Dr. Tommy Wood: Enhancing Brain Performance & Preventing Dementia

This transcript was generated using artificial intelligence and may contain errors.

Andy Galpin

The science and practice of enhancing human performance for sport, play and Life. Welcome to Perform. I'm Dr. 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, 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 in a 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 brain bringing that to the forefront. So we really are more understanding 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 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.

Tommy Wood

Thanks so much for having me. I'm really excited to be here with you.

Andy Galpin

There's a lot of things I want to get into today, things that you and I have chatted about before, but most of the Things that I actually don't know the answer to. Hopefully I can pry some information out of you about enhancing brain performance, things that we can do now in the short term as well as long term brain health. But I think before we can get to that, for my own personal sake, I know I say some of these things 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?

Tommy Wood

I think one issue that's come up a lot recently 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 test, like an IQ test? And then there are tests for a whole bunch of other functions, like executive function, or response inhibition, trying to suppress the desire to make a response, which is an important part of planning. And the prefrontal cortex plays a big role there, also testing working memory and all these other things that we might. Or our ability to learn and remember in short periods of time. 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 real problem is that while they do relate slightly to the different functions you and I would want to do from day to day, that's an imperfect association. And beyond that, there are a whole suite of cognitive functions or things that we do with our brain that you can't really measure with those tests. So part of the problem is defining what is it that you want your brain to do. 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.

And you can do some standardized tests of creativity and stuff like that, but it's just not the same. So I think 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.

Andy Galpin

Brain in doing that, 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 reaction time, memory, word recall, executive function. Is that a fair way to characterize it? Or should I add a third part there?

Tommy Wood

Or I think about brain health more holistically. And in reality, we know that structure and function in the brain are directly linked. 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. So I wouldn't even necessarily separate them out 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 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 minute to minute performance and enhancing that as well as what's your long term trajectory of function? And you know, are you then at risk of significant detriments of function and dementia long term?

Andy Galpin

Right. Like, clearly, if I have some physical structure damage in my brain, I won't have the acute performance either. Right. I'm going to 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, 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?

Tommy Wood

Because of the redundancy in the structural systems, you don't necessarily have a direct one to one connection 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 some atrophy, here's some loss of volume or here's damage in a certain area. So I think that may just be partly because of the resolution of the things that we can measure. So maybe we get to a point where you have a really, really strong MRI and we can see in very fine detail all the little blood vessels and all the 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're losing a function, there's probably going to be a structural correlate of that. But in all likelihood, because function is also going to be driven by nutrient status, mitochondrial function, some of these other things, you might start to have issues with function before you see a structural issue on brain scan or something like that.

Andy Galpin

Okay, 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?

Tommy Wood

The, the way that I think about the brain is because I'm, I'm a bit of a meathead, as you know. Yeah, I, I enjoy lifting weights and the more time I spent studying the brain, the more the brain could 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 strong and jacked, you need to apply mechanical tension to the skeletal muscle. Right. Regardless of everything else that you do.

And you can improve that response with sleep and nutrition and things like that, but no stimulus, no response. 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 lifespan.

Andy Galpin

That's really interesting because almost always when we hear this stuff talked about, we hear it in the sense of neuroplasticity. Right. So you have a capacity issue, some neurological adaptation, which, you know, 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 recall, whatever. Right. But what you're actually saying is there's also a 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.

Tommy Wood

Well, obviously the, the space within the skull is limited, but to some extent you do have a larger brain. And we know that with aging in particular, and as you follow a trajectory, say into dementia, your brain gets smaller, you get atrophy of the brain, you can Then see increases in the volume of the brain in response to certain stimuli. So you can get, particularly once the volume of the brain has started to decline as you get older, you can see then a response in terms of volume with stimulus, certain stimuli. So that's not just neuronal connections, but part of it is. So you have greater density of connections. That's the neuroplasticity, new neurons talking to each other. Early on in the loss of volume of the brain, 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 before aptosis. Yeah. And if you're not using them right, they will then follow that trajectory, but that can be recovered. Plus, neurons make up less than 50% 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. You know, the extracellular matrix is really important in terms of all the proteins that sort of regulate how the cell. 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 going on at the same time.

Andy Galpin

Man, I'm totally guilty of that. I know certain aspects of the brain change physically in a good or bad way in response to perturbations, but I just always give it the neuroplasticity to it. So I'd love to come back to that. I want to know more about it, but I gotta ask, 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 neuroplastic and achieves an adaptation response to stimuli. So I'm more interested in where you stand on that global argument. First of all, is there even an argument? Is it pretty well scientifically established? Where does that field lie? And then overall, tell me, can we actually improve cognitive function?

And then for sure, if we can, I want to know how.

Tommy Wood

So again, it really depends who you ask and how you're measuring cognitive function?

Andy Galpin

I'm asking you.

Tommy Wood

Yeah, you're asking me. But if you were to sample a large number of cognitive neuroscientists, 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. And this is partly driven by how we're testing it, which we've kind of covered. And yes, we know that people who spend longer in education, they have 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 the test. So then when you're thinking long term, which we'll come back to, I think there is a good amount of evidence that we can improve cognitive function when you're in a period of decline. But then if you're thinking right now, how can I improve my cognitive function?

I think the way that I think about it is again, related to skill development and what it is that we actually want our brains to do. And the human brain, more so than any other species, is evolved to adapt to the environment so that it can optimally perform within that environment. 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, 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 the same 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've attained it?

Andy Galpin

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Tommy Wood

Yes.

Andy Galpin

If I want to improve memory, practice memory. And this probably expands to any way we would define cognitive function for a normal, young healthy person. So actionable step number one would be simply that if you want to get better at writing. That was one of my favorite. I had a friend, several friends who are writers, and it's stunning how low energy, last minute that they can pull up, smash out 3,000 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? Are there any particular types, whether this is maybe exercise or nutrition or brain training devices or tactics that have a more wide ranging, again, broader applicability? Or is it all pretty much they're going to be good on their individual one and then have very little transfer.

Tommy Wood

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 been the problem with brain training, 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 better functioning person out in the real world. But if your near transfer is relevant to you, say it's writing or some other kind of specific skill or language, 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 train certain aspects of decision making in the prefrontal cortex, they seem to be associated with some file transfer. Just you get better at regulating your own internal thought and decision making processes.

And that relates to a wide variety of scenarios. Then some of the other things that you mentioned, like exercise is one that supports and it's exercise specific. So resistance training and aerobic training have effects on different areas of the brain.

Andy Galpin

Both good, but different.

Tommy Wood

Yeah, both good but different. But then that applies to functions more broadly. Right? You're going for a run and that aerobic exercise is particularly good at improving certain aspects of memory. And so it doesn't matter what you're memorizing. Right. Memory is broadly enhanced.

So some of the lifestyle factors that we know are critical for brain health and cognitive function. They broadly support cognitive function as well as skill learning in the first place. But then some specific skills may be just related to that skill as you use it.

Andy Galpin

Okay, I'm going to give you a couple of avatars here, and I'm asking this personally. Imagine because you've worked with athletes across, I mean, just every sport imaginable, you've worked with industry folks, you've worked with non athletes, you've done concussion stuff, you've done aging stuff. So you're all over the map in terms of your skill set. So with this, somebody comes to you and says, hey, look, my brain's healthy, I'm 40 years old, I'm not super worried about dementia and Alzheimer's, things like that. My lifestyle factors are 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, reaction time. What, like where would you start with that individual in terms of what you said at the beginning?

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 but maybe two or three things here to start off that generally work pretty well.

Tommy Wood

So generally I think about when something like that comes to me and they say I'm healthy, my brain works great, 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 tests, determine some nutritional status, becomes really critical for the brain. We can deal with poor nutritional status and the brain works just fine early in life. But if you're trying to know, maximize everything we know, vitamin D, iron status, magnesium, B vitamins, omega 3s, some of these, and 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 to address.

Andy Galpin

Would you mainly say those are energy metabolism markers? As long as your energy metabolism's fine, you're probably okay.

Tommy Wood

This is an interesting thing 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, 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 version of that, then you start to see a decline in cognitive function and brain volume as well. So yes, energy regulation is really important, but some of those nutrients have their own 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 3s but they don't work, or we give B vitamins but they don't work, but they haven't taken the other into account. And it makes perfect sense because if you want DHA, the long chain omega 3 fatty acid, to sit in the synapse where you want it to help communication between two neurons, it needs to first get into the brain and that requires usually healthy insulin 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. 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 vicids become important. So some of these things are directly structural as well as being functional. Thinking about energy and mitochondria.

Andy Galpin

I don't want to lose the plot. I'll come back to our avatar here in a second. I have 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.

Tommy Wood

So right now you probably can't. You and I are in the process of developing what should be a fairly simple 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 gonna 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, you know, really button up the details with making sure that all you have all your nutrient ducts 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 nutrient deficiency, they're going to have lower cognitive function. And there's, there's, you know, dozens, hundreds of studies that show that.

Andy Galpin

Do they need to necessarily be at a technical deficiency there or if they're, you know, say bottom 10th percentile, they should pay attention. Do we have any insights into where those cutoffs start to lie for these metrics?

Tommy Wood

Yeah, probably. You're, you're right that in general, what we consider to be a deficiency nowadays is usually you're below the normal range, right? You're in the bottom 2.5% of some nutrient marker and you're going to have some. Your day to day cognitive function is not your main issue. There's going to be even bigger problems than that. But there are some cutoffs for all of these things in general, say blood sugar regulation. You want to make sure that normal fasting Blood sugar, not pre diabetic.

Beyond that, there's probably not that much benefit from being lower than that. But something like homocysteine is a marker of methylation status. Generally if you went to a lab, the normal range is 13, 15, bottom.

Andy Galpin

End, 5, high end, 13, 14, 15.

Tommy Wood

And most people will say you sort of target below 15. In terms of cognitive function, it probably needs to be less than 11. Some people would go a little bit lower than that for things like cardiovascular disease risk. But then similarly for omega 3 fatty acids, if you do something like the omega 3 index, you probably want to be like ideally over 6%, maybe close to 8% or higher. And like I said, those, those two things interact.

Andy Galpin

Yeah. I would say that in our experience, if you are above 9 to 10 for homocysteine, we're, we're looking very seriously at other things.

Tommy Wood

Yeah.

Andy Galpin

And an Omega, you'd be surprised how many are under five.

Tommy Wood

Yeah.

Andy Galpin

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 decline, like it just disappears from these people really quickly, which is really of no surprise. So coming back to us, then we check those blood markers, then what for that?

Tommy Wood

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 framework for thinking about that. So sleep and all these other things, stress mitigation. I'd definitely 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 thing. Your avatar probably has quite a cognitively stimulating job, which we know increases long term cognitive function and decreases the risk of dementia long term. So then I would think about 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, all his exercise is in the gym and it's unimodal, then he picks up an open skill set sport. He goes to play pickleball or learns to skateboard.

Andy Galpin

God forbid. No more people playing pickleball. Don't do that, Tommy.

Tommy Wood

If he has never spoken another language, then he learns a language. Some of these things. It's interesting when you look across the literature, the one activity that probably ticks a lot of these boxes and seems to really support cognitive function as well as mental health is dancing. And because that brings in play, it's an open Skill, there's music, it's social. So a dance class with his partner would be a great way to sort of integrate a bunch of these things together.

Andy Galpin

Cognitive demanding. What does that actually mean?

