Um The the stimulants broadly have do seem to have the that trade off that we mentioned with caffeine. So there's a recent study.

that came out and compared caffeine to uh metholphenidate and some of the other stimulants that are regularly used. students and yeah yeah you know to you know when they're studying or, you know, the clinical population like ADHD who actually you know might might benefit from them and you tend to see something tend to see something similar. So you you might improve on one aspect of cognitive function, but especially certain aspects of executive function seem to decrease.

What's interesting is that a lot of um you see this in the uh say the the psychedelic um microdosing literature, um you see it in the cannabis literature. People think They're more creative or they think they have improved cognitive function, but actually if you measure it objectively, they don't.

And it it it actually parallels some of the caffeine research where people You just set the whole internet on fire. Sorry. Um and so what what often happens is people think they're functioning better. And this has happened in some caffeine studies as well. They think they're functioning better, but actually objectively they're functioning worse. So there's this decoupling of the subjective and the objective again. Um and none of this is inherently bad.

It's just knowing what it is you're trying to achieve in the given moment. What what is that? Because you see the same thing in sleep literature. If you sleep deprive people, not even to extremes, six hours a night, things like that, you'll see routinely cognitive function decreases. like massively with almost not always but a lot of times no subjective change. Yeah. So people think, I'm totally fine, I'm totally fine, I'm totally fine and then on a standardized test they're hot garbage.

Like what's actually happening that makes you feel like you're is it just the acute self preservation something must be going on here that is catastrophic or important, so we're gonna maintain like total

short term focus and just disregard like the real world. Like what is happening here? It's funny because you often see the opposite in sleep literature, which is where, you know, like Ellen Langer's work where they randomized people to sleep for eight hours, but they told them they slept for five hours. Right. So

They slept a perfect amount and but they thought I didn't sleep well, therefore I'm not gonna perform well and they're not gonna be able to do it. And actually perform it. Yeah. And and they don't perform well because they because they have this expectation. So I think For for some of it, there's there is this aspect aspect of what do you expect to happen and thoughts drive physiology. Like we know But and there's ton yeah, we can do that across blood sugar control, um, sleep.

Um, even how physical activity affects mortality. We've done it with lifting weights. Mm-hmm. We we actually put different numbers on the barbell. We ran a couple of these randomiz uh of uh deception studies. Yeah. With it. Yeah, like you will definitely PR. Yeah. If you think the bar is fifteen pounds lighter than it is, you will absolutely PR. They've done it with uh anabolic steroids. Yeah, yeah. Right. That was the one of the most famous ones. Yeah. Yeah. Yeah.

What a tremendous one. Yeah. So some of it is just purely driven by expectation. And I think this translates into everything in terms of how we think about our cognitive function. It's like, what are we expecting from ourselves today? And that becomes a self-fulfilling. because our thoughts drive our physiology and then you get the result that you expect.

But sometimes, like you said, you in in the in the opposite scenario where you haven't slept well, you think you're fine and you can still measure um an you know an objective decrease in function. still some r like baseline requirement that we have these things in place for for cognitive functions. So some of it's driven by expectation, but expectation isn't going to be enough to overcome

Right, really significant differences. Yeah. And we saw this a ton at Absolute Rust initially and we've seen this in in various aspects where Sat and setting and habit override most small effect. In other words, if you wake up in the morning and you brew coffee and then you walk your duck and you do the whole routine and then you sit down at your computer and then you start writing.

then that is gonna have a massive nootropic effect, not necessarily simply because of the caffeine in that particular case, but because your brain body knows the pattern of when we get down here, this is when we do our deep work. Right. So if one day you got switched out something else there, you would not have as much of a

problem as you would maybe if the setting is switched. Right. So that it's it's not that the caffeine did or didn't work. It's the whole yeah set and setting that brings the experience. From a sleep perspective, if you have a certain habit, a certain behavior that then promotes quality sleep. Or does the opposite, that's the pattern that you'll see. Right. So you can try all the sleep supplements you want. It's not going to matter if you have this chaotic, yeah, like sleep.

So you're not saying that those things aren't doing anything, it's just that the benefit is potentially only gonna be seen if the rest of the situation is captured and clear because there's just too much noise in that overall system. And that makes a ton of sense. Um from me. Um, we've mentioned this stuff a couple of times, but I wanna go back just a little bit

to our avatar. Let's say that person's good. We did as much as we could on him. But now let's say he or she is saying, Okay, I'm not normal cognitive function. I don't think I have brain disease. It's brain fog. Right. I'm just and it's not perceptive. It is noticeable. It was real. There's this big decline.

Um, you hear a lot of these certainly in the last couple of years about potentially long COVID. Uh happened when I after I got COVID or didn't or got a whatever and just for whatever reason we're down there. How does somebody know what that actually is? Uh How uh are there tests that you can take? Are there online surveys or things that the average person could try? And then secondly, you know, again, what do I do to improve that?

This is another controversial area, the idea of brain fog, which I kind of use interchangeably with the more formal definition which is subjective cognitive decline. That's brain fog's way nicer sound. So when you when you look at the um the sort of the stages of dementia now they they include some of these pi some of these periods. So first, you know, everything's good, no subjective or objective change. And then next

There's probably a subjective decline before you see an objective change in function, right? Or at least that's assuming that you don't have years of longitudinal cognitive function tests in this person, which nobody So if you you feel like I have this brain fog, I I feel like something's not quite right, but if I gave you a bunch of standardized cognitive function tests, you'd be within the normal range and I'd say there's nothing wrong with you. Right.

But there's quite a lot of research now suggesting that that subjected decline, which you know has a lot of overlap with the idea of breaking. then is associated with improv improved or increased risk of first mild cognitive impairment, which is like the next step of cognitive decline, and then dementia. Obviously, not everybody who gets brain fog is going to get

I don't want to say that right. He just terrified the internet. Set him on fire earlier. Now they're all terrified that. And and that so that is definitely not true. suggests that that could be a signal of some kind of impending issue or the beginnings of initial issue of an of an initial issue. Now, most of that in that in that stage is thought to be reverse.

Even if you ask, you know, dusty old neurologists who think about who've thought about this, they would tell you and that if you look at the the sort of the spectrum that's in published papers, they'll say that at this stage it's reversible. So then you have to think about well, what are the potential contributors? to this. And There are just the same old basics that are gonna come up again.

And so we all we already covered the nutritional stuff. That is that like you said, you've even seen that um in your own clients. Right, you address some basic nutritional things and a lot of this stuff lifts immediately. I'd probably say Sixty percent of our clients.

have a subjective score of of cognitive function of five or less out of ten. Yeah. Right. So whether they actually have brain for don't like n over half of our people think that their brain is functioning poorly. Yeah. And I would say our success rate is over ninety percent.

with all that. Yeah. And we've done lots sometimes it is more complicated, but a lot of the times if you cover all the bases, w we have stunningly high results. Yeah. And that makes perfect sense if you think about or if if you think about the f the framework of how I think about cognitive.

And so maybe that's this is the time to kind of bring that. Um and'cause it would then relates to long term cognitive decline as well. So to kind of fit all these different pieces together and we've we've touched on a lot of them. I have what I call now the three S model, which is stimulus, supply, and support. And these are the three broad categories of the things that are required to maintain and sustain cognitive. And

Some inputs will cover many of those at the same time. Right. So they're like sometimes I've I've I've put up a picture uh in a lecture and said, here's here's my model and somebody's like Yes, but something goes there and there. I'm like, Yeah, I know. But it would just picture Yeah, it's just a picture. Right. Just kinda simplify it. But we've talked about stimulus and I think that's the primary driver of of a lot of cognitive function. But

In order to respond to stimulus, we need a few things. So in the supply bucket, we have um good cardiovascular function, right? Um what you see in the brain when you have uh an increase in activity in some network associated with some function is you see an increase in blood flow and direction of resources to that area. Um, this is the process of neurovascular coupling, right? So when neurons become active, blood vessels in that area dilate, we direct, we direct um uh resources to that area.

This requires a healthy vascular. Right. And so as it's almost exactly the same process of as what happens in the coronary arteries in the heart as we get into the process of heart disease. And therefore there's a lot of overlap in risk factors for heart disease and risk factors for dementia. Probably because of that vascular component.

So everything that would improve cardiovascular health health then helps to support this, exercise being one, but obviously other aspects of maintain you know, making sure you have low cardiovascular risk, blood pressure, you know, lipids if necessary, all the Then you need some kind of energy source, right? For most

parts of the brain, most of the time it's gonna be glucose. Uh, but it certainly could be lactate, it could be ketones, right? So and they need to get there and they need to be able to get to get to get across and that that's where some of the energy toxicity piece comes into play. Um, and then you need nutrients to build and maintain the structures of the brain. And we've talked about omega-3s and B vitamins being critical components. So that's kind of

That's the supply part, right? If you want to actually create a response to a stimulus, you need all of those things in place. Then you the support side is a few things. One is are you allowing the opportunity for the brain to respond to stimulus?

And again, to return to our uh gym analogy, everybody knows you don't get bigger in the gym, you get bigger when you rest, right? And the brain is exactly the same. So sleep being critical to that. Um, an absence of Chronic uncontrolled or uncontrollable stresses is a big point as well. And

When I've like tried to uh I I we're we're currently writing a paper that sort of like lays out this in a in a more academic way. Um, sort of like a a systems approach to cognitive function. And when you talk about stress. in the support side, even sort of like other neuroscientists in the field of people get a little bit um uncertain about that because when you look at stress and what it does to the brain, in many senses

It is a cognitive demand. It creates like neuronal hypermetabolism. So you almost have to think about it as. Overtraining. Right. So it's preventing the ability, right? It's it's junk volume for your brain. It's preventing the ability to to to So that's part of it. And then you also want to avoid um any kind of uh exposures that prevents some of these.

uh adaptations from happening. So al you know, excessive alcohol, smoking, you know, air pollution is really common. Um and so If you're trying to address the brain thong in an individual, these are all the areas that you have to think about, right? You have to think about um energy metabolism, vascular health, um, sleep, stress, other exposures. Uh we already talked about nutrient states. And There, you know, some other things that can inhibit this process include chronic chronic inflammation.

So that's where I think long COVID starts to come into play. And we know that you can see uh chronic inflammatory processes in the brain, you know, in certain individuals who have um ongoing symptoms after COVID. you see the same thing often years or decades after certain traumatic brain injuries and the amount of residual inflammation that you have in the brain um relates to then cognitive function or cognitive deficits in that individual.

How you address that becomes tricky, but that's o also not going to be necessarily relevant to the vast majority of people. So that framework I think gives you then a chance to say, well, where is the is the likely deficit or where's the issue that we're most likely to focus you know, gonna see benefit? And Why it's also important, I think, to think about it in that kind of framework is that

these risks and components aren't linear. Like when we when we talk about risk factors for cognitive decline or cognitive issues, you just get a list of 12. Some people it's 50 risk factors. And They talk about it as if you have to hit all of them perfectly in order to see improvements in cognitive function. And that's actually not true. They interact and they synergize.

So we know that if you have high blood pressure, uh you'll offset some of that risk if you sleep better. And if but if you don't sleep well, you'll offset some of that risk if you do extra So you don't have to perfectly hit everything in order to like Plug all the holes in the roof, which is one of the analogies that's kind of used for these processes. Actually, you can pull a few levers a little bit, and you'll you'll then almost see or often see outside.

