257 ‒ Cognitive decline, neurodegeneration, and head injuries: mitigation and prevention strategies

1. 0:00 – 0:08

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to "The Drive" podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:08 – 3:27

   Tommy’s professional work, unique skill sets, and interests

   1. PAPeter Attia0:10

      Hey, Tommy. Good to see you again. Uh, it's been, gosh, about six months since I last saw you at, uh, at COTA, which of course will become ... We'll, we'll talk something about why you and I would run into each other at COTA given our mutual interest in Formula 1. Um, but, uh, there might be some people listening to this who aren't familiar with you or your work, though, though it's certainly been referenced and you've been on a number of podcasts. So, um, you know, you're ... Well, why don't you give us a little bit of your background, and we'll, uh, [laughs] we'll, we'll, we'll kinda go from there.

   2. TWTommy Wood0:38

      Sure. I, I do have a, a varied, um, experience and, and background, which I think is, is useful for the bunch of things that, that I do, but also sometimes slightly confusing because people will know me from one arena but not know the work that I do, uh, elsewhere. Um, so I, I'm an Assistant Professor of Pediatrics, uh, and Neuroscience at the University of Washington in Seattle. Um, the majority of my work there is in basic, uh, animal preclinical research in brain injury. Uh, we look at ways to treat the injured, uh, newborn and pediatric brain, and we also, uh, do some work in traumatic brain injury. Um, but sort of before I got to that point, um, I trained as, uh, as a medical doctor in the UK. Uh, I worked as a doctor in central London for a couple of years before I did my PhD in Physiology and Neuroscience. Um, so though I'm not, um, a sort of reg- a registered medical doctor currently, I don't have an active medical license, um, I do have med- do have medical training, and that sort of helps inform a lot of the work that I do. Um, alongside that sort of formal training pathway, I spent a lot of time working with athletes. I was an athlete myself, um, as a student. Um, I spent some time coaching, uh, athletes, particularly rowers, and, uh, that was my main, my main sport. Um, and then later on during my PhD and when I was doing my postdoctoral work, I worked with a company that, that worked with athletes, um, trying to improve, uh, performance or, or their overall health and their longevity in sport. That was probably the, the main thing that, that we really saw a lot of people wanting to, to focus on. Um, so I have this kind of track along the side where I've, I've worked, uh, with athletes in various ways and then sort of through that got to working with Formula 1 drivers in particular through a company called Hinsa. I know you've had our, our good mutual friend Luke Bennett on the, on the podcast before. Um, so that's kind of where, where I do some, some additional work is, is, uh, in athletic performance and health. Um, and in addition to that, uh, also have some interest in long-term cognitive function, so we look at how the brain responds to injury. We look at how to, uh, repair that or mitigate, uh, injury processes, but what I'm really interested in is how do all these things kind of tie together, so how do aspects around lifestyle and the environment affect how your brain functions throughout your entire lifespan. Um, and so I work with, uh, some dementia charities in the UK, uh, related to that, and I'm also a founding, uh, director of the British Society of Lifestyle Medicine, so particularly interested in how, you know, we can use lifestyle to im- improve population health.

   3. PAPeter Attia3:18

      Thanks, Tommy. That's, that makes a ton of sense hopefully for people now to understand the, the varied nature of your, your, both your skill set and your interests. So, um,

3. 3:27 – 19:58

   Age-related decline in cognitive function and memory

   1. PAPeter Attia3:27

      let's just, let's just start by diving into cognitive decline, and is it ... And, and I defer to you, Tommy, of how you wanna do this. Would you like to do this starting with the pathologic cognitive decline vis-a-vis dementia, or do you prefer to talk about it through the, uh, the sort of more ubiquitous age-related cognitive decline?

   2. TWTommy Wood3:46

      So we can start with age-related, uh, cognitive decline because that's pretty well described. So if you look across large population sets, uh, you'll see that with increasing age you see a pretty linear decrease in standardized cognitive function, and that's across all the different types of way that, that you can measure cognitive function, aspects of executive function, working memory, um, and except for one type of cognitive function, which is historical memory. Uh, and that's probably because of the way that those memories are encoded. They're sort of moved from the main, um, memory, uh, storing machinery to ... and they're kind of spread throughout the cortex, and they're sort of protected from some of the, um, changes that happen as we get older. But in general, you just see this steady decrease in cognitive function as people, uh, get older. If you then transla- translate that to what we might call some kind of pathological cognitive decline, which would then lead into frank dementia, which is, um, sort of, uh, a long-term loss of significant, uh, cognitive capacity or, you know, cognitive dysfunction, then you might see an accelerated trajectory. So there's some period of what we call mild cognitive imp- impairment, which you can, uh, diagnose with some standardized cognitive tests, and then eventually that will continue into, uh, frank dementia, which there are many subtypes. But the one that probably people are most familiar with and are most concerned about for themselves is Alzheimer's disease or Alzheimer's dementia. Um, and there are probably multiple things that, um, drive both of those paths, but in some individuals there's th- this accelerated decline that then ends up in, in then having the diagnosis of dementia.

   3. PAPeter Attia5:37

      Tommy, let's go back to the beginning of that and just make sure that we've given people a real sense of what cognition actually is. You know, one of the most common things I hear from my patients is some sort of complaint around memory Uh, so just yesterday I was talking to a patient and he was lamenting the fact that-- Not lamenting the fact, I mean, he, he noted the fact that he had been recently remarried. He was very happy about that. But said, you know, one of the unintended consequences of getting remarried is he just inherited like 100 new people in his life, right?

   4. TWTommy Wood6:12

      [laughs]

   5. PAPeter Attia6:13

      Because all of the folks who, you know, were his wife's side of the family and her friends and stuff are now kind of a part of his life and he said, um, "I can't remember their names. It's the-

   6. TWTommy Wood6:23

      Mm-hmm

   7. PAPeter Attia6:23

      ... the ability with which I can meet a person, remember their name is decidedly different from when I was 20 years younger." So he's in his late 50s contrasting this with being in his late 30s. So obviously that's one component of cognition. It, it, by the way, is hands down the one I hear people most complain about. I don't hear many people complain about decreased executive function-

   8. TWTommy Wood6:46

      Mm

   9. PAPeter Attia6:46

      ... decreased processing speed. I, I would suspect it's 'cause maybe most people aren't pushing those to their limits and/or we don't have as readily available tools to internally discern, um, decreases in that. But, but can you just-

   10. TWTommy Wood7:02

       Mm

   11. PAPeter Attia7:02

       ... expand more broadly on overall this, both the depths of cognition and, and what it entails, but also this phenomenon that I'm sure y- the moment someone hears what you do for a living, they're probably-

   12. TWTommy Wood7:12

       [laughs]

   13. PAPeter Attia7:13

       ... right up to you at a party giving you the same complaints.

   14. TWTommy Wood7:17

       Uh, a- absolutely. And the-- it's very difficult actually. You know, so you can, um, define, you know, these domains of cognitive function. You've essentially already defined them, executive function, which is, um, usually around complex decision-making. But you might, for the average person, it might be, you know that time when you think about saying something but then you realize it's a bad idea to say it, right? That's executive function. That's the, your, your prefrontal cortex is jumping in and saying, "You know, that's a really bad idea," you know, even if it sort of flashes through your mind. Um, but then you have, you know, various aspects of, uh, short-term and long-term memory, um, processing speed, uh, reaction time is pr- is probably, um, important as well. Um, however, when you talk to individuals about, uh, cognitive function, they obvious- they have their own, um, things that they want to be good at, right? So it's very personal from an individual. Yes, we can, we can put, do, use a standardized battery of tests, and that's what's done, uh, clinically. Um, but there's usually some aspect of function that they notice is declining over time or that they want to be better at and then they can, they can sort of put focused attention into improving that and I believe that you can improve that pretty much any stage, uh, of life. So that's part of it. And you mentioned memory and of course this is, uh, something that, that people will mention the most or w- and will notice in themselves. Uh, but there's actually two different parts to memory and it's, it's different probably in, in most people even in the setting of sort of standard age-related cognitive decline and in those who have, you know, some kind of pathological cognitive decline. The first part of memory is encoding that memory in the first place, right? The information comes in and your brain, you know, signals through acetylcholine a- and other neurotransmitters to actually say, "This is something that we want to recognize and store." And that's the process that seems to be particularly lost in those with pathological cognitive decline. Uh, that's why things like cholinesterase inhibitors were, um, or w- you know, and are still used in, in Alzheimer's disease because that helps to bolster some of those encoding, uh, processes b- through acetylcholine signaling.

   15. PAPeter Attia9:33

       And, and this takes place pr- predominantly in the hippocampus?

   16. TWTommy Wood9:37

       Yes. Well, uh, that's where a lot of the process starts.

   17. PAPeter Attia9:40

       Okay.

   18. TWTommy Wood9:40

       Um, but over time, you know, you can get, you get, uh, consolidation and these m- memories get, may get moved around. Like particularly, like we talked about historical memory, they get shifted throughout the neocortex which is basically the rest of the, the outside, uh, uh, of the brain. The, the other aspect is retrieval, right? There's information in there and it's getting it out. Um, and retrieval is, you know, retrieval speed is something that seems to slow down with age. Um, but part of it, you know, often we think of this as, as pathological. Part of it may be that over time you just accumulate more information and the more information that's in your hard drive, the harder it is or the longer it takes to, to bring out a certain piece of information.

   19. PAPeter Attia10:22

       Yeah, this is sort of the argument that Arthur Brooks used that as we're aging it's, um, your, as you add memories you're, you're creating volumes in a library and-

   20. TWTommy Wood10:30

       Yeah

   21. PAPeter Attia10:30

       ... the more volumes in the library the longer it takes the librarian to go and get the specific reference they're looking for. Um, how do, how can we figure out the relative contribution of library size versus librarian speed-

   22. TWTommy Wood10:45

       [laughs]

   23. PAPeter Attia10:45

       ... when it comes to, uh, you know, accessing these memories because, um, I guess this is another maybe way to think about that but the example that resonates for me personally is I either meet somebody and can't remember their name but five minutes later I can or I want to-- I have an idea, I want to sort of say something about it and at the last minute I can't remember but then 10 minutes later I kind of remember. So, so it's not that it's not there but boy it took me a long time to get it.

   24. TWTommy Wood11:20

       So I think in reality it's probably very difficult to parse all of these out, um, and so I don't think we can pretend that, that we know exactly the relative contributions. However, some of this is certainly affected by other factors and that's something that you can, um, take into discussion with say individual patients or, or individuals who are concerned about their memory. So it seems like, um, sleep impairment or some kind of s- uh, sleep deprivation or, you know, suboptimal sleep impairs retrieval So, you know, then that could maybe open up a discussion about sleep. Um, there's some, uh, subjective stress seems to also play a role here. So I think some of it is accepting that your library, uh, is larger, and some of it is thinking about other factors that may be, um, impairing or, or, you know, allowing for that process to be suboptimal such that retrieval, um, i- is harder. Um, an- another part that comes into play here, which is, is also important and it, and it, it falls into that same line of thinking, is that as your library gets bigger, your librarian becomes more selective in terms of the things that they want to actually put on a bookshelf. So imagine as you've met hundreds of people in your life, thousands of people, you add 100 new people, um, it's very easy to say, "Do you know what? The first time I meet this person, I may never see them again."

   25. PAPeter Attia12:51

       [laughs]

   26. TWTommy Wood12:51

       So maybe it's not actually worth encoding that memory, and you become more selective in what actually gets stored. So that may be part of it, uh, as well. And these are not necessarily pathological processes. These may be your brain doing its normal job of, "Well, how do I figure out what's worth storing? And then how do I retrieve what I've decided to store?"

   27. PAPeter Attia13:09

       This may be a question that goes beyond your level of expertise, so I apologize if I'm asking you something outside of the scope. But, um, I guess what is a memory physically -

   28. TWTommy Wood13:19

       [laughs]

   29. PAPeter Attia13:19

       ... and why is there a finite amount of storage? So if I, if I, uh, I have an understanding of why a hard drive is finite, and if I only have two terabri- terabytes on a hard drive and I keep adding, you know, video to that, eventually at some point there is no more storage capacity. I don't think I have enough of an, an understanding of what a memory is and why it would therefore have a physical constraint.

