#851: Dr. Tommy Wood — How to Future-Proof Your Brain from Dementia

27:40and then they would give people B vitamins or omega-3s and then they didn't see much of an effect. What we found out later, you know, the scientific we, was that both are required in order to see benefit. So this was probably first seen in the VitaCog trial, which was run by David Smith at Oxford. And they found in individuals with elevated homocysteine, so that was a level above 13, giving B vitamins to reduce homocysteine significantly improved rate of brain atrophy and cognitive function, only in those who had an adequate omega-3 status. And the same thing was seen in the B-proof trial subsequently.

28:16And then the opposite, which was seen in the omega-AD trial where they gave omega-3 fatty acids, but they found they only saw benefit in individuals who had a low enough homocysteine. It's thought to be because if you want DHA to be in a membrane, in a cell, in your brain, it needs to be attached to some kind of phospholipid, right? fats don't just like float around. They're part of these phospholipids that sit inside the cell membrane. And that requires it to be attached to a head group. These head groups are usually derived from choline or an ethanolamine, although those can be converted from one to the other.

28:53And in order to do all of that kind of biochemical attaching and placement requires methylation. It's very methylation dependent. So it's thought that in order for DHA to its job, you need adequate methylation status so that all those processes can run. And if you only have one or the other, then you won't see benefit. Got it. Yet another reminder for long-term listeners, this will come as no surprise, but you got to get blood tests, comprehensive blood tests, and really track this stuff with trend lines over time. But that's a much longer conversation, but suffice to say, you need the orchestra, right?

29:29Or you need multiple legs of the stool. It's not just one leg of the stool. All right. So let's maybe return to, I'm going to use a term that's a little dangerous to throw around, but kind of first principles or fundamentals maybe is a better way to phrase it. I'm terrified, as many people are, of this thing called Alzheimer's disease. And you could throw in dementia, cognitive decline in general. And conversely, very interested in extending health span. I'm not totally convinced that we're going to get to 150 years, 200 years, like all the tech billionaires might want to have us believe. But it does seem, certainly if I look at my own health span, kind of local maximum right now for myself, it's not really just capacity right now compared to prior generations.

30:21I feel very good about it. So I feel like I can extend that runway. And cognition for me is just the most, one of the most, maybe the most important pillars of that. Because having seen multiple people disintegrate cognitively, they don't just lose their ability to remember. They basically lose their identity. They lose their ability to emote. It's a loss of the self. I mean, it's a death before death almost in a way. So really would love to do anything possible with the right risk-benefit ratio to avoid it. But fundamentals. Should we talk about, I'm going to fuck this up, August Dieter? Augusta Dieter?

31:02Dieter? How do you say this name? August Dieter, I think. There we go. All right. Who is this person? Because I'm guessing most folks will not recognize the name. Certainly, I didn't recognize the name. Hadn't seen it until I got a couple of notes from you prior to hopping on. So August Dito, or if you read some of the original papers, August D was Alzheimer's index patient. So Alois Alzheimer, that Alzheimer's disease is named after, was a psychiatrist in the early 20th century. And he took a particular interest in individuals who had sort of rare or unusual cases of pre-senile dementia. So what we now call, what now most of us call Alzheimer's disease, which is sort of a late onset dementia, was called a senile dementia, which just meant that it occurred after 65 years old.

31:56That was not what Alzheimer studied. He studied unusual dementias where people who were quite young, sort of in their 40s or 50s, experienced significant cognitive decline and dementia and Augustita was one of them. He then, after studying them as a psychiatrist or working with them as a psychiatrist, after they died, he then looked at their brains under a microscope. So he was the first person to see amyloid plaques, tau tangles that are now sort of pathognomonic. They're like what we consider to be sort of required as part of Alzheimer's disease. But it's just interesting that what we have now is not what he studied.

32:31So over time, people thought that the brains of individuals who had this sort of early onset Alzheimer's or these early onset dementias that Alzheimer's studied and those who have this late onset dementia that we now call Alzheimer's disease, those brains looked very similar under a microscope. So they've kind of lumped together. Although we do still have two kind of broad forms, the early onset Alzheimer's, which is usually a single genetic mutation in something like a presidin gene or the amyloid precursor protein gene that then creates a picture that's much more like what Alzheimer's studied or the late onset Alzheimer's, which is what most people think about when they think about Alzheimer's disease is probably somewhere between 95 % and 99 % of cases of Alzheimer's.

33:12And there is a genetic component to risk, but it seems to be much more tightly tied to lifestyle and the environment and other lifestyle factors that we have some control over, hopefully. And the reason why Auguste D 'Eso is interesting to me is because I don't think she actually had Alzheimer's disease as we would now think of it. There have been groups that have taken sections of her brain from Alzheimer's old collections, and they've done genetic studies, and she didn't seem to have any of the genes that cause early onset Alzheimer's disease or any of the mutations that cause early onset Alzheimer's disease.

33:48She wasn't an ApoE4 carrier. I think she was 3.3, if I remember correctly. So she didn't have any of the genetic risk factors. So what caused this and caused this so young, I think she was in her 50s, right? It's still actually unknown. Some people think, there've been some recent retellings of the story. Some people think that she may have had neurosyphilis and neurosyphilis actually causes amyloid accumulation. It looks very similar to Alzheimer's disease. neurosyphilis, meaning she had syphilis and it got into her brain. Got it. Yeah. And that can look very similar under a microscope, especially a hundred years ago or more than a hundred years ago when we were just sort of first starting to look at brains under microscopes.

34:29And then others have suggested that it could have been more sort of psychiatric nutrient deficiencies, certainly very common could have been, you know, just like the other components of her environment. She was by all accounts a sort of like a downtrodden housewife that maybe didn't get sort of much engagement or stimulation or wasn't particularly well treated at home and that could have sort of precipitated it and we don't actually know but many of these things kind of it just seems interesting that it's probably quite likely she didn't have Alzheimer's disease at all. Wild. Alright. So I'm going to take this in a few different directions and as per usual turn it around to be self-serving for yours truly but I'm going through some of the notes that I had for our conversation.

35:14And I'm sure I will have mentioned this in the bio and intro at the very top of this show. But I have this bullet in front of me. And I just want to make sure this is something you feel is defensible. 45 to 70 % of dementia is preventable through lifestyle. Is that a defensible statement? Yes. As far as we think it can be defensible. I'm not trying to put you in the hot seat. I'm just saying like, I don't know where that number comes from. So I can tell you where that number comes from. I mean, that sounds great. Yeah. I mean, that seems like a ray of sunshine and a pretty gloomy possible conversation, right?

35:47Where people think you're just like, okay, there's genetic determinism. You got this thing and you're screwed. If you have a bunch of it in your family, you're also screwed, et cetera. But it seems like there's a lot you can do to right the ship for a period of time. Okay, so where does 45 to 70 % of dementia is preventable from lifestyle? Where does that number range come from? So 45 % comes from the most recent edition of the Lancet Commission report on dementia prevention, which is overseen by Professor Jill Livingston and brings together all these different experts in dementia and its risk factors.

36:22And they sort of scour the research for observational studies and then as much as possible, interventional studies. A lot of it is epidemiological data, looking at different risk factors that have a consistent relationship with dementia risk. and then you do these sort of statistical calculations to look at something called population attributable risk which is essentially saying if I eliminated this risk factor entirely from the population what percentage of dementias would I expect to no longer happen? That's essentially what it means. And all of these different percentages add up to 45%. So it's a couple of percent for smoking it's 7 % for low level of earlier education, it's like a percent for alcohol, then there's hypertension, hearing loss, or sorry, high blood pressure, hypertension is the fancy medical word, high blood pressure, hearing loss, obesity, low physical activity, and all these different percentages add up to 45%.

37:26There are some things that are on that list, or that aren't on that list that I think should potentially be included. So like sleep loss or poor sleep and insomnia is not included. Late-life physical activity was discussed in the report, but was not included, even though there seems to be some good evidence there. So actually, that suggests that there may be more than 45 % that are preventable. And there are other studies, like there was one big study done from the UK Biobank data by Professor Yintayu that estimated that up to 72 % of dementias were preventable. If this was going to happen, this would require a complete societal overhaul, because a lot of this risk comes from low socioeconomic status, low educational and work opportunities, like all these other things that are kind of baked into societal risk for dementia.

38:14But others are things that we have more control over, like level of physical activity, whether we smoke, whether we drink. So some is directly under our control. That's probably something like 15 to 20%, maybe more. And some is kind of driven by these maybe biggest kind of societal risk factors. but if you did all of that and we managed to completely change how everybody lives and all of these risk factors the idea is that you know maybe even up to three quarters of dementia cases could be entirely prevented now that's very different from saying that i could guarantee that you will not get dementia right that's not the same thing we're talking about this stuff at the population level and i have to say this because if i talk about your physical activity or sleep or nutrition, and these are really important for dementia risk, somebody will always say, well, my family member did all that stuff and they still got dementia.