So before we transition to this next area, if I had to summarize, if I feel like my cognitive function is fine, I'm not having any deficit right now, but I wanted to improve it, then Searching for novel tasks is probably the way to go. Uh ideally ones that have multiple sensory inputs. So smell, memory, different forms of cognitive function, creativity, uh Executive function like different aspects novel task of there. And avoid

ex you know, extended or continuous task switching. Because we know that's a significant stressor that's going to be very relevant to the avatar that you're existed. Yep. Thank you for that. If on the opposite where I feel like I have some sort of cognitive f uh dysfunction, uh I've lost it, then we go after the three S model and we figure out, presumably, Where in those wh where area of that I'm struggling the most with? So is it the the supply area? Is it um

Uh or the other ones, uh yeah, so supply and support. Or it could still be stimulus, right? Or stimulus, right? So maybe I'm not doing enough different things. Maybe there's some hole somewhere. So more than likely You've got a hole in your game somewhere that's either then causing excessive energy. You feel like your energy is low, but what's actually happening is you're burning a lot of energy and you don't really realize it because

your stress load is high. Yeah. And that's actually literally burning fuel in your brain, right? To keep that managed. Um, I would say of the of the people I'm talking about that we coach at RT, that has that ninety percent. Um I don't think we've seen anybody that has a problem outside of that. Yeah. Oftentimes they think that. Mm-hmm. They are for sure convinced that there's something

off the wall going on. And that has occasionally happened. But most of the time, I mean I'm not simply saying the basics. Most of the time if we do a full true analysis of sleep, stress management, movement, daily uh format, so how your actual life is structured, hydration and um mental health on top of nutrition, blood work, things like that. Something is generally very, very bad. Yeah. And they may not see that, perceive that.

But once we get that cleaned up, sometimes it's been as simple, honestly, as hydration. Yeah, that's that um I didn't mention that. But would you know fits right into that supply side, right? It's it's stunning. A cr a critical component. Sometimes it's low, sometimes it's high. I've talked about this so many times now, but Particularly females. They just stress drink water. They just chug it. And we're like, You can't drink two gallons of water a day.

I'm being a little bit hyperbolic, but not much there. And you lower that back to normal and like headaches go away, function comes back and you're like, Oh, I feel smart again. So th those are I think really insightful things that we can do. Today's episode is sponsored by Renaissance Puridization. If you want to put on muscle through science-backed training programs, look no further than Renaissance Periodization.

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Last little thing I wan I wanna ask about before we move forward to something you've kind of been alluding to, but that is vision training. You mentioned reaction time and I'm bringing this up because we see this actually a lot with our athletes and people tend to not realize it. The first time I caught wind of this was actually a number of years ago working with high level major league baseball players. There's some actually some cool work out of Japan. It found that the variant

in major league baseball players, the batting successful batting average, it was something absurd. Like seventy percent of variance was all in visual. Mm-hmm like ocular metrics explained almost everything. And that's when I was like, whoa. If we really think we're gonna service our baseball players better, if we're not touching and testing and monitoring and improving vision, like we're spit we're we're going after pennies on the dollar here. So what do we know about

testing vision outside of of course unique glasses, like things like that. And then Like can I get that tested? How do I get that tested? And then what do I do to improve it if I can't test and just again are there exercise, are there breath work? Are there nutrition? How do we improve vision? Supplements, whatever. Recently we've done some work um also in Formula One drivers with Vision because this is a big part of the

a part of their job and it it's i it's s essential. They'll probably you start to lose some visual acuity pr before you're gonna lose A lot of other functions. The eyes are an extension of the brain, essentially. So a lot of the stuff that we just talked about actually applies here.

Um really. So that basic stuff should improve vision as well. Yeah. And I uh did some analyses with some large population data sets um in order to try and answer some of this question. Of course, it's in a general population. But if you're looking at different aspects of visual acuity, even just measured with like a a standard test.

You'll see that uh blood sugar control, nutrient status, all of these things, also, you know, smoking and all that kind of stuff, all those same risk factors that we know are important for cognitive function, they then relate to to visual acuity as well. So those same principles come into play and all those same nutrients are gonna be important as well because you you you're essentially firing neurons from the eye into the brain, right? It's it's it's it's the same process.

When you then think about uh Um, there are a whole uh bunch of different platforms that you can do uh do this with depending on you know, how much money you have and what you have access to, but like right eye is a is one that's you know fairly good, certainly looks at different aspects of eye tracking, which is important um for athletes, but also after concussions and and things like that.

You can also do much more complex um eye imaging like optimal tomography that can give you a a much better idea of the the the structure of the eye itself and if there's any potential issues there. when you then think about visual training A lot of it comes down to similar principles. And actually there's a big overlap between um the your visual training and both physical and cognitive training.

Because part of it is neurological and part of it is physical, right? You are training muscles in the eye. So when we start to lose visual acuity, you can reverse. with essentially progressive overload of um the ocular muscles by just trying to focus on something that's just beyond the the the reach of your of your c current visual. Similarly, if say it's like dark light constantly. is the same. We spend a lot of time exposed to the same um intensity of light indoors.

Um and so then we that may be part of the reason why we lose some um dark light contrast as we get older. There's a nutritional piece as well. But like how often do we see and try and see in true dark and how often do we see in bright light?

And it's not that often because we're not exposing ours ourselves to those differences um in in light levels. So you can then do um Training with like visual So when I was trying to put together a program uh to for a f for say a Formula One driver th the that wanna try and v maintain visual tracking. There are some off the shelf things that you can use. There's some nice evidence for something like NeuroTracker, um, where you do multiple object tracking.

Um, that's probably not nearly as complex as you would need to do when driving a Formula One car. But for somebody who's done no visual training, there's some reasonable evidence to say that multiple object tracking just on your computer can im improve some aspects of of vision. And then beyond that, it's just thinking how do you create more and more complex situations where you you then train these muscles. So um I spoke to uh a friend of mine who's uh

former special forces and does a lot of this kind of training uh with individuals. And so one of his favorite uh tasks is to use a a baseball that you hang on some kind of string. And then you have um either letters or some kind of symbols on it.

So then you can first start with uh the ball just hanging still and vertical, and then you can practice, say, focusing in the far distance, focusing on uh a symbol on the ball, then focusing even closer, right? So you can practice uh quickly switching visual depth. But then you can also do things like make the pendulum swing and then you have to trap

you know, a certain symbol as the ball rotates and then also do that by changing by you know quickly changing visual fields. And so then you're essentially tr um training all these different parameters of vision, both visual field as well as um Uh looking all the different directions that you might choose to look. So the extremes of peripheral vision and as well as up the up gaze and downgas.

And it seems that, right, you probably can't overcome a huge visual deficit, right? But a lot of these different uh features of vision do seem There's a old thing we used to do in baseball where you have a bucket of balls and you throw balls to a hitter and the hitter

uh has to identify different numbers and letters. Right. So you're gonna imagine you got a bucket of balls there and you got a one on one of the balls, the next ball has a B on it and so on like that. And then you throw it and the battery only has to hit the ball but then say that was four. Yeah. That was F, things like that. Are you telling me that that might plausibly actually work? Yes.

You vindicated every nineteen eighty space ball hitting coach. Normal normally it's like some of these uh old school training methods just seem like hazing and uh they're kind of these attritional processes, but some of it might actually work. Okay. So you could do things like that. Uh we see this a lot of the times in combat sports and stuff as well. We throw different numbers out there. I think what you said at the beginning then makes a ton of sense. This is

It's the same exact principles of training your muscle, which were the same as training your physical brain. Yeah. And now your eye, right? Progressive overload, it is stimuli, it is changing things. There's a variety and then it is intention and focus. So you couple those things together. You could probably come up with just about any drill. Yeah. Yeah. You really wanted. It like doesn't matter a whole heck of a lot.

Um, vitamin A, carotene. Like what what about things like this? It makes sense if you Wikipedia really quickly what those things are. Um for clearly there's evidence if you've got certain physical cognitive or or physical issues in your eye.

especially from like a vitamin A deficiency. Yeah. Then of course it's gonna work. But for the normal person, and the reason I'm asking this is I know of multiple companies now that sell very specific, very expensive supplements. For vision. Yeah. For normal vision to enhanced vision, for special forces, for certain sporting populations.

I know you don't know the data on all these. I don't even know them, but in general, is it plausible that they work? Is it completely implausible or do we not know? So a lot of supplements that we use to boost any function or are used to boost any function like testosterone. Of visual boosters, there you there's probably going to be a benefit in the setting of an insufficiency or deficiency, but then increasing above that, you're not you're you're not.

um any benefit. For some people, um, right, retinol is important. We know retinol is important in the eye. Some people due to genetic polymorphism aren't as good at converting beta carotene into retinol, right? So maybe there's some inter inter individual variability there. But no, like more isn't isn't gonna be better. Um, certainly other things do seem to suggest some benefit and it's kind of like

squint a bit and and uh it might help. But some of the antioxidants, you know, lutein, astanthin, zeazanthin, they seem to be associated with improvements in cognitive function and sometimes a supplement. There are trials that show some of those supplements can improve uh visual acute. some other aspects of vision. Yeah, actually that's like reasonably well demonstrated at this point. My as my question with those trials are always

Are you simply seeing a metric of somebody who had suboptimal physiology? Oh, I'm sure. Yeah. Probably in in most scenarios because we know that most people have. some nutritional requirement or, you know, metabolic health issue or something like that. So then if you're you have a bunch of oxidative stress in your eye'cause you're prediabetic, then you know, uh uh an an antioxidant then can get that can get into that system is likely

Yeah, right. Um which is not to say you shouldn't use it. Yeah. Right. If this is your first entry into enhancement for that individual as a coaching tool. That that happens, right? Sometimes you struggle with people and you're like, you know what, I'm just gonna give them an easy win because we've been trying the nutrition, we've been trying to not get get them to stop drinking as much and they won't, but then they see benefit there. So I actually don't wanna yeah, dismay that too much.

Um, we take a different approach, of course, generally. Uh, and so we we haven't really seen much benefit in those folks, but I'm not I'm not surprised by that.

So you've mentioned this multiple times now, uh ander whether it be from the energy toxicity or your uh uh metabolic and energy sustained principles with cognitive function. But I'm wondering like how specifically Things like creatine actually enhance. brain function. We m you can tweak this actually from both angles. Whether this is like actual cognitive function, first of all, does it? Like if I take creatine right now, am I gonna

have a improvement in cognitive function and then what about long term brain as well? So kind of two part question there about creatine specific, I guess we'll just start there. Yeah. And then how actually it's it's doing those, if it is at all. So whether you would see a significant benefit from creatine right now probably depends a little bit. Are you you you take your dose of ten grams and like what are you gonna see? Uh it probably depends a little bit on your context. But

You you probably saw the recent paper that showed that after one night of sleep deprivation, you know, creatine can overcome some of those deficits. Cognitively. Cognitively. Yeah. And that's like that was actually shown um a few years ago uh with skill uh rugby skills in rugby players. You may have seen that paper as well, where they had uh players after a period of sleep deprivation, they gave them either creatine or caffeine and saw similar improvements in

like rugby specific skills compared to a placebo. Yeah, with a very different mechanism here, right? You're talking about a stimulant and versus a fuel. Right, totally absolutely relate both of those to energetics in some way because caffeine is overcoming or is inhibiting the metabolic Down regulation caused by adenosine, which is part of what drives sleep pressure and the need for sleep, is you accumulate.

uh metabolites like adenosine, they then um sort of suppress metabolic activity in the brain, um, which then is associated with reduced function, and something like caffeine overcomes that, whereas creatine can acutely uh provide a buffer. uh an energetic buffer that allows you to maintain function in the face of um sort of increasing metabolic pressure to to sleep. So even though different mechanisms, they kind of maybe converge on on something similar.

I know a lot of people who, you know, every time they take creatine they notice like an immediate sort of boosted some kind of cognitive function. Yeah. Um and there's there's been a lot of discussion over the years about whether creatine negatively impacts sleep.

Um, for that reason, it's sort of it's slightly stimulating for some people. Um, I've certainly found that in myself. Like if I take create I I work out in the afternoon, if I take creatine after my workouts, I don't sleep as well. But if I take it first thing in the morning, it's fine because I've kind of separated it. And not everybody's like that. And certainly we know that

uh responses to creatine are very heterogeneous, right? Some people see totally b uh big uh big responses, some people see see smaller responses. And some of it's maybe related to Methylation status because creatine, uh, when we make our own, which we make a lot of, is the most uh methylation intensive process in the body. You spend mo like more of your methyl groups producing creatine than anything else.