   30. TWTommy Wood13:45

       So there have been ... And I will, uh, absolutely agree with you, this is, this is beyond my area of specific expertise. Um, but, uh, I know that this is a topic that is hotly debated where, uh, some people have said that comparing human memory to a hard drive is, you know, e- essentially it's a complete fallacy. It's nothing, it's nothing like that. Um, and so there's, you know, y- we, we use it because it's something that we can understand. It helps us, you know, sort of apply a very complex, uh, process to our own thinking and understanding of how our brains might work. But in reality, that is not how, how memories work, and there shouldn't be a limit on capacity in the same way that there is with a physical hard drive. Um, however, you might still understand that, uh, there are, uh, probably still a finite number of things that your brain will choose to, um, to encode and store for the, for the same reasons that it, it may ... You know, you, you only want to have the information that's, that's probably maximally useful for your survival, for want of a better way, uh, to, to, to think about it. And then, you know, that, that puts some, some constraints on, on how the system sets up what it decides to, to store and then retrieve.
4. 19:58 – 32:57

   Improving brain function with the right level and type of demand

   1. PAPeter Attia19:58

      So of all the things you said there, I think the one that we're, we're kind of gonna click on first, I guess, would be this idea of, uh, demand-

   2. TWTommy Wood20:07

      Yeah

   3. PAPeter Attia20:07

      ... and what we ask of the system. So in, in certain areas, as you point out, it's, it's pretty intuitive, right? Um, you cannot maintain muscle mass without putting the muscles under significant demand that is so strenuous that you wouldn't be able to maintain it indefinitely, right? You wouldn't-

   4. TWTommy Wood20:27

      Yeah

   5. PAPeter Attia20:27

      ... you know, if I look at the workout I did this morning, I wouldn't be able to do that to my muscles or to my heart indefinitely. You can do it for a few hours, but as you point out, if, if it, if for nothing else through sleep, but even more than that, there are just days when you wouldn't push that hard. Um-

   6. TWTommy Wood20:43

      Mm-hmm

   7. PAPeter Attia20:44

      ... and so, so in, in other words, it, you sort of think of exercise as a hormetic stress.

   8. TWTommy Wood20:50

      Yeah.

   9. PAPeter Attia20:50

      Um, now I haven't thought about it this way, but, but there are certain organs for which I, I would guess that that's not true, right? I mean, does the liver need to be stressed? Like do the hepatocytes need to feel the insult of ethanol to otherwise perform well? I, I, I guess I haven't thought about it through the lens of kidneys and, uh, and, and the liver and stuff. What, what do we know about other organs and their need to do what, say, the heart does or skeletal muscle does?

   10. TWTommy Wood21:17

       So I've, I've thought about the liver-

   11. PAPeter Attia21:18

       Mm

   12. TWTommy Wood21:18

       ... um, in particular, and I think you can s- you can say that the, the, the case holds particularly with, with, uh, alcohol exposure as, as a, as, as the example. That's what, what you said, and that's what I think of as well. Not that, um, the liver doesn't function without alcohol exposure, but if you, if it wants to, um, optimally deal with a certain type of, um, uh, product, say ethanol, it wants to metabolize it, then we know that with chronic alcohol exposure before we get to the point where the, the, you know, we, we damage the liver, um, you see an upregulation in cytochrome P450 2E1. You see an upregulation in aldehyde dehydrogenase. You see an upregulation of, uh, mitochondrial, uh, function and metabolism to regenerate NAD, which is sort of like the rate limiting step for alcohol detoxification. So yes, if you stress the liver with alcohol, it will upregulate its function in order to have a greater capacity when the next, um, you know, the, the, the next drinking session occurs. So I think there are-

   13. PAPeter Attia22:23

       Mm

   14. TWTommy Wood22:23

       ... um, sort of parallels across multiple organ systems.

   15. PAPeter Attia22:26

       Yeah. And just make sure listeners aren't hearing this and thinking, "Oh, he's telling us to drink more, to drink more." No, I think what you're saying is, uh, and we would all agree that the health benefits of alcohol are none. But you're saying-

   16. TWTommy Wood22:37

       Yes

   17. PAPeter Attia22:37

       ... before you get to destroying your liver with alcohol irreversibly vis-a-vis cirrhosis, if your goal is to be able to drink two drinks a day, you have to drink daily. Like you, you're gonna, you're gonna have a better job tolerating two drinks if you occasionally have a drink as opposed to if you never have a drink. I mean, that's sort of what you're basically saying.

   18. TWTommy Wood23:00

       Yeah. That, that's right. And so if you want your, your... If you want an organ system to function in a specific way, so you want your brain to function, uh, improve its function in a, in a, a sp- specific domain, or you want your body to func- you know, your skeletal muscle or your cardiovascular system to function better in a specific domain. You wanna train for a marathon, or you want to be a competitive powerlifter, right? You apply, um, a relevant stressor that's, like you said, it's hormetic, and you r- give time to recover and adapt to it, and then you get an increased capacity later. And so I think that that's very relevant for the brain. Uh, but I might use, um, exercise as, as a way for people to better understand it 'cause you can kind of see that happening. But then to kind of draw that analogy out, um, you might say, "Okay, there are o- other sort, other organ sy- or other organ systems where there's evidence that that's, that's the case as well."

   19. PAPeter Attia23:54

       So let's go back to the brain and talk about what might be a difference between kind of a positive versus a negative demand. So, um- I'm sure most people listening to this podcast right now are under some cognitive demand. We're-

   20. TWTommy Wood24:09

       [laughs]

   21. PAPeter Attia24:09

       You know, we're, we're not just sitting here idly shooting the breeze. We're, we're talking about stuff that for, for most of us requires some thought, some concentration-

   22. TWTommy Wood24:17

       Mm-hmm

   23. PAPeter Attia24:17

       ... to pay attention to this. So, uh, you know, is listening to this podcast for, for different people producing different levels of cognitive demand, for example, depending on their level of familiarity with the subject?

   24. TWTommy Wood24:31

       Yes. Um, a- a- absolutely. And again, I think that the idea of cognitive demand is relative to the individual as well as what they want their, their brain to, to function best at. Um, however, when we think about cognitive demand, I think there's, there's multiple different ways that you can come at it. So when I think about generating skills, um, or maybe just brain development more broadly to start with, you know, you might think about how does, uh, a toddler interact with their environment such that they're developing motor skills, language skills, social skills. And it's often this, you know, concerted effort for a short period of time where you are right at the limit of your current capacity, being able to stand, being able to walk, being able to climb a tree, being able to pronounce a certain word. And then, um, you know, you know, maybe you could put, put a timeframe on it. Maybe it's somewhere between, you know, 20 or 30 minutes, something like that. You know, co- you know, adults may be able to do this for longer. Um, right at the ed- edge of your skill set, and then, you know, probably there's some failure in there because the process of failure m- sort of up regulates our, the, the processes of focus and, and attention as well, up to a point before we get frustrated. Uh, and then there's some rest and recovery. Your toddler is gonna sleep a bunch after they spent, uh, a lot of time exploring the environment, trying to improve their, their s- their motor skills. And I think that kind of provides an idea of the type of focused attention, um, that you put into something that then drives plastic reorganization, which is what we care about. We want to try and drive an increase in functional capacity in some domain, uh, of cognitive function, and so it's probably going to be something that, that looks like that. Um, and there are benefits to continually doing things at the level of your current, uh, capacity, right? If you're an athlete, you're not always pushing the boundaries. You're, you know, you're not always doing a redline session that, that drives a bunch of a- adaptation. So, and, and I think the, the brain is similar. Um, but that's very different from how most adults perform in their day-to-day work, where, yes, it's very ... It feels cognitively demanding, but you're multitasking, task switching, so you're never providing focused attention on a specific subject. Um, and you're also not really providing that sort of stimulus to increase skill in a specific area necessarily. Um, so even though so- even though you feel busy, even though something feels cognitively de- demanding, I don't think that those, um, stimuli are the same in terms of what's, what's driving, um, you know, a s- a, a, a functional change, um, in some s- some area of the brain.

   25. PAPeter Attia27:30

       Yeah. It's a very important point you raise, and it, of course, always begs a question that I have when people tell me or when I feel this way myself, that, you know, I just can't remember things. I'm just not as facile cognitively. And, and I always just wonder where distraction and lack of focus-

   26. TWTommy Wood27:49

       Mm

   27. PAPeter Attia27:49

       ... fits into the mix. So, um, w- w- are there any kind of heuristics for what is too much task switching, what is too much distraction? Because as you said, it's ... You feel very busy sometimes, and I, and I, I actually went through a little bout of this yesterday. I was really trying to get a lot of things done, and then one more thing got put on my plate, and I had this window of 10 minutes where I accomplished literally nothing by t- by toggling back and forth between three different emails, text, WhatsApp, and a document I was trying to work on, and I, I just couldn't get anything done. I mean, that's ... To be that debilitated is pretty unusual for me, but in that moment or, or that w- in that 10 minutes, I, I, I, I accomplished exactly zero. I would've been better off for 10 minutes literally just walking around the house or walking around the block. Um, so, so clearly there was sort of a threshold there, but, but do you have any way to think about what that looks like and where you've crossed a line into being, you know, busy and unproductive rather than busy and productive or focused and productive?

   28. TWTommy Wood28:55

       So I would probably make the argument that humans in general cannot multitask in the way that you describe it. Um, and again, we can sort of break this out. There are probably two different types of, of multitasking. Um, one is the performa- the automatic performance of learned subroutines that kind of just happen, and you could do multiple of them at the same time. So say you're a dancer, um, and you're running subroutines, the, the steps you've learned interacting with a partner, inter- you know, listening to the music. You know, you are technically multitasking, but those are all sort of learned subroutines that are essentially happening automatically or, you know, subconsciously. What you're describing as multitasking is that process of focusing on one thing, then another thing, then another thing, and we know that there's a loss function in terms of the t- you know, the time it takes to get back onto a new task from, from the previous task, and it's something in the order of, you know, like people have said 20-something seconds, right, for you to, to kind of refocus onto something. So say you're, you know, s- switching your focus every minute or two. The amount of time you actually have to, to focus on one specific task is dramatically reduced because, you know, a significant portion of that is just spent with your brain figuring out what it is you're asking it to do. So in that setting, um, so say you're, you're doing things that allow you to to enact learned subroutines in your work, you could probably do that continuously and there's less of this sort of stressful demand, uh, on, on your, on your attention. But if you're needing to directly focus on multiple things at the same time, then switching from one to the other, I would argue that the majority of people cannot do that well, even though they may think that they can.

   29. PAPeter Attia30:46

       Yeah, one way that I think about this in terms of exercise is if I'm doing a, a steady state, you know, aerobic efficiency, we, you know, call it a Zone 2 workout on a stationary bike, I can listen to a podcast and an audiobook and be completely focused on it. I can still manage to be on a bike and pedal. I don't have to worry about traffic or anything like that, and I can be focused. But if I'm doing-

   30. TWTommy Wood31:08

       Mm-hmm
5. 32:57 – 39:54

   Formula 1 as a model for how to perform under high cognitive demand and how to increase multitasking capacity

   1. PAPeter Attia32:57

      Well, well this is actually kind of a nice quick way to segue, and I wanna come back to this, but just let's talk about Formula 1 for a second. So-

   2. TWTommy Wood33:03

      Yeah

   3. PAPeter Attia33:04

      ... you know, you and I have been fans of this sport for a very long time, but I think a lot of people listening to this have become fans of F1 through Netflix's, uh, Drive to Survive series. Of course, if you're listening to this and you don't know what Drive to Survive is, I, I recommend you go back and watch the last two seasons at least. Um, but I think anybody who's watched the sport will appreciate how much they need to be able to do well driving. And on a personal level, this is something I can relate to 'cause I spend a lot of time in a car and in a simulator, and I am nowhere near being able to do what a driver does. So for folks to get a sense of this, first of all, they're traveling at speeds that are simply unbelievable, right? Their straight line speed is, you know, 200 to 200 and up to 220 miles an hour, depending on the, the, the setup they have for that race. And the amount of things that they have control over on this computer that masks array as a steering wheel in front of them is unbelievable, right? So between every corner, they're making some adjustment. They're switching the brake bias with one knob, which shifts the emphasis or force between how much brake is on the front wheels versus the rear. They're altering the slip angle of the differential, which is allowing inner wheels versus outer wheels when they're going around corners to move at different relative speeds. They're obviously adjusting drag reduction system when appropriate. They're adjusting access to battery power if they're passing or overtaking or trying to defend. I mean, there's simply no shortage of things. Oh, and by the way, they're pushing a radio button to talk to their engineer who's talking to them the whole while. [lip smack] So I will just say, Tommy, I have been driving for nine years. I can't come close to managing all of these variables in the simulator even, let alone... I mean, the most I can handle when I'm driving is driving and talking and maybe adjusting brake bias here and there. But, but I'm, I'm just so beyond my capacity to do any more. So how do these guys do so much? And I think more importantly for those of us who can't, what do we need to do to get better at that capacity? Or is it just so sport specific, and because these guys have been driving karts since they were five, things that I have to think about while driving, they don't. Is that, is that simply what it comes down to?

   4. TWTommy Wood35:36

      I hon- I honestly think that's, that's a lot of it. Um, many of the things they're doing, you know, like we talked about th- this idea of multitasking being running several learned subroutines at the same time, which the b- which the human brain is, is, is very good at. That's essentially what they're doing for a lot of those, a lot of those functions. Um, and if you've spent your entire life as a race- as a racing driver, which they have essentially, right? They've been karting since they were young kids, um, these guys, then, you know, when the compute setup changes, uh, or, you know, there are new things on the car based on new regulations, right? They're just stripping off a top layer and adding on a new one. So, like, the, what they have to learn is very minimal compared to everything else that, that's, that's probably happening automatically. So yes, I mean, there's a huge, um, cognitive demand and, and probably a lot of what You know, they're actually using their, their brain power for in the moment is, you know, you're reacting to others, right? You- that's, that you can't-

   5. PAPeter Attia36:34

      Yeah, it's racecraft

   6. TWTommy Wood36:34

      ... you can't learn that. Yeah, exactly.