39:06So we're talking about probabilities. We're not talking about, I can definitely guarantee that somebody will avoid dementia, but I think we can definitely say you can stack the deck massively in your favor through a whole variety of actions that should decrease risk long-term. All right. So part of the reason that I make this very self-interested is because I'm self-interested. The other part is that I think the personal is very easy for people to concretize for themselves. So they can interrogate how they're behaving, what they might do differently, what they might add, what they might subtract.

39:44So let me tell you some of what I am observing and then some of what I'm doing. And I would love for you to identify or maybe speak to things that are low-hanging fruit or reasonably accessible that are missing. So a few things. Lots of folks in my family currently who I'm caring for in one way or another deteriorating very quickly with what has been called Alzheimer's. Again, kind of a tricky diagnosis. not sure how much they're actually looking at whether it's beta amyloid tau or anything else but certainly in some cases these blood relatives are apo e33 so i'm like huh also raises the question of is there an undiagnosed infection maybe it's an sti who knows right like i i don't know what the answer is to that it's kind of another line of testing perhaps so i've been trying to do a few things for myself, recognizing that if someone starts to really show obvious symptoms that can't be easily explained away in their 70s, let's just say, the process probably started, what, decades earlier, right?

40:56I mean, the cars have started to pile up, the machinery has started to break a lot sooner. So it would seem like the earlier you intervene with better lifestyle changes, et cetera, the better off you'll be. So I've got the fasting and the ketogenic diet and all of that stuff, right? Which I do regularly. I've got the exogenous ketones, which like you, I use sparingly. I don't use them all the time because particularly like before this conversation, I took 11 milliliters of a ketone monoester. But I think once all is said and done. It's basically 51 % 1 ,3-butane dial. And I have some concerns around 1 ,3-butane dial specifically in chronic use or at sufficiently high doses, say 30 plus per day.

41:41So I tend to use it for special occasions like this, toast, have a glass of champagne, have some exogenous ketones and off to the races. All right. So there's the ketone piece, which I think is non-trivial. There's the, for the most part, avoiding crazy glucose spikes all the time, right? Occasionally I'll have like Christmas, sure. I had a bunch of cookies. Like who cares? It's Christmas. It's fine. I had a bunch of pie. But I have a CGM on right now. I had a continuous keto monitor on at the same time for about 28 days. I'm really interested to look at all of that. But I'm generally following like a slow carb diet or Mediterranean style diet.

42:19I am getting enough omega-3. I know that because of fish intake and also when needed, supplemental intake. I do seem to be a poor methylator. So I'm taking B vitamins, L-methylfolate, all of that stuff. Tracking blood once a quarter. So I've got super comprehensive stuff on that side. Zone three training, I do find it as boring as watching paint dry, even when I'm listening to a podcast or watching a Netflix miniseries or something. But probably doing two to three sessions a week of let's call it 30 to 60 minutes walking every day lots of walking and we'll come back to that because actually i can't resist we probably will come back to it but walking 4 000 plus steps a day reduces dementia risk 25 optimal 10 000 steps daily and then reverses hippocampal shrinkage two percent increase versus expected one to two percent decrease that's the bullet that i highlighted.

43:16And then weight training a couple times a week. I could keep going. I'm not going to bore people to death with this Dr. Evil life story. But I will say that I've also wanted to get a snapshot of what things look like. So I'm going to be having a call. I won't mention the company by name because I haven't done all of my due diligence. They have some scientific advisors who I think are very credible, but have done brain MRI. I've done the blood draws, the DNA tests, everything else. Because I'm APOE34, and looking at the brain MRI, I mean, I'm a muggle, right? So I probably shouldn't be allowed to sort of grab the wheel when driving on the MRR reading, but I wanted to look at the data.

43:58It seems like, and who knows how defensible this is, but my MRI predicted brain age based on hippocampal volume, et cetera, et cetera, et cetera, is 46 instead of 48. So I wasn't thrilled about that. I'm like, well, all right, not sure what else I can do. Maybe a flood dose of Ibogaine. Actually, it's pretty interesting data around that from Nolan Williams, but not something I would recommend to most people, including myself. So there's that. Did a whole battery of cognitive testing through this startup. Now that came in at brain age of 20 years predicted, 28 years younger than your chronological age, but you can kind of beat the test.

44:44There's some gamification, so I don't know how heavily to weigh this, right? So brain age of 20 years, man, sounds great. There are certain aspects that are harder to game, like reaction time testing. Okay, so I had like 267 milliseconds basically versus 406 milliseconds. Okay, great. There could be some training effect, like learned training effect, but then there's like number span, focus, I won't bore everybody with that, but word pairs, names and face pairing with mnemonic devices. If you train yourself, you can really sort of game the test. And TBD on like proteomics, I'm getting all sorts of stuff drawn to try to get an accurate baseline of where I stand now so that I can measure all of the effect, hopefully, of these interventions over time.

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48:42So do your due diligence.

48:46what would you say are like there are 20 things i could mention but like here are three or four that i would also pay attention to so first a couple of comments on all the stuff that you mentioned about what you're currently doing so i think i've already mentioned that I think that there's a lot of promise for ketones. I'm not sure that ketones necessarily have to have a place in prevention. And I'm not sure that you would necessarily need them from a prevention standpoint. There are some reasonably good data. So like the medium-chated reglyceride work from Stephen Kinane's lab is quite compelling.

49:28In early Alzheimer's disease, taking MCT oil seems to increase the C2-acetate uptake into the brain. This is associated with improvements in cognitive function. And this is overcoming what looks like an energetic deficit in individuals who have Alzheimer's disease. And this is something that, again, it's one of those things that are pathognomonic, right? We think that we see this, and this is kind of like part of the picture of Alzheimer's disease. We see that like, this is Alzheimer's. Can I pause for one second? Yes. Real quick, don't lose where you are. We're talking about MCT oil. Number one, if people want to play with MCT oil, be close to a bathroom when you start.

50:03And if you combine it with double espresso and creatine, definitely have some depends around. The second is the ketogenic diet for me, just to briefly provide a little more context, is also for its, I think, plausible anti-cancer effects and just kind of all-cause mortality plus mental acuity. I just think a lot faster when I have more metabolic flexibility with something like intermittent fasting. That's another thing I do a lot of where my body has just got the machinery to produce ketones. But yes, I hear you. Okay, MCTs. So the thought being here, there's a difference between what you find works really well for you versus what the listener thinks they should have to implement for themselves.

50:48And so I'm now going down the road of why I don't think we all need to be in ketosis to prevent dementia. So I think from a therapeutic standpoint, I mean, it seems to be beneficial, overcoming this energetic deficit that we see in Alzheimer's disease, particularly early Alzheimer's disease, or maybe it's easier to overcome earlier on. And one of the ways we look at this is with something called a PET scan. So you do an FDG PET, you give labeled glucose molecule, you inject that, you see how much gets into the brain in individuals with Alzheimer's disease, less glucose is getting into the brain.

51:20We've traditionally come at it from the point of that glucose can't get in, right? there's some kind of metabolic disease, insulin resistance. This is where the idea of type 3 diabetes has come from, insulin resistance in the brain, that glucose isn't getting in. But a PET scan cannot differentiate between the glucose can't get in versus the brain isn't asking for that glucose in the first place. And there are actually some very nice studies that looked at brain activation and glucose uptake in response to cognitive stimulus in individuals with Alzheimer's disease. And what they see is that, yes, at baseline, there's less glucose being taken up into the brain of individuals with Alzheimer's disease.

51:58But if you stimulate that brain cognitively, it can take up glucose just fine so that you get into the range of a normal healthy brain in early Alzheimer's disease. Once you get to like advanced stage dementia, it's too late. But at that early stage, I think part of the reason why we're seeing less glucose uptake is because those parts of the brain are less active because we're just not using them as much. And just like glucose uptake into the muscles, which is demand driven, you work your muscles, they ask for more glucose, they take more up. The brain seems to be the same, at least early on.

52:31So I think we think a lot about the supply side, right, the energetic supply side, but I don't think we think enough about the demand side, how to create energetic demand in the brain such that we are maintaining glucose uptake, maintaining energetic state. And then doing that also maintains all the metabolic machinery that you really care about in terms of long-term function. All right, so if I'm hearing you correctly, and this is something I've chatted with Dom D 'Agostino about, but I'm wearing this CGM. So I've got this device on my arm that tells me what my glucose levels are at any given point in time with whatever, three-minute sampling or something like that.

53:11You got to calibrate that with a finger prick, by the way, folks. But if I eat a meal and then I don't go for a walk, my glucose spikes and I might conclude, wow, my muscles are really not accepting glucose. My muscles are bad at accepting glucose, but that's not actually true in my case, right? If I go for a walk or I do some light exercise, I guess it's like glute four transporters or whatever, get all jazzed up and help that glucose to be better disposed into muscle tissue. And like you said, in the case of the brain and people referring to Alzheimer's as type 3 diabetes, it's like, wow, the brain can't use glucose or it's very bad at using glucose.