Um and so it could be related to that as well as uh, you know, a whole host of uh you know, how much creatine do you normally have in your diet and and things like that? So if I've gotten genetic testing done and I'm uh No No, don't do it. Shh don't go there. Okay, so I I think based on your reaction maybe you have just give us a a little bit of an uh a insight into your fever thever fever there. So

Um, whenever whenever somebody talks about methylation, they immediately start talking about genetic testing. And there's a lot of that out there right now. genetic polymorphisms do uh change the functional level of enzymes related to methylation. The one that people talk about the most is MTHFR. Um different um you know different polymorphisms within uh MTHFR change the activity of that enzyme. You know, in a test sheep, right, if I take you right in theory.

And then they do in some ways relate to other markers of methylation. So um Homocysteine, we mentioned briefly earlier, is a is a is a is an important marker for you know risk factor of a wide variety of diseases. It's directly related um to your current methylation status. Um But in most cases an elevation of homocysteine related to those pol polymorphisms is driven by some kind of nutrient deficiency or insufficiency.

Sometimes your requirement is slightly higher because of a polymorphism, but in general, I have yet to see a study that would change my mind when I say I can

Tell everything I need to tell from a blood test, I can tell from your phenotype, and there's no additional information that I get from your genotype. Whereas the opposite is not true. If I just measured your genetics I don't know what's going on with you, and I still need to measure your bl your your your uh B vitamin levels and your B vitamin states is your methylation state.

So for most people, measuring those polymorphisms is not helpful. But what it does is it drives a huge amount of fear because people are like, I'm a poor methylator. Like, what does that even mean? Like you're continuously methylating, right?

You all right, if you're if you don't methylate you die. Yeah. Right. You can't turn genes on and off. You you literally can't do anything. So we create this massive nocebo around uh these different polymorphisms, which I think is is net harmful when, yes, sometimes this is an issue, but if you have a significant um

decrease in MTHFR function of like in air air quotes um related to an MTHFR polymorphism, all you have to do to see a significant reduction in, say, homocysteine, is make sure that you're eating the recommended daily allowance of rib flavor. Because like it's it's not hard. It's it's not hard. It's it's literally nothing. And that's because the polymorphisms change how M T H F R bind to F A D.

which is the the the proton carrier that that enzyme uses. So all you need to do is uh slightly increase availability of riboflavin to be converted into F A D and that's it. And it doesn't require superdoses, just it literally just two milligrams a day. It's not There's also a very low relationship. between those polymorphisms and actual homocysteine. Oh yeah.

Like very sub one percent. So I've yeah, and I've published a paper on that actually for that exact reason. I'd I'd I did these uh big simulation studies looking at the the normal distribution of homocysteine by M T H F R polymorphism. from published data, and essentially about one percent of your home assistine is predicted by by your level of activity of your MTH.

Yeah, so why not just measure the homo sixty I I did a whole episode on genetic testing in season one, so p please feel free to go back and listen to that if you want. Um so we'll we'll move on for now uh'cause we can get aggressive there. But I I think what potentially is interesting here is say somebody has done that testing. So it doesn't matter, they've already paid the money, yeah, they're in. So, you know, tough luck.

And potentially they've had or think or or are actually low with methylation status, would that person then potentially be more likely to be a hyper responder to creatine for that exact reason? Or would that's what I've

hypothesized, but I and maybe this studies if this study's been done, somebody sent it to me because I'd love to see it. But I I think that might be the case. Uh that would make sense because so much um Like of so much of your methylation currency is spent on creatine production and if you know, you have to decrease some of that production because you know, you're quote unquote a a poor methylator or you have poor methylation status, poor B vitamin status.

then it would make sense that you would sacrifice some creatine production um and then would respond better to creatine supplementation. Uh but so in theory, yes, but I don't think anybody's actually looked at that. I wonder if it works the opposite way then as well. So somebody who's had potentially Uh well exclude placebo, which is a large portion portion of this, but

Uh people that have had some sort of genetic testing done, then gone on high doses of B vitamins and held felt a a massive response. Yeah. I wonder if those people could also then simply just go to creatine instead. Yeah. Which is I will say safer.

But a little bit less uh risky, right? Um not a lot of downside to creatine, not a lot of downside to B vitamins, but more. Like you're gonna you're gonna get other consequences that you maybe didn't realize you're you're going after with high doses of depending on which vitamin vitamin B you go after. Um Potential downsides. Yeah. Things you can go after. What's what's interesting is that unfortunately

these kind of questions haven't really been addressed in the literature. Right. So I I can quote studies on supplementing with B vitamins in individuals with elevated homocysteine. Um and right, we know we know how that can be important. And but then we can also talk about

studies where they give doses of creatine. And particularly when you've started particularly in older populations and those who've maybe started to see some element of cognitive decline, you see a greater effect size of supplementing with creatine.

But I don't think anybody's looked at like, well, what if you gave one or the other? Or is there a trade-off? Um, these are like super interesting and important questions, but because of the the sort of the reductionist evidence-based medicine model that we currently have. We just like try one thing at a time and don't necessarily consider the context

I'm vitamin B is I'm all for. That's great. I just know that a a reasonably high percentage of people will get really nauseous or have GI distress from them. And so for those folks, so it potentially maybe creatine is a little bit of an alternative option if you think you have a methylation or you actually do, either way, and B vitamins don't sit well with you. Especially at that dosage. And maybe creatine gives you some percentage of that benefit as well. Certainly we've done um

Yeah, so w you know, when I was working with a lot of individuals in you know in a similar arena to to what you do now, um you know we went this is taking getting you've got thousands of people with their blood work and providing individualized protocols. This is what you've done for A very, very long time. And when and this is sort of like general population as well as with athletes.

And if um, you know, B vitamin status looked okay, but maybe homocysteine was still elevated or, you know, you know, we we needed other strategies to help bring down homocysteine then creatine and choline, um, or lecithin, which is a you know a plant a plant derived um source of phosphodolcholine. Um they they were were good alternative options or something you could add on top. Yeah. Okay.

Why then does creatine help with cognitive function if it does? And we'll get back to that second part of that two-part question. Um, is it the methylation support that's giving you? Is there other mechanisms? What exactly is creatine doing for the brain? I think One one of the things that I've found most interesting across strategies that seem to improve like robustly improve cognitive function um either across the lifespan or in multiple different groups.

Is that they usually do more than one thing. And anytime we've tried something that only does one thing, it doesn't work. Yeah. Uh that's just like uh a lesson from neuroscience in general and also a lot of Uh just like developing drugs in in medicine in general. Yeah. Um And so I think it's probably gonna be a bit of all these things. So uh we know that that home assistine is a risk factor for cognitive decline. Um and that

Probably because it's a marker methylation status, right? So are you able to uh generate, say, uh, membranes in in cells in the brain, like we talked about earlier? But equally, uh, homocysteine can directly increase the accumulation of hyperphosphorylated tau, which is one of the sort of markers of you know, risk factors of dementia. It's a marker of you know, previous brain trauma and uh a number of other things.

So it may contribute to cognitive decline in a number of ways. And so if creatine is offsetting some of that issue, you may have some benefit there. Then there's the energetic piece, right? It's uh it's it's gonna give you short term a short term energetic buffer as phosphocreatine, um, in neuronal cells. And the brain is the most metabolically expensive organ in the body on like a

uh, you know, calories per or watts per gram um comparison. And so you know, anytime you have either a suppression of metabolism, say uh, you know, um adenosine or some kind of acute injury, uh, and that can either be a stroke, it could be cardiac arrest, it could be brain trauma, where you have um some kind of deficit in energy production, then creatine also seems to potentially be beneficial, although

Um some of the studies suggest you can supplement afterwards, but most of the benefit seems to be if it's on board beforehand. And of course a lot of this

from animal models because you can't do that you know easily in in humans. So some of it's as an energetic buffer. And then some of it um you know one thing that creatine seems to do is to uh help stabilize and regulate calcium handling in mitochondria, which is related to acute injuries, but also to to long-term um mitochondrial function, which then supports long-term um cell function in the Really quickly, I don't want to drag this down too far, but you've mentioned it multiple times.

What is methylation? So why does it matter? And just real quick on the Yeah, so uh methylation is basically the the transfer of methyl groups, which is basically a one carbon group or a carbon with uh three hydrogens that gets moved around. And uh this is used to uh convert different metabolites um in in in the body in like multiple different cellular reactions, like you you change uh a molecule from one into another by methylating it.

But it's also really important for things like um gene regulation. So people might have heard of biological age, epigenetics, the major um form of epigenetics and Gene regulation and you know the the sort of the more common measures of epigenetic biological age all are all based on methylase. So you have uh these uh what are called CPG islands on DNA, which is where essentially the cell puts on these methylation tags which regulates whether a gene is turned on or off.

And these um these tags seem to shift over over time that's associated with b biological aging. So it's this really central process that drives, you know, So many different parts of bio. It's in every cell of your body. It's on DNA. It's on protein. It's moving a carbon is hard. Yeah. Like chemically, right? So It's gotta be a major thing to get it to move off of one, which changes the entire function. Yeah. So it's I I think the way that you state it is very nice. It's it's a core biological

You don't adapt, you don't grow, you don't shrink, you don't go any direction without mastellation. So thank you for that. Now we have a little bit of understanding of why that's

Um then regarding the creatine in the brain, the second part you said was fueling. Mm-hmm. Walk me through how creatine actually you you mentioned it kind of quickly, uh with a just a touch of jargon there, which yeah uh for the folks that don't know what an intermediate uh and a substrate are, how is creatine actually providing fuel for your brain?

Um and then on the second part of that is well, what's the normal fuel for our brain? When you think about Uh different energy systems and I think people could uh watch endless lectures from you talking about different energy systems in in uh in exercise and those principles in some ways are very similar um in the brain.

Although the majority of cells in the brain are, you know, like like we said earlier, derived uh derive energy from glucose, goes through glycolysis, then enters the electron, you know, the uh pyruvate and la and or lactys pyrovate goes

in the mitochondria. But there's all of that is done to generate high energy phosphates via usually or mainly ATP. Right. So ATP is your energy current uh sort of a a much shorter term um energy currency or that allows you to recycle ATP when you've used it up is the phosphorcreatine So um your creatine is phosphorylated with a high energy phosphate and you use that to regenerate ATP.

So for very energetically expensive uh processes where you you can't get enough energy through a that longer process that glycolysis and aerobic metabolism, then the buffer comes from the phosphorus. And it seems that even for normal cognitive function, um, there is some benefit from having s more of that buffer on board, um, uh, both acutely and So just like your muscles or any other part of your system, they have to rely on energy. Uh the nerves.

Need energy to conduct, right? And so people, I guess, sometimes don't always grasp the fact that your brain, when we say it's energetically demanding. It's because it's going through a ton of metabolism. We have this connotation that muscle and metabolism, yeah, kind of thing. But the brain is metabolism as well. Your basal metabolic rate, the amount of energy you burn throughout the day, your fast or slow metabolism, all these things are

It's in your brain as well. And so it produces energy much like anything else. It can use fat as a fuel source, theoretically. It can use carbohydrates. ketones or anything else and then creatine, uh, just like it is in your muscle, provides that stoichiometry of of one to one, right? So not a lot of energy per molecule of creatine. So it gets used up and turned and burned quickly.

But the upside is it gives you that energy really fast. And so while you're maybe slow to metabolize and you mentioned this, so we'll bring it up, your brain will actually then generate lactase.