   7. PAPeter Attia36:37

      Yeah. Yeah.

   8. TWTommy Wood36:37

      And so that's where most of their attention is, and everything else is, is, is probably, is, is happening automatically.

   9. PAPeter Attia36:42

      Now, when you have drivers that move up the ranks, and there's a pretty big jump from F3 to F2 from a complexity of the car standpoint, and again from F2 to F1, w- are there things that coaches will do with the drivers during those big transition years to really help them get up to speed? Um, you know, I'll give you an example. I, I don't think this is an example of what I'm accomplishing, but just people are probably very familiar with watching the drivers before races play sort of half physical, half cognitive games, right?

   10. TWTommy Wood37:15

       Mm-hmm.

   11. PAPeter Attia37:15

       Where they have, like, little lights on a board and they have to touch them, or they're playing catch or juggling or doing all these sorts of things. Are those things doing anything to sharpen their brain, or do they just look cool?

   12. TWTommy Wood37:27

       It ... Probably a, a, a bit of both, but I would argue that, um, for some drivers it, it certainly seems to, to be beneficial, and it's very different from, from driver to driver. Um, however, uh, there are definitely drivers who, you know, when they move up the ranks or even, you know, those who've been in Formula 1 for a long time, they'll have a, a dummy steering wheel, right? So they can, you know, move through the patterns of, of doing everything, you know, even if they're not on track. And this is, this is often the same as, you know, when we're learning subroutines. So, so say you, you're learning a new dance. You'll do the steps one by one without music, then you'll start to, then you'll start to string them together, right? Then you'll add complexity. You'll ... And, you know, it's, it's the same thing. So there are multiple opportunities for them to practice some of these skills even though they don't get a huge amount of time actually racing on, on, on the track. Um, when you're thinking about the, the sort of reaction, um, games that some drivers are doing and, and some of them may, may do it in terms of, you know, practicing starts. Um, and again, you know, they'll have sort of a, a dummy set up to do that or, you know, balls and, and reaction ... uh, you know, reacting to somebody throwing something. Um, some of it is probably, um, some of it may be placebo, right? It helps them feel like they're, they're getting ready, which is great, and anything you can do to improve that, you know, you would welcome. But then the other part of it may be moving you onto the appropriate part of the Yerkes-Dodson arousing cur- arousal curve, right? Which basically says that there's this U-shape or inverted U-shaped curve of, like, how aroused you are and how you perform.

   13. PAPeter Attia39:03

       Mm-hmm.

   14. TWTommy Wood39:04

       And that curve is different based on the sport. Um, and so some period where you're having to focus and react but also remain relatively relaxed, um, because that's, that's in- incredibly important, right? You wanna be fast off the start line, but then the first thing you have to do is get into turn one when you have eight guys around you trying to navigate at the same thing, and you have to, you have to react to them. So if you were very tense, you know, that, that would, uh, decrease your performance in that setting. So I think some of it is just getting you to the point where you're focused but then also relaxed. You know, if you're doing it with a, with a, with a, some kind of skill-based thing that requires you to also, um, you know, be relatively fluid. So it could be, like, catching a ball suddenly, right? You can't do that if you're very stiff and tense. So it ... I think it's some, you know, some of it's this balance of getting into the right mindset before you then have, have, have to do, do something once you get into the car.

6. 39:54 – 48:42

   Advice for the person reaching middle life looking to mitigate cognitive decline

   1. PAPeter Attia39:55

      Now, most of us have ... You know, we're never gonna be professional drivers or athletes, and certainly as we're aging, those, the need for really complex motor skills and cognitive skills may go down. But what is the equivalent that you think about for a person as they reach middle life and they're thinking about transitioning, you know? Or what lies ahead of them as they, as they transition into, into older age? In other words, w- what is that apex set of skills that they need to be able to have to give them the, the highest amount of physiologic headroom possible to avoid or minimize this age-related decline and, and more importantly potentially even avoid the pathologic stuff that we haven't talked about yet but will come to?

   2. TWTommy Wood40:42

      I, I think a lot of it, again, is probably quite individual, right? If you want to be able to perform a specific task, right, you want to be able to drive cars for as long as you're able, right?

   3. PAPeter Attia40:55

      Mm-hmm.

   4. TWTommy Wood40:55

      The next four or five decades. So then you would, you would want to push your skills as far as you can in that arena whi- while you're able. And then you have, like you said, maybe we'll talk about more about this idea of headroom. You, you cannot, at least not yet, we cannot completely stop the aging process. But you may be able to slow the decline and/or if you increase your, the, the level of capacity, it will take longer to get to a point where, you know, function is lost such that you can no longer engage in that activity. Um, the ... You know, w- when you're thinking about the brain, you know, there's a whole bunch of things related to language skills. Um, obviously, um, memory is important. Um, but how you interact with your environment and, and I think social interaction is, is critically important and something that is, is probably, um, under-discussed in relation to long-term cognitive function. That's, that's, that's a critical aspect as well, particularly as people spend less time, um, with others, um, uh, sort of because of, uh, societal, uh, effects. But when you think broadly about how cognitive function declines with age, it seems to mirror very closely the amount of demand that we put on our brains, and again, a- across, you know, how society is constructed. Because cognitive function essentially increases from birth To some peak in late teens or in your early 20s, which is the period of formal education. It is your job to learn, right? It's your job to develop skills. That's when most sports are learned, um, that's when languages are learned. That's when skills are learned. And then after that, you essentially spend a bun- a bunch of time doing the same thing over and over, or you become hyper-specialized in one specific skill, and that's rewarded in, in a number of jobs, right? And so say you're a surgeon, you want a lot of those processes to be automatic. You don't want to have to think about all of them continuously, right? So it's beneficial. It makes you better at your job. Um, but there's much less, uh, room for that period of, of skill-building or putting in, you know, effort into developing or providing those kinds of stimuli that then drive plastic reorganization in the brain and may increase headroom. So I think some of that natural decline with aging is a function of how we use our brains in general, uh, in society. And then there's a, a, a drop-off when we retire, and we can, we can see that in, in various different types of data sets where those who retire earlier seem to experience cognitive decline sooner. And that's probably because the, the cognitive demand that we do get in our daily lives, the majority of that comes, comes from work. So the ... You know, an important answer, I think, is, you know, if you're trying to maintain a basic set of cognitive functions, is to actively work on ways to increase headroom, increase absolute capacity throughout the lifespan. Because at, I mean, at some point capacity will decrease, but you want to push that out as far as you can. You know, hopefully you'll die of something else before, you know, you lose, you know, the majority of your cognitive capacities.

   5. PAPeter Attia44:24

      Yeah. I mean, again, I, I think everybody's aware of the anecdote, right? Where boy, you know, Sally was just sharp as a tack, and then she retired and all of a sudden it all went to hell in a handbasket. But-

   6. TWTommy Wood44:36

      Mm-hmm

   7. PAPeter Attia44:36

      ... y- you know, you hear this so many times that you realize there must be something to this. It, it can't just be, you know, an observational phenomenon that's best explained by something else. There may be other contributors to it.

   8. TWTommy Wood44:51

      Mm.

   9. PAPeter Attia44:51

      Maybe people who are retiring younger also have more health challenges. Maybe they're of lower socioeconomic sta- I mean, you could come up with a lot of confounders that could explain this.

   10. TWTommy Wood45:00

       Yeah. Yeah.

   11. PAPeter Attia45:01

       But, but I suspect that there is also a signal there. There's some fire in the, in the, uh, uh, the presence of that smoke that says, you know, if you retire and in its place add nothing cognitively, um-

   12. TWTommy Wood45:16

       Hmm

   13. PAPeter Attia45:16

       ... you know, w- you could expect to see a decline. I also can't help but wonder how much of this has to do with sense of purpose, which again, I think maybe falls outside of kind of s- you know, we're now getting, we're, we're getting really warm and fuzzy outside of the scientific discussion. But-

   14. TWTommy Wood45:32

       [laughs]

   15. PAPeter Attia45:33

       ... but y- you know, it's, it ... The question I always have is, look, retirement should be thought of maybe as a financial decision. Maybe retiring means I no longer need to work for money, but I'm gonna work on something else. And-

   16. TWTommy Wood45:45

       Hmm

   17. PAPeter Attia45:45

       ... if that something else is not as cognitively demanding, right? Let's say you go from being an accountant where, you know, it's pretty cognitively demanding. You're have to be ... You know, you're in a spreadsheet all day. Um, and you say, "Well, look, I'm 65, I'm done with that, and I don't need to work anymore. But now I'm gonna go and do something in the y- you know, I'm gonna do something philanthropic where I'm gonna work for, you know ... I'm, I'm really interested in homelessness," as an example. "I'm gonna go and do X, Y, and Z." Well, you, you probably have more sense of purpose. You might derive more satisfaction from that, uh, even though it's not as cognitively challenging. Do we have any sense of how that factors into it, or is that just so far outside of our ability to, to kind of understand risk?

   18. TWTommy Wood46:25

       The majority of, of studies that have looked at this have ... I guess they fall into two camps which partially answer your question but don't necessarily answer it fully. Um, the, the first is looking at, you know, the removal of that stimulus through, through retirement. And it's been done in, in several population-based studies. They usually account for medical conditions that, you know, might cause you to retire early, 'cause that's an important con- that's an important confounder. Um, and when you look at other studies, there are, you know ... there's evidence to suggest that late in life cognitive activity, so whether you regularly play chess or you dance or you do something else that, that, that's cognitively stimulating, that's protective against, um, incident dementia or cognitive decline. Um, so the two parts of that would say that removal of work as a major cognitive stimulus inc- increases risk but that adding some other kind of cognitive stimulus mitigates that risk. Um, and there are several studies where you do some kind of y- cognitive training, maybe it's, uh, computer-based brain training in older adults in their, you know, 70s. You s- can see significant improvements in cognitive function. Um, and if you think about all the things that are most protective in terms of, of preventing cognitive decline ... There was a, a big meta-analysis done by, uh, uh, Jintai Yu, who's a, uh, professor in Shanghai, looking at all the different potentially modifiable factors for cognitive decline. The two most important protective ones were early in life education, which I think of as increasing headroom. So the more you learn and skills you develop early in life and the longer you do that for, the greater headroom you have. And then late in life cognitive activity, which then provides that protective factor. So I think there's enough evidence, you know, as much as we can right now, and most of this is observational although there are some interventional trials in older adults. You can say that if you're no longer working, if you replace it with cognitively stimulating activities, you're probably mitigating, you know, all of that risk or at least most

7. 48:42 – 53:25

   Tasks and activities that support and improve cognitive function

   1. TWTommy Wood48:42

      of it.

   2. PAPeter Attia48:42

      And we've discussed this a little bit in the podcast in the past that not all cognitive tasks are created equal. So, you know, for example, the, uh, my reading of the literature was there wasn't, wasn't any evidence that doing crossword puzzles is necessarily going to do anything for you other than make you better at doing crossword puzzles.

   3. TWTommy Wood49:00

      Yeah.

   4. PAPeter Attia49:00

      Um, but dancing, now that's a bit different actually, um-

   5. TWTommy Wood49:04

      Mm-hmm

   6. PAPeter Attia49:04

      ... because no two steps are ever exactly the same. You're always sort of problem-solving, especially if it's sort of complicated dance. Um, you know, solving a business problem is more elaborate than doing Sudoku or whatever it's called, where it's, you know-

   7. TWTommy Wood49:18

      Mm

   8. PAPeter Attia49:18

      ... they're just sort of little predictable word games. And so, um, would you agree that maybe what you replace it with, there's also some variability in the complexity of that, and the less color by numbers or paint by numbers it is, the more likely it is to... Well, I mean, let's use that example. Painting by numbers versus painting, right? The, you're both painting, but in one case-

   9. TWTommy Wood49:41

      Yeah

   10. PAPeter Attia49:41

       ... it's a much higher level of, of, of cognitive load.

   11. TWTommy Wood49:46

       Yeah, and I think there are, there are two streams of evidence that, that are maybe, that maybe support this. So one is around, uh, cognitive activities performed on a computer. So there are a, a number of different ways to do online brain training. Um, there's a system called BrainHQ which probably has the best, um, evidence to support. It was actually developed by s- um, one of the researchers who sort of did, um, a whole bunch of the sort of primary basic research in terms of how we learn in the first place, uh, back in the '90s. Um, and they've, they have some nice data that shows that if you do these complex, uh, training games which are often, uh, reacting to something, uh, or, you know, shifting focus, right? Uh, they, they require you to be... They're very interactive. Then you can see parallel improvements in things like, uh, verbal memory and executive function. So things that you actually care about in real life. You're not just getting better at the game-

   12. PAPeter Attia50:42

       Yeah

   13. TWTommy Wood50:42

       ... you're getting better at certain cognitive functions which is what you really care about. Um-

   14. PAPeter Attia50:45

       And that, that program is called what?