53:55But if I'm hearing you correctly, the additional question that they should be asking is, is it just that or is the brain not asking for glucose, the equivalent of the GLUT4 transporters. Is the brain basically offline? It's a car up on blocks. But if you take it down, yeah, it's going to use gasoline just fine. If that's the case, I guess it's just a call to action for more stimulation of the brain. When I was first just coming across your notes that you sent prior to this conversation, I went on ChatGPT and I was like, what are the most glucose-intensive activities for the brain? and they gave me a bunch of mental exercises, which isn't exactly what I was looking for, but I could have prompted it better.

54:41And it said, but even still, the sort of improvement or increase might be plus less than 10 % in terms of the total. And then I was like, well, are there other activities such as physical activities that might increase glucose uptake in the brain? and it gave me a whole list. But rather than regurgitate that, are all types of stimulation created equal or are there some sort of 80-20 analysis like, okay, there are some tools that are better for the job? Yeah, so... when looking at this purely in relation to glucose uptake, those data don't exist. So we're going to have to extrapolate further than that.

55:22And I think that's important because a decrease in glucose uptake is just a signal that that area of the brain isn't as metabolically active, which means we're just not using it as much at the simplest level. So then if you think about various activities that we could use to stimulate the brain, which do seem to be protective in various different ways, both they can enhance coagulative function in the short term and then protective against dementia in the long term. this ties very nicely to the comment that I was going to make about your physical activity routine because this is where I think some things could be layered on when you look at the different physical activities and or exercise and how they affect the brain different types of exercise affect the brain differently so you certainly need a smorgasbord of all of them to kind of get a global support for the brain but something that seems to be particularly beneficial is It's coordinative exercise or open skill exercise, plus or minus things that have a navigational component.

56:19And these are essentially sports or activities where you're constantly having to respond to the environment and adapt. That's what makes them open skill rather than closed skill or unimodal exercise like going for a jog or sitting on a bike or something like that. So when they compare sports or activities that have the same amount of physical challenge, but different amounts of cognitive challenge because of the open skill nature, you see greater benefits in terms of brain structure, improvements in cognitive function. And open skill just means high level of unanticipated variety or variety? What is that?

56:55Both. So it basically has a greater amount of complex motor skill required. Some of it can be learned. So dancing is one example, right? So because you learn the steps of a dance. Single strongest activity for dementia prevention. Am I overstepping there? Yeah, probably. If you look at physical activity and the effect that it has on cognitive function, and also mental health. Yeah. But in terms of both mental health, so studies in depression, as well as studies looking at different activities that people do and the risk of dementia and studies where they randomize people to different types of activity, including dance.

57:37Dance seems to have the highest sort of effect size compared to other types of physical activity. But there's multiple components to dance, right? So you have to learn the steps, but there's also a social component, there's a music component. All these things are probably like part of the magic source together. But open skill sports also include board sports or ball sports or team sports where you're having to like react to the environment and other people around you. Do you say bull sports like rodeo? What are we talking? No. Oh, balls. B-A-L-O. It's not going to be good for the TBI to get people on top of bulls, but I think bull sports would probably be good if you could avoid the TBI.

58:18Actually, probably right up there. Similarly, martial arts, also good as long as you don't get punched in the head a bunch or kicked in the head a bunch. Or choked out too much. So beyond the physical strain that these exercises have, they seem to have an additional aspect of requiring reaction speed, challenging processing speed, learned complex motor skills. They seem to have an outsized effect in terms of cognitive function. Something else is kind of an aside, but just based on the physical activity component, when you're looking at more aerobic or even like closed-scale unimodal running, cycling kind of sports, the benefit seems to be intensity dependent.

58:59So yes, if you're not doing anything, then going for a walk and walking a certain number of steps a day is going to be great, beneficial, decreased dementia risk, absolutely. But looking at hippocampal structure and function, for instance, which you mentioned, right, you're talking about measuring your hippocampus on an MRI scan, higher intensity activities seem to be better. So probably the longest study where they ever did something like this, they had people, this was an Australian study where they had people do the Norwegian 4x4 protocol, three times a week for several months. Oh my God. And so for anybody who doesn't know what this involves, it's four sets of four minutes on a treadmill at 85 to 95 % of your maximum heart rate.

59:39With four minutes rest, you do that four times. It is miserable. I mean, that's like, pretend like you're being chased by wolves through the snow for four minutes and then take a four minute rest and then do that. Yeah. Four times. Yeah. Okay. Right. But they saw significant improvements in hippocampal structure and function that were maintained for several years after the end of the trial. Several years? Several years after the trial. So a few months. Yeah. And then sustained for several years. Yeah, I think they followed them up for five years after the end of the trial. That makes it much more interesting.

1:00:13Okay. And I think a lot of this is driven by lactate. so when we talk about the various things that support the brain through exercise we often talk about bdnf brain derived neurotrophic factor which is increased with exercise but the bdnf that you produce that you can measure in the blood that's produced by the muscles during exercise doesn't really get into the brain very readily most of the bdnf we have in the brain is produced locally and it's actually driven by things like lactate so lactate does get into the brain the more lactate you have in the blood the more gets into the brain and then that acts as a histone deacetylase inhibitor that activates the bloodstream BDNF ketones do the same thing osteocalcin which is released when we sort of load the bones structurally rise released from bones seems to do something similar so generating lactate seems to be beneficial because probably because one of the things it's doing is it's generating more BDNF that then is associated with improvements in hippocampal structure and function.

1:01:14So as long as you're doing sports that have some high degree of intensity, so you're regularly producing lactate and then either in the same sport or separately doing these sort of high skill, high reaction time, open skill kind of sports, that's probably going to be beneficial from a exercise standpoint. I'm still completely stuck on the three times a week, basically VO2 max training, right? For a few months, is a few months, like three or four months? Or how many months was it? The study was either six or 12 months. I can't remember the intervention period. It was one or the other. And with durable effects over a follow-up period of five years or something like that.

1:01:55That is a great investment. That makes it a much more compelling sales pitch for me. And I've done plenty of VO2 max training in the past, but it's not necessarily fun, right? I mean, I will say, if you can, again, avoid getting your arms snapped, exhibit A right here with my elbow surgery. But if you can avoid the breaking limbs and getting choked out too frequently, something like jujitsu is actually fantastic because you might have three to five minute rounds and then you take a break for a round and then you go back in. And chances are, depending on who you're rolling with, it's going to be pretty intense.

1:02:34Obviously, it depends on how competitive the gym is. but the durability is just remarkable. That is really, really, really, really interesting. Now, is the threshold for sufficient intensity? I imagine it varies tremendously from person to person depending on lactate threshold, right? But for you, do you need to do something approaching the Norwegian four by four to cross the threshold sufficiently in your mind, or does something less suffice the problem with having just one i mean it's one very good study but just having one study on this is that we get really focused on the protocol but i think that anything that is regularly producing you're getting above your lactate threshold you're generating significant you know several millimoles of lactate i don't think people need to measure it but you know if you're getting 6, 7 plus, something like that, right?

1:03:36You're definitely going to be in that range. Is there something like people use a talk test, for instance, Peter Uttia talks about this for zone two training, where you can kind of have a conversation in belabored short sentences, but you don't really feel like it as an indicator that you may be roughly in zone two. Is there an equivalent for that range of lactate? Not that I know of. 10 % from puking into a bucket. Yeah, because it's definitely going to be misery related. So if I think about a lot of the training that I did as a student, I was a rower, right? And this is something... Oh, brutal.

1:04:14You love misery. Actually, I don't love misery enough, which is probably why I wasn't as good a rower as I could have been. But there are lots of protocols where you're doing relatively short sprints with relatively long rest periods that still generate large amounts of lactate. And so in studies where they've done this, you're talking about 30 seconds flat out on a bike or a rowing machine with several minutes of rest times six, eight, 10 rounds. By the end, you can generate a lot of lactate without having to do something continuously for several minutes at a time. I was just reading that one of the favorite training protocols for one of the like world champion rowers was 45 seconds i mean flat out like completely flat out on the rowing machine within six minutes of recovery but doing that you know several times and then at the end you're generating several millimolar of lactate so i think anything like that that's going to get you in that zone it just requires maximum effort for even just like 20 to 40 something seconds even with several minutes breaking between you're going to be hitting that.

1:05:27So I imagine the gold standard, do you have some guy in a lab coat and with a clipboard who pricks your finger or something and does these blood draws to determine the millimolar concentration of lactate? Is there a breathable option as there is with ketones, right? Where you can measure acetone through something that looks like a breathalyzer as opposed to a finger prick for BHB. Is there something that is, does anything like that exists it would make it a little ah no they're working on continuous lactate monitors just like you would have and some people do sort of have those they're right near being commercially available so some people do have access to those already but equally i would argue that it doesn't matter that much just like go and do something really really hard for a short period of time and do that a few times over and do that relatively regularly like that's probably enough majoring in the minors that you need to do to kind of get that benefit.