So if you're thinking really hard and thinking a long time, are you like feeling the burn in your brain? Is that lactate building up? Is that what's happening? I don't think uh lactate doesn't accumulate, it just gets generated and and used. You probably couldn't Um you you could you could probably measure um so so this is where I I think creating becomes important and and you potentially if if I put

microdialysis needles really, you know, accurately in certain parts of the brain, and then you s you start to upregulate the use of that network for a specific function. Because there's gonna be a slight delay between increased ATP production. Um

and the requirement, right? You need you you actually need that energy before you realise you need it, right? Everything that we see and do has essentially already happened because of the time lag that it takes for us to actually interpret the those actions. So

that energy is needed immediately. And it could be that because of the lag in the system, you know, upregulating uh energy production, that's where creating becomes important in in in a network as you activate Then you would probably start to see uh locally if you could measure you know measure it with say carbon thirty metabolism or something like you could have a radio tracer on your on your lactate and you could see that your astostrides, which make your lactate,

For your neurons will probably increase production because your neurons are more active in that area, they're going to require more energy, they've used up their phosphocreatine system, and then the astrocytes locally are going to produce more lactate. None of it's going to accumulate because it's getting used, but flux through the system is probably. Yeah. This is potentially why people have looked a lot at lactate as a supplement or as a

medication or therapy for various aspects of of brain injury and uh brain damage. I don't wanna go to this into too much detail because I covered a whole episode in season one, episode ten. Uh all on a paper that that you led with Doctor Federica Conti and m myself and and some other folks as well.

on what we know exactly regarding supplementation and nutrition for brain injury. So this is concussions, CBIs and things like that. So you can go and watch that whole episode and download that whole grade for all those details. But in that paper, I remember we had a very short section regarding lactate. Yeah. And what do we know about lactate for concussions and stuff like that? And so before you answer that.

I want to set the stage just a tiny bit. Um you can feel free to maybe double tap on Cretine a little bit here since we we brought it up. But I think it's really important. You have I've seen you give the best explanation I've ever seen of what a concussion actually is and what it is not. And so maybe just quickly tell us.

uh your egg analogy and uh and then that'll help explain a little bit of why uh maybe these things um do or don't work for there. So um how how does a concussion actually work? Today's episode is sponsored by Momentus. Momentus makes the highest quality supplements on the market, period. Many of you know me and you know that I do not trust the vast majority of supplement companies.

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to zoom out for a second, I th I think one of the reasons why We have really failed to produce consistent therapies or reproducible therapies for concussions is because we don't study them properly and we don't study them properly because we don't understand. Hard to fix when you can't define. Exactly. And so what is normally done or the when people think about a concussion and if you read papers, you'll still see this um consistently. Experts in the field talking about it.

Um, or you know, you imagine a head getting bashed and then like the brain banging around inside the skull, like hitting one side of what hitting one side of the skull, then banging and hitting the other side. And that's what they call a contra coup injury, which is basically you see some injury on the opposite side from from where the impact occurred. The brain is

You know, it it's mainly fat and water, and it is then surrounded by fluid, and it's inside a solid box. And that fluid is full of salt. That fluid is full of salt. If you take a solid box full of water, even if it's got something very fragile inside, and you shake it really hard.

That fragile thing does not bang against the sides because the water is right buffers it or the you know, the CSF or the the fluid. I saw you do this. Yeah. It was the c one of the coolest things I've ever seen. You took an egg

And you put it in a jar with salt water. It I don't remember the concentration you put it in. Oh, it's just like normal that normal sideine. Yeah. And you, you know, screwed the top of a ball jar or whatever it was and you shook the living crap out of the egg and the yolk didn't break. Yeah. At all. No. Because it's not hitting anything. No.

Smash together. It stays right in the m it stays right in the middle. I w at in that moment I went, I I what? Like everything because I had said that always. I did not know that until you showed me that. Yeah. Not me, but you're showing other people. And I was like, wow. So if if you could, while I'm shaking it, image the jar, what you would see is you would see distortions um along the surface of the egg yolk inside inside.

So there are distortions. So the egg instead of being a perfect circle turns into an oval. Yeah. It's not smashing against the wall. It's just being distorted and and it's being um accordioned. Exactly. Squished and and pulled back apart. Right. So how we generally study concussion?

is the other version of of the egg experiment, which I also showed, which is that you have your your egg yolk in your solution and you leave a big chunk of air in the top of the jar. You shake that, immediately it turns into salad. Right. Immediately you disperse that egg yolk th throughout the lake. That's how we normally study conclusions.

But what happens um if you then look at where injury is in people who've had concussions. So like you look at individuals who have uh CTE, right, they probably have some ongoing history of concussions. It's happened multiple times. If you look at where the injury has accumulated, it's not at the surface of uh of the brain. It's not the brain banging against the skull. What's happening is that these distortions, like waves of energy that are transferred through the brain,

At the interfaces of different parts of the brain. So particularly the interfaces between the gray matter on the outside and the white matter underneath. Yeah. It's connective tissue. Yeah. They're tearing the connective tissue. Yeah, so right at the usually right at the base of the sulci. So you think about the brain is really wrinkly, right? Those are the gyre. The the sort of the divots in between those wrinkles, the sulci, at the base of those.

That's where you tend to see uh injury. And it's because you have tissues of different densities. Where then the distortion travels at different rates. So then you create this shearing effect at those interfaces. And then that's right. And if the shearing effect is very large, you can rip axons, you you so create direct direct axonal injury. Um, if it's a blast wave, then obviously you're not directly shearing anything, but you still

You still seem to injure those same areas because the energy wave is transferring through the brain at different rates. And so that's where the injury uh accumulates, is at those at those. So then how do things like creatine and lactate uh help do they work at all? And if so, how? I've been uh really excited about the potential for lactate in traumatic brain injury and and that uh excitement aligns very similarly to with ketones.

Um, but people have been talking about them for a long time and I'm still waiting for some good some good human studies. I've been probably talking about it for a decade online, like in front of people on podcasts and things like that. Yeah. So I b I believe that they could be beneficial, but we just haven't seen really high quality evidence yet.

However now that's clear, we haven't seen evidence that shows they don't work either. No. No, no. And if if I were to get uh a significant concussion or T B I like I'm going straight to the key to Nestors because I believe that there's a high chance of benefit with low Anybody who's like

I I don't have a randomized controlled trial to tell you that that's the case, but you know, I I think it could be better for the same thing. If it was my brain, that's that's what I would do. As an MD PhD in brain health, this is what you would do. Infer that for what you will, folks. Uh part of it is that it's essentially providing uh some kind of metabolic substrate in an area of the brain where there is impaired metabolism. So one of the consistent responses you see to an acute brain injury.

And again, strokes, cardiac arrests, traumatic brain injuries is what we call energy failure. So there's this uh gap between energy requirements and energy supply because you have dysfunctional mitochondria. Ketones and lactate can kind of bypass some of that and seem to be um less

uh le less energy energetically expensive or they're more energetically uh efficient in terms of generating ATP. Like the effect is small, but in that kind of setting a s a small effect uh may you know may be enough to help m to help minimize injury. There's also gonna be some other signalling effects that that could that could be beneficial. Um like

Both lactate and ketones have a whole range of other um anti inflammatory um neurotrophic kind of effects. So so lactate seems to help and ketones seem to help drive an increase in production in B DNF, brain derived neurotrophic factor, which could help.

Recovery. So beyond their effect on your metabolism, they may have these other downstream uh effects as well. But Another reason why this is important is that in the acute uh injury setting, the the brain may become relatively uh insensitive to glucose or glucose uptake decreases. So um but that doesn't seem to be the case because the the transporter is different and both ketones and lactate go in through the monocarboxylate transporters, which aren't necessarily effective.

ymwneud â'n ymwneud â'n ymwneud â'n ymwneud â'n ymwneud â'n ymwneud. In terms of energy production, but also they're maybe more likely to get into the brain in the setting of of an acute injury to help support Are they potentially less negatively influenced by inflammatory markers as well? Um Yes, potentially. Although I mean it kind of depends on w what's what's going on and how

I don't naturally associate physical structural damage with metabolic problems. What's the connection here? Why is it if I have a structural tear? This is a case in muscle, by the way. Yeah.

that my my brain is, well then it's inflammation, it's damage. So you need to give me something that's anti inflammatory, NCIDS or some other drug that is gonna reduce the inflammation. Or you need to give me something that's gonna repair the structure, DHA, fish oil, like some structural thing. Why are we seeing and having to deal with and why are metabolic

Issues so prevalent, glucose dysregulation, things like that. And then why is energetic the solution when we have a physical structural tear? So one of the reasons why you have impaired glucose metabolism is because of the And a normal inflammatory response creates peripheral insulin resistance in order to divert glucose to the immune system in order to in order to

So it has to have energy as the immune system has to get energy as well. So that that that's a good thing in order to generate a normal immune response, but can then cause issues in other tissues because they become insulin resistant, driven by the inflammatory. The direct metabolic effect of injury.

is due to the changes that happen at the cell or in in the nerves in response to that injury. So if it's um say like a direct shearing effect or um, you know, even in concussions where you haven't um Fully sheared neurons, you may have stretched them. Um, and you may have vascular changes that impair the ability to deliver oxygen to those tissues. And in all of those settings, you can get essentially a hyper stimulation of those neurons. So they start to fire a bunch.

When you get this hyper stimulation of of neurons, um and you see you can see this with low oxygen states or with, you know, acute sort of stretching, if you sort of acutely stretch the neuron. They increase their firing rate. That creates a large production of what we call excitatory um neurotransmitters, things like glutamate, uh which are that's the most common one. Yeah, the most common one, but there are there are there are others.

That then starts this sort of wave of increase in signaling. You then essentially hyperstimulate the downstream neurons. You get these big shifts. uh in calcium um within the cell and then that calcium impairs mitochondrial. And at very high levels can actually uh stimulate um what we call the m uh mitochondrial permeability transition, which is essentially the mitochondria saying, I can't take any more, and then that's that then triggers cell death.

So it's essentially an over stimulation which can be driven either by low oxygen or stretching, um, which then sort of creates this cascade that impairs my. You mentioned calcium again. That was also the third part of our uh criteria we talked about earlier, right? Like that having that third issue. So I wanna ask more about that. But let me see if I can summarize what you just said quickly. In the case of uh a brain injury.

You're gonna immediately have some sort of inflammatory response, which is a great thing, right? The whole point of the inflammatory response is to let your immune system know we need to divert attention and start physically, mechanically repairing collagen and whatever else is there, right? Unfortunately, those immune cells require energy. Mm-hmm. And so you have to then divert glucose to them. Yep. And the best way to divert glucose to them is to block it from going

Other places. Yes. Right. Now, in this short-term thing, we've basically given other areas diabetes. Yeah. Right? Like we've made them insulin resistant on purpose so that we can focus our glucose to the immune cell. The immune philos cells then show up to the place of injury. This is all a good thing. But because of that, we're gonna start running into, in fact, we could also be dealing with

tears and damage to the actual the membrane of the cells, right? Themselves could be physically torn, which then is gonna allow things coming in and out of the cell that we don't want and we have like calcium. Yeah. And having other problems with that. That's the normal process. If we were to then go take copious amounts of, say, anti-inflammatories at that stage. And this is probably one of the reasons why they don't do this, right? Um, we are probably going to run into issues.

Because we're blocking that natural process, right? So we want some sort of, I'm presuming, inflammation uh immediately, but probably not super excessive. But not small either, right? By the way, I'm guessing at all this because this is exactly how it works in bone and muscle. Yeah. So tell me when I start to deviate here, right? I'm I'm literally guessing. So I I'll jump in just quickly to say that um in general in in brain injury, everybody's thought that

These inflammatory responses to injury are a bad thing and we should try and um try and prevent them. And So far that that has generally failed. And actually there are some therapies, you know, nothing that's, you know, available right now, but there are some therapies that seem to augment

some of the initial responses to injury, inflammatory responses to injury. So like in a minute it looks worse, but actually that then ends up uh resulting in in improvement longer term. There are cascades of drugs. that pre-dose pro inf pro inflammatory cytokines and whole co and then give them to you. Uh-huh. So like give an exaggerated inflammatory response in in in again another tissue. I'm not surprised it's the same enough.

or in the brain. So once we get past that, the issue then becomes if that stays around too long. And now we're starting to damage mitochondria and now we're having an issue with regulating energy. And that's why then providing energetic support so that the cell can stay alive. Right. If that cell, now we're in the case of the cell, we're talking about the brain cell.

runs out of energy, then we're gonna die. Right. And so it's a hard time managing energy. And this is why probably initially in the case of an acute injury, we want to maintain temperature.

Right. That's I know that's one thing we covered uh a little bit in the paper, but I know you spend a lot of time on because of this process, right? When things get really, really hot metabolism. has a hard time hanging on, right? So things get overheated. Managing blood glucose in general so that this curve is normal, and then at that point, providing energetic.