   15. TWTommy Wood50:48

       BrainHQ.

   16. PAPeter Attia50:49

       And that's something that people would do online? That's like a game you would-

   17. TWTommy Wood50:52

       Yes

   18. PAPeter Attia50:52

       ... play online.

   19. TWTommy Wood50:53

       Yeah.

   20. PAPeter Attia50:53

       Okay.

   21. TWTommy Wood50:54

       Yeah, it's a sub- it's a subscription service. I have no relationship with it, but in terms of online brain training systems, it's been used in a, in a bunch of clinical studies as probably the, the, the best evidenced one in terms of creating sort of translational improvements in function. And then related to that, there are al- also studies using, uh, video games, um, where if you randomize people to play Solitaire versus Angry Birds versus, um, Mario 3D, um, like the, the 3D, um, the 3D game results in better improvements in, uh, working memory. And, um, uh, there are, there is some response in inhibition which is a version of, um, executive function. So the more complex, the more interactive something is, the, it seems to be the, the, the greater the improvements in cognitive function associated with it. Then related to that is work in, uh, physical activity.

   22. PAPeter Attia51:47

       Mm.

   23. TWTommy Wood51:48

       So you mentioned dancing. There are studies that have compared dancing to, um, uh, circuit training that is as cardiovascularly, uh, challenging but obviously without that element of social interaction, music, movement, steps, re- you know, reacting.

   24. PAPeter Attia52:06

       Yep.

   25. TWTommy Wood52:06

       Um, and you, and you see, uh, better improvements in the dancing group. And some people have termed this, um, open-skill versus closed-skill, um, physical activity. So closed skill is, you know, unidirectional, doing the same thing again and again. So like sitting on a, on an exercise bike, um, inside. You're not doing anything else at the same time except maybe listening to a podcast. Um, versus, uh, say, table tennis or badminton. So the, the physical nature of it, the, the cardiovascular stimulus is the same, but you're not reacting to the environment, um, and, and, uh, and other people. And when you do those open-skill, uh, type of physical activities, you seem to see some, some, some greater improvements in, in, in, uh, co- uh, cognitive abilities. So there's, there are those various things that say that the more domains or the more complex the interaction, you know, associated with the activity, the, the greater the associated improvements.

   26. PAPeter Attia53:01

       Yeah, the more variability there is, right? It's, you know, to be able to walk outside on an uneven surface where, you know, the slope is constantly changing and you kind of have to be able to physic- physically and cognitively be aware of what's beneath your feet is gonna be a lot better for you than walking on a treadmill-

   27. TWTommy Wood53:18

       Mm

   28. PAPeter Attia53:18

       ... or even walking around a track-

   29. TWTommy Wood53:19

       Yeah

   30. PAPeter Attia53:20

       ... in circles. Um, so, so let's talk a little bit now about the pathology side of this thing.

8. 53:25 – 1:11:48

   Neuropathology of Alzheimer’s disease: exploring the role of amyloid and tau proteins

   1. PAPeter Attia53:25

      So again, I think listeners to this podcast have, have a decent understanding about Alzheimer's disease and Alzheimer's pathology. We've certainly had a number of podcasts on the topic. But, but maybe let's just kind of refresh people's memories on the difference between Alzheimer's disease specifically and perhaps other kinds of dementia such as vascular dementia, frontotemporal dementia, uh, Lewy body dementia for that matter, and maybe even forms of dementia that don't necessarily fit neatly into these, uh, boxes.

   2. TWTommy Wood53:54

      Like you said, those, those, those are probably the four main types, uh, of dementia although there, there, there are other ones that then are associated with maybe other neurodegenerative conditions so, uh, uh, uh, the types of dementia associated with Parkinson's disease or, or ALS. They can be sort of complex and, and, and multi-domain and you might see changes in different areas of the brain. What the main thing that ties together Alzheimer's disease, and this is something that's worth digging into because I think both the, the genesis of the, the, uh, the eponym, uh, as well as how we now use it, um, is, is very interesting. But the thing that kind of ties together forms of Alzheimer's disease, and there are, there are, you know, two as we think about them, early onset, uh, Alzheimer's disease and late onset Alzheimer's disease. But what really ties them together is the, the neuro- neuropathology which is if you slice somebody's brain open Particularly, again, within the medial temporal lobe, that's where sort of like the, the primary, you know, atrophy, uh, and pathology seems to exist, although it can be, uh, throughout the brain, is amyloid plaques and, uh, tau tangles, hyperphosphorylated, uh, tau, uh, within the neurons. And this was how the disease was originally, uh, classified. There was a, a, an initial case, uh, Auguste D, who, uh, Alzheimer treated in, um, an asylum for several years and then looked at her brain after she died, and he saw these things under a microscope, then collected other cases where they saw similar things. And this was done right at the beginning of, uh, biological psychiatry where, you know, trying to find, uh, biology that, that, that explained, uh, psychiatric symptoms, and one of the things you could do at the beginning of the 20th century was look at things under a microscope, you know, after that person had died, and that's, that's, that's how they classified it. However, um, you know, well, whenever you want to, we can get into how actually these pathological hallmarks correlate very poorly with somebody's symptom burden and disease progression, and the reasons why they, they accumulate may be very different from person to person and, and may matter much less from one person, uh, to the next. However, it's these pathological hall- hallmarks that created the classification of what we call Alzheimer's disease.

   3. PAPeter Attia56:22

      Yeah. So, um, you know, it's funny, I wrote about this story in, in my chapter on, on Alzheimer's disease and, and pointed out that I, many years later, uh, you know, they exhumed, I guess, part of, uh, part of her brain and, um, lo and behold, she actually didn't have the sort of typical Alzheimer's disease that we see today, which is-

   4. TWTommy Wood56:43

      Mm-hmm

   5. PAPeter Attia56:43

      ... w- the disease that 99% of people with Alzheimer's disease get. A very small subset, she was in that subset, get a variant of the disease that is genetically predetermined. Uh, and I can't remember n- which one she had. Did, I think she had PSEN1, uh, or did she have APP? I don't, I don't recall.

   6. TWTommy Wood57:01

      No. It was, it was, it was PSEN1, but that's actually quite hotly disputed. Um-

   7. PAPeter Attia57:07

      Oh, interesting.

   8. TWTommy Wood57:08

      Yeah. So, uh, there was a paper in Lancet, uh, Neurology 2013 where they, they sequenced her brain and-

   9. PAPeter Attia57:14

      Yeah

   10. TWTommy Wood57:14

       ... and they, they supposedly found this mutation, but then another group got another sample of her brain and couldn't find any mutations, um, associated with f-

   11. PAPeter Attia57:22

       Oh, interesting

   12. TWTommy Wood57:22

       ... familial or early onset Alzheimer's disease. So, um, there's actually ... And then though her ... If she did have, uh, early onset, you know, a monogenic autosom- autosomal dominant mutation, um, it didn't seem ... There were, you know, some, some people have looked into her family history afterwards, and her children didn't seem to get it. So even if she had, um, a spontaneous mutation, it didn't seem to be passed on. So there are a lot of people who think that actually there's no evidence that she had, um, a mutation.

   13. PAPeter Attia57:51

       Wow. Well, that m- That, that may be the first correction I need to make in the, uh, second edition of my book because I, I noted that, that she in fact did have it, her PSEN1, and as a result it may be a different disease entirely, right?

   14. TWTommy Wood58:03

       Yeah.

   15. PAPeter Attia58:03

       It may be that PSEN1 mutation, PSEN2, APP mutations, which are all these essentially, es- essentially autosomal dominant deterministic mutations that result in people getting this disease and getting it very early. I mean, this is-

   16. TWTommy Wood58:16

       Mm

   17. PAPeter Attia58:16

       ... not uncommon for someone to be stricken in their ni- in their 40s, um, and certainly be dead before they're 60. Um, w- what is the alternative explanation? If in fact she did not have any of those mutations, um, what is the best case explanation for her disease, its severity, and the histologic findings?

   18. TWTommy Wood58:36

       Hmm. So, uh, by some telling of, of the story, um, as, uh, after examining her brain, Alzheimer was encouraged supposedly by his mentor, Emil Kraepelin, to gather together cases to sort of build this idea, this, this sort of common pathologic process. And again, it's sort of, you know, you're recounting history, so it depends on, on who's telling it.

   19. PAPeter Attia59:06

       Mm-hmm.

   20. TWTommy Wood59:06

       But some people say that actually Alzheimer was quite reluctant to try and group these people together because they were so different. Um, and I know you've, uh, sort of mentioned that, that famous line which is that once you've seen one case of Alzheimer's, you've seen one case of Alzheimer's, right? That's they're all so very different, and apparently this is something that Alzheimer felt as well. He wasn't sure that they should be-

   21. PAPeter Attia59:25

       Mm

   22. TWTommy Wood59:25

       ... grouped together. In the version of the story where she doesn't have an autosomal, a autosomal dominant mutation in PSEN1, um, it's that she did have some kind of, um, decrease in her cognitive faculties, um, and that which led her, you know, which w- you know, there were a whole bunch of environmental or other factors that, that could, could play into that, and we could certainly talk about that. But it led her husband to then put her into an asylum, and we know that one of, uh, you know, the fastest ways to, to trigger cognitive, uh, impairment or cognitive decline is to basically remove somebody from their environment and completely remove all stimulus, social in- social interaction, and all the things that ground them in, you know, who they are. So that version of the story says that because of the asylum that she was put in and the way that she was sort of completely disconnected from her normal environment, um, that then triggered an acceleration, uh, in her, in her cognitive decline which then, you know, may be a, a sort of a, you know, sort of like a, a maximized version of, of what we might see in, in individuals, uh, nowadays who experience, uh, cognitive impairment and then dementia.

   23. PAPeter Attia1:00:39

       Do we know her APOE4 status? When they were looking for PSEN1, did they check APOE?

   24. TWTommy Wood1:00:44

       That's a good question, but I don't, I don't know if they checked that or if anybody's checked that, or if they have, I, I haven't seen it.

   25. PAPeter Attia1:00:50

       Yeah. So, so let, let's sort of talk about the current state of affairs with Alzheimer's disease, and let's go back to a point you made earlier. Do you know what the discordance is between the presence of, uh, amyloid beta on a histologic sample, obviously taken postmortem, and the presence of and/or even severity of dementia-related symptoms in that person while they were alive, and the contrapositive of that, which is to say the severity of symptoms in a person while they were alive and the absence of amyloid beta on a pathologic specimen after they've died? What, what is the-- 'Cause in an ideal world, it would be a one-to-one mapping that is 100% concordant.

   26. TWTommy Wood1:01:37

       Mm.

   27. PAPeter Attia1:01:37

       Anyone who has symptoms will have amyloid beta on autopsy, and nobody who doesn't have symptoms will, and anybody who doesn't have symptoms never has it, and nobody who doesn't have symptoms will have amyloid, right? It's a, it's a perfect one-to-one mapping. Well, it's clearly not that, so how messy is it?

   28. TWTommy Wood1:01:55

       You-- It would be nice if we could, you know, put an, uh, an R squared or an R value, um, uh, on this to see how tightly correlated they are. Um, I think, you know, I have to reach deep into the, the depths of my memory, and if, if people have tried to do that kind of, um, correlation, it's, you know, the, the R is somewhere around .1 or something. Um, so you know, a couple of perce-

   29. PAPeter Attia1:02:18

       Which, which just means for people it's virtually uncorrelated.