1:06:25Sounds like my sled assignment. I do love my sled pushing and pulling. You can definitely wipe yourself out with that stuff. Okay. All right. Without necessarily the impact of me trying to run from wolves on a treadmill or something. Okay. I do want to take a brief commercial break, but it's not for any sponsor. It's just to mention, And then we're going to kind of dive straight back into the programming and discussion. But you have a book that is coming out shortly called The Stimulated Mind. It goes through all the stuff we're talking about and a lot more. People should pick it up. That's Dr.

1:07:01Tommy Wood, obviously. But The Stimulated Mind. There's so much horseshit and charlatanism floating around out there in the world of anything related to cognition and memory. It's part of the reason... It's going to... segue is a little awkward, but part of the reason I wanted to have you, I was like, that's part of the reason I wanted to have you on is not to highlight necessarily that, but the antithesis of it, which is someone with real clinical expertise, research credentials, who is also a practitioner, right? It's like you walk the walk. And I wanted to ask you, you mentioned supplements earlier, and of course, everybody loves to hear about supplements, but what are some that may not be on the usual list of suspects, so to speak.

1:07:52I mean, one I would love to hear you speak to is CDP choline. People might not think of xylitol as a supplement, but certainly you could argue that maybe there's a place for it. Do you want to add anything to that and just expand on those? but i think that the supplements that we have the best evidence for are really they start with those core nutrients that we could get from the diet but if we don't then we definitely should supplement so we've mentioned omega-3s b vitamins especially those involved in methylation so that's vitamin b12 folate which is b9 riboflavin which is b2 and b6 vitamin d obviously critical iron supplementation, particularly if people are anemic.

1:08:36So that requires a whole assessment for like why are you anemic in the first place, but often particularly more common in women. And many of the symptoms that women may experience around perimenopause are associated with inadequate iron status. So getting your iron status checked and addressed is really important. Magnesium, certainly critical as well. If we're thinking about other things that do seem to have both an acute and long-term benefit in terms of cognitive function then all the kind of antioxidant polyphenols are very interesting particularly those that come from berries but related ones and coffee tea on the skins of roasted nuts and seeds like they have similar effects and then so you mentioned choline and right at the beginning we were talking about omega-3s i think choline is critical because it's important as a head group for fats to be attached to in membranes.

1:09:30That's maybe one of the reasons why it's important for the brain. And various estimates suggest that we're becoming increasingly choline deficient as we stop eating things like eggs and liver, which are our richest sources of dietary choline. But there are randomized controlled trials in two different settings that we've talked about already. So one in older adults already experiencing some degree of cognitive decline, where supplementing with CDP choline, which is also called citicholine, seems to improve certain aspects of cognitive function. And then, again, after traumatic brain injury, there are meta-analyses that show that supplementing with CDP-choline can improve some neuropsychological outcomes, in particular after TBI.

1:10:11So, I think most of us can probably get choline from the diet, but in some of these cognitively degraded states, you might call them something like 500 to 1 ,000 milligrams a day of choline seems to be beneficial. Do you take it, or do you just get it from eggs? I get it from eggs and liver. And some seafood sardines have some choline in, as do some whole grains, like oats have some, quinoa has some. So all of it kind of adds up. So I don't supplement with choline. I do supplement with creatine. I don't have the perfect trial that creatine is going to prevent dementia, but I think we've seen enough interesting data across depression, again, sleep deprivation.

1:10:53Sleep deprivation. How many grams do you take daily? What's your standard daily dose? I take 10 grams every day. Single dose or divided? Doesn't matter. So I take it all in one go in the morning. There's some evidence that suggests that once you get above five grams, you probably start to saturate creatine uptake transporters. So you don't necessarily, maybe you don't take all of it up. But the reason why I take it all in one go is because I remember to take all of it in one go. Another reason is that I find creatine to be quite stimulating, glycogratically stimulating for me. So you took your ketones, I took my creatine before I got on this call.

1:11:31I took five grams of creatine too. And so if I take creatine later in the day, I don't sleep as well. It's very noticeable for me, but it's not, that's not the case for everybody. Some people take creatine and they don't notice the cognitive effect. It doesn't affect their sleep. So it's very different from person to person. So those are the reasons why I just take it all in one go in the morning. especially if you're going to take over 10 grams, 20, 30 grams, you're probably best splitting it up into several doses so that you absorb more of it. Yeah, 30 grams at one go also is tempting the gods to smite you with a really, really bad bathroom situation.

1:12:06So yeah, and a lot of people do mention GI side effects from creatine. I think some of that is due to the quality of the supplement that you're taking. Yep, I agree. So if you're taking like CreaPure creatine monohydrate, that's what most studies that have tested creatine have used. And there was actually a systematic review meta-analysis that just came out that found that across all the studies they could find compared to placebo, creatine didn't have any additional GI side effects. But also those studies use high quality creatine. Also, not all those studies use 30 grams. So you could certainly get to a point where you're going to start to have GI effects based on those.

1:12:45Yeah, I think it also has to do with the fact that my polypharm in the morning when I'm just getting booted up, it's like I might be having the coffee plus the creatine plus sardines with MCT oil. Yeah, I mean, there's a lot going into the cocktail of potential disaster, which you do acclimate to. Quick question before I forget. On lactate, is there any argument to be made for anything that you would ingest or otherwise put into your body, not to avoid doing the intense exercise, but to increase the amount of lactate that you uptake into the brain? Is that something that people have looked at or is that just risky business and to be avoided because you'll end up in like some type of acidosis or some other problem so people have looked at exogenous lactate itself right usually as lactate salts just like you people have looked at ketone salts you can bump up blood lactate a little bit but similar to ketone salts that you don't get nearly the the increases you do with with other compounds you don't need to do anything to increase brain uptake of endogenous lactate because the brain will generally just take up as much as you've got similar to ketones right i think i i didn't ask i misspoke when i was asking the question i guess it was just increasing the amount of circulating lactates your brain just sucks it up like a vacuum yeah i think you can make plenty of lactate yourself so you know another way to do it blood flow restriction is another great way to produce lactate with low load there are some studies where well, they have them do leg presses, but like sets of 20 leg presses wearing blood flow restriction cuffs will...

1:14:33Oh, man. That will get you up there as well. Again, several millimolar of lactate. It's not fun. I think I'd rather do the Norwegians 4x4. Yeah. Oh, wow. That's intense. So that's another way to do it. So if you, for whatever reason, don't want to do sprints on a row machine, you can probably get up there with some blood flow restriction under low load and high rep. But no, I don't think there's anything that I would take to increase lactate. Just because you can make it so easily yourself. Alright, so I want to hop on the blood flow restriction because what make and model do you use? What's your tool of choice for the BFR stuff?

1:15:12I use the B-Strongs. Excuse me? The company is called B-Strong? B-E. No, capital B, Strong. I have no affiliation with them other than I know some of the guys who work there but I paid for my device myself so it has leg and arm cuffs but it comes with a sphygmomanometer one of those blood pressure things to pump it up to get the pressure those are the ones I use nice and simple, I'm testing a few different ones right now so when you travel people think of exercise as this thing that involves potentially all sorts of machines and you need your kit There can be a lot of excuses or things that people imagine as obstacles that are not, in fact, obstacles.

1:16:00So talk to me about your exercise when traveling with blood flow restriction. What does it look like? So as my wife calls it, I have my gym in a bag, which I take everywhere I go when I travel. And it is a set of blood flow restriction cuffs and a set of bands. I use the Black Mountain Products bands, which come with handles. I like them because they come with a lifetime warranty. I break them and snap them all the time. And you just email them and be like, hey, this broke. And they just send you a new one. And they cost$40 or something. So super cost effective. For people who are not looking at Tommy, I mean, you're freaking gigantic.

1:16:38I mean, you look gigantic. You're wearing a very thick sweatshirt. I can still see your pecs moving around for God's sake. What are your dimensions here? Not to turn you into a Playboy Playmate or something. So I'm 6 '2". I'm usually 220 pounds. I usually hang out somewhere around 12 % body fat. Yeah, strong unit. Okay. But the reason that I brought that up is not to flirt with you. Although I'm not against that either. Oh, I appreciate that. Yeah, yeah. No, the reason I wanted to bring it up is people might think there's somebody out there who's like an internet keyboard jockey on Reddit who's like living in a basement and squats 135 and is like, oh, that guy must be some pencil neck dweeb.

1:17:17And it's like, no, actually not. He's pretty big. And yet, like you can get, sounds like a decent workout with bands that cost 40 bucks and blood flow restriction. How is that possible? What do you do? So when I travel, because I'm usually at work, conferences, I'm doing podcasts or whatever, like I don't have two hours to go to the gym, which I like to have if I'm at home. So I might do 10 to 15 minutes. And right, you put on the cuffs, legs and arms. I'll do some lunges, like bodyweight lunges. squats, presses, push-ups, and then bicep curls and tricep extensions. And that's probably it. So a pretty standard protocol, which is essentially in three to four minutes, you accumulate somewhere between 75 and a hundred reps.