Tommy Wood

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 theoretical concept, because 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 compared to somebody else? I mean, we can't. Like, what's the equivalent of volume in the brain, like, compared to, say, lifting weights, where I can quantify how many bicep curls did I do? What was the weight?

You could look at velocity and all these other things. We can't do that with the brain, so yet. 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, some of it is still a bit theoretical. 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 where exercise, like cognitive. Enhance the cognitive enhancement is where exercise science was decades ago, four or five decades ago, maybe.

So the principles all make sense. You can see it happen in animal models. You can measure the fact that these neurons were activated. But how you truly dig down and quantify the networks being activated and the level of that activation, or maybe what's required in order to see a response, that's something that still needs to be worked on.

Andy Galpin

Dance makes sense to me because you didn't say these words. But sensory input is a huge impact here, right? So proprioception, in the case of dance, it is hearing. You're feeling. You're feeling the other person, probably you're feeling the ground. You don't want to step on toes. Hearing it is rhythmic, 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. 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 proprioception.

Where am I at in space? What shot am I going to 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.

Tommy Wood

Right.

Andy Galpin

This is learning how you get better at. Better at sports. Right?

Tommy Wood

Yeah.

Andy Galpin

Where the cognitive demand piece to me sets a little bit differently. 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 demanding task. But in reality I can do that scrolling my phone pretty quickly. And hubris aside here, 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 or other folks I certainly know, say my just self as a graduate student, the whole day reading every word 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 going to be a high cognitive demand? If I'm sending an email, is that always going to be low? I know, for example, just speaking from my relationship, if my wife gives me information about something, I hang with the kids in school, that's the highest cognitive demanding effort I will have in my whole day. I'm like, wait, who, what's the kid's name again? I just have like 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. Because she's like, yeah, it's infuriating. She does the same, by the way. So to the point of saying like, is it the task itself?

Is it novelty? As long as I'm doing something different, where, where do we know that something is cognitive? Or where can we get closer to guessing?

Tommy Wood

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 case, it doesn't really work, really.

And it's probably because of the way that we use our brains nowadays. Nowadays. What you mentioned earlier, listening to your wife talk about something to do with the kids. And you said the only way that you can actually internalize it, if you like, if you give it your attention. So what that tells me is what you're doing is multitasking. 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 essentially you're not doing either or you're doing both or three things very, very poorly.

Andy Galpin

I think I set the world record for highest task switching cost ever. If I have to task switch like that, I have to literally sit down. I'm like, shake my head. I'm like, okay, hold on.

Gimme a minute. Okay. What? It takes the lag. It's like a bad video game.

It's so long on me. When I switch tasks, I'm just like. I focus my whole day on not doing that. Cause it is so catastrophic for me to have to do that. I'll. I can do the task, but I'll have no memory of it. Yeah, it'll be gone for forever.

Tommy Wood

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, you know, I've leaned into it. Like, the human brain cannot task switch like that efficiently.

People just can't do it. You may have to be able to navigate that for your job, but in reality, like Work by Gloria Mark shows how constant task switching is very stressful. And every time you switch a task, you have that cost of time, as well as the fact that if you're distracted from a task, maybe 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 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 a friend of mine, James Hewitt, calls the cognitive middle gear.

And you kind of imagine it. So I'll keep going over to my terrible exercise analogies, but it's kind of like spending all your time at threshold. It's incredibly, like, physically tiring, but the adaptation you get from it is kind of disproportionate to how much it drains you.

Andy Galpin

Yeah, yep, yep. This is the last couple of sets that you did where you got nothing different, but you got high fatigue.

Tommy Wood

Yes, exactly. And you're doing that with your brain all day.

Andy Galpin

Yeah.

Tommy Wood

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 done. And then the rest of the time, you're sort of. You're doing your sort of like your. Your zone two brain work. And that can be answering emails, like some of the basic stuff.

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

Andy Galpin

Your lab does mostly neonatal stuff. Right. So your actual scientific time is mostly spent in young developing brain. Right. You've clearly done work across the entire lifespan. Does that task switching energy increase as you get older? Because I feel like when I was a kid, I could task switch immediately.

I don't actually have a recollection of it being a problem as, like a grad student, but now I'm like, oh, my gosh, just detrimental. And 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's 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?

Tommy Wood

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 they're focused on, right? And essentially, for the first 30 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 finish adapting to its environment. And that adaptation is driven by learning these skills, social interaction, language, motor skills.

But particularly early on, that's all the brain is focused on doing. Right? I'm going to spend this next 10 minutes trying to stand up, and then I'm going to take a nap, and my brain is going to start to figure out all the inputs that it received during that period of time.

Andy Galpin

I've had some days like that, no doubt even now.

Tommy Wood

So then as you get into the teenage years, I think that you're right. Kids seem to be able to jump back and forth continuously, and that probably is. 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 a product 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 40s, 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 you're a kid, you have nothing else to do, 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 to the time, right? But you have these focused periods to just work on learning the skill, whereas you're learning French as an adult. It's like, well, I'll do 10 minutes of duolingo 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.

Andy Galpin

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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, we're not going to be on the next one quickly. So if we go to our 40 year old and we're back on this avatar, he's saying, okay, I just kind of want to enhance my brain function there. I drug us off track there pretty quick. So kind of coming back to that, what would be again, your recommendations of things to think about, stuff that he could generally try. You mentioned learning a language duolingo. Are there any other specific brain training things? Do those things work?

I guess we'll even start there. Nutrition supplementation, nootropics. Like what are things we can do in that? Again, I'm not diseased, I'm not hurting. We'll get to that later. Just feeling pretty good.

Tommy Wood

Yeah.

Andy Galpin

What can I do to make my.

Tommy Wood

Brain scans I think most brain training as it currently exists is probably not enough for us to see significant file transfer in that person in that, 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 primary stimuli that drives neural organization. And then all the downstream consequences of that. So compared to looking at puzzles on a computer screen, having some in depth audio and visual stimulus in a virtual reality environment is much more similar to the way that we normally develop complex skills and you know, drive brain development.

So I think we're going to see more and more of that coming online even in, you know, regular adults and actually in kids and older adults. The current technology for say video games, when in say a 3D, a complex 3D environment, it hasn't necessarily, there's been a bit in VR so far research, I think that's going to really explode over the next few years with like all the devices that are now available. But even like I think the game that has the most research is Super Mario World 3D. 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 cognitive function tests. So even that kind of new complex world, a lot of orientation, puzzle solving.

Andy Galpin

High effort, high focus.

Tommy Wood

Yeah, and you're going to die if you're not actually paying attention. And probably the same in Tetris, but not in Solitaire. And actually with increasing complexity you see increasing improvements in cognitive function. So providing these complex multidimensional and multisensory inputs, I think we already have some evidence that that can improve cognitive function in healthy adults. And I think we'll only see more of that in the next few years.

Andy Galpin

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. Fair characterization or no. If cognitive function is low, either maybe young or older, aging, something like a puzzle brain training brain HQ is probably the more most studied one. Many randomized controlled trials potentially can help. However, if you are kind of normal to above going past that, that's just not cognitively demanding.

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 functional physiological demand that provides enough of a stimuli to cause adaptation. So video games of that ill 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. 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.

Combat sports are of course are like fantastic for this.

Tommy Wood

Just don't get punched in the head too much.

Andy Galpin

Too much, yeah. 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 particular nutrients or styles of eating that are really bad for the normal non diseased person? Or what do we know about that side? Outside of energy toxicity, which you talked about long term was a problem.

Tommy Wood

Yeah. So in reality the answer is no, there's nothing that anybody has to avoid. There's some reasonable observational, epidemiological evidence to say highly refined diets high in ultra processed foods, which that classification is problematic because it includes protein powder, which I would happily recommend to people, but also Twinkies. Right.

Andy Galpin

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.

Tommy Wood

Yeah, exactly.

Andy Galpin

I don't know if we have the direct mechanistic research on that for this question, but we don't have to stretch our imagination as far to say there's so many other reasons why you should avoid that. Like just okay, so outside of that.

Tommy Wood

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 healthy individuals, in athletes we see some interesting improvements in broad cognitive function with say creatine supplementation, particularly in aspects of memory. So that's something that's always high on the list. Everything else that I think would go on the definitely take could also be related to the nutritional piece.

So magnesium status, vitamin D, all those other kinds of things. When you're then thinking about say supplements or nootropics, often what you see is that there's a trade off, that you enhance one function at the price of another. And that's fine, but that has to be a choice. You can't just take these things and think, I'M going to be better at everything because the brain doesn't work like that. Well, nothing in physiology works like that, generally.

Andy Galpin

No free passes.

Tommy Wood

No free passes, no biological free lunch. So then it's just going to depend on what you're trying to achieve. So if you've had issues with sleep or stress long term, then there are interesting things like Theanine, Ashwagandha, KSM 66, they seem to improve stress and also cognitive function in those settings, if you're thinking about trying to perform in the moment in a given sport. Uh, so I can, 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?

When you try and increase that or try and decrease or improve reactance, be decrease reaction time, then there are some. You know, the supplement that would first come to mind is caffeine.

Andy Galpin

Yeah, right, no doubt.

Tommy Wood

And it works. Right. We know that caffeine improves psychomotor vigilance and improves reaction time. However, we also know that at higher doses, caffeine decreases complex, complex scalability. Right. And decreases certain aspects of.

Andy Galpin

Imagine any scenario in which you would want to be driving 200 miles an hour on a thousand milligrams of caffeine.

Tommy Wood

Yeah, absolutely not. And so this. And. But 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 200 miles an hour, 150 miles an hour with 90 other cars around you, and you're plowing to the first corner.

Andy Galpin

Yeah.

Tommy Wood

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, but we can also use breathing techniques, exercise to kind of modulate some of that. So there are some supplements and depending on the task, maybe caffeine is the right one. For most people who are habitual caffeine users, you are generally just reversing the deficit caused by a caffeine deficiency at the moment, rather than enhancing function, which is fine. Yeah, we just had coffees before we came in here.

Andy Galpin

Right.

Tommy Wood

But then beyond that, it's going to really depend on the task and that's largely going to be related to arousal. What level of arousal is going to be ideal for the task that you're trying to perform. And each task is probably going to have a different ideal level of arousal.

Andy Galpin

It's really interesting you say that because with all the athletes we work with, there is a spectrum of caffeine use not only within the person, a person that. 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 50 migs or something like that. Like some little, little top off. But they don't want to have, they can't have that kind of neural control on very much caffeine.

Tommy Wood

Yeah.

Andy Galpin

At all. Many of them are just no caffeine period. Right. 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, all kinds of different areas of this. I know personally, I'm kind of unlike the golf world. I generally like, like one shot of espresso. Yeah, like that, that is like good for the day.

Just like kind of moldering around a little bit. If I have afternoon I want like decaf or quarter calf, then I'm like, that's like perfect for me. 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.

Tommy Wood

Yeah.

Andy Galpin

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 90% 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 have to think about every word that comes out of my mouth if I do the smallest half dose of alpha gpc.

Tommy Wood

That's a really great question. And the answer is I don't know what the. A lot of people I know really like it.

Andy Galpin

I've been wanting to know this for like a decade. By the way.

Tommy Wood

The, the reason why I can't answer that question is because there isn't that much like high quality research on alpha gpc. There's quite a lot on cdp, choline or citicoline. So another, another form of choline, which, you know, people say that alpha GPC is more likely to get into the brain, more likely to be turned into acetylcholine, but there isn't that much really good quality research. So when I talk about choline supplementation, I'll always fall back on citicoline because no more data. It's much better understood. So the reason why I can't answer your question is because I don't think anybody's really looked at that.