   30. TWTommy Wood1:02:21

       Yeah. There's a couple of percentage points maybe in the variability in cognitive function that's explained by, uh, the variability in, or the amount of amyloid that, that you have, and that's very clearly described in animal models as well as, uh, in humans. And we also, you know, there are several studies where they've made some very good drugs that can, you know, decrease plaque burden in the brain, but that doesn't seem to then correlate, uh, with later cognitive, um, cognitive functions and may have a high risk of, of side effects, although that's a whole other story that we won't, don't need to get into today. Um, so pretty much anybody who dies with dementia or experiences dementia will have some burden of amyloid plaque and, and tau tangles. Um, I don't think I know of a case where somebody had that without any. Um, and but we also know that these things naturally accumulate, uh, over time, and you can have people, you know, there are multiple cases where they've looked at the pathology where you have significant, um, a, a burden of these neuropathological har- hallmarks with no decrease, uh, in, in cognitive function. And so I think there's, or, or beyond what might be expected given that person's age. And so I think that opens, you know, th- there's a possibility that there's so- you know, there's some other factor. People are now thinking about other things that may come into play here. So, um, microglial, uh, function phenotype, and so microglia are the, the main immune cells of the brain. These are now be- being increasingly interrogated in, in Alzheimer's disease, dementia. You know, other processes might be important, so, uh, lysosomal function, um, is potentially, uh, important as well, which, which basically processes proteins, uh, for breakdown and, you know, that gets impaired and that may trigger some of the accumulation of some of these things. But the alternative is to maybe think that some of, some of these hallmarks may be epiphenomenal, right? They just accumulate, um, in the face of neuronal stresses, and I, and I'm, I'm speaking about this largely or pretty much only in, in the case of late onset Alzheimer's disease. Your brain is gonna get exposed to a bunch of things, um, be that decreasing metabolic function, be that smoking, vascular disease, and then as neurons get stressed, they start to de- se- se- secrete, uh, some of these proteins or accumulate some of them. And there are some lines of evidence that suggest that some of it's, uh, actually a, a beneficial response. So, uh, amyloid beta has some antimicrobial and meti- metal-chelating effects, so it may be this, actually a response-
9. 1:11:48 – 1:15:57

   Why Tommy believes dementia research funding should be focused on environmental and lifestyle-based risk factors

   1. PAPeter Attia1:11:48

      So let's talk about some of the other ideas, Tommy, and, and w- we can talk about some of them broadly, but I'd, I'd like to also hear sort of if you were, if you were, uh, you know, Alzheimer's czar for a day and it was your, your job to allocate, allocate funding for both, um, prevention and treatment, right? So to, to, to, if you were gonna allocate those types of dollars, presumably you'd want to have a strong sense of where to put those resources. But, but what are some of the other theories, right? Sort of vascular, metabolic, uh, you know, obviously there's a genetic component. So, so just tell me where you think it sort of shakes down and then, and then we can go from there as to what the implication is from where maybe we ought to be spending our resources.

   2. TWTommy Wood1:12:34

      It's important, you know, we've gotten this part, you know, this far, I've talked a lot about, uh, Alzheimer's disease. It's important for me to mention that, um, a lot of the, the work and thought I've done on the Serena is, is not on my own. You know, I primarily have worked a lot with, uh, Dr. Josh Turknett, who is a neurologist, which I am not, um, and obviously has a lot of sort of front-facing experience in this. And so a lot of these ideas as they come together, you know, we, we wrote a paper about the demand model. That's where, you know, some of this discussion comes from. But it's ve- it's very much a collaboration with, with, with him and others, so I, I won't pretend that I suddenly figured anything out by myself 'cause I certainly didn't. Um, nor can I say that I figured it out or else I'd, uh, be getting an invite from the King of Sweden, uh, sometime to go and, to go and meet him. Um, but When we look at late-onset Alzheimer's disease, I think we've gotten to the point where there's such a broad number of environmental and lifestyle-based risk factors that seem to be critically important. Um, that's really where I would focus my efforts. And you can definitely say that even if the, the brain is responding to neurological stresses or, you know, the absence of expected inputs with the accumulation of certain pathological hallmarks, there's still some upstream process that's driving that, and that's where I would want to focus. And, you know, I, I, I think our, our best evidence so far is in factors around diet, lifestyle and, and, you know, peripheral, peripheral health, you know, cardiovascular health being a critical, being, being an important one. There was a, a Lancet, uh, Commission report in 2020 that looked at dementia broadly and tried to estimate what amount of dementia, what proportion of dementia would be preventable. And they estimated that 40% of dementia is preventable based on, you know, population attributable risk and a bunch of different risk factors, um, you know, looking at physical activity, body composition, diet quality, smoking, hearing loss, which, uh, I, I think of as a, as a cognitive demand which is lost, uh, ed- educational status. And my guess is that this is actually an underestimate, um, because they didn't include sleep, they didn't include nutrient status, particularly homocysteine, uh, status, which, uh, other individuals have suggested has a population attributable risk, uh, of around 20%, uh, for late onset Alzheimer's disease. Um, and then they also, you know, when you, when you do these kind of assessments, right, uh, and, uh, you've written about this recently, when you do a population attributable risk or population attributable, attributable fraction, you say, "If we remove this entirely, what proportion of that disease would, would disappear?" And we have a, a mounting, um, sort of body of evidence that says that these risk factors interact. So when you do a population attributable risk, you say this is a linear effect, it's additive, right? This on top of this, on top of this. But in reality we know that they're actually-

   3. PAPeter Attia1:15:42

      They're interactive

   4. TWTommy Wood1:15:42

      ... they're actually interactive.

   5. PAPeter Attia1:15:43

      Yeah.

   6. TWTommy Wood1:15:44

      Yeah. So I think if you took into account other risk factors and more complex interactions between them, my guess is that the majority, uh, is probably preventable, uh, by focusing on some of those, uh, lifestyle and environmental factors.

10. 1:15:57 – 1:29:40

    Benefits of lowering homocysteine and boosting omega-3’s, and evidence-based supplements that support cognitive function

    1. PAPeter Attia1:15:57

       Can you say more about the homocysteine one? Uh, we definitely manage homocysteine very aggressively, so we're very liberal with our use of methylated B vitamins to keep homocysteine down. We typically target eight or nine as the-

    2. TWTommy Wood1:16:11

       Hmm

    3. PAPeter Attia1:16:11

       ... upper limit we want to see, even though the lab reference range says up to 13 or 14 is normal. Uh, do you have thoughts on that? And, and, and I guess also tell me about the, um, the mechanisms. Uh, uh, we're... Our concern is mostly through cardiovascular, by the way, uh, 'cause I think-

    4. TWTommy Wood1:16:29

       Hmm

    5. PAPeter Attia1:16:29

       ... w- there we have pretty good evidence that homocysteine, uh, impairs the clearance of two molecules, SDMA and ADMA, that impair nitric oxide synthase, which obviously has an important role in the cardiovascular, uh, endothelial world. Perhaps it does in the brain as well, I'm just unaware.

    6. TWTommy Wood1:16:48

       Yeah. So a lot of, a lot of the work, uh, in this arena, I think we have to be inde- indebted to, to somebody, uh, called, uh, David Smith. Professor David Smith, who's former, uh, chair and head of the Department of Pharmacology at the University of Oxford, uh, who's done a, a huge amount of work on homocysteine and cognitive decline. Um, and actually this, this, uh, dementia charity in the UK that I'm on the advisory board of, he is the chair of their scientific advisory board. Um, he has done a number of interventional studies looking at this. Uh, the main one is the VITA-COG study, um, where they, uh, randomized individuals with elevated homocysteine to, uh, a B vitamin supplement. It was a B12 and, and folate, uh, folic acid, um, and then looked at rate of cognitive decline and rate of brain atrophy. And they showed that if you could reduce homocysteine, and the, the greatest risk is, is with those with a homocysteine above 13. There's also an elevated risk in those with a homocysteine above 11. So the cutoff that I use for cognitive decline that's based on, you know, hard evidence in the clinical literature is, is 11. Um, and you can s- you can slow cognitive decline and brain atrophy, um, if you decrease homocysteine b- uh, beyond that point. Um, there's a number of potential reasons for this. Uh, the first is, you know, there may be a direct mechanistic effect related to the neuropathological har- hallmarks. So homocysteine seems to activate CDK5, which phosphorylates tau, and then also inhibit phosphatase 2A, which dephosphorylates tau. So it may contribute to the accumulation of, of tau tangles, hyperphosphorylated tau in neurons. Um, but then sort of more broadly and where I think, you know, the majority of the action is, um, and sort of excluding cardiovascular, is, uh, the importance i- of the methylation cycle in, um, creating functional neuronal membranes. And the reason why, uh, I think, uh, this is because of evidence of how homocysteine level or B vitamin supplementation interacts with omega-3 status. Um, uh, we know that if you want to try and put, uh, particularly a molecule of DHA into a lipid membrane, you need to attach it or you need to create a phospholipid. Uh, and that process, um, of creating phosphatidylcholine, say, which then attaches to your, your DHA so it can sit in your membrane, it's me- um, uh, it's very methyl intensive, right? So it requires, there are several methylation steps that, that, that require that to happen. When you look at, um, there are actually sub-analyses of several, um, randomized clinical trials that show... So in the VITACOCK study, what they showed was that the, the rate of brain atrophy was, uh, only slowed in those who had in, in the highest tertile of omega-3 status. Um, there was a study in the Netherlands, the B-proof study, uh, where they, they also showed that, um, the benefit was greatest in those who had the highest levels of DHA. Uh, and then there's also the Omega AD st- uh, study where they supplemented with EPA and DHA, but then they saw benefit in those who had the lowest levels of homocysteine. So there seems to be an interaction between B vitamin status and omega-3 status in terms of, uh, cognitive decline and brain atrophy, and the best way to think about that is, is, is probably both are required in order for DHA to, to be inserted in a functional way into, uh, a neuronal membrane. Um, so that's-

    7. PAPeter Attia1:20:26

       Let, let's pause there for one second, Tommy, 'cause I, I just-

    8. TWTommy Wood1:20:28

       Yeah

    9. PAPeter Attia1:20:28

       ... I wanna make sure people understand what, what it is you're, you're, you're saying here, which is if you lower your homocysteine from 13 or 14 to 9 or 10, all the while maybe taking some DHA, and we haven't talked about doses, but-

    10. TWTommy Wood1:20:47

        Mm

    11. PAPeter Attia1:20:47

        ... what are we thinking? One to two grams of DHA?

    12. TWTommy Wood1:20:50

        One to two grams a day. Yeah.

    13. PAPeter Attia1:20:51

        Yeah.

    14. TWTommy Wood1:20:52

        Yeah.

    15. PAPeter Attia1:20:53

        Doing those two things together, which don't require any medical care, I mean, anybody... I've never seen a person who with, you know, the right amount of methylfolate, methyl B12, sometimes some B6 is needed, y- you can pretty much always get your homocysteine into that zone-

    16. TWTommy Wood1:21:10

        Mm

    17. PAPeter Attia1:21:10

        ... coupled with, you know, a high quality DHEA. No affiliation with any of these companies, but I like Carlson's and Nordic Naturals as the two.

    18. TWTommy Wood1:21:19

        Mm.

    19. PAPeter Attia1:21:19

        Um, what would you say is the risk reduction? Would you, would you say that that's a 20% risk reduction in all caused dementia, just doing something like that?

    20. TWTommy Wood1:21:32

        That's what others have suggested. They've calculated population attributable risks, and they've... I... And it's actually, it's more than that because around 20% of-

    21. PAPeter Attia1:21:40

        Yeah, that was just the homocysteine. Yeah

    22. TWTommy Wood1:21:41

        ... that was just the homocysteine. Another 20% has been, uh, attributed to poor omega-3, ome- um, omega-3 status.

    23. PAPeter Attia1:21:48

        So, so this is kind of frustrating because I, I know that there are literally hundreds of thousands of people listening to us speak right now whose homocysteine is elevated, whose DHEA-

    24. TWTommy Wood1:22:00

        Mm-hmm

    25. PAPeter Attia1:22:00

        ... uh, DHA is low, uh-

    26. TWTommy Wood1:22:02

        Mm-hmm

    27. PAPeter Attia1:22:02

        ... DHEA is low, and, um, they are unaware and their doctors are unaware of everything you just said. And there's no drug, including a $30,000 a month drug, that is going to come close to that level of prevention. So w- why do you think there is such a disconnect in, in, in, in how we think about prevention? And we haven't even talked about the obvious stuff. Like, I'm just gonna leave the obvious stuff aside.

    28. TWTommy Wood1:22:33

        Mm.

    29. PAPeter Attia1:22:33

        You should sleep. Your sleep is important. Exercise is important. Not having type 2 diabetes is important. Controlling blood pressure is important. Not smoking is important. We're gonna take those off the table.

    30. TWTommy Wood1:22:42

        Yeah.
11. 1:29:40 – 1:33:29

    A unifying theory of dementia

    1. PAPeter Attia1:29:40

       all right. Let's move on from, from the, the topic that is, that is, that is disappointing to me, which is, one, having a winning lottery ticket in your pocket and not playing it, and two, um, being such a Puritan in one's view that you wouldn't think everything is on the table, right? I mean, my view is-

    2. TWTommy Wood1:29:59

       Mm

    3. PAPeter Attia1:29:59

       ... look, Alzheimer's disease and dementia in general, very, very complicated, formidable opponent. Ideally have as many things as possible in your, in your quiver.

    4. TWTommy Wood1:30:13

       Okay.

    5. PAPeter Attia1:30:13

       You should have, you should have a jab. You should have a right cross. You should have a left hook. You should have an uppercut. You should have all of the above. To somehow suggest we only want lifestyle or we only want supplements or we only want drugs, I've never understood that rationale. But you're right. It permeates into cardiovascular medicine. It permeates into cancer. It permeates into, into everything. And it's just created a bunch of silos of people who each have probably some, uh, some, some, some truth and some expertise, uh, but are, but are, you know, equally limited by their blind spots.

    6. TWTommy Wood1:30:46

       Mm.