1:18:02So 30, 20, 20, 20, or 20, 15, 15, 15, 15, something like that with 30 seconds of rest in between. Try and do one body part at a time, but you can superset them if you're kind of short on time. That's it. And kind of to your point, when we moved into this house, this was now eight years ago, I built my own gym here. But for a long period of time, I didn't have a gym. And I was working from home. And all I had was bands and BFR cuffs. And then it wasn't even the B-Strongs. It was like these really cheap ones that kind of look like something that somebody would use to kind of like draw your blood.

1:18:42yeah like train spotting yeah yeah exactly it looks like um it looks like a tourniquet like to tie off your leg if you've like blown off your foot and again they cost like 20 bucks they're probably not the best anyway so i had some of those and some like 40 buck bands and that was all i used to work out for like four or five months and i didn't lose any muscle mass or strength i just got straight back into it afterwards so like you can maintain and gain pretty well. BFR can be a little bit painful if you push it, but also very, very safe. It's been used in rehab, all these other things that frail individuals...

1:19:20Just for people who are like, what the hell are they talking about? I'll use an analogy. This isn't exactly what's happening, but imagine you had a small belt, tiny belt that you put around your upper arms under the shoulders, at the top of the biceps. let's just say it, keep it simple. And then I guess close to the hip, right? On the legs. Yeah, like right up in the groin. And you're partially occluding blood flow, right? So you're not totally cutting off blood flow, but you're making it a lot harder for blood to get to your arms and your legs. It's mainly blood to get out. So the blood can, you're not compressing the arteries where the blood gets in.

1:20:00You're stopping the blood from coming out. The venous return. Yeah, exactly. Okay, got it. Yeah. And the net effect is if you're like Arnold Schwarzenegger and you're like, ah, the pump, I feel like coming. Yeah. If you want to take that to like a 20x extreme and feel very, very, very uncomfortable, BFR is a great way to do it. Again, for people who are like, oh, come on, man, I squat 315 or whatever. Like, I'm guessing you probably squat like at least 315 or more. And what do you squat? I'm curious now. My best squat, a couple of years ago, 405 is my best squat. Better deadlifter than I am a squatter.

1:20:37What do you deadlift? What's your PR for deadlifting? 550. Yeah, it's up there. All right. And I think you would probably agree, if you put somebody in leg cuffs and you're like, yeah, do proper lunges, like knee to the ground and go for like 100 yards and come back. I don't even think most people could do that. But it's just like, you're going to feel it, right? You are absolutely going to feel it. All right, Jim in a bag. We'll link to all this stuff in the show notes as well. So I want to list off a couple of things here and then talk about, we can keep bouncing around a lot. Well, on these supplements, I'm going to kind of cut this short and we'll put things in the show notes.

1:21:20But the periodontal health, mouth health, and dementia, the connection there, hence the use of... xylitol, whether that's the gum, Epic, Kygum, or air purifiers, mouthwashes. We've got all this stuff. So I'm going to link to that in the show notes just in the interest of time. And certainly feel free to chime in. I want to talk about cognitive stimulation, right? So we spoke about dancing earlier. Could you speak to language learning and music? Because I'm realizing I I think accidentally I might have really helped my brain a lot early, which is great as a surprise. But also have next to me an Ohana ukulele, which was gifted to me, that has basically just been gathering dust.

1:22:15And after doing prep for this and then looking into it, I'm like, you know what? I should spend a couple of minutes a day just screwing around with this. It seems like a great use of time. But could you speak to music and language learning? So this actually, if we include dance, this comes back to something that we kind of started talking about earlier, which is what are these experiences or what are these activities that you can do with the brain that kind of maximally activate it or increase glucose uptake? And there was a really interesting study that came out recently called Creative Experiences and Brain Clocks.

1:22:53Creative Experiences and Brain Clocks? Yeah. So I'll break that down into different components. So kind of like when you did an MRI scan for your brain and all those other tests you did, there were various different ways that people could sort of like estimate how old the brain looks. And I don't know if that's hugely BS or not. I don't know. It's a bit of both. But in this context, I think it's kind of useful because when you think about what happens to the brain as it ages, there are a few things that happen, right? the structure changes different parts of it get smaller right you lose volume but then functionally also changes the different networks that we have in the brain that have different functions and activities they become less discrete and they become more distributed you get less of these kind of very functions specific tightly knit networks and connections and then everything just like becomes a little bit more loose and different areas of the brain get connected together and it's sort of like a bit more of a mishmash you get this increase in entropy initially what we call is brain entropy right it's not as discrete entropy then decreases again as we get towards the end stages of dementia just because there's not much going on in there unfortunately anymore sorry that's bad that's the best way i can put it and so when you look at different ways to quantify how old this brain looks one way is to look at the structure and the connectivity of the networks and how like discrete they are.

1:24:26Things like the front-to-parietal network, the salience network, right? The attention network, like these parts that are really important for like executive function, focus, attention, all this kind of stuff. And they tend to lose function as we get older. And the easiest way to do this is with EEG. So electroencephalogram where you measure the electroactivity in the brain. And so in this study, what they did is they took a whole bunch of different studies and they looked at these different creative experiences. So one was tango dancing, one was language learning. Then there was musicians, they had artists, and they also had video gamers.

1:25:02And they had an interventional study where they had people learn the video game. And it was StarCraft was the game that they used, just in case anybody was wondering. Although most, if we're talking about video games as a cognitive stimulus, the one that has the best evidence is Super Mario 3D World, just in case you were interested. Lots of studies of that actually and what they did is they compared amateurs to experts and then they also looked at the effect of an intervention where people actually were trained in this thing and as you increase in expertise in these different creative complex arts you see improved structure and discreteness of these like really critical networks that are susceptible to aging as we get older so but the effect was similar in tango dancers versus those who are bilingual versus those who are artists versus video gamers.

1:25:48So there's some core effect of these complex, like multi-sensory stimuli that require us to gain significant expertise and skill in order to perform them that seem to have this broad effect. So part of this is probably because we're training our brains to be able to focus and learn. And then part of it is just like the actual engagement in this complex task. And so when you look at, say, languages, two very good colleagues of mine at the University of Washington, Andrea Stocko and Chantal Pratt, they study individuals who are bilingual. And what they see, they've done this from both measuring brain activity and different types of cognitive function, and then trying to model what's actually going on.

1:26:33And what it looks like is that those who grew up bilingual perform better on tasks requiring executive function. So things like response inhibition, which is you kind of want to do something, but you stop yourself just in time. Normally, when I talk about it, it's like, you know, when you have these thoughts of like, oh, well, what would happen if I just opened this window and jumped out? Or you think something and you stop yourself just before you say it because it's a really bad idea because it's like your boss. How do they test that? Are they using like a Stroop test as I'm just throwing something out there?

1:27:07So often it's like a go, no-go task. You're presented with different stimuli and it's whether you react to it or not. But like a stroop is partly an example of that. But people don't know what a stroop is. You should explain it, yeah. Yeah, so you get shown words that spell a color and they are also colored. And then you have to respond based on whether the word spells the color you're looking for or is the color you're looking for. And so it requires you to juggle these multiple things. So yeah, they use tests like that. But basically, it seems that because you spend your entire life having to suppress one language while you activate another and then move back and forward, your brain becomes better at suppressing these different.

1:27:49So at the same time, interestingly, it seems you become less good at other things. So it's like none of this is good or bad, but people who are bilingual seem to be less responsive to what's immediately happening around them in the outside world. And that's probably, again, just because of how their brains have adapted to these different stimuli. But you do see that those who grew up bilingual have a decreased risk of dementia. Or if they do get dementia, they get it later. But you also see improvements if you train in a language. Even using an app on Duolingo, they've shown that in older adults, you use Duolingo.

1:28:24And of course, you have to actually move through it, not just stare at it for 30 minutes a day. But you see significant improvements in executive function. You see the same thing with music learning. So there is something to these complex, very human kind of skills that have these carryover effects into these kind of core components of cognitive function. I'd never heard about the response inhibition with subjects who are bilingual, but it might explain in a totally separate battery of cognitive testing that I did, which was much more rigorous, I think, than what I did a few days ago. My digit string memorization, despite all my mnemonic trickery, is very bad because it's only flashed for a second and then you have to do your best.

1:29:13If you gave me a bunch of time, I could use all my trickery. But if it's just a flash and it's kind of relying on, I guess, my hardware, then I'm very bad. To the point where people might have some concern, but I've always been like that. Conversely, with something like There was a test that was pretty much exclusively the Stroop test, but I had a few things that were very similar. And I was like, I'm exaggerating, but like 10 standard deviations outside of the norm. I was so much better that they were like, why are you so good at this? We've actually never seen something like this. And it could be studying all these different languages.