Andy Galpin

Anyone that tells me things like alpha GPC don't work, you're out of your mind. You're out of your mind because if I take a quarter of a dose, I can't think straight. So it absolutely works. I guess it depends on your point earlier.

Tommy Wood

Yeah, what it means by working.

Andy Galpin

How are you defining sort of work? Um, are there any categorical pros, cons to the things? 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 alpha 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?

Tommy Wood

There's been, as far as I know, a lot less research on those different, on those different trade offs. There was a little bit historically on some of the raster terms and showed something similar. Right. You might have an improvement in some aspect of executive function or memory, but then verbal fluency or some other aspect of cognitive function decreased in response. The stimulants broadly do seem to have that trade off that we mentioned with caffeine. So there's a recent study that came out and compared caffeine to methylphenidate and some of the other stimulants that are regularly used by students and when they're studying or the clinical population like adhd, who actually might benefit from them. And you tend to see something, tend to see something similar.

So you might improve on one aspect of cognitive function, but especially certain aspects of executive functions seem to decrease. What's interesting is that a lot of you see this in the, say, the psychedelic microdosing literature. 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 actually parallels some of the caffeine research where people.

Andy Galpin

You just set the whole Internet on fire. Sorry.

Tommy Wood

And so 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. And none of this is inherently bad. It's just knowing what it is you're trying to achieve in the given moment.

Andy Galpin

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 massively with almost, not always, but a lot of times no subjective change. 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. 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 going to maintain like total short term focus and just disregard like the real world, like what is happening here.

Tommy Wood

It's funny because you often see the opposite in sleep literature, which is where, you know, like Ellen Langer's work where they randomize people to sleep for eight hours, but they told them they slept for five hours. Right. So they slept a perfect amount. But they thought I didn't sleep well, therefore I'm not going to perform well.

Andy Galpin

And actually they.

Tommy Wood

Yeah, 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 that's the case, but. And there's ton. You know, we can do that across blood sugar, control sleep, even how physical activity affects mortality.

Andy Galpin

We've done it with lifting weights. We actually put different numbers on the bar bill. We ran a couple of these random of deception studies with it. Yeah. Like you will definitely PR if you think the bar is 15 pounds lighter than it is.

You will absolutely PR.

Tommy Wood

And they've done it with anabolic steroids.

Andy Galpin

Oh yeah, yeah, right.

Tommy Wood

That was the. One of the most famous ones.

Andy Galpin

Yeah, yeah, yeah. What a tremendous one. Yeah.

Tommy Wood

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 is like, what are we expecting from ourselves today? And that becomes a self Fulfilling prophecy because our thoughts drive our physiology, and then you get the result that you expect. But sometimes, like you said in the opposite scenario, where you haven't slept well, you think you're fine, and you can still measure an objective decrease in function, there is still some baseline requirement that we have these things in place for cognitive functions. So some of it's driven by expectation, but expectation isn't going to be enough to overcome really significant differences.

Andy Galpin

Yeah, and we saw this a ton at absolute rest initially, and we've seen this in various aspects where set 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 dog 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 it's not that the caffeine dealer didn't work.

It's the whole 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 soup routine. Right. So you're not saying that those things aren't doing anything. It's just that the benefit is potentially only going to 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 from me. We've mentioned this stuff a couple of times, but I want to 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.

It's not perceptive. It is noticeable. It is real. There's this big decline. You hear a lot of these certainly in the last couple years about potentially long Covid happened after I got Covid or didn't or got a whatever just for Whatever reason we're down there, how does somebody know what that actually is? 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?

Tommy Wood

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.

Andy Galpin

That's brain fog's way nicer sound.

Tommy Wood

So when you look at the sort of the stages of dementia now, they include 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 has. So if you feel like I have this brain fog, 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, Right.

But there's quite a lot of research now suggesting that that subjective decline, which, you know, has a lot of overlap with the idea of brain fog, then, is associated with improved. 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 dementia. Right. I don't want to say that right now.

Andy Galpin

You just terrified the Internet. You set them on fire earlier, now they're all terrified.

Tommy Wood

So that is definitely not true. But I think the fact that they are linked, at least at the population level, statistically suggests that that could be a signal of some kind of impending issue or the beginnings of an initial issue. Now, most of that in that. In that stage is thought to be reversible. Even if you ask, you know, dusty old neurologists who think about, who thought about this, they would tell you. And that if you look at 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 going to come up again and again and again. And so we already covered the nutrition stuff. That is that, like you said, you've even seen that in your own clients. Right. You address some basic nutritional things, and a lot of this stuff lifts immediately.

Andy Galpin

I'd probably say 60% of our clients have a subjective score of cognitive Function of five or less out of ten. Right. So whether they actually have brain far don't. Like over half of our people think that their brain is functioning poorly. And I would say our success rate is over 90% with all that.

Tommy Wood

Yeah.

Andy Galpin

And we've done lots. Sometimes it is more complicated, but a lot of the times, if you cover all the bases, we have stunningly high results.

Tommy Wood

And that makes perfect sense if you think about, if you think about the framework of how I think about cognitive function. And so maybe that's, this is the time to kind of bring that and because it 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 3S 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 function. And some inputs will cover many of those at the same time. Right. So sometimes I've put up a picture in a lecture and said, here's my model.

And somebody's like, yes, but something goes there. And there I'm like, yeah, I know, but it's a picture.

Yeah, it's just a picture. Right. Just kind of. But we've talked about stimulus, and I think that's the primary driver 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 good cardiovascular function. Right. What you see in the brain when you have an increase in activity in some network associated with some function is you see an increase in blood flow and direction of resources to the area of the brain.

This is the process of neurovascular coupling. So when neurons become active, blood vessels in that area dilate. We direct resources to that area. This requires a healthy vascular system. Right. And so as it's almost exactly the same process 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 and cognitive decline, probably because of that vascular component. So everything that would improve cardiovascular 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 those kinds of things, then you need some kind of energy source. Right. For most parts of the brain, most of the time it's going to be glucose, 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.

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 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 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, an absence of chronic uncontrolled or uncontrollable stresses is a big point as well. And when I've like tried, we're currently writing a paper that sort of like lays out this in a more academic way, sort of like 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 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 hyper metabolism. So you almost have to think about it as over training. Right? So it's preventing the ability. Right. It's junk volume for your brain that's preventing the ability to adapt.

So that's part of it. And then you also want to avoid any kind of exposures that prevent some of these adaptations from happening. So excessive alcohol, smoking, air pollution is really common. And so if you're trying to address brain fog in an individual, these are all the areas that you have to think about, right? You have to think about energy metabolism, vascular health, sleep, stress, other exposures. We already talked about nutrient status and some other things that can inhibit this process include chronic inflammation. So that's where I think long Covid starts to come into play.

And we know that you can see chronic inflammatory processes in the brain in certain individuals who have 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 relates to then cognitive function or cognitive deficits in that individual. How you address that becomes tricky. But that's also not going to be necessarily relevant to the vast majority of people who might be experiencing these things. So that framework, I think, gives you then a chance to say, well, where is the likely deficit? Or where's the issue that we're most likely to, you know, going to 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, you'll offset some of that risk if you sleep better.

But if you don't sleep well, you'll offset some of that risk if you do exercise. So you don't have to perfectly hit everything in order to 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 outsized benefits.

Andy Galpin

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. Ideally ones that have multiple sensory inputs. So smell memory, different forms of cognitive function, creativity, executive function, like, different aspects, all the tasks are there.

Tommy Wood

And avoid extended or continuous task switching because we know that's a significant stressor that's gonna be very relevant to the avatar that you adopted. Yeah.

Andy Galpin

Yep. Thank you for that. If on the opposite, where I feel like I have some sort of cognitive dysfunction, I've lost it, then we go after the 3S model and we figure out presumably where area of that I'm struggling the most with. So is it the supply area? Is it the ones?

Tommy Wood

Yeah. So supply and support. Or it could still be stimulus. Right.

Andy Galpin

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.

You don't really realize it because your stress load is high. And that's actually literally burning fuel in your brain. Right. To keep that vanished I would say of the people I'm talking about that we coach in RT that has that 90%, I don't think we've seen anybody that has a problem outside of that. Yeah, oftentimes they think that 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'm not simply saying the basics.

Most of the time, if we do a full, true analysis of sleep, stress management, movement, daily format, so how your actual life is structured, hydration and mental health on top of nutrition, blood work, things like that, something is generally very, very bad. And they may not see that, perceive that. But once we get that cleaned up, sometimes it's been as simple, honestly, as hydration.

Tommy Wood

Yeah, that. I didn't mention that. But it fits right into that supply side. Right.

Andy Galpin

It's stunning.

Tommy Wood

A critical component.

Andy Galpin

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 2 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 those are, I think, really insightful things that we can do. Today's episode is sponsored by Renaissance Periodization. If you want to put on muscle through science backed training programs, look no further than Renaissance Periodization.

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Again, that's rpstrength.com perform to Save up to $50 off of your subscription. Last little thing I want to 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 variance in major league baseball players, the batting, successful batting average, it was something absurd, like 70% of variance was all in vision.

Like ocular metrics explained almost everything. And that's when I was like, whoa, if we really think we're going to service our baseball players better if we're not touching, testing and monitoring and improving vision like we're spitting, we're going after pennies on the dollar here. So what do we know about testing vision outside of of course you need 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 the case may be.

Tommy Wood

Recently we've done some work also in Formula one drivers with vision because this is a big part of their, a part of their job and it's essential they'll probably you start to lose some visual acuity before you're going to 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 as well.

Andy Galpin

Really? So that basic stuff should improve vision as well.

Tommy Wood

Yeah, and I did some analyses with some large population data sets 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 standard test, you'll see that blood sugar control, nutrient status, all of these things, also smoking and all that kind of stuff, all those same risk factors that we know are important for cognitive function, they then relate to visual acuity as well. So those same principles come into play and all those same nutrients are going to be important as well because you're essentially firing neurons from the eye into the brain. It's the same process. When you then think about visual assessment, there are a whole bunch of different platforms that you can do do this with depending on, you know, how much money you have and what you have access to. But like right eye is, is one that's, you know, fairly good. Certainly looks at different aspects of Eye tracking, which is important for athletes, but also after concussions and things like that, you can also do much more complex eye imaging, like optimal tomography, that can give you a much better idea of 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 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 that with essentially progressive overload of the ocular muscles by just trying to focus on something that's just beyond the reach of your current visual acuity. Similarly, if, say, sort of like dark light contrast is the same, we spend a lot of time exposed to the same intensity of light indoors. And so then that may be part of the reason why we lose some 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 ourselves to those differences in light levels. So you can then do training with like, visual tracking. So when I was trying to put together a program to for, say, a Formula one driver that want to try and maintain visual tracking, there are some off the shelf things that you can use. There's some nice evidence for something like Neurotracker, where you do multiple object tracking. 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 improve some aspects of vision.

And then beyond that, it's just thinking, how do you create more and more complex situations where you then train these muscles? So I spoke to a friend of mine who's former special forces and does a lot of this kind of training with individuals. And so one of his favorite tasks is to use a baseball that you hang on some kind of string, and then you have either letters or some kind of symbols on it. So then you can first start with the ball just hanging still and vertical. And then you can practice, say, focusing in the far distance, focusing on a symbol on the ball, then focusing even closer. Right? So you can practice quickly switching visual depth.