Yeah. So those were kind of the three big areas for in the acute setting, um, where if you were to actually have a real injury and you were to get treatment in hospital, like that's Particularly temperature and glucose are probably the two things you're gonna pay attention to most, right? Yeah, if you're in an IC uh like a neuro ICU'cause you had a you had a s significant uh traumatic brain injury. then glucose regulation and thermoregulation are known to be critically important.

I think in the we kind of hypothesize that in much less severe injuries, these things are still relevant. So we should think about them. There haven't been a ton of trials in that area because they're hard to do. But it kind of makes sense that, you know, just because you don't have a massive injury doesn't mean that those things aren't important for What about things like at home brain tests? So they're whether these are

Uh technologies where you can test cognitive function? Maybe not. I doubt there's any at-home concussion tests that you can do. Um no. So most most concussion tests they're j yeah, generally r require either um some kind of baseline cognitive function test. So there's things like the um the impact test. Uh the the military have have their own version of this.

Um, there's other tests that are probably more sensitive to concussions called the g like the King Devic uh test, which is basically you have to read off uh a complex grid of numbers and letters that kind of like overlap if you can't read them properly. But you need like you need a baseline score and you need the same person to kind of administer it.

Um, you also see uh there are some some uh available devices where you can measure changes in event related potentials. So uh the electrical signal that you get if you s you know show somebody a l an auditory or visual stimulus.

um that seem to be pretty good predictors of like th there's actually been an effect of a concussion and then recovery. But all of this kind of requires some kind of specialist to be involved, usually. Um Uh more broadly in terms of c uh in terms of uh cognitive function.

What's interesting is that there aren't a ton of easily available cognitive function tests that you can like just do at home and do repeatedly. There are some apps and things that kind of have some of this stuff built in, but it's difficult to sta difficult to standardize. Um one uh Depending on if you have if you have, say, access to some kind of healthcare provider, there are um nice companies like Kraos which give a bunch of standardized cognitive function tests you can do at home.

On a desktop, a lot of um neurologists and uh neuroscientists use something like that. Um I think Um The main cognitive function test that I know of that anybody can do at home for free and is validated. is actually uh has been put online by a charity that I work with uh in the UK called Food for the Brain. And they have a a validated online cognitive function test that includes measures of um executive function, working memory, and processing speech.

And you can just like go on their website and you can just do it and you can track it over time. the and we're we we currently have a database of more than half a million people who've taken it and dozens of thousands of them also have done uh lifestyle questionnaires about

sleep and all those kinds of things we talked about. So we're in the process of doing a lot of research from that database. Like right at the beginning, we've just sort of be give be given access to be able to do some of that. But people can do that test. Uh I will say that In terms of cognitive function tests, it's one of the ones that has the biggest learning effect on the second attempt, just because of the way this test is structured.

Um, so if you're gonna do it and you wanna like track things over time, I would do it a couple of times in succession. So like you know it and then use the second or third time as your baseline and then track and then track it over time. Um

But there are there are a number of people now in this space because I can now go to Quest or Lab Corpor and I can get whatever blood tests I want, but I can't get a really good, well-validated um multidimensional cognitive function test. So that's something that you know we and other people have any other technologies, uh consumer based EEG things that uh you you can or cannot mention the exact products if you'd like, but just where does that field stand? I know that there's probably

Half a dozen or more that immediately come to mind. Um some of them sit in the front of my head, some in my ears, some back, but it's like walk me through again, you can spec specifics if you want or not, but the general lay land of at-home-based EEG technology.

I think it's an area where there's a ton of promise. Um it's just figuring out That's never a good start. No, but in a well I think in a in a good so I guess the short answer is is there anything that gives you everything you would want right now? Probably not. Um however with very simple EEG devices, um, and there are some that uh are set up in earphones, so I think the one that that I n I know is most uh widely available or at least will be soon is is is is a company called Neurable.

Um the one the frontal EEG like Muse is something that people are gonna be uh familiar with. And actually there were versions of the Muse that have the sensors around the ear as well. Some of the why does it matter if it's in the front of the forehead versus the ear? It depends. And it depends on what you're on what you're looking at.

w with some of my collaborators we're looking at different EG frequencies and people have heard of like alpha, beta, theta, delta, and the different uh like the relative uh frequencies and power of these different um frequen so like even within a frequency band. uh people will have different average frequencies and then uh the the sort of the the total amplitude of the wave is is the power and the the your mean frequency and power in those different frequency bands.

relates to different aspects of cognitive function. So uh certain aspects of alpha seem to predict um say learning speed for learning a second language and some other aspects of cognitive function. Um some companies have created like focus metrics. So like you can tell when your brain is focused. That's either based on um uh certain measures of alpha or sometimes they have like a alpha plus beta divided by delta plus theta or some kind of ratio of the different frequencies.

And that stuff is is pretty good. The problem is uh the Each individual company kind of focuses on one thing, right? So you're using it for neuro neurofeedback in kind of like a meditation type um uh setting. Yeah. Or you're using it to kind of tell when you're focusing well and then your focus is starting to drop off and maybe it's time to to take a break.

I think that you could get a lot more uh and and broader information about somebody's cognitive function over time with some of these technologies, even even simple setups, but just nobody's really done that yet. So Kind of selling focus or selling meditation, that stuff's great. Like, don't get me wrong, I think it's an important start, but I think there's a lot more that could be done if we had the right information and we sort of tracked in people.

Yeah. So the only well perhaps not maybe the only, but the the largest consideration there for the consumer is just that last point. Yeah. So it's going to be at least that I'm aware of that you're aware of. Any consumer-faced product there is gonna have one particular aspect of cognitive function, but it will almost certainly not test nor train and help you evaluate.

Other aspects of cognitive function, which is not their fault. This is a more than small technological limitations. Really charging, yeah, challenging.

The calcium question. Yes. Right. So w what does calcium have to do with this entire project? Why does it matter if calcium influx is happening or this um excitotoxicity with glutamate? What's that gotta do with it? And then Does calcium work then as a supplement I can take to enhance cognitive function, to deal with brain injury? Walk us through the store with calcium. So I I think this is another area where um

the brain and and muscle kind of tell a similar story, right? We know that uh muscular contract and the heart, right? The muscular contraction is driven by cycling of um calcium. And a lot of signaling processes including mitochondrial function and then um the the transfer of um information um across cells in the brain is driven by waves of calcium.

And so that then, you know, opens and closes um different channels, it you know, activates or deactivates different energies processes, it regulates mitochondrial function, uh, just like it does um in in the muscle. So when you have large, like excessive or unregulated um influx of calcium into a cell,

you know, one of the prototypical downstream effects is mitochondrial dysfunction and eventually uh like mitochondrial death. And you know mitochondrial death you essentially have cell dip. So totally totally that's what you're going to see is cell depth. Um so

When you then think about like calcium as a supplement, obviously th those those two things don't go directly together. Uh you can't take more calcium and then have better regulation of um energetics in the brain, unfortunately, because it's just a lot more complicated. But I think this is where some other things come into play. Like we know that like so vitamin D is really, is really important uh for cognitive function. One of its role I mean, it's essentially a steroid hormone, but one of it

roles is in the regulation of calcium. So that, you know, that it could be playing a role there. We know like magnesium and calcium play together and often uh sort of like playing off one another, we know that magnesium is really critical there. So

Some of these other factors that we know are important for cognitive function may be playing a role through regulation of calcium. But if you were just gonna take more calcium, um, it's unfortunately it's not gonna just end up in your brain and improve cognitive function unless Yeah, for whatever reason you were calcium deficient, which is

relatively rare. Usually it's other factors, um, vitamin K status, you know, other things that that are that are playing a big role there. Yeah. I mean, uh w what's the RDA for calcium thousand milligrams a day? Yeah. Like something like that, right? You don't rarely see people or you don't often see people. It might be a little like seven or eight hundred milligrams. It's not that much. Okay, maybe you see less than. Yeah. Pr pretty I mean a smidgen of broccoli. Yeah. And it's like

Some dairy, like you're you're you're probably there pretty much. Yeah, you're not gonna smash that up there. And also seems to be one of the the minerals particularly that doesn't like to be outside of its window. Yeah. In the sense that if you get a little bit high on magnesium, as particularly if you are really physically active, that's probably okay. In fact like Oftentimes that's good.

Uh you don't want to do that with calcium. No, and it's even more tightly it's even more tightly regulated because it's essentially a trigger for so many and like it's how so many biological processes. Your heart will stop. Yeah. So you need it to be able to read it. Yeah. Way low, way high. So it's not one uh for and for those cases, I mean, thinking back over your career. How many times do you think you've recommended

calcium supplementation based on blood work or things like that. I think the only time we routinely recommended it was in Like osteoporotic older individuals, but you were taking it with vitamin D and we were trying to, you know, cover some other bases as well. So like just giving like calcium on its own, I don't think I've ever recommended. So not in your performance enhancement with your athletes, not in your practice as a medical doctor, none of those things, right? I don't think I've ever

So magnesium, like ubiquitously. Yeah. Like everybody hugs people down with it. Totally. And but calcium is probably not one of the ones. So probably not one of the markers we're gonna go after for either cognitive enhancement or the brain injury, things like that. Okay.

You have said three things thus far in our conversation that have irritated probably many people. You r remind them what they are? I am. And then I wanna see if we can go for a fourth. Okay. One thing you said was that uh things like microdosing, psychedelics and marijuana probably don't potentially don't necessarily enhance creativity.

They certainly enhance your perception of it, but maybe actually you're not doing better work. You're just high and think your stuff is great when it sucks. Uh-huh. Okay. That was number one. whole internet will hate me for that too. The second thing you said was actually that you're you're fairly convinced at this point that we can actually enhance cognitive function, which doesn't sound controversial to some, but for others are gonna be really upset about that. And

What you mean by that is general. So it that is transferable to other modes of cognitive function. As we just talked about, focus is not the same as executive function, that's not the same as word recall, et cetera. And that that can be improved. And we laid out various cases for that. Third one you said was that in fact concussions and brain injuries are not your brain slamming.

against your skull. Uh that probably could happen. It's plausible, but most likely you have either temperature or distortion or metabolic issue or combinations of those. Fourth one, and I've heard you on record, so true or false here, you are of the opinion that dementia.

And late onset Alzheimer's, not early onset, to be clear, are one hundred percent preventable. I've never said a hundred percent. Okay, all right. Okay. I I would say so Um and this really at at this point shouldn't be controversial because again Dusty neurological institutions led by establishment individuals would say the same thing. Um that I would say that so

The the party line is that forty five percent of dementia is probably devent uh preventable. That's from the Lancet Commission run by Gil Livingston and a bunch of experts across Across the world it was just updated. It used to be forty percent, now it's forty five percent. They inc increased the number of risk factors that they included. I would say it's a good thing. Easily the majority,

'Cause there are some things that they didn't include. Sixty plus percent, seventy plus percent. So other estimates, um, so say uh Yin Taiu, who's at Fun uh Fudan University and his group have done a ton of uh modeling and prediction from large population data sets, they think that somewhere between, you know, up to 70 something percent of dementia is preventable if we were able to address all the different risk factors. Okay, so this is an enormous departure from what the lecturer.

Right. So not only potentially is a departure from the scientific community, but if you were to walk down the street and just ask people about first of all, they'll call it Alzheimer's probably. Right. Yeah. Um, but dementia, uh I don't know anyone who thinks that this is anything besides this just happens with age or it's like cancer where it's just a bad luck of the draw. Potentially some people might think, oh, it's, you know, if I drink a lot of alcohol

But I don't think many people think it's anything besides those ones. So not only are you saying that that is not the case, but it is in large part Even forty percent is impressive, but probably more realistically, 70 plus percent of dementia is extinguishable. So two part question. Is this a prevention issue or is this a reversal?

There are certainly some people out there who who, working with individual clinical cases, have said they have seen what they feel is reversal about Simon's disease. That I I'm still not it hard. Like what'cause once you've reached that point of significant atrophy and significant pathology, it's very difficult to um restore function andor, you know. Reverse or structurally, you're talking about the thing. So this is all this is all prevention.