1:29:50I don't know. Maybe. So do you know what? I'm actually the same. And we're kind of convincing ourselves that this is real just because it's the case for us. But I often do cognitive function tests on people we work with in studies and that kind of stuff. And we do this full battery, all the things that you mentioned. And on every test, you know, memory, all these other things, I'm just like, I'm perfectly average, right? And you kind of, you always think that, oh, I'm so smart. So therefore I should be like, what X standard deviation? But no, I'm like perfectly average on everything except for response inhibition tasks or the Stroop test.

1:30:23Then I'm like, and I also grew up speaking multiple languages. So I don't know that. Maybe that's the thing. We don't know. Which languages for you? So I speak Icelandic. My mom's Icelandic. So half my family were in Iceland. And then I lived in Germany and France when I was a kid for various periods of time. And then I did my PhD in Norway. And I taught in the medical school. So I had to learn Norwegian so that I could teach Norwegians medicine. Wow. That's hardcore. Yeah, there's quite a few. And for people out there who are like, well, I wasn't raised bi or trilingual, I didn't really even get started until I was 15, 16.

1:31:00I always assumed I was very, very bad at languages for reasons that were mostly related to the schooling and not to any inherent ability. But I'm also thinking about tango as an example, because I spent a lot of time doing tango. That was, I'm not sure if you have any familiarity with this chapter in my life, but in 2004, basically spent like six to eight hours a day doing tango in Argentina and competing ultimately and going to the world championships and all this craziness. But you have the physical component, but like you said, it's actually a pretty complex cocktail. And in my case, you not only had, sure, you have the dancing, but you also have Spanish, right?

1:31:44I was learning Spanish at the same time. And then you have the music. And I'm wondering if studies have been done looking at the effect of listening to or having to track different types of music versus producing music. Has anyone looked at that? Not as much. Certainly, frequent music listening is associated with a low risk of dementia as much as you can get rid of all the sociological pieces of that. There are some studies looking at training adults in musical theory, which requires actually listening to music and then pulling out the different components that seem to be, again, associated with similar benefits to, say, learning to play a musical instrument.

1:32:29And so I think even some of that attentive listening and actually sort of engaging with the music as a listener seems to have some of the benefits in addition to producing the music yourself. Yeah, because with dance, obviously, if you actually have a hope of dancing well, you have to listen very, very carefully to the music. And in particular, I mean, you could have choreographed dancing, but what interested me about tango, which I didn't realize in advance of getting to Argentina, is that the vast majority of it, tango de salón, is improvised. So if you're going to compete in that particular style of tango, salon tango, you don't know what music's going to be played.

1:33:12And then they just serve up whatever the songs happen to be. So you're not only responding to the music, but you're memorizing music. In any case, makes me want to get back to Argentina. Maybe it's all that time off. That's why your hippocampus has been catching up with you. Yeah, exactly. Oh, add that to my litany of complaints. So I wanted to highlight something. You've mentioned this. I don't think we need to spend a lot of time on it right now, but sensory loss, hearing, vision, right? Getting AIDS slash surgery as soon as possible, since those seem to be so correlated to increased risk or onset of dementia, I want to mention two things and then I'll let you rip.

1:33:59The second one is now I'm kind of paraphrasing here, but like error detection triggers adaptation. So like the importance of failure, because with a lot of the hand wavy pseudoscientific games and this, that, and the other thing that are sold for helping supposedly, right? Helping people with memory, cognition, etc. A lot of them don't seem to check that box. So maybe if you could speak to the sensory loss and then the kind of error detection and defining that and the importance of it. There are several studies that suggest that sensory loss, particularly vision loss through cataracts and hearing loss through age-related hearing loss, presbyacusis, are associated with an increased risk of dementia and that this risk is reversible.

1:34:51So if you have cataract surgery, then that increased risk is no longer there. And if you get hearing aids, again, that risk is no longer there. Of those two, randomized controlled trials have only been done with hearing aids, and they only showed significant benefit in those who were at an increased risk of dementia for other reasons, so like poor health, cardiovascular disease, these other things. So it may be that it's kind of exacerbating other underlying risks. But equally, we can think about two broad reasons why sensory loss might lead to cognitive decline and why often as people get older they're like i don't want to get a hearing aid because then i'm like then i'm old right conceded defeat yeah and so this happened with my mom actually and she recently got hearing aids and i encouraged i was like as soon as there's a thing that you need you should get it and it's had a dramatic effect on our quality of life and so we know that if you lose an input to an area of the brain, that area of the brain is going to decrease function as a result, right?

1:35:51It's no longer being used. And with the process of allostasis or constantly adapting to the demands that are placed on you, that part of the brain is just going to diminish its function. So that's part of it. But I think a bigger part is that when you lose senses, you no longer engage in the world in the same way that you did previously. You go out of the house less, you socialize less, you do less tango dancing, right? Because you don't feel like you can engage with it in the same way. so I think there's a lot of benefit from recovering lost senses that's not the same as so if you are born or if you never had sight or you never had hearing that's not associated with increased risk because you learn to engage with the world in other ways right so it's the loss of that engagement that I think is important then the error part the easiest way to think about this is that if we're trying to improve function and structure of certain parts of the brain that allows us to have greater reserve, you know, greater total capacity.

1:36:50And therefore, if we do lose some volume or some capacity as we get older, right, we have more to lose. So we're less likely to get to the point where we have significant deficits. In order to drive improvements in structure and function, right, we need to drive these processes that we call neuroplasticity. New connections, new branches, all the supporting machinery, the other cells that are necessary, right? We think a lot about neurons, but there's a whole bunch of other cells and stuff in your brain. that are really important as well, that are part of this response to stimulus. But to drive neuroplasticity, you essentially have to have a difference between capacity and expectation.

1:37:28The best way to uncover that is with mistakes or errors. Well, it's kind of like muscular training to failure. Exactly, yeah. If you don't ever get to the point where you're no longer capable of doing the thing that you want to do, nothing needs to change. You can already do it. Yeah, exactly. Your body doesn't need to adapt. Exactly. Yeah, so that's essentially it. And this is what becomes important in dancing, learning languages, learning music, right? Is that you having these opportunities to fail, to kind of get beyond your current capabilities. And like, that's what drives the processes of learning and plasticity.

1:38:03What else do you have in your personal regimen of non-negotiables? You've got, obviously, you're lifting weights. You're doing your blood flow restriction torture every once in a while. I don't know if you're much of a ballroom dancer. I was a field raver in my youth, but I was never much of a ballroom dancer. Get that man some glow sticks. So, you know, I have a few. Part of the reason, a big part of the reason I got elbow surgery was to get back into rock climbing, which I think is just a phenomenal, phenomenal sport for mental and physical development. I mean, it's just a kinesthetic puzzle on a wall.

1:38:52I mean, I was really inspired over the last two years seeing people in places like Colorado, Idaho, Utah, where I'd go into these gyms and you see people in their 60s and 70s who are doing stuff that I can't even imagine doing physically. And they meet a couple times a week. And I was like, wow, okay, if you can have that kind of longevity in this sport, like that seems like a great investment. Plus, I just really, really enjoy doing it. But what are some other non-negotiables, right? If you look at all the possible things you could do, all the things you do, and you're like, all right, these are the things that are meaningful and that I stick with consistently, what falls in that bucket, right?

1:39:36Because a lot of people will get these like 27 things, 47 things you can do to improve your brain health lists or whatever. And even if they want to do all of those things, there's no way they're going to. There's a question of sustainability or adherence as well. Yeah, what are some of the other non-negotiables for you? The one that we haven't talked about that really is non-negotiable is sleep. Yeah, let's talk about it. I think this is the major thing that's missing from these studies looking at dementia prevention as a risk factor. I think inadequate sleep really seen in so many studies now that's associated with increased risk of dementia.

1:40:12So that's something that I very consistently make sure that I get enough of. That's like the one thing that really is non-negotiable. Like I can, I don't mind if my diet gets a bit crappy for a few days, or I don't mind if I can't get to the gym for a few days. Like this stuff integrates over months and years. Like, but if I can only focus on one thing, then sleep is really critical for me. But I will say one thing that I've noticed a lot was that historically, I used to really get in my head about my sleep. And I know this is gonna be the case for many people who have tracked their sleep or used wearables or thought about the importance of sleep, right?

1:40:49And so something that changed recently, particularly because I spent a lot of time looking at the research, and this also affected me at home because my wife was like, if you don't sleep and then you don't get your coffee, like, I don't want to be around you because... Just picked up a moderate heroin habit? No.

1:41:06A lot of it was honestly self-induced because I thought I didn't sleep well, therefore I'm not going to function well, I'm going to be grumpy, like all this kind of stuff. And we know that this is influenced by outside factors. It's influenced by our own thought processes. There are studies that have shown this, randomizing people to be told by their wearable they didn't sleep well, even though when they slept just fine. And what you see, long-term sleep is critical, right? Absolutely. And any sleep you can get more than you are having now, the better, right? So if you sleep six hours a night, you can get six and a half, great.