    7. PAPeter Attia1:30:46

       So, um, let's go back to the pathology again just really quickly. Um, w- what is sort of your unifying theory on these, these things? So whether it is the, the, the homocysteine, the, uh, limitation of omega-3 marine based fatty acids, we didn't even get into glucose hypometabolism, but it's something we've discussed a lot on the podcast.

    8. TWTommy Wood1:31:08

       Yeah.

    9. PAPeter Attia1:31:08

       I think people are very familiar with hypometabolism. Whether we talk about low-grade ischemia and the vascular, microvascular disease, how do you think it's ... Do, do you think it's all working its way through a final common pathway of neuronal damage which leaves the tombstone in its wake, and that's the only thing that's basically common to them is that they leave the same tombstone?

    10. TWTommy Wood1:31:28

        Yes. That's, that essentially summarizes my current thought process. And the ... So again, working, uh, with others, I think, you know- including, uh, David Smith, Josh Turk, and Y- uh, Yinyu Cao. He's, um, I mentioned earlier he did this big meta-analysis on, um, modifiable factors, uh, risk factors for cognitive decline, and, you know, trying to build this, like, systems approach to cognitive decline or, or late onset Alzheimer's disease. And so then my current thought process is that all of these things are necessary, healthy vascular supply, you know, some kind of metabolic substrate that is taken up, um, and, and, and available to neurons of the brain, you know, that you have the, the nutrients required to build, uh, quality, uh, structure, that you have, um, the absence of things that may impair some, uh, r- repair process. Like you, you, you mentioned a bunch of them, uh, which, which are, are clear risk factors like smoking. And then, you know, to kind of tie everything together, you create, you, you require demand on the system that drives, you know, creates a stimulus for adaptation. Those things are required in order to respond to that stimulus, and then you have a period of recovery and adaptation that allows for, you know, cons- consolidation and plasticity. And any individual may have an issue in one or more of those areas, but then what ties them together is the tombstone that they leave in their wake. But, you know, the, the exact way that that looks, the exact number of tombstones, say, or how those tombstones look or, you know, what else is going on is probably an expression of things like, you know, genetics, uh, and, and other factors which then explain some of that, some of that variability. But that's kind of... Yes, it's maybe the, the, the final common pathway, but everything that's important is happening upstream of that.

12. 1:33:29 – 1:39:24

    How muscular strength can help with both the prevention and survivability of dementia

    1. PAPeter Attia1:33:29

       Before we leave dementia, I'd like to talk a little bit about one of the strongest associations I've ever seen with mitigating risk, which is strength. Um-

    2. TWTommy Wood1:33:38

       Hmm

    3. PAPeter Attia1:33:39

       ... so the, you know, this is often demonstrated with simple measurable things like grip strength. But I don't think it's the, the strength of your grip and the ability to open a jar is particularly important. It's just that, you know, very high levels of grip strength, very low levels of grip strength, uh, the variability here is a great proxy for overall strength. People with a very strong grip-

    4. TWTommy Wood1:34:00

       Hmm

    5. PAPeter Attia1:34:00

       ... they're able to carry really heavy things, and that requires strength all the way up and down their chain. Why do you think strength has such an important bearing on both the avoidance of dementia, so from an incident standpoint, and also survivability? So just to give people some numbers, when you compare the top 10% or so of people from a strength perspective to the bottom 10%, it's about a 70, seven zero, percent reduction in both incidents and mortality associated with all-cause dementia. A- again, that's, [laughs] when you start to think of like things that we have some control over, um, this also rises to the top of the list. I'm not, I'm not suggesting that someone at the bottom can be at the top within a year. But if you think about this over the course of your life, this is all... this is something we can all aspire to. What do you think from a physiologic standpoint explains such a stark relationship?

    6. TWTommy Wood1:34:59

       S- so when you talk about, or when... my experience of talking about muscle mass and muscle strength with, you know, hard, uh, outcomes, say dementia or all-cause mortality, uh, you know, usually the response is, "All right. Calm down, bro. Um, clearly you like to lift weights and, you know, therefore you think that that's the answer to everything. And, um, you know, people who are healthier are stronger and that, like, that's just the, the, the confounding factor." But I, I think we have, um, good evidence that, that that's not the case. Uh, the main one being that you can take individuals in their 70s, um, you can put them on a very basic resistance training program, and you can see improvements both in, like, uh, white matter connectivity, you can do an MRI scan, or you can test them on various tests of cognitive function and you see improvements, uh, as a result, um, you know, of, of, of this, uh, training program. So then if you think, if you wanna, uh, think about potential reasons why, uh, the simplest is that some kind of novel movement is a direct neuromuscular stimulus. You are stimulating the brain to create new connections, driving plasticity because, you know, you're, you know, the recruiting of motor fibers, that, that motor skill is in itself a stimulus, a, a cognitive stimulus. But then, uh, w- we also know that the amount of muscle, the muscle that you have and the amount that you move it, um, it's a, it's an important glucose sink. So if you think about, uh, blood sugar regulation, and we know that prediabetes and type 2 diabetes, like you said, are significant risk factors for, uh, cognitive decline and dementia. So, you know, it may be, you know, you're increase- increasing glucose flux that helps regulate blood sugar. Uh, we also, you know, if you're moving your muscles, uh, there's this sort of still exploding, uh, area looking at myokines, um, so things released by muscle tissue that may support, uh, brain function, um, IGF-1, VEGF, BDNF, brain-derived neurotrophic factor that may support, uh, neuronal function, be sort of survival factors to, to, to keep neurons around. Um, we know that exercise is also, you know, through a hormetic process, anti-inflammatory. So chronic inflammatory conditions we kind of mentioned earlier but, you know, can be associated with increased risk of dementia and your decreasing systemic inflammation, uh, through the, uh, through physical activity. Um, so that kind of group of things, I think all of those are, are playing a role. I don't know exactly which is most important, if any. Um- Frankly, I'm not sure I really care that much because I know that it's a very important intervention. So, um, and, and again, it's documented that it can actually work, and you can implement it pretty much at any stage. So one of the reasons, you know, probably why... one of the reasons why it is so beneficial is because it has these multiple pleiotropic effects, and they're, they're probably, you know, addi- you know, at least additive if not synergistic. Um, as well as, yes, there, there will be a certain amount which says that the healthier you are, the stronger you are. So there's a little bit of that. But then there's a whole bunch of things on top of that.

    7. PAPeter Attia1:38:14

       Yeah. When, when, when, when I'm met with similar resistance, uh, no pun intended, to, to the idea of the importance of strength and muscle mass, I, I usually respond with something which is, "Look, even if strength training and, uh, meaning have a high degree of strength and muscle mass and cardiorespiratory fitness, even if all of those things didn't add a single day to your life, in fact, even if they shortened your life by six months, they would still more than be worth it in terms of the quality of your life."

    8. TWTommy Wood1:38:43

       Hmm.

    9. PAPeter Attia1:38:44

       Especially in that final decade, which is something that most people unfortunately don't want to pay attention to until they're in that marginal decade, as I call it. And you realize that at that point, having poor movement, being in pain, having low strength limits your capacity for doing just about everything that, that people would find pleasure in, whether it be playing with their kids or simply going for a walk or, you know, carrying out any basic activity of daily living at the extreme level. So, um, anyway, I think, I, I think it's, it's a, it's a fitting way to end our discussion on this before we transition. So

13. 1:39:24 – 1:58:33

    Head injuries: comparing concussions against traumatic brain injuries (TBIs), mitigating the damage after an incident, and the long-term management of head injuries

    1. PAPeter Attia1:39:24

       the other thing I wanted to talk with you about, Tommy, is another area where, where you have a great amount of expertise, and that is around head injury. Um-

    2. TWTommy Wood1:39:30

       Hmm

    3. PAPeter Attia1:39:30

       ... about, uh, oh gosh, 10 years ago, I had a friend that suffered a very significant head injury, uh, riding a bike down the street, and a jogger bolted out between some parked cars, didn't notice him riding, and they hit head to head.

    4. TWTommy Wood1:39:49

       Hmm.

    5. PAPeter Attia1:39:49

       Uh, you know, the jogger got the worst of it because he was wearing a helmet. But nevertheless, they were both devastated by this. He was going about 40 kilometers an hour. Um, she sustained multiple fractures to her head. Um, but he sustained a concussion that was so bad that basically he wasn't himself for about two years. Um-

    6. TWTommy Wood1:40:09

       Hmm

    7. PAPeter Attia1:40:09

       ... he's more or less himself now. Um, can you explain what a concussion is?

    8. TWTommy Wood1:40:16

       Even, even this, uh, like the idea of what a concussion is, is quite hotly debated. Um, but in general, you would classify a concussion as a mild traumatic, uh, brain injury. Uh, with more severe traumatic brain injuries, you might think of like complete open skull fractures and, you know, direct penetrating trauma to the brain, things like that. So this is, you know, the skull remains intact, but there has been some transmission of force or, um, a, a, a wave, a blast wave, say if it's, if it's a blast injury that's been transferred, uh, to the brain. Then at some level, in order to have symptoms of a concussion, you have some kind of disturbance of neuronal function, and that can either be because of, you know, abrupt loss. So there are some, you know, significant head, uh, impacts in particular where you can get shearing of, of axons.

    9. PAPeter Attia1:41:15

       Hmm.

    10. TWTommy Wood1:41:15

        Um, a, you know, direct axonal injury of, of the neurons, and then you, that, you know, that cell is essentially, is essentially lost as you sort of ripped it apart. Um, but even more, um, you know, milder impacts may cause, uh, disturbances that include like the, the, a neuron firing when it shouldn't. This can then sort of create this pattern of activation again that's not expected or i- in an area of the, the brain where it's, you know, it wouldn't normally occur in a way that it wouldn't normally occur. And then this can then cause these downstream processes within cells that can cause, uh, mitochondrial damage, swelling. You know, you then might see the accumulation of certain, um, pathological proteins. So tau is, is like, just like you see in Alzheimer's, uh, dementia is also a response to, um, a neuro- like direct neuronal injury i- in a concussion. I, I work with a, a neurosurgeon whose, uh, definition of concussion is any impact or force to the brain that causes the disturbance of function of one neuron. Um, unfortunately, that's not something that we can measure, uh, 'cause you probably need multiple or, you know, large sections of the brain to, to have, uh, aberrant function for, for you to be able to actually measure it or detect it. Um, but, you know, those are the various processes that are going, y- you know, going on, uh, you know, when you get a, a head impact.

    11. PAPeter Attia1:42:37

        So it could be as, as quote unquote "mild" as just a headache for a few days, um, following a, a head trauma, or it could be, you know, in the case of this friend of mine, for a couple of years, uh, light was... They had a lot of photosensitivity. They had a lot of auditory sensitivity. They had difficulty, you know, processing things. They were much more irritable. Are... H- how common are those types of, you know, more severe symptoms than just a headache for a few days after a, a hit to the head?

    12. TWTommy Wood1:43:08

        So in reality, it's quite difficult to, to say how common things are because millions of concussions happen every year in the, in the US, uh, alone, most of which probably go unreported. Um, and so it's only when you see more significant symptoms or, you know, something's, you know, it's happened in front of a... So you're playing sport, it's happened in front of a doctor, you know, you, you, you get a formal assessment. And, you know, the downstream effects are q- you know, are varied, you know, can be around, uh, you know, verbal effects, photosensitivity, um, noise sensitivity, uh, effects of memory, focus, um- ... reaction time, you know, depending on, on, on how you're measuring things. And probably, um, some of it is exactly which area of the brain, uh, was, was impacted, and then there's, there's a systemic response aspect as well. So there are, um, you know, we ... It's ... You, you can only really do this in animal studies, but, um, part of the process of, of, um, the, the sort of the disease process after traumatic brain injury is a systemic immune response that seems to sort of contribute, uh, to, to, to some of the symptoms. So, you know, how much of an inflammatory response do you get? How much of a fever do you get? Um, that can then, you know, cause s- s- some issues throughout the brain, um, a- a- as well.

    13. PAPeter Attia1:44:33

        So what do we know about the short-term management of concussion and the long term, and what is the relationship between a concussion and a traumatic brain injury, which are terms that I think most, most people are hearing. And of course, the term TBI in the past decade, uh, is, is sort of more front and center for people. Uh, I, I suspect in large part due to two things, right? Probably, uh, uh, greater understanding of, uh, TBI occurring in the battlefield and also in at least one sport, American football, though obviously it occurs-

    14. TWTommy Wood1:45:04

        Mm

    15. PAPeter Attia1:45:04

        ... in more than that.