But then you can also do things like make the pendulum swing, and then you have to track a Certain symbol as the ball rotates, and then also do that by quickly changing visual fields. And so then you're essentially training all these different parameters of vision, both visual field as well as, you know, 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 down gaze. And it seems that, right. You probably can't overcome a huge visual deficit. Right. But a lot of these different features of vision do seem to be trainable.

Andy Galpin

There's an 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 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 batter only has to hit the ball. But then say, that was four. That was F. Things like that.

Tommy Wood

Yeah.

Andy Galpin

Are you telling me that that might plausibly actually work?

Tommy Wood

Yes.

Andy Galpin

You vindicated every 1980s baseball hitting coach.

Tommy Wood

Normal. Normally, it's like some of these old school training methods just seem like hazing and they're kind of these attritional processes, but some of it might actually work.

Andy Galpin

Okay, so you could do things like that. 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 and now your eye. Right. It is 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 that you really wanted. It, like, doesn't matter a whole heck of a lot. Vitamin A, carotene.

Like, what about things like this? It makes sense if you Wikipedia quickly what those things are for.

Clearly there's evidence. If you've got certain physical, cognitive, or physical issues in your eye, especially from like a vitamin A deficiency, then of course it's going to 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.

Tommy Wood

Yeah.

Andy Galpin

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?

Tommy Wood

So a lot of supplements that we use to boost any function or I used to boost any function, like testosterone boosters or these kind of visual boosters, 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, you're not going to see any benefit. For some people. Right. Retinol is important. We know retinol is important in the eye. Some people due to genetic polymorphism aren't as good at converting these carotene into retinol. Right. So maybe there's some inter individual variability there.

But no, like more isn't going to be better. Certainly other things do seem to suggest some benefit and it's kind of like squint a bit and it might help. But some of the antioxidants, you know, Lutein, astansin, zeaxanthin, 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 visual acuity and some other aspects of vision.

Andy Galpin

Yeah, actually that's like reasonably well demonstrated at this point. My, my question with those trials are always, are you simply seeing a metric of somebody who had suboptimal physiology?

Tommy Wood

Oh, I'm sure, yeah, probably 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 because you're pre diabetic, then you know an antioxidant that can get into that system is likely to show benefit.

Andy Galpin

Yeah, right. 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 going to 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 want to dismay that too much.

We take a different approach of course, generally and so we haven't really seen much benefit in those folks, but I'm not surprised by that. So you've mentioned this multiple times now, whether it be from the energy toxicity or your metabolic and energy sustained principles with cognitive function. But I'm wondering how specifically things like creatine actually enhance brain function. We, you can take this actually from both angles. 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.

Tommy Wood

Yeah.

Andy Galpin

And then how. Actually it's, it's doing those, if it is at all.

Tommy Wood

So whether you would see a significant benefit from creatine right now probably depends a little bit. You take your dose of 10 grams and what are you gonna see? It probably depends a little bit on your context. But you probably saw the recent paper that showed that after one night of sleep deprivation, creatine can overcome some of those deficits cognitively. Cognitively, yeah. And that was actually shown a few years ago with skill, rugby skills in rugby players. You may have seen that paper as well where they had 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.

Andy Galpin

Yeah. With a very different mechanism here.

Tommy Wood

Right.

Andy Galpin

You're talking about a stimulant and versus a fuel. Right? Totally opposite, yeah.

Tommy Wood

So however, you could probably relate both of those to energetics in some way because caffeine is overcome or it's inhibiting the metabolic down regulation caused by adenosine, which is part of what drives sleep pressure and the need for sleep. As you accumulate metabolites like adenosine, they then sort of suppress metabolic activity in the brain, which then is associated with reduced function. And something like caffeine overcomes that. Whereas creatine can acutely provide a buffer, energetic buffer that allows you to maintain function in the face of sort of increasing metabolic pressure to sleep. So even though different mechanisms, they kind of maybe converge on something similar. I know a lot of people who every time they take creatine, they notice an immediate sort of boost in some kind of cognitive function yet. And 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. I've certainly found that in myself. Like if I take, 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 away. And not everybody's like that. And certainly we know that responses to creatine are very heterogeneous Right. Some people see totally big, big responses, some people see these smaller responses, and some of it's maybe related to methylation status.

Because creatine, when we make our own, which we make a lot of, is the most methylation intensive process in the body. You spend more of your methyl groups producing creatine than anything else. And so it could be related to that as well as a whole host of how much creatine do you normally have in your diet? And things like that.

Andy Galpin

So if I've gotten genetic testing done and I'm, no, no, don't do it, don't go there. Okay, So I think based on your reaction, maybe have just give us a little bit of an insight into your favor there.

Tommy Wood

So whenever, whenever somebody talks about methylation, they immediately start talking about genetic testing and there's a lot of that out there right now. Yes, genetic polymorphisms do change the functional level of enzymes related to methylation. The one that people talk about the most is mthfr. Different polymorphisms within MTHFR change the activity of that enzyme in a test tube. Right.

Andy Galpin

If I.

Tommy Wood

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 to your current methylation status. But in most cases, an elevation of homocysteine related to those polymorphisms is driven by some kind of nutrient deficiency or insufficiency. Sometimes your requirement is slightly higher because of a polymorphism. But, 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 B vitamin levels and your B vitamin status, your methylation status. 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. If you're, if you don't methylate, you die. Yeah, right.

You can't turn genes on and off. You literally can't do anything. So we create this massive nocebo around these different polymorphisms which I think is net harmful. When, yes, sometimes this is an issue, but if you have a significant decrease in MTHFR function, like in air quotes 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 riboflavin. It's not hard at all. It's not hard. It's literally nothing.

And that's because the polymorphisms change how MTHFR bind to fading, which is the proton carrier that that enzyme uses. So all you need to do is slightly increase availability of riboflavin to be converted into fad, and that's it. And it doesn't require super doses, just literally just 2 milligrams a day. It's nothing.

Andy Galpin

There's also a very low relationship between those polymorphisms and actual homocysteine. Oh yeah, like very sub 1%.

Tommy Wood

So I've. Yeah. And I've published a paper on that actually for that exact reason. I, I did these big simulation studies looking at the normal distribution of homocysteine by MTHFR polymorphism from published data. And essentially about 1% of your homocysteine is predicted by your level of activity of your MTHFR enzyme.

Andy Galpin

Yeah. So why not just measure the homocysteine?

Tommy Wood

Exactly.

Andy Galpin

I did a whole episode on genetic testing in season one, so please feel free to go back and listen to that if you want. So we'll move on for now because we can get aggressive there. But 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 they're in, so you know, tough luck. And potentially they've had or think 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.

Tommy Wood

That's what I've hypothesized. But I. And maybe this study's. If this study has been done, somebody sent it to me because I'd love to see it, but I think that might be the case. That would make sense because so much like so much of your methylation currency is spent on creatine production and if you know you have to decrease some of that production because your quote unquote, 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 and then would respond better to creatine supplementation, but so in theory, yes, but I don't think anybody's actually looked at that.

Andy Galpin

I wonder if it works the opposite way then as well. So somebody who's had potentially well exclude placebo, which is a large portion of this, but people that have had some sort of genetic testing done, then gone on high doses of B vitamins and felt a massive response, I wonder if those people could also then simply just go to creatine instead, which is, I won't say safer, but a little bit less risky. Right. Not a lot of downside to creatine, not a lot of downside to B vitamins, but more you're gonna get other consequences that you maybe didn't realize you're going after with high doses of, depending on which vitamin B you go after, but less potential downsides, I would think that you can go after.

Tommy Wood

What's interesting is that unfortunately these kind of questions haven't really been addressed in the literature. So I can quote studies on supplementing with B vitamins in individuals with elevated homocysteine. And we know how that can be important. But then we can also talk about studies where they give doses of creatine. And particularly when you start, 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?

These are like super interesting and important questions. But because of 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 around it.

Andy Galpin

I mean, vitamin B is. I'm all for. That's great. I just know that a reasonably high percentage of people will get really nauseous or have GI distress from them. And so for those folks, 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.

Tommy Wood

Certainly we've done, you know, so, you know, when I was working with a lot of individuals in, you know, in a similar arena. So to what you do now, you.

Andy Galpin

Know, this is taking people's. Thousands of people with their blood work and providing individualized protocols. This is what you've done for a very, very long time.

Tommy Wood

Yeah, yeah. And when and this is sort of like general population as well as with athletes. And if, you know, even status looked okay, but maybe homocysteine was still elevated or, you know, you know, we needed other strategies to help bring down homocysteine. Then creatine and choline or lecithin, which is a, you know, a plant, a plant derived source of phosphatidylcholine. They, they were, were good alternative options or something you could add on top.

Andy Galpin

Yeah. Okay. Why then does creatine help with cognitive function if it does? And we'll get back to the second part of that two part question. Is it the methylation support that's giving you, Is there other mechanisms? What exactly is creatine doing for the brain?

Tommy Wood

I think one of the things that I found most interesting across strategies that seem to improve, like robustly improve cognitive function 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, that's just like stunning. A lesson from neuroscience in general and also a lot of just like developing drugs in medicine in general. And so I think it's probably going to be a bit of all of these things. So we know that homocysteine is a risk factor for cognitive decline and that's probably because it's a marker of methylation status. So are you able to generate, say, membranes in cells in the brain like we talked about earlier? But equally, homocysteine can directly increase the accumulation of hyperphosphorylated tau, which is one of the sort of markers of risk factors of dementia. It's a marker of previous brain trauma and 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 going to give you short term, a short term energetic buffer as phosphocreatine in neuronal cells. And the brain is the most metabolically expensive organ in the body on calories or watts per gram comparison. And so anytime you have either a suppression of metabolism, say adenosine or some kind of acute injury, and that can either be, it could be a stroke, it could be cardiac arrest, it could be brain trauma where you have some kind of deficit in energy production, then creatine also seems to potentially be beneficial, although 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 evidence comes from animal models because you can't do that easily in humans. So some of it is an energetic buffer and then some of it, you know, one thing that creatine seems to do is to help stabilize and regulate calcium handling in mitochondria, which is related to acute injuries, but also to long term mitochondrial function, which then supports long term cell function in the brain.

Andy Galpin

Really quickly, I don't want to drag this down too far, but you've mentioned it multiple times. What is methylation? Why does it matter?

And just real quick.

Tommy Wood

Yeah, so methylation is basically the transfer of methyl groups, which is basically a one carbon group or a carbon with three hydrogens that gets moved around. And this is used to convert different metabolites in the body in multiple different cellular reactions. Like you change a molecule from one end to another by methylating it. But it's also really important for things like gene regulation. So people might have heard of biological age. Epigenetics, the major form of epigenetics and gene regulation and the sort of the more common measures of epigenetic biological age are all based on methylation status. So you have these, 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 and off.

And, and these tags seem to shift over time. That's associated with biological aging. So it's this really central process that drives so many different parts of biology.

Andy Galpin

It's in every cell of your body. It's on DNA, it's on protein, it's moving. A carbon is hard, like chemically. Right. So it's gotta be a major thing to get it to move off of one, which changes the entire function. So I think the way that you stated is very nice. It's a core biological thing.