Case studies, maybe things like that that like yeah in terms of reversal. Yes. Dementia is the same case or just Alzheimer's? Most of this is focused on Alzheimer's. But some people will say, you know, in in certain cases of frontotemporal dementia or Lewy body dementia, they've seen significant improvements in cognitive function. And it's by generally addressing the same things. But I I wouldn't come here and promise reversal. But I do think prevention um there's m you know massive

Slowing down onset or slowing down progression is certainly a thing. Yeah. We we we we'll talk about that separately. I'll keep it going. I'll bring it back to that. So there's reversing, they're stopping the progression, and then they're stopping it from happening. Yes. So okay, continue on with the prevention. So um and I I think all of all of this is essentially um all of this is connected and and the same risk factors apply essentially.

Uh regardless of where you're trying to intervene. It probably just gets harder the further you go. So when uh they classify them in the Lancet Commission report, they sort of classify them by stages of Lancet. So early life, the most significant uh modifiable risk factor is is education. So the more years of education you have, the lower your risk of late.

And uh then late life cognitive stimulus also becomes import important. And uh that's that's been shown uh again in meta-analyses by uh uh Professor Yin Tai Yu's group and is incorporated in into this uh Lancet Commission report. So I think that's a good place to start because it fits with my worldview that stimulus is really important. That's always good. And so

Um and you have by the way, you and Josh have a paper, open access paper. We'll fully link to that in the show notes so you guys can go fully read that. But yeah, continue on if if you want to read this whole breakdown.

Um that paper will be up for you. So you can kind of hear uh think about this idea and again it's sort of d driven by that same idea that stimulating t like the function of a tissue is directly proportional to the stimulus applied to it. The liver's the same, the immune system's the same.

And so when you look at trajectories of cognitive function across the line Um, and there are you know multiple meta-analyses, and it a lot of this has to be observational. But what you see is that um those who have more years of education, they have a higher peak of cognitive function. And that's you know, you spend more time, you know, devoting more resources to in enhancing cognitive function. I I got I'm sorry to cut you off for like the fourth time, but I have to linger on that point.

It makes intuitive sense that the more time I spend on education, the enhanced cognitive function I have. Right. But that's not what you just said. What you just said was you reach a higher peak. Yeah. I hope people are sinking in on what the heck that that means, right? We all can progress, we can improve, but getting to a higher total maximum peak. is really it's not the same as just increasing in speed. And it's it's what's stunning me about this, and I'll keep going back to it.

You will see the same thing with bone. Right? The maximum bone density you get is going to be predicted by what you did between ages 10 to 14. Now the rate of increase is like pretty much ubiquitous. Like up and down is the same. But determining how high that peak is is all about what you do in that window. Yeah. So I'm I'm just like so stunned right now. That uh I I knew the increase, right? I could certainly would have said, hey, would you improve cognitive function? Like, yes, if you train.

But I w I d was not anticipating you would say that that the height of that peak is gonna be determined by that as well. Yeah. Because you're gonna deal with that the downside the rest of your life. Exactly. Yeah. And so uh you know, a lot of other things go into that, but you generally see that people that the higher your uh so if you think about peak cognitive function, which depending on

what it what cognitive function you're looking at and how you measure it, the peak is going to be somewhere between 20 and 30 years old. And it generally an individual peaks sometimes around sometime around the time they finish formal education. Right. So all that kind of lines up to say that the more time you spend on that, the higher the peak

And at that peak, the peak is higher in those who on average who have longer longer education. Across multiple methods of testing cognition. Yeah, cognitive function. Yeah. And Right. You have to talk about the fact that, you know, different people get access to longer periods of and like so all of that plays right. Socioeconomic status plays a big role and access plays a big role here, right?

But I think in the Lansick Commission report they said that five percent of dementia was preventable if just like everybody got adequate yeah, got adequate education. And the reason for that is so if we then imagine some trajectory of cognitive decline. Um, that occurs in everybody on average and like the rate is is different and we can I th we can change the rate of decline. But if all you did was educate people more early in life, they would have a higher peach.

the rate of decline would be the same, but they'd reach the point of dementia later, right? Because they've started from a higher peak. The same rate of decline means they reach dementia later and, you know, maybe they die of something else first and they never get dementia. So like that's that's how that We will see. Quickly define age there early in age. Is that like adolescence? Is that high school? Is that all of it? Just kinda ubiquitously. In in terms of what? Uh you just said that the

The higher mortgage we give them early in life. Oh yeah. So this is just like the traditional education years. Right. So like you go up. Not a specific hey, between age five and eight is the most No, so it's it's just total years of education. So did you do complete high school, like bachelor's degree, graduate school, like the it's sort of a roughly linear relationship. Okay.

And then um there are several studies that show that late life cognitive um engagement or stimulus and they've measured it with like how often you go like you read books and g go to museums and all these kinds of things or they've done it through like how cognitively stimulating is your work. That then also slows or is associated with a slower rate of decline and also a slower uh uh or a lower risk of dementia. So there was one uh study they actually included

They sort of stole the forest plot from it and they included it in the Lancet Commission report. They had early life education and then they had how cognitively stimulating your job was. And what they saw was that people who had uh more early life education um and but not a stimulating job. And cognitive stimulating job. And people who had less early life education, but a cognitively stimulating job later in life, they had about the same risk of dementia.

So you can offset um uh a lower education early in life with more cognitive stimulation later. The lowest risk was obviously those who had both. But um it's yes, there's a huge amount of benefit you get from that early stimulation through education. But it's not like you're, you know, written in stone like this is your destiny, now I have a higher risk of dementia if you didn't get that, because there's lots of evidence to suggest that stimulation

either through your job or other things will then slow that decline later in life. So so you can still do something about it later on. It's so interesting because you're like halfway between muscle and bone now. Yeah. Such that The the muscle you develop as a child has almost no bearing on how much muscle you can develop. If you start lifting weights for the first time at fifty.

Your rate of increase in muscle growth will be the same as if you lifted weights when you were 10 or not, or basically anything like that. So in there in that case, like earlier development has very little bearing on progression, like so how the rate of increase. That said, bone is the opposite. Like the whatever you get basically as a kid, in large part is gonna determine where you're at there. So you have this halfway house of. Where muscle is not reliant upon.

you know, when you're a kid, bone was almost entirely. And now what you're saying is like brain is a little bit of both. You gotta either one. Right. You can do it early in life, you can do it late in life. Obviously both is great.

Or worst case here, and and I would have to imagine, I don't know if you actually know the numbers here, but the folks that were the double dipping on the bad side. Mm-hmm. So no education and low cognitive demanding job, I have to imagine they're Rates of Alzheimer's. and uh dementia as well as progression is probably the most aggressive

By by an order not maybe not a magnitude, but some fold. Yeah, so in in this um uh in this paper was published in the B in the BMJ a few years ago, that like that was your reference group and then everybody else just did just did better. Just two point oh, two point sevens. Yeah, just doubling over there.

Okay. So I guess if you had a great childhood education, tremendous. Don't rest on your laurels. Continue to challenge cognitive demanding, whatever that may be. If you didn't though, you still can yeah regain much of that by doing something. Just don't use that to have your mind numbing job um as we are there. So it is in either case largely preventable. The I think the the departure here is

Um early onset Alzheimer's is is a different ballgame entirely here, right? We're not I don't want to spend too much time here, but now you're probably looking at

Probably opposite. Like seventy plus percent is maybe even higher is genetic and just bad draw here. So so I think just just to finish the the the first piece, like we think about life stages and they think about the life stages of risk factors, then um in the middle of life a lot of what they're talking like talking about is body composition, physical activity, um

smoking, alcohol, you know, all the stuff that we've talked about already. In terms of if we eliminated those, we could eliminate yeah you know, the uh related uh dementia. And then one thing that we haven't talked about before, or at least not related to this, is Sensory inputs. So that's some of the late life risk factors they talk about. Obviously, brain trauma is another one in midlife. Yeah. But no, uh sensory emphasis are like vision and hearing. Yep. So there's now a

pretty good body of evidence suggests that if you have cataracts, you have a higher risk of dementia, that dem that risk is reversed. If you have cataracts surgery, if you have hearing loss like presbyacusis, as you get older, you have a higher risk of Dementia that is reversed, particularly in high risk people, uh if you get hearing aid.

So if you start to lose a sense, right, and a lot of people just like I'm gonna battle through because, you know, I don't wanna have a hearing aid or whatever. Oh d don't do that. You know, if if you start to have hearing loss, Get a hearing aid because that's gonna be associated with a lower So making sure you're still getting those sensory inputs into the brain remains really critical.

So don't lose your sense of smell, don't lose your vision, don't lose your hearing. Probably in the I'm gonna guess fifty to sixty year range, like if you start getting in that age window and you start seeing precipitative declines in any of those functions and You want to reverse that as quickly as you possibly can. Um, because

What you've been saying all day. Yeah. If you can't hear, stimuli doesn't go in there, then that part of your brain presumably dies. It makes perfect sense, right? You're not using those networks anymore, so they're gonna decline, but then the all you know, everything else they're connected to is gonna be affected. I assume the same thing is true with the other.

Pro perception in terms of balance. Mm-hmm. Things like that. Right. So make sure that you continue to train balance, work on balance. I think this is a pretty easy story to tell. for exercise in nature. Yeah. Right. Exercising in the outdoor, like exercising inside in the gym is great. But now you're outside, you're going up and down, you're seeing different things, hearing, smelling.

Like so on and so forth. Differing light exposures, like the effect of say seeing green spaces on autonomic nervous system regulation. Yeah, there's a ton of different ways that that that could. Okay. So

I I'm on board there. Um it's highly preventable. You said this earlier as well. You talked about exercise a bunch. Um this was one of the more stunning parts about our earlier conversation when you said and I I'm I'm stupefied that I never made this connection. I've said this a thousand times. A thousand plus thousands of times. And like I never really grasped the fact that

When you exercise, you're going to have neurological, neuroplasticity, nerve, nerve, nerve. But then the actual structure of the brain. And I promised we would, I wanted to come back to this. So here we are coming back to it. like the second time I've actually come back to a topic I said I wanted to come back to but

I want you to explain this to me about how it's actually what what aspects of the what areas of the brain physically are improved by exercise. Does it det type determine or does it depend on the type of exercise? Is strength training different? Um, do we know any details about the exercise? Is it a certain amount of sets or reps or styles? Like what do we know? Um, so what do I do and how does it actually help? And then the last part about that is

Is there a a law of hey, I didn't start soon enough. Yeah. So now it's too late. Right. So give me the jabs on how

Lifting weights makes my brain what do you call it? Like bigger, bigger muscles, bigger brains, more bigger, more brainier. More bigger, more brainier. There you go. I've heard you say that before. Um So a a good place to start is the the first ever study I think that was done that showed that you could increase the size of a certain part of of the brain in humans was with an exercise.

It was published in two thousand eleven. Exercise for the win. I'm telling you folks, exercise scientists run science. You just don't like to admit it. Uh so this is published in PNAS in two thousand eleven and what they did is they called that recent. Yeah.

Oh wow. Yeah. So there's the so like before then we knew that so if you just looked at brains of people who'd recently died, you could see that there were certain areas of the brain that were there were there was some neurogenesis, particularly the dentate gyrus of hippocampus.

But to actually physically see an increase in size of a part of the brain, this is the hippocampus, which is generally just thought to get smaller and smaller over time. That hadn't that hadn't been seen before. Yeah, hard hard to do in humans. Yeah. And so

The other side of that is that we don't know if there's more neurons being generated. We know it's bigger, right? So this is like it could be glia, it could be extracellular matrix. There's a whole bunch of things that go into that. But that doesn't necessarily matter.

we can we see improvements in in uh brain uh structure and volume with an exercise intervention. So what they did in this study, individuals in their 60s and 70s, they had them do a walking program 40 minutes three times a week for

That's it. Brisk walking. And that was enough to significantly improve or increase the size of the hippocampus. These are non-exercisers. These are non-exercisers. Yeah. And they sort of like worked their way up to a certain intensity and they did it for 40 minutes for each other. The imp increases in size of the hippocampus correlated with improvements in VO2 max, which also correlated with improvements in or increases in production of BDNF brain-derived neurotrophic.