1:41:37Like, don't think that you have to sleep eight hours, right? If you can get an extra half an hour, that's amazing. But in short periods of time, actually sleep deprivation doesn't have as much of a negative effect on cognitive function as we think. And this is just important so that we can go about our day-to-day lives and perform well when we don't sleep well. Especially when you have a chalk bag full of creatine at your desk. So like, yeah, the creatine helps. But equally, like we travel, we have kids, right? All this kind of stuff. Sometimes you're just not going to sleep well. But in short periods of time, over like a few days, what happens is that processing speed slows down, but accuracy doesn't.

1:42:12So the quality of your work is just as good. It just might take you a little longer. And mood is affected much more than performance. So actually, we don't perform less well, we just feel more grumpy about how we performed. So actually, knowing this, I then just completely changed how I approach my sleep. So if I didn't sleep well, I'm like, do you know what? I'm actually going to be fine. Then it turns out I am fine. So that's like, yes, sleep is critical. but how we think about these things i think is really important so like important factors are going to be avoiding excessive alcohol don't smoke but then two things that we you mentioned we haven't touched upon fully i'll kind of like briefly talk about one is air quality and air pollution which is a significant risk factor for dementia a lot of these studies are quite recent looking at say wildfire exposure and things like that but even living near roads like in the short term is associated with greater cardiovascular risk higher blood pressure which you can improve with having an air filter of all the different like metabolic type risk factors for dementia high blood sugar and high blood pressure are the two most important lipids and other things are important as well but those are consistently the highest risk factors managing blood pressure is really important and if so you live near somewhere where there's a lot of air pollution then air filters certainly seemed to help there.

1:43:37And then oral health was the final one. So like, I say this because I appreciate that I'm British and I'm going to tell you, you should go to the dentist. So historically, when I lived in the UK, I did not go to the dentist very frequently. And actually the first time I went to the dentist here in the US, I have this one metal crown from back when I was a medical student and my dentist looked at it and he was like, you didn't get that done in the US. That was his first comment. But gum disease to gingivitis, especially if it advances to periodontitis, is significantly associated with an increased risk of dementia.

1:44:15This is probably both due to an increased systemic inflammatory effect, plus those bacteria can get into the bloodstream. They're found in atherosclerotic plaques in heart disease. They've been found in amyloid plaques in the brain. So treating gum disease is really important, whatever that requires. And that's why I mentioned xylitol to you because there are several studies showing that xylitol gum or xylitol mouthwash can improve the oral microbiota, decrease some of these cavity and periodontitis causing bacteria like strep mutans and porphyromonas gingivalis. So it's just like a really low risk kind of thing.

1:44:54There he is with his gum. Piece of gum in my pocket. a low risk thing to consider and i don't think they've looked at it by apo e4 genotype but things that have an anti-inflammatory effect or decrease inflammatory burden seem to have an outsized benefit for those who are apo e4 carriers and so gum disease would obviously be one of those that's worth keeping an eye on that's part of the reason not to keep banging on this drum because i know it's not the shoe that fits everyone but that's another reason for my fascination with ketones. Just remarkably anti-inflammatory on a couple of different levels.

1:45:31So for folks who might be wondering, and we'll put these in the show notes as well, air purifiers, do you mind if I just read from this email that you sent to me? Because of course, I'm such a stickler. I'm like, what exactly make and model? So I'll just read from this. The blood pressure study I mentioned, this is I equals Tommy, used the Health Mate, that's one word jasper is good that's jspr as are most of the blue air one word blue air models tailored to the size of the room the coway c-o-w-a-y air mega is a good budget option so we'll link to all these in the show notes this is one god with travel such a pain in the ass although i have i think it was james nester who wrote the book breath who was giving me just some horrifying sort of quantified self data related to looking at like co2 concentration in various hotels and airplanes and so and so he i don't think he'll stay in a hotel that has sealed windows i think it's kind of part of his policy yeah high co2 really negatively impacts sleep like lots of people in a small room that's not ventilated that can definitely negatively impact sleep so So we always have a window open or something for that reason.

1:46:48Anything else that you do for sleep, besides not becoming too orthorexic about it and freaking out on the wearables and stuff, which is a real thing for sure. So besides recognizing that you're going to be fine, humans have been dealing with this for a long time, what else would you say? I would imagine there are things people have probably heard, like keeping the temperature, sort of whatever it might be like 65 to 70 degrees Fahrenheit etc other things that you find particularly helpful things that have helped me a lot I stop work before dinner I don't do work after dinner unless I really really have to and that that helps a lot because I find I ruminate a lot more if I if I do work late into the evening a basic shutdown routine I put on the blue light blocking glasses they're probably just placebo at this point but like I put them on and like my brain is like oh it's bedtime and then i read fiction before i go to sleep i have a quite a recent purchase was an eight sleep which has been amazing because i tend to get quite hot when i sleep that's helped a bunch so it's kind of helped stay cool and then i wear an eye mask which i really like for you know blocking out light there were also some very nice studies on that one of my favorite studies looking at eye masks you ever see this one where in the control group they had them wear like a zorro mask so they were still wearing a mask but like the eyes were cut out.

1:48:07And this was during the summer when light would come in early in the morning, would disrupt sleep. And they saw significant improvements in cognitive function in those wearing the regular eye mask versus like the Zorro. Yeah, so it's hilarious. That's probably my list. I'm going to ask you something specific about sleep, but just because I have it in front of me to ask you, vitamin K2, do you supplement K2 or do you get it from something else? I do generally supplement just like a few micrograms a day, maybe 15 or 20. But that's mainly because it comes with my vitamin D that I will supplement particularly in the winter.

1:48:44In the summer, I get plenty of sun exposure on bare skin, but in the winter, can't do that in Seattle. But I also don't mind a little bit of natto or some fermented foods that would have K2 in as well. So don't need to supplement. Stinky spider webs. If anybody likes the sound of stinky spider webs, try natto, N-A-T-T-O. It's the one that Japanese people like to give foreigners to watch the face. Some people like it. I can handle a little bit. I can handle a little bit. I mean, I grew up eating rotten shark in Iceland, so... Oh, that stuff is so fucking bad. I went to this place called Hotel Ranga.

1:49:23I think it's Ranga to bring my family. My mom had always her whole life wanted to see the Northern Lights. And so we went there in the middle of the winter. By the way, folks, not a whole lot of light. It's like twilight for a few hours. That's all you get. But there was some fermented shark celebratory day. And we drove to what looked like, and I think it was a gas station, but had a restaurant attached to it and ate this fermented shark. I don't even know how to describe, how would you describe it? It was like, I mean, fermented shark, as you would imagine, but like eating something soaked in like ammonia, like the pungency when it hits your sinuses is like smelling salt.

1:50:06Yeah, because it is ammonia. So to make Greenland shark, which is the type of shark edible, so Greenland sharks don't have kidneys. So their tissue, their body accumulates urea, right? Because they can't, they don't pee it out. So in order to make it edible, that urea has to break down to ammonia. Then it becomes... Edible, in quotation marks. And so it is ammonia that you're tasting, but it's like it's got the texture of tuna and the taste of a really, really, really strong blue cheese that you peed on. I will say I wasn't really hankering for a return trip to that particular gas station to eat fermented shark, but watching my brother try to eat it It was one of the most entertaining moments I'd had in a long time.

1:50:58So you know you're supposed to alternate shark with brendavien, which is Icelandic aquavit. You eat the shark, then you use the brendavien to take away the taste of the shark, you use the shark to take away the taste of the brendavien, and then you just continue that until... So you just get hammered enough that you don't care that you're eating fermented piss shark. Exactly. There is one thing that's... So actually, I don't mind the shark that much. There's one thing that's much, much worse. If you ever have a chance to try surströmming, which is a Swedish fermented herring in a can. That is the worst thing I've ever put in my mouth.

1:51:27It's terrible. It's like when you open the can, actually, if you look it up, there are all these YouTube videos of people who like get it in the US and they open it and like the smell comes and they immediately throw up. It's like you open the tin and you like take out these like rotting bones of herring that you kind of put on bread. Highly recommended. Yeah. All right. I don't know what I'm doing for near years. All right. So sleep, do you have a position on the DORAs, on the dual orexin receptor antagonists? I've chatted with folks, including Matt Walker, who's very credible in the space with respect to sleep research.

1:52:09the potential that DORA's could help with the clearance of beta amyloid, what is it, P-tau-217, et cetera, and possibly be of some help in preventing the accumulation of things that later contribute to Alzheimer's. It's not like the vote is in and it's 100%, but there seems to be a couple of interesting publications around it, including Inhumans. Do you have a position or any thoughts on it? So like very quickly, we know that sleep quality and quantity affect amyloid accumulation in the brain. That can be seen over short periods and long periods. And some of that work is from Matt Walker's lab.

1:52:54And he's even done studies that show that later in life, if you can improve the amount of sleep that you get, that's associated with a lower overall amyloid burden. I think that some of this, like we get very focused on amyloid. It's a part of the picture of Alzheimer's dementia. Just like you said, it's not the full picture. But I think we look at it and it's a marker for all the things that you should be clearing out of the brain when you sleep that you aren't, right? Amyloid is one of those things. There are probably many other things as well. So the DORAs have now several studies in different states, in insomnia, in sleep apnea, these states where we know people are getting lower quality sleep, and they certainly seem to improve that.