You don't adapt, you don't grow, you don't shrink, you don't go any direction without methylation. So thank you for that. Now we have a little bit of understanding of why that's important. Then regarding the creatine in the brain, the second part you said was fueling. All right, walk me through how creatine. Actually, you mentioned it kind of quickly with just a touch of jargon there, which for the folks that don't know what an intermediate has substrate are, how is creatine actually providing fuel for your brain? And then on the second part of that is, well, what's the normal fuel.

Tommy Wood

For our brain when you think about different energy Systems. And I think people could watch endless lectures from you talking about different energy systems in exercise. And those principles in some ways are very similar in the brain. Although the majority of cells in the brain are, you know, like, like we said earlier, derived, derive energy from glucose, goes through glycolysis, then enters the electron, you know, the pyruvate and, or laxative pyruvate goes into the electron transport chain 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 currency, sort of a much shorter term energy currency or that allows you to recycle ATP when you've used it up is the phosphocreatine system.

So your creatine is phosphorylated with a high energy phosphate and you use that to regenerate ATP. So for very energetically expensive processes where you can't get enough energy through that longer process, that glycolysis and aerobic metabolism, then the buffer comes from the phosphocreatine system. And it seems that even for normal cognitive function, there is some benefit from having more of that buffer on board, both acutely and chronically.

Andy Galpin

So just like your muscles or any other part of your system, they have to rely on energy. 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 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, it could use ketones or anything else. And then creatine, just like it is in your muscle, provides that stoichiometry 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 lactate.

Tommy Wood

Yeah.

Andy Galpin

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.

Tommy Wood

I don't think lactate doesn't accumulate. It just gets generated and used.

You probably couldn't. You could probably measure. So this is where I think creatine becomes important. And potentially, if I put microdialysis needles really accurately in certain parts of the brain, and then you start to upregulate the use of that network for a specific function, because there's going to be a slight delay between increased ATP production and the requirement you actually need that energy before you realize you need it. Everything that we see and do has essentially already happened because of the time lag that it takes for us to actually interpret those actions. So that energy is needed immediately. And it could be that because of the lag in the system upregulating energy production, that's where creatine becomes important in a network.

As you activate it, then you would probably start to see locally. If you could measure it with, say, carbon 13 metabolism or something, you could have a radio tracer on your lactate and you could see that your astrostrites, 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 increasing.

Andy Galpin

And this is potentially why people have looked a lot at lactate as a supplement or as a medication or a therapy for various aspects of a brain injury in brain damage. I don't want to go into this in too much detail because I covered a whole episode in season one, episode 10, all on a paper that you led with Dr. Federica Conti and myself and some other folks as well, on what we know exactly regarding supplementation and nutrition for brain injury. So this is concussions, tbis and things like that. So you can go and watch that whole episode and download that whole grade for all those details there. But in that paper, I remember we had a very short section regarding lactate, 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.

You can feel free to maybe double tap on creatine a little bit here since 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 your egg analogy and then that'll help explain a little bit of why maybe these things do or don't work for there. So how does a concussion actually work? Today's episode is sponsored by Momentous. Momentous makes the highest quality supplements on the market, Period.

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Tommy Wood

Off to Zoom out for a second. 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 them properly.

Andy Galpin

Hard to fix when you can't define.

Tommy Wood

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 consistently. Experts in the field talking about it, you'll hear something like the slosh effect or you imagine a head getting bashed and then the brain banging around inside the skull, like hitting one side of the skull, then banging and hitting the other side. And that's what they call a contrecoup injury, which is basically you see some injury on the opposite side from where the impact occurred. The brain is, you know, it's Mainly fat and water. And it is then surrounded by fluid. And it's inside solid box.

Andy Galpin

And that fluid is full of salt.

Tommy Wood

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. Well, it buffers it or the csf, the fluid.

Andy Galpin

I saw you do this. It was one of the coolest things I've ever seen. You took an egg and you put it in a jar with salt water. I don't remember the concentration you put it in.

Tommy Wood

Oh, it was just like normal siding.

Andy Galpin

Yeah. And you 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.

Tommy Wood

Yeah.

Andy Galpin

At all?

Tommy Wood

No.

Andy Galpin

Because it's not hitting anything. No, it's smashing.

Tommy Wood

It stays right in the middle.

Andy Galpin

In that moment, I went, what? Like everything?

Because I had said that always. I did not know that until you showed me that. Not me, but you're showing other people. And I was like, wow.

Tommy Wood

So if you could, while I'm shaking it, image the jar, what you would see is you would see distortions along the surface of the egg yolk inside this jar. So there are distortions.

Andy Galpin

So the egg, instead of being a perfect circle, turns into an oval. It's not smashing against the wall. It's just being distorted. And it's being accordioned.

Tommy Wood

Exactly.

Andy Galpin

Squished and pulled back apart. Right.

Tommy Wood

So how we generally study concussions is the other version of the egg experiment, which I also showed, which is that you have 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 dressing. Right. Immediately you disperse that egg yolk throughout the liquid. That's how we normally study concussions. But what happens if you then look at where injury is in people who've had concussions? So you look at individuals who have 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. Of the brain. It's not the brain banging, it's the skull. What's happening is that these distortions, like waves of energy that are transferred through the brain is 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.

Andy Galpin

It's connective tissue.

Tommy Wood

Yeah.

Andy Galpin

They're tearing the connector.

Tommy Wood

Yeah. So right at the. Usually right at the base of the sulkai. So you think about the brain is really wrinkly. Right. Those are the gyri, the. The sort of the divots in between those wrinkles, the sulci at the base of those.

That's where you tend to see 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. So you create direct. Direct axonal injury.

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 accumulates, is at those interfaces.

Andy Galpin

So then how do things like creatine and lactate help? Do they work at all? And if so, how?

Tommy Wood

I've been really excited about the potential for lactate in traumatic brain injury. And that excitement aligns very similarly with ketones. But people have been talking about them for a long time, and I'm still waiting for some good human studies.

Andy Galpin

Been probably talking about it for a decade online, like in front of people on podcasts and things like that.

Tommy Wood

Yeah. So I. I believe that they could be beneficial, but we just haven't seen really high quality evidence yet.

Andy Galpin

However, now that's clear. You haven't seen evidence that shows they don't work either. No, the studies just aren't being done.

Tommy Wood

No, no. And if, if I were to get a significant concussion or tbi, like, I'm going straight to the ketone esters because I believe that there's a high chance of benefit with low risk. Anybody who's like, I don't have a randomized control trial to tell you that that's the case, but, you know, I think it could be.

Andy Galpin

If it's your brain.

Tommy Wood

If it was my brain, that's what I would do.

Andy Galpin

As an MD, PhD in brain health, this is what you would do. Infer that for what you will, folks.

Tommy Wood

Part of it is that it's essentially providing 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 arrest, traumatic brain injuries, is what we call energy failure. So there's this 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 less energetically expensive or they're more energetically efficient in terms of generating ATP. Like the effect is small, but in that kind of setting a small effect may be enough to help minimize injury. There's also going to be some other signaling effects that could be beneficial. Like both lactate and ketones have a whole range of other anti inflammatory neurotrophic kind of effects. So, so lactate seems to help and ketones seem to help drive an increase in production in bdnf, brain derived neurotrophic factor, which could help recovery.

So beyond their effect on your metabolism, they may have these other downstream effects as well. But another reason why this is important is that in the acute injury setting, the brain may become relatively insensitive to glucose or glucose uptake decreases. But that doesn't seem to be the case because the transporter is different. And both ketones and lactate go in through the monocarboxylate transporters which aren't necessarily affected in that state. So some of it could be that particularly ketones might be more metabolically efficient in terms of energy production, but also they're maybe more likely to get into the brain in the setting of an acute injury to help support.

Andy Galpin

Are they potentially less negatively influenced by inflammatory markers as well?

Tommy Wood

Yes, potentially. Although I mean it kind of depends on what's going on and how they're getting in.

Andy Galpin

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, that my brain is. Well then it's inflammation, it's damage. So you need to give me something that's anti inflammatory, NSAIDs or some other drug that is going to reduce inflammation. Or you need to give me something that's going to 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?

Tommy Wood

So one of the reasons why you have impaired glucose metabolism is because of the inflammatory response. And a normal inflammatory response creates peripheral insulin resistance in order to divert glucose to the immune system in order to, in order to respond.

Andy Galpin

So it has to have energy, the immune system has to get energy as well.

Tommy Wood

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 response. The direct metabolic effect of injury is due to the changes that happen at the cell or in the nerves in response to that injury. So if it's like a direct shearing effect, or even in concussions where you haven't fully sheared neurons, you may have stretched them 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 hyperstimulation of those neurons. So they start to fire a bunch when you get this hyperstimulation of neurons. And you can see this with low oxygen states or with acute sort of stretching.

If you sort of acutely stretch the neurons, they increase their firing rate. That creates a large production of what we call excitatory neurotransmitters, things like glutamate, which are.

Andy Galpin

That's the most common one.

Tommy Wood

Yeah, the most common one. But there are others that then starts this sort of wave of increase in signaling. You then essentially hyper stimulate the downstream neurons. You get these big shifts in calcium within the cell, and then that calcium impairs mitochondrial function, and at very high levels can actually stimulate what we call the mitochondrial permeability transition, which is essentially the mitochondrial saying, I can't take any more. And then that then triggers cell death. So it's essentially an overstimulation which can be driven either by low oxygen or stretching, which then sort of creates this cascade that impairs mitochondrial function.

Andy Galpin

You mentioned calcium again, that was also the third part of our criteria we talked about earlier. Right. Like that, having that third issue. So I want to ask more about that, but let me see if I can summarize what you just said quickly. In the case of a brain injury, you're going to 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, and so you have to then divert glucose to them.

And the best way to divert glucose to them is to block it from going other places. Right. Now, in this short term thing, we've basically given other areas diabetes.

Tommy Wood

Yeah, Right.

Andy Galpin

Like we've made them insulin resistant on purpose so that we can focus our glucose to the immune cells. The immune 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 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. 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 immediately, but probably not super excessive.

Tommy Wood

Yes.

Andy Galpin

But not small either. Right. By the way, I'm guessing all this because this is exactly how it works in bone and muscle. So tell me when I start to deviate here. Right.

Tommy Wood

I'm literally guessing I'll jump in just quickly to say that in general in, in brain injury, everybody's thought that these inflammatory responses to injury are a bad thing and we should 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 response to injury. So like in a minute it looks worse, but actually that then ends up resulting in improvement longer term.

Andy Galpin

There are cascades of drugs that pre dose pro inflammatory cytokines and whole and then give them to you like give an exaggerated inflammatory response in again another tissue. I'm not surprised it's the same in bone 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 in the case of the cell we're talking about the brain cell runs out of energy, then we're gonna die.

Tommy Wood

Right.

Andy Galpin

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.

Tommy Wood

Yes.

Andy Galpin

Right. That's. I know that's one thing we covered a little bit in the paper, but I know you spent 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 support. So those were kind of the three big Areas for in the acute setting, where if you were to actually have a real injury and you were to get treatment in hospital, particularly temperature and glucose are probably the two things they're going to pay attention to most, right?

Tommy Wood

Yeah. If you were in a neuro ICU because you had a significant 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, you know, quote unquote, just a concussion compared to, you know, a major brain trauma.

Andy Galpin

What about things like at home brain tests? So there whether these are technologies where you can test cognitive function? Maybe not. I doubt there's any at home concussion tests that you can do.