    16. TWTommy Wood1:45:07

        Yeah. So like, like I said, the, um, concussion is generally considered, uh, you know, within the ... So T- so all of these are TBIs, traumatic brain injuries-

    17. PAPeter Attia1:45:17

        Okay

    18. TWTommy Wood1:45:17

        ... of, you know, var- various severities. A concussion is sometimes also known as a mild traumatic TBI, a mild traumatic brain injury or mTBI. And then, and I, and I, and I think this is where probably most of our, you know, focus today will be on because, you know, the more severe brain injuries, so say if you do have skull fractures or penetrating head trauma or you have, you know, significant loss of consciousness that requires, you know, intensive care, it ... That requires specialist neurosurgical treatment that's, that's probably beyond what most people here will be thinking about. But if instead you're thinking about concussions on the sports field or blast related or s- or sub-concussive, uh, uh, exposures which might happen again, uh, in sports or in the military, um, and there's increasing evidence that says that sub-concussive, um, impacts or, or blasts ... So, uh, a- an example would be sniper fire, right? You essentially have a mini explosion happening right next to your head, um, s- several times a day, right, if you're, if, if you're in the range practicing. And there's some evidence to suggest that even that over time the damage can accumulate and cause, uh, issues with cognitive function. And there you call it sub-concussive because each individual one doesn't necessarily cause symptoms. But depending on how you define s- uh, concussion, you may or may not get, um, symptoms anyway, so there's kind of a gray area there. But, you know, each individual one would ... You wouldn't be able to detect it really.

    19. PAPeter Attia1:46:50

        Mm.

    20. TWTommy Wood1:46:50

        Um, but the damage seems to accumulate over time. If you have a significant, um, head impact, so say on the sports field is probably again where people are most familiar with it, there's probably two aspects that are worth separating. So there's the, there's the formal medical process and medical assessment that you should undergo, and there will ... People who made, you know, in, uh, multiple sports now, they may have some baseline cognitive testing so that when you do get a concussion they retest you. They make sure that you get closer to, uh, your previous baseline before you're allowed to play again, so things like, um, the impact, uh, assessment is often used in, um, sort of youth and college sports. Um, and so there's that part. But then what I'm particularly interested in is how can we mitigate the effects of an impact initially, like are there supplementation or other strategies that we can do to make the, the athlete who's ... or somebody who's at high risk of concussions more resilient to that impact, um, and are there other things that we can do to support a recovery or minimize the effect of, of the impact? So with the, with the short-term sort of post-concussion management, there are, um, two or three things that I think are particularly important. So the first is thermoregulation, and which is basically managing normal body temperature. My PhD was actually looking at the effects of temperature on response to brain injury, uh, and it's very clear that the hotter your brain gets after an injury the worse your outcome. Pretty much any type of brain injury, stroke, traumatic brain injury, you know, uh, also these neonatal and pediatric brain injuries that I study. And we know that a lot of sports happen in heat stressed environments. So you're on the field, you're hot already, or you're out in the sun, and if ex- experimentally, if you heat that brain up first, which happens during exercise, and then you have an impact and then that brain stays hot, that can ... That seems to, to worsen outcomes. So getting somebody out of a heat stressed environment, cooling them down if you need, if, if you need to and you, and you can, use external me- um, external ways to do that. You can use things like Tylenol to help, uh, uh, regulate body temperature, and that particularly becomes important because this, uh, at some point a few hours later an inflammatory response is gonna kick in, and it's very common to get fever. There's been a big, um, you know, I mean, it's decades of work-

    21. PAPeter Attia1:49:28

        How long does that, um, the, does the, does the f- um, sort of power or potential of that intervention last? So if a person has a concussion, you know, at 2:00 on a Sunday afternoon-

    22. TWTommy Wood1:49:43

        Mm

    23. PAPeter Attia1:49:43

        ... is ... Should they be in an environment of taking Tylenol and cooling themselves off for the rest of the day, or is that something that would ... you'd wanna carry out for a couple of days and just continued round-the-clock Tylenol to keep, uh, to prophylactically ward off fever?

    24. TWTommy Wood1:49:58

        That's a great question, and it's something that the field probably still struggles with. Um, but a, a period of 24 to 72 hours after the initial injury is probably the most critical. Um, the, the most important thing is preventing fever, and the reason why, the reason why, uh, fever causes issues is because you cr- you increase the mismatch between metabolic rate and capacity to produce energy to match that metabolism. And so if you have mitochondrial dysfunction, you're basically increasing that gap in terms of required energy production, which then, um, exacerbates the injury.

    25. PAPeter Attia1:50:38

        Any evidence for cooling, Tommy? So for example, I mean, obviously as you know from your work, um, when you're doing, uh, certain types of heart surgery, you can actually cool the patient to 19 degrees Celsius. At least back when I was training, that was the sweet spot. I don't know if, what the temperature is today. But if you were, um, basically doing anything where you had to cross-clamp the aorta, uh, and prevent cerebral perfusion, you would, you know, uh, you would, you would cool the patient, literally have ice around their head. The anesthesiologist would cool the patient. Um, and obviously that was very protective. So is there any evidence that someone sustaining a concussion should go beyond just getting out of the sun and taking Tylenol, but perhaps be laying down and be, you know, bathed or at least have their head covered in ice?

    26. TWTommy Wood1:51:24

        So the, the short answer is no, there's no evidence for that. Um, and then there's a long story to, to answer that question. So in animal models, and again, this is something that I've, I've published extensively on, hypothermia is magic for acute brain injuries, right? If you can decrease core temperature by three to four degrees Celsius for, you know, three, you know, 24 hours to 72 hours after the injury, you, you get a significant reduction in, in brain injury. In one specific scenario, and that's acute, um, acute, uh, brain injury in babies that have some kind of issue around birth, therapeutic hypothermia, so cooling to 33.5 degrees Celsius core temperature for three days is the standard of care. It was brought into the resuscitation guidelines in 2010.

    27. PAPeter Attia1:52:15

        And, and they, they do that just externally. They're not using ECMO or anything like that.

    28. TWTommy Wood1:52:18

        Yeah.

    29. PAPeter Attia1:52:18

        Okay.

    30. TWTommy Wood1:52:19

        No. Uh, so if, uh, the ... So some of those kids can go o- on ECMO, but that's because of respiratory failure.
14. 1:58:33 – 2:03:07

    Is hyperbaric oxygen treatment helpful after a TBI?

    1. PAPeter Attia1:58:34

       okay, another topic I wanna ask you about is, uh, hyperbaric oxygen, and presumably this will be in the chronic phase, not, uh, I mean-

    2. TWTommy Wood1:58:44

       Yeah, okay

    3. PAPeter Attia1:58:44

       ... maybe someone's looking at this in the acute phase, but, but so, so address it as you see fit. But clearly I see a lot of people talking about hyperbaric oxygen. I get asked about this all the time from patients. Uh, I'm quite ambivalent about this, so I'm, I generally think the hyperbaric oxygen industry is a racket. Um-

    4. TWTommy Wood1:59:03

       Mm

    5. PAPeter Attia1:59:03

       ... I think there are definitely indications for it. There are clearly pl- places like wound healing where I think it matters. Uh, you know, I, I probably think the opportunity cost notwithstanding, there might be... it might be reasonable to consider hyperbaric oxygen for, for, for brain injury. Um, but I haven't really found any compelling data, so it's possible I just haven't been looking hard enough and, and obviously you're closer to it. So what, what's your state of the understanding of the, the role of that?

    6. TWTommy Wood1:59:35

       I think the, the phase is critically important, um, firstly because in the acute phase of injury, there we- there is evidence that hyperbaric oxygen can be detrimental. Um, there are... I've, I know of some studies where they've tried to, uh, get hyperbaric oxygen in as early as possible after traumatic brain injury, and they've had an increase in negative, uh, side effects. I don't think those studies are published yet, but I've certainly heard of that work, um, going on.

    7. PAPeter Attia2:00:04

       So presumably just creates more reacti- more reactive oxygen species in a, in a hyperinflammatory-

    8. TWTommy Wood2:00:09

       Exactly

    9. PAPeter Attia2:00:09

       ... environment.

    10. TWTommy Wood2:00:11

        Exact- That, that's exactly it. And again, so if you have, you have impaired function and then you try and shove a bunch of extra oxygen in there, you're, you're essentially just driving oxidative stress. Um, and the... I know, I, I know of some people who have actually, you know... There have been significant, uh, injuries in like professional sports, and they've immediately got- gotten that person in the chamber. That is not something that I would recommend, and I don't think there's evidence to support it. Longer term, so in the chronic phase, I think there's, there's a possibility of benefit. And again, you know, there is some data out there to suggest that those after concussion or traumatic brain injury, they may see, um, improvement after exposure to, to multiple rounds of hyperbaric oxygen. However, there are a couple of things that just, you know, should drive some equipoise currently. One is that most of these trials are single arm, uh, you know, uncontrolled studies, and it's actually quite hard to create, to create a control group in hyperbaric oxygens, um, studies because you, you can tell when the chamber is being pressurized. And so to try and create a scenario where you have a sham effect that may-

    11. PAPeter Attia2:01:20

        Mm

    12. TWTommy Wood2:01:20

        ... create the same placebo is quite tricky. Um, the second is that, um, you know, a lot of the, you know... I, I read a, a study where they're like, "You know, these people, they all improved. You know, we did six months of hyperbaric oxygen. They got it twice a week." And in my mind, you're just invoking Voltaire, um, where they s- where... who said that medicine is the art of entertaining the patient while nature cures the disease, right? That brain was gonna get better anyway. Having said that, I think there, there are some, there are some, you know, sort of early data that suggest that, you know, improved, uh, cognitive function, you know, maybe you're respor, uh, restoring, uh, m- uh, metabolic, uh, function within the brain, mitochondrial function with, um, some periods of hyperbaric oxygen. It probably takes several, um, uh, uh, several rounds, so like- Maybe like a couple of months, at least 30 plus exposures seems to be required. And again, this is sort of like anecdotal. I've seen people's pilot data. This is not large randomized controlled trials or anything like that. Uh, but there, there... I, I think there is potential benefit, and, you know, part of it-

    13. PAPeter Attia2:02:24

        And by the way, how long-

    14. TWTommy Wood2:02:25

        Uh, may be-

    15. PAPeter Attia2:02:25

        How long after? You're saying any time after 72 hours, or you'd wait even longer potentially?

    16. TWTommy Wood2:02:31

        I'd probably wait a couple of weeks, would be my guess, until sort of like the f- the full initial phase of the injury has, has, has resolved. Um, and-

    17. PAPeter Attia2:02:40

        And, and y- and you're basically saying two 60-minute sessions weekly, and, and they're doing this to what depth, or what's the whatever metric of barometric pressure?

    18. TWTommy Wood2:02:50

        I think, I think generally they do two, two, two atmospheres I think, I think is, is g- is generally what's, what's done.

    19. PAPeter Attia2:02:54

        So, so two atmospheres an hour at a time twice a week, and potentially several months.

    20. TWTommy Wood2:02:59

        Some kind... Yeah.

    21. PAPeter Attia2:02:59

        Yeah. Well, it's certainly long enough for Voltaire to, to take over. Um-

    22. TWTommy Wood2:03:04

        [laughs]

    23. PAPeter Attia2:03:04

        ... it's very, it's very difficult to know.

15. 2:03:07 – 2:12:16

    Supplements that aid recovery from a TBI: creatine, DHA, and choline

    1. PAPeter Attia2:03:07

       What about supplements such as creatine monohydrate and our good friends, the omega-3, the marine omega-3 fatty acids, DHA and EPA? Do they play any role here in, in supplementation if a person is not using them, i.e. adding them, or is there any benefit for using, uh, higher doses than people might n- might use? We typically, you know, talk about using five grams of creatine monohydrate daily.

    2. TWTommy Wood2:03:33

       Mm.

    3. PAPeter Attia2:03:34

       Talked about that in the past on the podcast. Lots of benefits associated with creatine monohydrate use, both cognitively and physically. Um, and we talked about, you know, two, two or three, maybe even up to four grams of EPA/DHA having, um, benefit. Uh, what, what's the, what's the evidence for their efficacy here and, and how do you think about dosing them?

    4. TWTommy Wood2:03:54

       So I think the doses are, are very similar, but I, I do think, uh, there's a strong case for, for benefit. Um, there's, you know, no good study that gives every... you know, a bunch of people creatine before they get, uh, traumatic brain injuries. That's one of the problems with, uh, TBIs. It's difficult to predict, therefore it's hard to d- hard to do, you know, good quality prophylactic studies. But in animal models, you can see that if you supplement with creatine for several days, um, you know, the optimal period may be five to seven days, uh, with a, with a loading type dose, so the equivalent of, you know, .2 grams per kilo, something like that, which would, you know, for 20 grams per d- per, per, uh, 20 grams per day for a week. The equivalent in, in both rats and mice before a traumatic brain injury is, is significantly neuroprotective. That kind of dose and time period, so something like 20 grams a day for a week, has been shown to s- significantly increase brain creatine levels by doing something like, uh, magnetic resonance spectroscopy. You can point an MRI scanner at the brain, and you can see the levels of creatine in it. At the same time, uh, there have been some studies in, in high school football athletes that have looked at that same measure over a, a football season and seen that related to the number of impacts that the, the kid gets, there's a decrease in brain creatine in the dorsolateral prefrontal cortex and the primary motor cortex, so suggesting that creatine is being used up, um, by im- impacts, and, you know, it provides this sort of short-term pH and, and energy, uh, buffer that, that may be protective when, when there's a, when there's an impact.