1:53:31I think that in individuals who have some kind of sleep issue, be that insomnia, something else that's going to prevent high quality sleep, then improving that is certainly going to be beneficial. Right now, the door is now the best option. Previously, people recommended trazodone, which was like, we talked previously like the least worst option, because it doesn't negatively affect sleep architecture, unlike many of the other sedatives that people might use to help sleep. But if you're sleeping fine, or you manage to maintain high quality sleep as you get older, I don't think we need to start taking doors to prevent Alzheimer's because I think your sleep is probably already doing the job that it's doing.

1:54:11And there are studies that show that increased cognitive stimulation in older adults improves sleep quality or that engaging in cognitively stimulating activities helps to offset some of the potential increased risk that we would have with poor or less good deep sleep, which is when a lot of this clearance happens. So I think a lot of the other things that we mentioned already, physical activity, we know improves sleep quality. So I wouldn't jump straight to Dora's, but in somebody who does have insomnia and say CBT for insomnia doesn't help them, or some of these other things that we can do to improve sleep and those don't work, and you've ruled out anything sinister, then I think they're now our best option to help support sleep.

1:54:55All right. We have covered a lot. I want to know why you decided to do something very difficult, which is write a book. The Stimulated Mind. What was the driver behind this and who is the book for? I like to joke that the book is for anybody with a brain. The subtitle is about preventing dementia, but really a ton of it is just about cognitive function and cognitive performance in general. So even people who are younger and aren't thinking about dementia yet, although, like you said, it's worth thinking about it earlier than you think. I think for most people who think about how their brains work or want their brains to perform better and or want to prevent or minimize their risk of dementia long term, it's got what I think are the big rocks and the tactics for how to address those that we know substantially increase dementia risk.

1:55:47all those things we talked about earlier that kind of contribute to those dementias that are potentially preventable. And the reason I wrote it is because I didn't think that book really existed. Like people might focus on one particular area or they might focus on everything, right? There are books on dementia prevention that are just like endless tables of blood tests and supplements and this stuff that just like most people are never going to do, right? It's not going to be sustainable. I didn't really see a middle ground. But equally, I wanted it to be very heavily referenced. So if people want to get into the references, I have a reference list.

1:56:25It's going to be 2000 papers, all in humans. And it's cited in the text, right? I have like little superscript citations. You teased the subtitle a little bit. It's a good subtitle. I've so want to give it some real estate here. So the stimulated mind subtitle future proof your brain from dementia and stay sharp at any age. I'm looking at the Amazon page for the first time. I hadn't looked at it. I had no idea that you know Kelly and Juliette Starrett. Those are two very close friends of mine. And you got a very nice quote from Dr. Kelly and Juliette for the book. That's fantastic. I only really connected with them about a year ago, but they've been some of the most, I just have, like, they've been so, so helpful.

1:57:08Like, what do you do when you wrote a book and How do you get it out there? And how do you get people to read it? Like they've given me so much of their time and help. They've just been they've been amazing. Yeah, they're fantastic. All right. So Dr. Wood, that's you, explains that a brain that improves with age is the result not of expensive pills, far off discoveries, or strict lifestyle optimizations, but rather of actions within our control. Diet, sleep, physical activity, social connection, stress tolerance, and obviously it goes on and on. But clearly you have a lot of very practical, specific advice that people can implement.

1:57:44And what else makes this book different? So I think those things that I mentioned make it different. I think it's very practical and approachable, but very science driven. And if people want to like dig into the references that those are available. And then I think like towards the end, right, after I've given you like, there's all these different areas where we talked about nutrition, sleep, physical exercise, I give like how you would approach each of those things in terms of supporting cognitive function and minimizing dementia risk. But then I kind of bring them together in a model of how I think people can implement this in our daily lives.

1:58:18Like, how do I just pick one thing? And actually, does picking just one thing help to support like the overall function of the brain? And the answer is yes, it does. Because when you sleep better, to say if you focus on improving sleep, you're more sociable, you're more likely to engage in cognitively challenging tasks, your blood sugar improves, your blood pressure improves. So just changing one area, suddenly the whole network shifts in your favor. And that's the case from almost anywhere where you kind of approach it. And I think that means that people are much more likely to actually start doing this stuff and realize that it doesn't require a ton of work to start moving the needle.

1:58:56And then these things, you know, sort of compound over time. All right. The stimulated mind, folks, go grab a copy. Obviously, you know I hate when people say obviously but I'm going to say it obviously Dr. Tommy has the credentials, has the expertise has the bona fides with respect to research in humans and has provided a lot that you can use in this conversation and a lot more is in the stimulated mind so check it out. Why on earth is your ex-account called Dr. Ragnar? Oh. I first started blogging around the the time you first started podcasting, I remember listening to your first interviews with Dom D 'Agostino back in the day when I was in my PhD chair, kind of writing blog posts.

1:59:43But my middle name is Ragnar. So I created a website. It was Dr. Ragnar. That was initially where I did my stuff. So let me think about this for a second. I'm going to make myself probably regret asking this question. But what is Ragnar? Does Ragnar mean anything? Because now I'm thinking of Ragnarok. And if those two have any connection, does it mean anything in particular? No, so you're right. Ragnarok is like the final battle for Valhalla. And actually, there are some online gaming accounts where I use the name Ragnarok. But no, I think what it means, the translation for the Old Norse is like, wise counselor.

2:00:21I think that was another reason why I picked it. Because it was very self-important as a 30-year-old health blogger. but it was my grandfather's name. And then these names sort of get passed down in the family. Technically it should have, because I was the first born grandson. It should have been my first name, but my dad was English and it was like, people are just going to make fun of him at school. He's going to get bullied if he's called Ragnar. It's very cool now, right? Because of Vikings and like all these other TV shows where Ragnar now appears. I mean, you could make it work, but Dr. Ragnar Wood also has kind of a strange combo.

2:00:59Yeah, yeah. One, two to it. Yeah. All right. Got it. At Dr. Ragnar. R-A-G-N-A-R on X for people who want to check it out. To be honest, I don't use X. So you can follow me on X, but you won't see anything. But people can find, presumably there's something at DrTommyWood.com, D-R-TommyWood.com. So that's the home base online. Instagram. Instagram. At Dr. Tommywood, again, D-R-Tommywood. At Dr. Tommywood. All right, folks. So you got it. Check out The Stimulated Mind. I'm a huge fan of what you do. I am going to try to improve my chesticle and arm situation with more use of BFR and bands. And is there anything else you would like to say before we wind this to a close?

2:01:48Anything you'd like to ask of the audience, point them to, requests, complaints? anything that comes to mind? No, other than, you know, if you do happen to pick a copy of the book and you do have any complaints, do send them to me. One of the reasons why I wanted to make it so that like every statement that I have in the book has a citation. You can go, you can read that paper. If you disagree with my interpretation of it, I want to know. Like I can't promise that I have all the answers. So that will help me learn more. So yeah, if you have a complaint, just tell me about it. All right, Tommy.

2:02:22I really appreciate all the time, man. This was great. I took tons of notes for myself, which is always a good sign. Thanks for carving out a bit of time to be on the show. Really appreciate it. Thanks so much for having me. This was so much fun. For everybody listening, as per usual, we'll provide copious links and show notes at tim.blog.com and until next time, be just a bit kinder than is necessary to others and also to yourself. As Jack Kornfield says, if your compassion does not include yourself, it is incomplete. Thanks for tuning in.

2:03:21that I send out every Friday to share the coolest things I've found or discovered or have started exploring over that week. It's kind of like my diary of cool things. It often includes articles I'm reading, books I'm reading, albums, perhaps gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcast guests. And these strange esoteric things end up in my field and then I test them and then I share them with you. So if that sounds fun. Again, it's very short, a little tiny bite of goodness before you head off for the weekend, something to think about.

2:03:56If you'd like to try it out, just go to tim.blog slash Friday, type that into your browser, tim.blog slash Friday, drop in your email and you'll get the very next one. Thanks for listening. Folks, tax season is upon us. Fun, fun, fun. It always has a way of forcing us to look at our finances, whether we want to or not. And if you're dreading that moment, it's a lot to pull together. There are ways to make your finances easier and far less stressful. Today's sponsor, Monarch, is the all-in-one personal finance tool. It's used by a bunch of my friends. It's used by my employees, designed to help make your life easier.

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2:05:41What many of you may not know is that I actually run two private invite-only communities for some of my projects. The No Book, which eventually will come out after God knows how long, and Coyote, the card game. And the feedback from those groups has been absolutely invaluable. Moreover, perhaps most important, the connections that members have made and the interactions have been just a joy to behold. It's been so much fun. And I generally view communities as headache after headache after headache, way back in the day with like B Bulletin and whatever, and not to slam those guys. But man, oh man, running communities can be a pain in the ass.

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