Tommy Wood

No. So most concussion tests generally require either some kind of baseline cognitive function test. So there's things like the impact test. The military have their own version of this. There's other tests that are probably more sensitive to concussions called the Kingdevic test, which is basically you have to read off a complex grid of numbers and letters that kind of like overlap if you can't read them properly. But you need a baseline score and you need the same person to kind of administer it. You also see there are some available devices where you can measure changes in event related potentials.

So the electrical signal that you get if you show somebody an auditory or visual stimulus that seem to be pretty good predictors of like 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 more broadly in terms of 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. Are some apps and things that kind of have some of this stuff built in, but it's difficult to standardize one depending on if you have, say, access to some kind of healthcare provider. There are nice companies like Kreos which give a bunch of standardized cognitive function tests you can do at home on a desktop. A lot of neurologists and neuroscientists use something like that. I think the main cognitive function test that I know of, that anybody can do at home for free and is validated is actually has been put online by a charity that I work with in the UK called Food for the Brain.

And they have a validated online cognitive function test that includes measures of executive function, working memory and processing speed. And you can just like go on their website and you can just do it and you can track it over time.

The and weird. 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 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 given access to be able to do some of that. But people can do that test. 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. So if you're going to do it and you want to track things over time, I would do it a couple of times in succession so you know it and then use the second or third time as your baseline and then track it over time.

But there are a number of people now in this space because right. I can now go to Quest or LabCorp and I can get whatever blood tests I want but I can't get a really good, well validated multidimensional cognitive function test. So that's something that you know, we and other people are working on any.

Andy Galpin

Other technologies, consumer based EEG things that you can or cannot mention the exact products if you'd like. But just where does that field. Stan, I know that there's probably half a dozen or more that immediately come to mind. Some of them sit in the front of my head, some in my ear, some back place like walk me through again. You can speak specifics if you want or not. But the general lay land of at home based EEG technology, I think it's.

Tommy Wood

An area where there's a ton of promise.

Andy Galpin

It's just figuring out that's never a good start.

Tommy Wood

No, but in. Well I think in a good. So I guess the short answer is is there anything that gives you everything you would want right now? Probably not. However with very simple EEG devices and there are some that are set up in earphones. So I think the one that's that I know is most widely available or at least will be soon is a company called Neurable. The one the frontal EEG like Muse is something that people are going to be familiar with.

And actually there are versions of the Muse that have the sensors around the ear as well. Some of the.

Andy Galpin

Why does it matter if it's in the front of the forehead versus the ear?

Tommy Wood

It depends. And it depends on what you're on, what you're looking at. With some of my collaborators, we're looking at different EEG frequencies and people have heard of like alpha, beta, theta, delta and the different, like the relative frequencies and power of these different. So like even within a frequency band, people will have different average frequencies. And then the total amplitude of the wave is the power. And your mean frequency and power in those different frequency bands relates to different aspects of cognitive function. So certain aspects of alpha seem to predict, say, learning speed for learning a second language, and some other aspects of cognitive function.

Some companies have created focus metrics so you can tell when your brain is focused. That's either based on certain measures of alpha or sometimes they have alpha plus beta divided by delta plus theta or some kind of ratio of the different frequencies. And that stuff is pretty good. The problem is that each individual company kind of focuses on one thing. Right. So you're using it for neurofeedback in kind of like a meditation type 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 take a break.

I think that you could get a lot more and broader information about somebody's cognitive function over time with some of these technologies, 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 it in people over time. Yeah.

Andy Galpin

So the only. Well, perhaps not maybe the only, but the largest consideration there for the consumer is just that last point.

Tommy Wood

Yeah.

Andy Galpin

So it's going to be at least that I'm aware of that you're aware of. Any consumer face product there is going to 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.

Tommy Wood

Yeah. It's difficult.

Andy Galpin

Really. Yeah. Challenging the calcium question.

Tommy Wood

Yes.

Andy Galpin

Right. So what does calcium have to do with this entire project? Why does it matter if calcium influx is happening or this excitotoxicity with glutamate what's that got to 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 story with calcium.

Tommy Wood

So I think this is another area where the brain and muscle kind of tell a similar story. Right. We know that muscular heart.

And the heart. Right. The muscular contraction is driven by cycling of calcium. Right. And a lot of signaling processes, including mitochondrial function. And then the transfer of information across cells in the brain is driven by waves of calcium. And so that then opens and closes different channels.

It activates or deactivates different energetic processes. It regulates mitochondrial function just like it does in the muscles. So when you have large excessive or unregulated influx of calcium into a cell, one of the prototypical downstream effects is mitochondrial dysfunction. And eventually, like mitochondrial death. And mitochondrial death, you essentially have cell death.

Andy Galpin

That's what you're going to see is cell death.

Tommy Wood

So when you then think about, like calcium as a supplement, obviously those two things don't go directly together. You can't take more calcium and then have better regulation of energetics in the brain, unfortunately, because it's just a lot more complicated than that. But I think this is where some other things come into play. We know that. So vitamin D is really important for cognitive function. One of its role, I mean, it's essentially a steroid hormone, but one of its 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 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 going to take more calcium, it's. Unfortunately, it's not going to just end up in your brain and improve cognitive function. Unless, you know, for whatever reason, you were calcium deficient, which is relatively rare. Usually it's other factors, vitamin K status, you know, other things that, that are playing a big role there.

Andy Galpin

Yeah. I mean, what's the RDA for calcium?

Thousand milligrams a day. Like something like that. Right. You don't. Rarely see people or you don't often see.

Tommy Wood

It might be a little like 7 or 800 milligrams. It's not that much.

Andy Galpin

Okay. Maybe you see less than. Yeah. Pretty. I mean, a smidgens of broccoli.

Tommy Wood

Yeah.

Andy Galpin

And it's like some dairy. Like you're. You're probably there if you eat any.

Tommy Wood

Dairy, you'll hit your RDA of calcium.

Andy Galpin

Yeah. You're not going to smash that up there. It also seems to be one of the. The minerals particularly, that doesn't like to be outside of its window.

Tommy Wood

Yeah.

Andy Galpin

In the sense that if you get a little bit high in magnesium, particularly if you are really physically active, that's probably okay.

Tommy Wood

Yeah.

Andy Galpin

In fact, like, oftentimes. That's good.

Tommy Wood

Yeah.

Andy Galpin

You don't want to do that with calcium.

Tommy Wood

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 are regulated.

Andy Galpin

Your heart will stop.

Tommy Wood

Yeah. So you need it to be at a radio.

Andy Galpin

Your brain will stop. Like it's not a good thing. Yeah. Way low, way high. So it's not one. And for those cases, I mean, thinking back over your career, how many times you think you've recommended calcium supplementation based on blood work or things like that?

Tommy Wood

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 cover some other bases as well. So just giving, like, calcium on its own, I don't think I've ever recommended.

Andy Galpin

Yeah. 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 given it, though.

So magnesium, like, ubiquitously.

Tommy Wood

Yeah. Like, everybody hose people down with it.

Andy Galpin

Totally. And. But calcium is probably not one of the ones. So probably not one of the markers we're going to 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.

Tommy Wood

I want to remind them what they are.

Andy Galpin

I am. And then I want to see if we can go for a fourth.

Tommy Wood

Okay.

Andy Galpin

One thing you said was that 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. Okay. That was number one.

Whole Internet will hate me for that, too. The second thing you said was actually that 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 going to be really upset about that. And what you mean by that is general. So 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. That probably could happen.

It's plausible, but most likely you have either a temperature or distortion or metabolic issue or combinations of us there. 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 100% preventable?

Tommy Wood

I've never said 100%.

Andy Galpin

Okay, all right.

Tommy Wood

I would say so. And this really, at this point shouldn't be controversial because again, dusty neurological institutions led by establishment individuals would say the same thing. I would say that the party line is that 45% of dementia is probably preventable. That's from the Lancet Commission run by Gil Livingston and a bunch of experts across the world. It was just updated. It used to be 40%, now it's 45%. They increase the number of risk factors that they included.

I would say it's easily the majority because there are some things that they.

Andy Galpin

Didn'T include.60 plus percent, 70 plus percent.

Tommy Wood

So other estimates, so say Yin Tai Yu, who's at Fudan University and his group have done a ton of modeling and prediction from large population data sets. They think that somewhere between up to 70 something percent of, of dementia is preventable if we were able to address all the different risk factors that contribute to it.

Andy Galpin

Okay, so this is an enormous departure from what the lexicon. 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?

Tommy Wood

Yeah.

Andy Galpin

But dementia, 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 call it even. 40% 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?

Tommy Wood

There are certainly some people out there who, working with individual clinical cases, have said they have seen what they feel is reversal of Alzheimer's disease that I'm still not hard because once you've reached that point of significant atrophy and significant pathology, it's very difficult to restore function and, or, you know, reverse or structurally, you're. Yeah, structurally, but then also to respond to some of the things that we know improve cognitive function. So this is all, this is all.

Andy Galpin

Prevention case studies, maybe things like that, that like in terms of reversal dementia is the same case or just Alzheimer's.

Tommy Wood

Most of this is focused on Alzheimer's. But some people will say, you know, 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, but I wouldn't come here and promise reversal, but I do think prevention, there's massive potential slowing down onset, slowing.

Andy Galpin

Down progression is certainly a thing. We'll talk about that separate. I'll keep you going, I'll bring you back to that. So there's reversing. They're stopping the progression and they're stopping it from happening. So, okay, continue on with the prevention piece.

Tommy Wood

And I think all of this is essentially all of this is connected and the same risk factors apply essentially across the board, regardless of where you're trying to intervene. It probably just gets harder the further you go along. So when they classify them in the Lancet Commission report, they sort of classify them by stages of life. So early life, the most significant modifiable risk factor is education. So the more years of education you have, the lower your risk of later dementia. And then late life, cognitive stimulus also becomes important. And that's been shown again in meta analyses by Professor Yin Tai Yu's group and is incorporated into this Lancet Commission report.

So I think that's a good place to start because it fits with my worldview that stimulus is really important.

Andy Galpin

That's always good. 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 continue on. If you want to read this whole breakdown, that paper will be up so.

Tommy Wood

You can kind of hear, think about this idea. And again, it's sort of driven by that same idea that stimulating like the function of a tissue is directly proportional to the stimulus applied to it. The liver is the same, the immune system is the same, muscles are the same. And so when you look at trajectories of cognitive function across the lifespan and there are Multiple meta analyses. And a lot of this has to be observational. But what you see is that those who have more years of education, they have a higher peak of cognitive function, and that's. You spend more time devoting more resources to enhancing cognitive function.

Andy Galpin

I'm sorry to cut you off for 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. But that's not what you just said. What you just said was you reach a higher peak. I hope people are sinking in on what the heck that means. 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 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 gonna be predicted by what you did between ages 10 to 14. Now, the rate of increase is 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. So I'm just, like, so stunned right now that I knew the increase. Right. I could certainly would have said, hey, would you improve cognitive function?

Like, yes, if you train, but I was not anticipating you would say that. That the height of that peak is gonna be determined by that as well.

Tommy Wood

Yeah.

Andy Galpin

Because you're gonna deal with that. The downside, the rest of your life.

Tommy Wood

Exactly. Yeah. And so, you know, a lot of other things go into that, but you generally see that people like the higher your. 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 gonna be somewhere between 20 and 30 years old. And it generally an individual peak sometimes 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.

Andy Galpin

Longer education across multiple methods of testing cognition, cognitive function. Yeah.