So in a sediment sedentary population, right, we know we can see improvements in in uh the structure of the brain with with exercise, with aerobic exercise. What was interesting is that in this study, they didn't necessarily see significant improvements in cognitive function. They saw improvements in structure, but function didn't necessarily track with it. Part of this is probably an intentional.

piece. So there was a very recent study that looked at um different levels of intensity of exercise, aerobic exercise again, and structure and function of of hippocamp of the hip. So again, so now we're thinking about memory related uh test. And they found the greatest benefit in individuals doing uh high intensity exercise training. And it was essentially the Norwegian four by four project, like four minutes at, you know, uh seventy-five to eighty percent uh max VO like VO.

Um uh heart rate. Sorry. And they saw maintenance of structure of volume of the hippocampus compared to control groups where it kind of where those decreased and main and uh improvements in in cognitive function they think related to the area of the brain. So Some um aerobic activity of any kind in people who are sedentary if it improves uh uh their cardiovascular fitness.

Then you're going to see improvements in brain structure. To see correlated improvements in brain function intensity is probably going to be important. They're in that study, they're generating a ton of lactate, right? Whereas they weren't in that original. Right. So that that could be that could be one one way of doing that.

Um, in general, what you see across multiple studies is that the gray matter of the brain, so now we're talking the the outer cortex and the hippocampus primarily, seems to be benefited by aerobic exercise. And in general, aerobic exercise seems to be associated with improvements in memory, right? Again, with hippocampus is is is really important there. You know, if we think about the amount that you have you have to do, it's essentially gonna be

You know, two or three times a week, some kind of activity that is improving your cardiovascular fitness wherever you've started from, right? But probably at least once a week doing something that's very kind of some kind of sprint type or high uh high intensity interval training. At least that's what sort of aligns with the literature. In terms of resistance exercise, you see benefits in different areas. So resistance exercise seems to primarily benefit the white matter.

Which kind of sits between the cortex and the deep brain. It's and right, that's where you have your myelased axons, your like the fast connections. Um like that's the hyper speed zone. The hyper speed zone is the transfer of information from the brain to the body and throat. And uh so we actually just published a review paper talking about the studies where they'd done a resistance training intervention compared to a control group and then looked at brain structure over time.

And this is what you see is improvement either improvements in the white in the white matter or prevention of decline of the structure of the white matter. Um, and then that's also associated with um improvements in cognitive function, particularly with resistance training in executive. So, like prefrontal cortex function. So, different areas of the brain affected by different types of exercise, which are then associated with different improvements.

The uh minimum effective dose um see for like sustained improvements seems to be two sessions a week. Um like Super standard six to eight exercises covering the whole body for three sets of eight to twelve reps, just like the most basic resistance training program, twice a week for at least six months, and you see significant improvements in brain structure and associated chromosomal.

So those are kind of the different ways that those different exercises kinda come together. Then then you get more of like a glow if you do both, hopefully some kind of global improvement.

So it is Never been shown, I know this, but it would based on all that be reasonable to presume if I wanted to develop an exercise program that was specifically targeted with the primary objective of keeping my brain as healthy as long as possible. Not necessarily my body composition or muscle or strength or anything like that. Um, I wanted to do an exercise program for that. One could theoretically say, okay, lift weights a couple of days a week in exactly what you mentioned.

Five to eight exercises, whole body. Yeah. That'd be two days a week. One day a week, do something that is closer. Let's just even say the Norwegian four by four. That's a great option. Yeah. Four minutes of the highest amount of work. People get mad when you describe this as Four minutes of max effort or all out. Yeah, yeah, yeah. You can't go all out for four minutes. But the the highest amount of work you can do for four minutes

Rest for four minutes and do it again. I don't really think, friends, like I cannot imagine a world in which that specificity matters. Yeah. You don't have to do the four, you could probably do just about any type. Of high intensity. endurance conditioning work and it would probably be the same. But let's just say for simplicity, you did four by four once or twice a week. Was that those interventions? I think they were doing it three times a week. Okay.

But if you're doing other aerobic exercise and s and resistance training, I think you're gonna Yeah, you're probably not gonna need to do like a four by four three times a week. That's that's pretty dang hard. Especially for six months. Yeah. Yeah. I I'm gonna say realistically, as an exercise scientist, I'll give you permission to cut that to two. Yeah. And then maybe one to two or three sessions a week of the more lower intensity

standard endurance exercise, cardio, uh whether this is even physical activity, walking. Yeah. Uh or would they actually need to do more like fifty, sixty percent heart rate for that kind of cardiovascular adaptation? So, you know, this is the this is the The age old question is like Like what's the exact intensity required to see a specific adaptation? I think that And and it's the same I uh we did a we did a podcast talking about the four by four on your podcast. On on my podcast. And um

Then somebody was like, Well, what if I can't maintain my heart rate in that zone for that long? Or like just do yeah, right. Do whatever you can for four minutes and you right, you'll get better over time. And so I think it's the I think it's the same thing. Yeah. Like If it's a if it's a casual stroll, you're probably not getting um adaptation. But

You know, equally if if a brisk walk is hard work for you, right, then that's gonna be that that that's gonna be a good good place to be. Yeah, I this one riles me up so much because I I get it, people want like specific numbers. But I'm so...

resistant to do that because it doesn't actually matter usually. Yeah. It it's a c it's a rough concept of where you're at. So if those numbers help you, great. But something like that, um, here's the reality. Don't think that your brain all of a sudden won't adapt if you do have

If you did one day of lifting, one day of intervals, and a couple of days of walking, it's better than the zero. Oh yeah. It's a lot better. Yeah. Right. So you don't have to hit that minimum number to get any effect whatsoever, right? Probably getting closer to that final destination. But if that takes you six months,

Or six years to get to where you can handle that, that being that little three, you know, protocol we talked about, it's fine. Yeah. Like get there eventually and you and you'll probably get um much of the benefit, which which is great. This actually answers a big question that I have dealt with a lot. Uh you and I actually have a a paper together again that you led where we found physical strength.

predicted, I think it was five percent of cognitive function, right? And I'll s I'll say that again. Like physical strength predicted five percent of cognitive function. I have talked about people have talked about at length how leg strength How grip strength, grip strength fires people up, right? And and the common claim here is like, oh, grip strength is just a proxy for overall health. Yeah.

And certainly true. Um, if you look at research on folks that have dementia, you'll see a I think actually one paper found, I can't even think it was UK Biobank paper, but a half a million people in it found that I think thirty percent was explained by low grips rate. Yeah. Right. And there's a recent study showing that frailty precede like

precedes uh like Alzheimer's by by several years uh on average. Multiple years, I'd imagine, right. And and right, if you're frail, you're not doing all the things that we know continue to stimulate or support brain. So what I want you to kill, and prob perhaps this is a fifth thing that'll irritate the internet that we're gonna call it is the idea that this stuff, the grip strength, leg strength, is exclusively

an indirect or a a correlation, right? Of course there's some. Yeah. Folks who are struggling with dementia are probably also then gonna struggle with movement and there'll be a backward direction, right? There there'd be a causation, but it would kinda be backwards. Yeah. So end this horrible idea that strength is only a correlation to brain health.

And you just actually kinda answered the question before, which is like, how is it actually console? But then spell this out as directly as possible so I can cut this clip and send it to people every damn time I get told it's just a correlation.

Technically, people are right. A lot of this comes from epidemiological research. No. Correlation isn't causation. Um, however, there are several studies we just talked about, some where you randomize somebody to a resistance training intervention, their strength improves.

Brain function improves, right? Brain structure improves. And actually, related to the point that you're making, in that in one of those studies, yes, you see sustained improvements in white matter structure with two sessions a week, but you've got improvements in cognitive function with just one.

Right. So you don't they're these effects, particularly if people aren't doing much exercise, are essentially linear. And like So I I can If you could ask for a more causal function and structure benefit and in a dose response. So what else do we have? That essentially says it's causal, right? Yeah. And people are so depending on the type of research, of course, people are right.

What people also don't necessarily understand is that in a perfect epidemiological study, If you could account for every confounding. and, you know, mediating and moderating relationships. What you have left is causation. That is like that is a definition of causation. So yes, epidemiological studies technically don't show causation, but if you could It's difficult because you you don't always get the variables you want, right?

You can determine causation from an epidemiological study. That is possible. That's allowed in, you know, a frequentist model of statistics. I'll count that as like four point five thing that the internet's gonna get mad at. Yeah, you uh don't don't think people understand basic statistics with that. Um Right. The people have worse physical health. Right. We know so in the study that we did, if you had higher uh blood blood sugar, higher HBM on C, you had lower strength.

But I think that's also bi directional, right? Um, if we think about the potential mechanisms by which this happens, you have uh if you're doing things that improve strength, that's a direct neuromuscular stimulus. We've already talked about the importance of stimulus. The next important thing is that your skeletal muscle is your biggest and most important glucose sink. So if we're thinking about the importance of energy regulation,

then your muscle, like the more muscle you have and the more you move it, the greater amount of glucose you can move through that system. And there's I mean, this has been done for decades and decades and decades. So your your skeletal muscle and your physical activity two of the best ways to improve glucose handling and energetic handling more broadly.

And then the final piece is that when you uh contract your muscles, you release a whole bunch of stuff, right? Your muscles are organs. So lactate, BDNF, MOTC, IRECIN, uh LACFE, like Pick your metabolite cytokines, extrachines, myokines, like whatever like whatever it is, like pick your favorite metabolite du jour. Right.

Um, we're still discovering on it like taurine. We're still discovering on a like on a weekly basis the things that are released during exercise that have broad, broad benefits. So like all of that comes together to suggest that um yeah.

It's a bi-directional relationship, but by improving muscular size and strength and function, and those usually go together, but not always, depending on you know who you are, um, that's there is four or five, if not more, different mechanisms that would directly relate relate to improvements in I hope that ends the conversation. I'm gonna move on, although we could probably have done a whole conversation just on that. But one little piece here.

It makes sense to me energetically, based on what you just described. It makes sense to me from a Neuromuscular perspective that the strength training works backwards, right? And so the same neurological system that makes you squeeze your hand together, it starts in your brain, keeps on How does the white matter?

What's the stimuli from exercising muscle? Because it makes sense when I think about muscle. It doesn't happen this way, folks, but as a teaching point, if you think about I lifted some weights. the muscles that I contracted, they pulled, they got stretched, they contracted, they got damaged. Again, it doesn't happen this way, but I can I can paint that picture in my head.

I'm not stretching the tissue in my brain when I'm lifting weights. So how am I generating more or preserving my physical tissue outside of the metabolic and the um the astrocytes and the nervous? Yes. So I think all of those play play an important role. Um For instance we know that as

As we age, things like changes in b in metabolic health and white matter structure in the brain probably better track with cognitive function than say something like amyloid accumulation in your brain. Actually, the the the trajectory follows more closely. And that's gonna be related to um so so the white mass traject trajectory is gonna be related to things like metabolic health for the for the reasons we talked about. Um but I think there's a direct

stimulating effect, right? As you are You know, the both learning the new skill of of of like the muscular control requires to uh move uh weight in that way. I think you're directly stimulating some of those pathways. So

Pathways related to like motor pathways associated like white or white matter pathways associated with motor control. I think you're directly stimulating those, which we and then we know as you stimulate those, you offset all those things we talked about earlier in terms of adaptations that improve structure and function.