    5. PAPeter Attia2:05:36

       And those kids are taking 20 grams a day throughout the season or five grams a day?

    6. TWTommy Wood2:05:41

       No, these are, these are two separate lines of evidence.

    7. PAPeter Attia2:05:43

       Oh, so, so-

    8. TWTommy Wood2:05:43

       So one is that, yes-

    9. PAPeter Attia2:05:44

       ... that's just looking at innate or endogenous creatine.

    10. TWTommy Wood2:05:47

        Yeah, that's... Yeah.

    11. PAPeter Attia2:05:48

        Okay. Got it.

    12. TWTommy Wood2:05:48

        So they're not supplementing.

    13. PAPeter Attia2:05:49

        Yeah.

    14. TWTommy Wood2:05:49

        It's just looking at endogenous levels of creatine that decrease throughout the season, and that's related to impacts. So we know that with standard dosing of creatine, we can increase, uh, brain creatine levels, and we also know that, uh, with impacts, uh, brain creatine seems to decrease. And one of the, um, one of the thought processes behind something called second impact syndrome, which is that you have a concussion, you recover okay, you seem to be doing okay, that first con- that first concussion or that first impact doesn't have a big effect, but the s- the next one has a much big... has an outsized effect.

    15. PAPeter Attia2:06:21

        Yeah, we saw an aw-

    16. TWTommy Wood2:06:21

        And one of the-

    17. PAPeter Attia2:06:22

        ... awful example of this in the NFL this year with the Dolphins quarterback, right?

    18. TWTommy Wood2:06:26

        Yeah. Yeah, exactly. And, and one of the things that may be happening there, some people think that at least part of that is you've depleted-

    19. PAPeter Attia2:06:32

        It's creatine depletion

    20. TWTommy Wood2:06:33

        ... brain creatine with that first impact, and then there's a greater effect of the second impact. And there's probably maybe multiple things that happen, 'cause brain choline also seems to decrease i- in a simi- in a similar manner. Um, then, so I, so I think there's, there's a, there's a case to be made for prophylactic creatine in those who are at high risk. If you n- can, you know, estimate when you're gonna be at highest risk, I may do a loading period, 20 grams for a week, so, you know, you can increase brain creatine. But then after impact, you know, there are several studies that... and, and I think this is what you've talked about previously, where, um, uh, creatine may improve some of the problems that happen after a concussion. So we know that creatine can offset some of the, um, the cognitive deficits caused by sleep deprivation, and, and sleep can be an issue with those with concussion. Um, in multiple studies, creatine supplementation improves cognitive function. Uh, that seems... You know, the, the greatest effect seems to be in those who are oldest, uh, but if you have some deficit in cognitive function, uh, which may be related to creatine if it's through a concussion, then, uh, supplementation may be beneficial. Um, and finally, there's some evidence that it may, uh, help with mood. Um, creatine has been tested in two randomized controlled trials where they've added it on top of SSRIs in those who responded poorly or, or incompletely to the SSRIs and saw improvements, um, in, in depression symptoms. So I think there's multiple reasons why if you're at high risk of a TBI or you've had a TBI, it's worth thinking about creatine supplementation.

    21. PAPeter Attia2:08:01

        And, and presumably, if you have long enough time, just being on five grams daily will get you, will, will get you what the 20 gram loading dose do, so you... 'Cause again, the, uh, to your point, i- if you c- if, if you can't predict when you're gonna have a TBI, you can't always be taking 20 and waiting. If you just took five-

    22. TWTommy Wood2:08:16

        Yeah

    23. PAPeter Attia2:08:16

        ... every day, you'd ... produce similar levels of, uh, of, uh, within the brain. Um, and tell me about your thoughts on, on EPA or, or DHA-

    24. TWTommy Wood2:08:27

        Mm

    25. PAPeter Attia2:08:27

        ... specifically around this.

    26. TWTommy Wood2:08:30

        For related to concussion, I think DHA, um, is probably the, the, the more important one. Um, and it, it, it's very similar actually to some of the processes that we thought about with cognitive decline, you know, around neuronal structure and normal, uh, neuronal function. There was, uh, one nice study where they looked at supplementing with different levels of DHA, again, throughout a high school, uh, uh, football season, and what they saw... They supplemented with either two, four, or six grams of DHA, and actually all of those groups, um, and n- with no greater benefit with a higher dose, um, saw a decrease in player-related circulating neurofilament light, which is a, a, a marker of neuronal injury that you can pick up, um, you know, when, when you get, you know, c- when you g- when you g- when you get a concussion. So across the season, neurofilament light tended to increase in the athletes, but that was mitigated in the DHA supplementation groups.

    27. PAPeter Attia2:09:24

        Is that a biomarker you see in the blood, or is that something you see on an, on a... Can you tag for it on an MRI?

    28. TWTommy Wood2:09:30

        No, it's a biomarker you see in the blood.

    29. PAPeter Attia2:09:32

        Interesting. Um, are there any other supplements that you think should be a part of the toolkit for basically anybody? I mean, here's the reality of it is I... we're all kind of at risk for TBI. I mean-

    30. TWTommy Wood2:09:46

        Mm-hmm
16. 2:12:16 – 2:20:22

    Demands faced by F1 drivers, and testing interventions to improve their performance

    1. PAPeter Attia2:12:16

       Tommy, this is super interesting. Uh, uh, amazingly, we have not really spent much time on F1. Um, [chuckles] m- maybe I'll c- maybe I'll close with one F1 related question. Um, for the, for the casual observer of F1, maybe someone who knows a little bit about it, but not a lot, you, you've obviously... you get to spend a lot of time on the inside of F1. W- what's-

    2. TWTommy Wood2:12:39

       Mm-hmm

    3. PAPeter Attia2:12:39

       ... something that you think would surprise the, um, the casual observer about the sport and maybe something about the demands of the driver? What, what do, what do you think would, would kind of endear people to pay closer attention to F1, which is, of course, my secret ambition with this podcast?

    4. TWTommy Wood2:12:57

       So I'm not sure if, if this, uh, q- qualifies as, as, as your la- f- for your last request, but, but the thing that surprised me the most is probably related to the first things you said. Um, you know, w- and, and that is how much attention is paid to the health and performance of the driver relative to the health and performance of the car. Historically, in F1, the car was everything, right? Yes, I mean, y- and then basically you would just bring in a driver who was good, and that was it. You'd let them get on with it. And because of the amount of travel, the amount of media commitments... So I mean, they probably spend half their time with media commitments, right? Rather than working on the car or working with the engineers or in the simulator, whatever, you know. So, so probably the, the amount of time they have to do things like that. But because of all of that, the, the capacity to do a bunch of things related to their health and performance is, is quite small, right? They just, they just don't have that availability of cognitive or time resources to do it. So there's, you know, they'll, they'll spend a bunch of time with their, with their coach or trainer on, in the gym, aerobic work. All that stuff is important. But then things on top of that, it's very variable from driver to driver how much they focus on it, and it's also variable how much they're willing or interested in, in focusing on that. So- What was useful to me going into that world is, and I, I imagine you would be the same, right? You'd show up and be like, "I have a list of 100 things that are gonna help. Um, here it is." Uh, and, um, when you work with professional, uh, or high-level endurance athletes, right, solo athletes, they're all fo- It's, it's all their own performance. They're... And they're usually type As. They will do it. They will do all 100 things, no questions asked. In that setting, you have to be really certain that the thing that you're asking that driver to do is gonna be, is gonna be beneficial. So, you know, even if you don't have hundreds of randomized control trials, you have to be, you know, you, you're really working with that sort of, this idea of positive asymmetry. So like very little risk, very high potential benefit. Whatever, whatever it is. And you're also selecting that one thing, you know, uh, instead of the 99, the 99 other things on your list. So it really forces you to focus on what's gonna be the most impactful thing that's actually likely to be able to make it into, you know, the, the sort of the driver's processes and, you know, you know, have, have, have a, a strong feeling that that's the thing that you should really be focusing on.

    5. PAPeter Attia2:15:34

       Yeah. The, the, the, the opportunity cost is so great that, um, and there's so many other demands, as you said. I mean, understanding the balance of the car, understanding how they can... Uh, 'cause I think what most people probably also don't understand that we take for granted as, as sort of diehards is, you know, you've got 23 races in the year. Every race the car has to be a little bit different.

    6. TWTommy Wood2:15:57

       Yeah.

    7. PAPeter Attia2:15:58

       E- every circuit is different. So, uh, a street circuit like Monaco has pretty much nothing in common with a big track circuit like Monza. And, you know, a circuit that has lots of high-speed corners without many low-speed corners is totally different than the reverse. And-

    8. TWTommy Wood2:16:16

       Hmm

    9. PAPeter Attia2:16:16

       ... you know, s- s- circuits with long straightaways where you want very low drag, very different from circuits that are short and fast. And each of those changes everything about the dynamics of the car, changes everything about how temperature gets into the tires, stays in the tires, degrades, track surface, all these things. So, you know, they, the minute they finish that race on Sunday, they've got two weeks, sometimes one week, to completely change the car-

    10. TWTommy Wood2:16:45

        Yeah

    11. PAPeter Attia2:16:45

        ... to optimize it for what they think it's going to do and behave the next week. And the driver has to be ready to do that. And yeah, and then, you know, someone like you comes in and says, "All right, like, we've only got this much time to get you physically ready." And of course, the jet lag demands are sort of insane, right? I mean, it's, uh-

    12. TWTommy Wood2:17:02

        Yeah

    13. PAPeter Attia2:17:02

        ... it's, it's really hard to fathom how much they are crisscrossing the globe. I'm sure, um, actually, there's a, there's a great, um, little video I saw on, on Instagram that showed [laughs] like the flight path of the season. Uh-

    14. TWTommy Wood2:17:16

        [laughs]

    15. PAPeter Attia2:17:17

        ... and it did, it did it to the awesome, like, F1 theme song. It's just-

    16. TWTommy Wood2:17:21

        Oh, yeah

    17. PAPeter Attia2:17:21

        ... it's, it's so perfectly done. Um, w- without naming any names, um, what, what, um, intervention or advice that you've given a driver are you most proud of in terms of the impact it's had on his performance?

    18. TWTommy Wood2:17:39

        So I think, um, something that, that I really, um, en- enjoyed, or I thought was really impactful recently, was, um, helping a driver who was focusing on time off the start line. Um, a- and of course, you know, in general, I'm not directly interacting with the driver. The driver has a coach, and, you know, a lot of the interactions is me and the coach and tinkering with things. The coach goes away, obviously has other people they work with and, and kind of implement things. But there's, um, basically various different ways to get, um, get the driver, uh, ready to react. I think my AirPods, my, my AirPods have died.

    19. PAPeter Attia2:18:22

        Oh.

    20. TWTommy Wood2:18:22

        So getting the driver ready to react, um, and have an optimal reaction speed off the line, but then you also want to balance that against the sort of how they might react later in the race 'cause that's the, the, the arousal curve we, we talked about earlier. So there were various things that we tried in terms of, um, uh, training reaction time. There were some supplements we tried out. So, um, things around, uh, caffeine timing and dose. Um, uh, uh, I think, uh, tyrosine is an interesting one that, that may also be beneficial. I think we tinkered with that a little bit. Um, creatine was obviously something that, that, that came into play. Uh, there are other skills that I think translate, um, uh, across that kind of thing, like, uh, playing the drums. So you have to be relaxed, but you also have to be, you know, timing i- is, is critical. Uh, I don't think that one was ever imple- implemented, but that was a, the, a thought process that, that, that we talked about. So, and you know, there were a whole bunch of things that happened and a whole bunch of things that were changed, and the outcome improved. I can't say that anything that I did made the difference, but at least, you know, we reached, we reached the end goal, which was, which was a, a nice process of sort of, uh, scientifically tinkering with things to, to, to, to get our end goal.

    21. PAPeter Attia2:19:36

        Well, Tommy, thank you very much for, uh, humoring my, uh, my endless fascination with F1. And, um, thank you more than that for, for, for making time to, to share with me and everybody listening, um, all of these insights. Uh, this was a fascinating discussion. Uh, I, I seem that the, the more I learn about the brain, the less I know, uh, which is a, a common refrain for, for, for anybody, I guess, who's trying to get deeper and deeper into subject matter. So, um, anyway, thank you very much, Tommy, and I, uh, I hope to see you this year at, at COTA.

    22. TWTommy Wood2:20:08

        Yeah. Likewise. Uh, thanks so much, uh, for having me. I, I certainly feel the same, uh, about the brain, and that's one of the reasons why I'm so fascinated with it and I really appreciate, uh, the time, uh, to talk to you, and then obviously everybody, uh, for listening as well.

    23. PAPeter Attia2:20:20

        Thanks, Tommy.

    24. TWTommy Wood2:20:21

        Thanks.

Episode duration: 2:20:32