Tommy Wood

And Right. You have to talk about the fact that, you know, different people get access to longer periods of, 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 Lancet Commission report, they said that 5% 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 that occurs in everybody on average. And like, the rate is. Is different and we can, we can change the rate of decline. But if all you did was educate people more early in life, they would have a higher peak, 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 that's, that's how that then happens.

Andy Galpin

We also quickly define age there. Early in age, is that like adolescence?

Is that high school? Is that all of it just kind.

Tommy Wood

Of ubiquitously in terms of what you.

Andy Galpin

Just said, that the higher mortgage we give them early in life.

Tommy Wood

Oh, yeah. So this is just like the traditional education years, right? So, like, you go up, not a specific.

Andy Galpin

Hey, between age 5 and 8 is the most.

Tommy Wood

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, there's sort of a roughly linear relationship.

Andy Galpin

Okay.

Tommy Wood

And then there are several studies that show that late life cognitive engagement or stimulus, and they've measured it with, like, how often you go, like you read books and 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 or a lower risk of dementia. So there was one 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 more early life education, but not a stimulating job and cognitively 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 a lower education early in life with more cognitive stimulation later in life. The lowest risk was obviously those who had both.

But yes, there's a huge amount of benefit you get from that early stimulation through education. But it's not like you're now 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 that suggests that stimulation either through your job or other things will then slow that decline later in life. So you can still do something about it later on.

Andy Galpin

It's so interesting because you're halfway between muscle and bone. Now, such that 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 50, your rate of increase in muscle growth will be the same as if you lifted weights when you were 10 or not or basically like that. So in that case, like earlier development has very little bearing on progression. Like so the rate of increase. That said bone is the opposite. Like whatever you get basically as a kid in large part is going to determine while you're out there.

So you have this halfway house of where muscle is not reliant upon. You know, when you're a kid, bone is almost entirely. And now what you're saying is like brain is a little bit of both. You got 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 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, so no education and low cognitive, demanding job, I have to imagine their rates of Alzheimer's and dementia as well as progression is probably the most aggressive there by an order not, maybe not a magnitude, but some fold.

Tommy Wood

Yeah. So in this paper was published in the BMJ a few years ago, that was your reference group and then everybody else just did better, right?

Andy Galpin

Just 2.0, 2.7. 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 regain much of that by doing something. Just don't use that to have your mind numbing job as we're there.

So it is in either case largely preventable. I think the departure here is early onset Alzheimer's is a different ballgame entirely here. Right. I don't want to spend too much time here. But now you're probably looking at probably opposite, like 70 plus percent is maybe even higher is genetic.

Tommy Wood

Yeah.

Andy Galpin

Bad draw here.

Tommy Wood

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 in the middle of life, a lot of what they're talking, like talking about is body composition, physical activity, 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 related 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, don't retire. Yeah. But no, sensory inputs are like vision and hearing.

Andy Galpin

Yeah.

Tommy Wood

So there's now a pretty good body of evidence suggests that if you have cataracts you have a higher risk of dementia. That dementia, that risk is reversed. If you have cataract surgery, if you have hearing loss like Presby acusis as you get older, you have a higher risk of dementia that is reversed.

Particularly in high risk people. If you get hearing aids. So if you start to lose a sense. Right. And a lot of people just like I'm going to battle through because you know, I don't want to have a hearing aid or whatever, don't do that. You know, if you start to have hearing loss, get a hearing aid because that's going to be associated with a lower risk of hearing dementia. So making sure you're still getting those sensory inputs into the brain remains really critical.

Andy Galpin

So don't lose your sense of smell, don't lose your vision, don't lose your hearing. Probably in the, I'm going to guess 50 to 60 year range. Like if you start getting in that age window and you start seeing precipitous declines in any of those functions and you want to reverse that as quickly as you possibly can because of what you've been saying all day.

Tommy Wood

Yeah.

Andy Galpin

If you can't hear stimuli, doesn't go in there, then that part of your brain presumably dies.

Tommy Wood

It makes perfect sense. Right. You're not using those networks anymore, so they're going to decline, but then everything else they're connected to is going to be affected.

Andy Galpin

I assume the same thing is true with proprioception in terms of balance, things like that.

Tommy Wood

Right.

Andy Galpin

So make sure that you continue to train balance, work on balance. I think this is a pretty easy story to tell for exercise and nature.

Tommy Wood

Yeah.

Andy Galpin

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.

Tommy Wood

Differing light exposures, like the effect of say seeing green spaces on autonomic nervous system regulation or like there's a temperature is different. Yeah. There's a ton of different ways that.

Andy Galpin

Yeah, okay, so I'm on board. There is highly preventable. You said this earlier as well. You talked about exercise a bunch. This was one of the more stunning parts about our earlier conversation when you said and I'm stupefied that I never made this connection. I've said this a thousand times, plus thousands of times, and 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 promise we would. I wanted to come back to this. So here we are, coming back to it. It's 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 aspects of the.

What areas of the brain physically are improved by exercise? Does it determine or does it depend on the type of exercise? Is strength training different? Do we know any details about the exercise? Is it a certain amount of sets or reps or styles?

Like, what do we know? So what do I do? And how does it actually help? And then the last part about that is, is there a law of, hey, I didn't start soon enough, so now it's too late. Right. So give me the jazz on how lifting weights makes my brain. What do you call it, like, bigger.

Bigger muscles, bigger brains. More.

Tommy Wood

Bigger. More brainiac.

Andy Galpin

More, bigger. More brainia. There you go. I've heard you say that before.

Tommy Wood

So a good place to start is the first ever study, I think, that was done, that showed that you could increase the size of a certain part of the brain in humans was with an exercise intervention. It was published in 2011.

Andy Galpin

Exercise for the win. I'm telling you, folks, exercise scientists run science. You just don't like to admit it.

Tommy Wood

So this is published in PNAS in 2011, and what they did is.

Andy Galpin

Oh, that recent.

Tommy Wood

Yeah.

Andy Galpin

Oh, wow.

Tommy Wood

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 there was some neurogenesis, particularly the dentate gyrus of the 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. Before.

Andy Galpin

Yeah. Hard. Hard to do in humans.

Tommy Wood

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 brain 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 a year. That's it. Brisk walking.

And that was enough to significantly improve or increase the size of the hippocampus.

Andy Galpin

These are non exercisers.

Tommy Wood

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 three times a week for a year. The 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 factor. So in a sedentary population, we know we can see improvements in the structure of the brain 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 intensity piece. So there was a very recent study that looked at different levels of intensity of exercise, aerobic exercise again, and structure and function of, of hippocamp.

Of the hippocampus. So again, so now we're thinking about memory related tests. And they found the greatest benefit in individuals doing a high intensity exercise training. And it was essentially the Norwegian 4x4 Pro, like four minutes at, you know, 75 to 80% max, like VO2 max 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 improvements in cognitive function they think related to that area of the brain. So some aerobic activity of any kind in people who are sedentary, if it improves 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 in that study. They're generating a ton of lactate. Right. Whereas they weren't in that original walking study. Right. So that could be, that could be one, one way of the win again.

So 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, the hippocampus is really important there. If we're thinking about the amount that you have to do, it's essentially going to be two or three times a week, some kind of activity that is improving your cardiovascular fitness wherever you've started from, but probably at least once a week doing something that's very intense, right, Some kind of, some kind of sprint type or high, 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 of the brain.

So resistance exercise seems to primarily benefit the white matter, which kind of sits between the cortex and the deep brain. And right, that's where you have your myelated axons, your fast connections like that, the hyperspeed zone. The hyperspeed zone is the transfer of information from the brain to the body and throughout the brain. And 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 matter or prevention of decline of the structure of the white matter. And then that's also associated with improvements in cognitive function, particularly with resistance training, executive function function. So like prefrontal cortex function.

So different areas of the brain affected by different types of exercise, which are then associated with different improvements in cognitive function. The minimum effective dose for like sustained improvement seems to be two sessions a week, like super standard six to eight exercises covering the whole body for three sets of eight to 12 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 cognitive function. So those are kind of the different ways that those different exercises kind of come together. Then you get more of like a glow if you do both. Hopefully some kind of global improvement in cognitive function.

Andy Galpin

So it has 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, 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, a couple sets each, that'd be two days a week, one day a week, do something that is closer to, let's just even say the Norwegian four by four.

Tommy Wood

That's a great option. Yeah.

Andy Galpin

Four minutes of the highest amount of work. People get mad when you describe this as four Minutes of max effort or all out.

Tommy Wood

Yeah.

Andy Galpin

You can't go all out for four minutes. But 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. You don't have to do the four. You could probably do just about any type.

Tommy Wood

Yeah.

Andy Galpin

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.

Tommy Wood

I think they were doing it three times a week.

Andy Galpin

Okay.

Tommy Wood

But if you're doing other aerobic exercise and, 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.

Andy Galpin

That's pretty damn hard. Especially for six months extended periods of time.

Tommy Wood

Yeah.

Andy Galpin

Yeah. I'm gonna say realistically, as an exercise scientist, I'll give you permission to cut that to two.

Tommy Wood

Yeah.

Andy Galpin

Per week. And then maybe one to two or three sessions a week of the more lower intensity standard endurance exercise cardio. Whether this is even physical activity. Walking.

Tommy Wood

Yeah.

Andy Galpin

Or would they actually need to do more like 50, 60% heart rate for that kind of cardiovascular adaptation?

Tommy Wood

So, you know, this is, that, this is the, the age old question is like, it, like what's the exact intensity required to see a specific adaptation? I think that.

And it's the same. We did a podcast Talking about the 4x4 on your podcast on my podcast. And then somebody was like, well, what if I can't maintain my heart rate in that zone for that long? 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, I think it's the same thing.

Andy Galpin

Yeah.

Tommy Wood

Like if it's a, if it's a casual stroll, you're probably not getting adaptation. But you know, equally, if a brisk walk is hard work for you. Right. Then that's going to be, that's going to be a good, good place to be.

Andy Galpin

Yeah. This one riles me up so much because I get it, people want like specific numbers, but I'm so resistant to do that because it doesn't actually matter usually.

Tommy Wood

Yeah.

Andy Galpin

It's a, it's a rough concept of where you're at. So if those numbers help you, great. But something like that. Here's the reality. Don't think that your brain all of a sudden won't adapt.

Tommy Wood

Yeah.

Andy Galpin

If you do half that.

Tommy Wood

Yeah.

Andy Galpin

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. 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. Like, get there eventually and you'll probably get much of the benefit, which is great.

This actually answers a big question that I have dealt with a lot. You and I actually have a paper together again, that you led, where we found physical strength predicted, I think it was 5% of cognitive function. Right. And I'll say that again, physical strength predicted 5% 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 the common claim here is like, oh, grip strength is just a proxy for overall health.

And certainly true. If you look at research on folks that have dementia, you'll see, I think actually one paper found, I can't even think it was UK Biobank paper, about a half a million people in it found that. I think 30% of Alzheimer's death was explained by low grip strength. Yeah, Right.

Not a small number.

Tommy Wood

And there's a recent study showing that frailty precedes Alzheimer's by several years on average.

Andy Galpin

Multiple years, I imagine.

Tommy Wood

Right. And if you're frail, you're not doing all the things that we know continue to stimulate or support brain function. Right.

Andy Galpin

So what I want you to kill, and perhaps this is a fifth thing that'll irritate the Internet that we're going to call it, is the idea that this stuff, the grip strength, leg strength, is exclusively an, indirect or a correlation. Right. Of course, there's some folks who are struggling with dementia are probably also then going to struggle with movement. And there'll be a backwards direction. Right. There'd be a causation, but it would kind of be backwards causation. Right. So end this horrible idea that strength is only a correlation to brain health.