And then more broadly, I think that's where some of the um the signaling pieces come into play. What's interesting is that there is an overlap in some of the things that are produced in aerobic exercise versus um resistance training, but we do see uh region-specific effects. So it's probably there's like some some coupling of of what's going on what's going on, like a specific stimulus.

plus um the sort of the hormonal mil milieu or the myokines and things that that are released. Um And I think it's that's a good idea. some combination of that. It's really hard to test these mechanisms in humans and It's actually also really hard to get rats to do bicep curls. So um it's quats as easy, but yeah, yeah. Or um because they they have like they do like uh they do um weighted

Weighted wheels, right? So it's kind of like a a weighted Jacobs ladder kind of thing is what they do for resistance training in rats. Um but I think it's some combinations. If you look at this from the muscle, skeletal muscle perspective, I should probably have be saying it that whole I always say muscle. Skeletal muscle. All right. A little bit different.

It doesn't require damage. Yeah. There's another thing that people have this this false thought of you have to break a muscle down to grow back, which is fundamentally not only not true, but it actually doesn't happen very often. It's not generally what's causing muscle damage. It's not causing soreness. It's not causing and it's definitely not the stimulus. You can simply change energetics. Mm-hmm. And stimulate muscle growth, skeletal muscle growth.

I can't see why you couldn't do that in the brain. Yeah. It's the same thing. It doesn't require a stretch and a damage. Yeah. All of these adaptations are driven by an increase in energetic flux, right? That's what it is at its most basic state. And then that's what that drives

um neuroplasticity, it drives autophagy, it drives, you know, all these other uh regulatory processes that we know are um are involved in aging and reversing those. Um and so anything you can do Right, locally in muscle, improve increasing energetic flux through aerobic exercise, you know, and then the same this any any stimulus in the brain, you're increasing the amount of energy that's moving through the system, that acts as a stimulus that then the same same process.

Is that why you think those different modes of exercise produce different actual brain adaptations? I think that's part of it. Yeah. Um, sort of but all of those things seem to you know, dissecting those exact pathways hasn't been done. But it Um if you think about well, you get you get lact you know, you do a heavy set of leg press, so you release a ton of lactate, right? Um

But and you release a lot of lactate when you do the four by four protocol, but you get different you seem to get different responses in the brain. So it's the the the combination of of multiple things sort of. All right, fascinating. Uh we're gonna press the button on more things you're gonna aerotate the the world about.

I don't need the full dive here. Give me the The what we used to say in the nineties and two thousands, the reader's digest version. I only now recently realized that kids have no idea what that means. No. That analogy now people are like the what? Like, all right, T L DR. Yeah. T L D R well nobody reads anymore. Yeah. Right. You mentioned tau and amyloids. Yeah. And for folks that don't know this story, these for many years have been

surrogates or markers of of would you say brain aging, brain damage? Or yeah, sort of the brain pathology that's then leads to Alzheimer's disease. Right. And then recently some information came out that uh And m perhaps we'll just leave the person nameless, but one of the prominent scientists in this area had we'll just say

Not necessarily fake data, but there there was some controversy. And so I've seen reactions that are on one side of the equation of like, okay, he he just used a couple of pictures. in grants. Scientists do this all the time. He didn't fake data. He just kinda got lazy. You submit grants and grants and grants and you're using a representative image to show a concept. Like it's not that

All the way to reactions and the other side of the equation, which is okay, thirty years of research in this area is all thrown out now. Yeah. Um If you feel like you can't answer this quickly, then that's okay. Feel free to pass. But uh where at do we know um should people still be worried about this approach?'Cause you can test it. People pay to get it tested. How much should we worry about tau uh in relation to brain health? Yes, so yeah

This is a it's a long question to answer because essentially it it starts with uh Alaris Al Alzheimer and and his mentor Emil Krappelin in Germany in the beginning of the twentieth century. Um however Um, I think we can say that there has been this overriding or there's still the overriding idea that Alzheimer's disease is driven by something called the out the amyloid cascade hypothesis.

Um uh amyloid precursor protein is produced in the brain normally. It's really important for neuroplasticity, a whole bunch of things. If you if you like got rid of outside of um APP and amyloid entirely, basically the brain doesn't function at all. Um and but there's one sort of this precursor protein gets can get cut in different ways by these secretases. One version of that um accumulates to create these sort of waxy amyloid plaques.

When that happens, that then stimulates the pro the production of tau. So tau is normally part of the microtubule cytoskeleton of neurons, like really important for like directing um axons and where they go and how they connect. And it sort of dissociates from that, becomes phosphorylated and accumulates. And then that damages. Yeah, and then that sort of damages neurons and that's associated with losses.

Yeah. You will see basically an inverse relationship with sleep efficiency or sleep quality and tau buildup. Like you you could pick this in any realm of there and and it'd be hard to ignore all of those papers. So um I I think This certainly plays a role. I think the and there's been an increasing number of voices that say that there are other things that have to be playing a significant role here as well. So we've become really hyper focused on this one pathway.

when this pathway, like you said, is triggered by a whole bunch of things that we know have effects beyond how it affects that pathway, right? We know that sleep is important regardless of the fact that if you don't sleep, you accumulate a bit more amyloid in the brain, right? So and we know that uh tau accumulates after head trauma. But there are other effects that head trauma has beyond its effect.

So we've kind of really hyper focused on this pathway, but there's a bunch of other stuff that's happening at the same time. And I think we could while we shouldn't throw the baby out with the bathwater, because some of that is certainly playing a role, I think we'll miss.

um a huge amount of benefit from pe uh in people if if we don't focus on the other things that are going on So th I think there's an even though and so that there's been some studies in with amyloid where you know a similar problem. You know, uh some issues with the data, uh maybe some of it was duplicated or fabricated. I think there's enough evidence to suggest the other thing. This is playing a role. I just think the role is probably smaller than we've kind of

Uhumed it to have. Yeah. I mean, I'll say that for you because I'm not in this field. You may have to say face a little bit, but I can only speak of this from my area. And I've seen this game play out where um the funding sources, the national funding sources, just start onslaughting, and probably for good reason.

Initial papers come out, it gets really exciting, and they just put all the dollars on one particular thing. And this is by my read of the situation from the outside in this is basically what happened, right? And it becomes really hard with anybody else with an idea. or an approach or a metric to get funding because they're just throttling it all on one area.

And then when information like this comes out it becomes really disheartening and upsetting to folks who got their ideas shut down for careers and going, We told you to stop focusing on that and and I think that's somewhere in the neighborhood of a fair criticism.

If people are interested in this history, they should read the book How Not to Study a Disease by Carl Herrup, which kind of documents this exact process. And that step that you were talking about, this happened with the NIA, the National Institute of Aging. Yeah. They essentially said that, um

Alzheimer's and amyloid were synonymous through uh uh a few different position papers over time. And so then it came to the point where if you wanted to start study Alzheimer's disease, you had to had to study Alzheimer's. That doesn't mean that amyloid doesn't play a role. It just means that they they kind of purposefully ignored um a lot of other research of of important things that are that are uh taking part in the process. Man, just Beyond frustrating. Yeah. Just the

Whatever. Okay, we'll s we'll save our piece on that. Uh I've got a handful of really quick

questions just to finish us off here. But before we do that, a really fast recap. You've you've irritated the world on at least five points. Uh and gave us a lot uh a lot of light on if you wanna enhance cognitive function, you're good, but you're trying to go to great. You talked about a lot of different ways to do that. Searchful novelty. in probably vision and hearing and brain training and and different things like that. And an important note there is just because that actual cognitive task

Is impressive or complicated. It doesn't necessarily mean it's cognitively demanding, especially if you've been doing it a long time, right? If whatever that task. Uh if you're having some sort of depth of the episode. Brain fog we'll call it. And you called it some other technical word. I'm gonna call it keep on a brain fog, right?

Make sure that you don't have some sort of holistic hole that is burning, literally burning extra cognitive energy. And so it's not that you have brain fog per se, it's just that you are actually low on cognitive fuel physically because of external stress. Or sleep or alcoholic, some other micronutrient deficiency is is most likely uh at play there, right? That's that's the most likely explanation. Or inflammatory from long COVID, like some of the

Um percussions are not your brain slamming against your skull wall. And then a lot of strategies to what they actually are, and that explained why those strategies work. Um and then that things that like marijuana and psychedelics not to dwell on them, we spent very little time on discuss that further. Uh but perception is not necessarily the same as subjective uh in terms of cognitive function. And I forgot the other ones you irritated people with, um, but we covered many of them.

So lastly, really fast because you covered a lot of areas. I tried to do my best to to ask kind of the quick questions along the way, but I I surely missed plenty. Um so question number one is if somebody has questions for you on these things, what's the best way that they can learn more from you? Can they contact you directly? How does this work? The best place is probably uh so I have a podcast.

the Better Brain Fitness podcast. Uh Josh Tuchnett, who's a neurologist, is is my co host. Neuroscientist and a neurologist working together. So and then we can come at it from those relative uh points. And so if it's more clinical, he'll cover it. If it's more, yeah, basic science or

statistical or something, then I'll come for it. I'll I'll cover it. And that's a weekly show or every other week or something like that. Yeah. And so on YouTube and all the normal places. All the normal places. And uh so you can uh it's a question and answer style show. So you submit a question and then we'll answer it one question every episode. Um and so That's nice because if you have a question, somebody else probably has that same question and then other people can um can benefit from it.

Um and then uh equally you can on my Instagram uh at Dr Tommy Wood uh you can you can DM me but I might direct you towards the podcast because then Don't DM him. Just go to the podcast first. Um but you also have uh uh uh your sub stack as well. Yeah. Which is a f I love this format.

Yeah. So um It's free. It's free. Free substack, uh Best of Barian Fitness Substack. When you sign up, when you put in your email, uh you get emailed a PDF which covers all the nutrients and blood tests that we would recommend just like basic.

for peop for people who worried about um uh long term cognitive function. So all the stuff we talked about today. But they can get that direct PDF to them. That'll be emailed directly to you. And then like every time like we have a news article or a podcast or whatever that c that comes Okay. there is an option to pay there. They don't have to though. Right. But if they do pay, then they can get access to additional questions one on one. Like is that how it works? Yeah. So we have um

There is a an op you can always opt to pay for Substack, although you don't like all of our content is free. But if you do pay then we do um we've just started doing some AMAs, so you can join us on a Zoom call and just ask us where we literally live per in person. Live in person. Wow, crazy. Yeah I don't know how you do that. You're wild man. Um and if they want to come visit your lab at the University of Washington and get their brain tested, is that uh is that an option? Yeah. Uh C B D.

T V D Coming soon. Little spoiler friends there, so not yet. Okay. Um you've been in uh incredibly gracious With your time and expertise, man, really appreciate it. It's always fun hanging out. Uh uh Bummer, we didn't get to lift weights this time, but perhaps perhaps next time. The last thing I want to ask you here.

I'm putting you on the spot. All right. If you got anointed to the Maha board, the Make America Healthy Again, and you said, Dr. Tommy Wood, you are an MD, you're a PhD from Oxford and Cambridge, and now at the University of Washington. What would be your first, most important, biggest charge? You would say, This is what I want to get done to make America's brains. I don't know if healthier again is the right word, but we'll just say make them healthier. Um I think just because it

It would be two pronged. One is Educate people to know that you can slow and prevent cognitive decline and improve cognitive function, right? Because in order to change that, you need to know it's possible. And most people don't. And then I would focus on the importance of cognitive stimulus. And the reason for that is other aspects supposedly of what's gonna happen in that movement are gonna address metabolic health and other things that we know are important, but the idea that

cognitive function is driven by cognitive stimulus is still sort of underappreciated. So that would be that would be my uh my primary directive. And as part of that I might dramatically decrease funding for mouse studies. Hmm. Interesting. And this is from someone who does animal research in your life. And a lot of what we do does not relate to humans at all or doesn't end up relating to humans.

Yeah, ends up as a failure. So well, I can assure you, my friend, when your name comes up on that ballot, I will tick that box and vote for Dr. Wood uh on the thing. So thank you so much, man. Appreciate you being here. Thank you so much for having me. This has been really great.

I hope you enjoyed that conversation with Dr. Tommy Wood. To follow along and learn more from Tommy, I encourage you to check out his social media as well as his free podcast and Substack accounts. Direct links to all of those will be provided in our show notes. and I would encourage you to check them out there. Thank you for joining for today's episode. My goal as always is to share exciting scientific insights that help you perform at your best. If the show resonates with you,

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