And you just actually kind of answered the question before, which is like, how is it actually causal? 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.

Tommy Wood

Technically, people are right. A lot of this comes from epidemiological research. Correlation isn't causation. 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 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 session a week. Right. So you don't. These effects, particularly if people aren't doing much exercise, are essentially linear and like.

Andy Galpin

So if you could ask for a more causal function and structure benefit and in a dose response.

Tommy Wood

Yeah. So what else do we need?

That essentially says it's causal. Right?

Andy Galpin

Yeah.

Tommy Wood

And people are. So depending on the type of research, of course people are. Right. You can't tell.

You can't tell. Causation. However, what people also don't necessarily understand is that in a perfect epidemiological study, if you could account for every confounder and 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 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.

Andy Galpin

I'll count that as like 4.5 thing that the Internet's gonna get mad at. Yeah. You don't think people understand basic statistics with that?

Tommy Wood

So. Right. People have worse physical health.

Right, we know. So in the study that we did, if you had higher blood blood sugar, high HbA1c, you had lower strength. But I think that's also bi directional. Right. More insulin resistance, that's going to worsen muscular function. But if we think about the potential mechanisms by which this happens, if you're doing things that improve strength, that's 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 are two of the best ways to improve glucose handling and energetic handling more broadly. And then the final piece is that when you contract your muscles, you release a whole bunch of stuff, right? Your muscles are organs. So lactate, bdnf mot C, irisin, lac fee like pick your metabolites, cytokines, extra kinds, like whatever, like whatever it is.

Like pick your favorite metabolite du jour. 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 yes, 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 who you are, there is four or five, if not more different mechanisms that would directly relate to improvements in cognitive function and brain health.

Andy Galpin

I hope that ends the conversation. I'm going to 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. And so the same neurological system that makes you squeeze your hand together, it starts in your brain, keeps alive. 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 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, the astrocytes and the nervous system side.

Tommy Wood

Yes. So I think all of those play an important role. For instance, we know that as we age, things like changes 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 trajectory follows more closely and that's going to be related to, um, so, so the white mass trajectory is gonna be related to things like metabolic health for the, for the reasons we talked about. 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 required to move weight. In that way, I think you're directly stimulating some of those pathways.

So pathways related to like motor pathways associated 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. 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 resistance training. But we do see region specific effects. So it's probably there's like some coupling of what's going on, like a specific stimulus plus the sort of the hormonal milieu or the myokines and things that are released.

And I think it's 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 it's.

Andy Galpin

Squats is easy, but.

Tommy Wood

Yeah. Or because they. They have like, they do.

Like they do weighted. Weighted wheels. Right. So it's kind of like a. A weighted Jacob's Ladder kind of thing is what they do for resistance training in rats. But I think it's some combination of those things.

Andy Galpin

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.

Tommy Wood

Yeah.

Andy Galpin

There's another thing that people have 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 stimuli to grow. You can simply change energetics and stimulate muscle growth, skeletal muscle growth. I can't see why you couldn't do that in the brain.

It's the same thing. It doesn't require a stretch and a damage.

Tommy Wood

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 neuroplasticity. It drives autophagy. It drives all these other regulatory processes that we know are involved in aging and reversing those. And so anything you can do locally and muscle improve increasing energetic flux through aerobic exercise.

And then the same 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 processes occur.

Andy Galpin

Is that why you think those different modes of exercise produce different actual brain adaptations?

Tommy Wood

I think that's part of it, yeah. Sort of. But all of those things seem to you know, dissecting those exact pathways hasn't been done. But it, if you think about, well, you get, you get lacked. You know, you do a heavy set of leg press, you release a ton of lactate. Right. 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 combination of multiple things sort of coming together.

Andy Galpin

All right, fascinating. We're going to press the button on more things you're going to irritate the world about. I don't need the full dive here. Give me the, the what we used to say in the 90s and 2000, 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, tldr, tldr.

Tommy Wood

Well, nobody reads anymore.

Andy Galpin

Right. You mentioned tau and amyloids. And for folks that don't know this story, these for many years have been surrogates or markers of, would you say brain aging, brain damage or.

Tommy Wood

Yeah, sort of the brain pathology that then leads to Alzheimer's disease.

Andy Galpin

Right. And then recently some information came out that 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 was some controversy. And so I've seen reactions that are on one side of the equation of like, okay, he just used a couple of pictures in grants. Scientists do this all the time. He didn't fake data.

He just kind of 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 big a deal all the way to reactions on the other side of the equation, which is, okay, 30 years of research in this area is all thrown out.

Tommy Wood

Now.

Andy Galpin

If you feel like you can't answer this quickly, then that's okay, feel free to pass. But where at do we know should people still be worried about this approach? Because you can test it. People pay to get it tested. How much should we worry about tau in relation to brain health?

Tommy Wood

Yes. So this is a, it's a long question to answer because essentially it starts with Alois Alzheimer and his mentor Emil Kraepelin in Germany in the beginning of the 20th century. However, 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 amyloid cascade hypothesis. Amyloid precursor protein is Produced in the brain. Normally it's really important for neuroplasticity. A whole bunch of things. If you got rid of APP and amyloid entirely, basically the brain doesn't function at all.

But there's one sort of this precursor protein gets. Can get cut in different ways by these secretases. One version of that accumulates to create these sort of waxy amyloid plaques. When that happens, that then stimulates the production of tau. So tau is normally part of the microtubule cytoskeleton of neurons. Like really important for directing axons and where they go and how they connect. And it sort of dissociates from that becomes phosphorylated and accumulates and then that.

Andy Galpin

Damages buildup of tau is generally associated as a bad thing.

Tommy Wood

Yeah. And then that sort of damages neurons and that's a associated with loss of.

Andy Galpin

You could pick your poison here. If you look at sleep, you will see basically an inverse relationship with sleep efficiency or sleep quality and tau buildup. Like you could pick this in any realm of there and it'd be hard to ignore all of those papers.

Tommy Wood

So 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. And we know that tau accumulates after head trauma, but there are other effects that head trauma has beyond its effect on tau.

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 a huge amount of benefit in people if we don't focus on the other things that are going on at the same time. So I think there's an even though. And so there's been some studies with amyloid where a similar problem, some issues with the data, maybe some of it was duplicated or fabricated.

I think there's enough evidence to suggest this is playing a role. I just think the role is probably smaller than we've kind of assumed it to have.

Andy Galpin

Yeah, I Mean, I'll say that for you, because I'm not in this field. You may have to save face a little bit. But I can only speak this from my area of science. And I've seen this game play out where 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.

Tommy Wood

Yeah.

Andy Galpin

On one particular thing. And this is by my read of the situation from the outside. And 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 I think that's somewhere in the neighborhood of a fair criticism.

Tommy Wood

If people are interested in this history, they should read the book how not to Study a Disease by Karl Harrop, 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. They essentially said that Alzheimer's and amyloid were synonymous through a few different position papers over time. And so then it came to the point where if you wanted to study Alzheimer's disease, you had to. Had to study amyloid. That doesn't mean that amyloid doesn't play a role. It just means that they kind of purposefully ignored a lot of other research of important things that are taking part in the process.

Andy Galpin

Man, just beyond frustrating. Yeah, just the. Whatever. Okay, well, we'll save our piece on that. I've got a handful of really quick questions just to finish us off here. But before we do that really fast recap, you've irritated the world on at least five points and gave us a lot of light on if you want to 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.

Search for novelty and probably vision and hearing and brain training 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 may be, if you are having some sort of deficit. Brain fog, we'll call it, and you called it some other technical. Or I'm going to 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 stressor or sleep or alcohol. Like some other micronutrient deficiency is most likely at play there. Right. That's the most likely explanation or inflammatory from long Covid. Like some of the process like that 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.

And then that things that like marijuana and psychedelics not to dwell on them. We spent very little time on those. We could probably discuss that further. But perception is not necessarily the same as subjective in terms of cognitive function. And I forgot the other ones you irritated people with, but we covered many of them. So lastly, really fast, because you covered a lot of areas. I tried to do my best to ask kind of the quick questions along the way, but I surely missed plenty.

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?

Tommy Wood

The best place is probably. So I have a podcast, the Better Brain fitness podcast. Josh Turknet, who's a neurologist, is my co host.

Andy Galpin

Neuroscientist and a neurologist working together.

Tommy Wood

And then we can come at it from those relative points. And so if it's more clinical, he'll cover it. If it's more know, basic science or statistical or something, then I'll come from. I'll. I'll cover it.

Andy Galpin

That's a weekly show or every other week or something like that. Yeah. And so on YouTube and all the normal places.

Tommy Wood

All the normal places . And so you can . It's a question and answer style show . So you submit a question and then we'll answer it one question every episode . And so that's nice because if you have a question, somebody else probably has that same question . And then other people always . Yeah . Can benefit from it . And then equally you can my Instagram @ Dr . Tommy Wood, you can . You can DM me, but I might direct you towards the podcast because then don't DM him .

Andy Galpin

Just go to the podcast first. But you also have your substack as well.

Tommy Wood

Yeah.

Andy Galpin

Which is a. I love this format, by the way.

Tommy Wood

Yeah. So it's free. It's free. Free substack. Better bearing fitness substack. When you sign up when you put in your email, you get emailed a PDF which covers all the nutrients and blood tests that we would recommend just like basics for. For people who are worried about long term cognitive function.

So all the stuff we talked about.

Andy Galpin

Today, but they can get that direct.

Tommy Wood

PDF to them that would be emailed directly to you. And then like every time, like we have a news article or a podcast or whatever that. That comes through the substack.

Andy Galpin

Okay. And there is an option to pay there. They don't have to though.

Tommy Wood

No.

Andy Galpin

But if they do pay, then they can get access to additional questions one on one. Like, is that how it works?

Tommy Wood

Yeah. So we have. There is a.

And 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. We've just started doing some ama, so you can join us on a zoom call and just ask us where we.

Andy Galpin

Literally live in person.

Tommy Wood

Live in person.

Andy Galpin

Wow. Craziness. Yeah. I don't know how you do that. You're wild, man. And if they want to come visit your lab at the University of Washington and get their brain tested, is that.

Is that an option? Yeah.

Tommy Wood

Tbd. TBD coming soon.

Andy Galpin

Little spoiler friends there. So not yet. Okay. You've been in incredibly gracious with your time and expertise, man. Really appreciate. It's always fun hanging out. Bummer. We didn't get to lift weights this time, but perhaps next time.

The last thing I want to ask you here, and 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.

Tommy Wood

I think just because 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 know that it's possible. And then I would focus on the importance of cognitive stimulus. And the reason for that is other aspects supposedly of what's going to happen in that movement are going to 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, my primary directive. And as part of that, I might dramatically decrease funding for mouse studies in Alzheimer's disease, because I don't think that's.

Andy Galpin

Gotten us anywhere interesting. And this is from someone who does animal research in your life.

Tommy Wood

I do that for my job. Yeah. And a lot of what we do does not relate to humans at all. Or doesn't end up relating to humans at all.

Andy Galpin

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 on the thing. So thank you so much, man.

Appreciate you being here.

Tommy Wood

Thank you so much for having me. This has been really great.

Andy Galpin

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 and you want to help ensure this information remains free and accessible to anyone in the world, there are a few ways that you can support.

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