The Peter Attia Drive - #356 - AMA #73： Preserving brain health, optimizing exercise programming, improving body composition, and more

00:00:00.000 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.

00:00:15.820 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access

00:00:20.280 the AMA episodes in full, along with a ton of other membership benefits we've created,

00:00:24.900 or you can learn more now by going to peteratiyahmd.com forward slash subscribe.

00:00:30.600 So without further delay, here's today's sneak peek of the ask me anything episode.

00:00:38.820 Welcome to ask me anything AMA episode 73. For today's AMA, we're answering a mix of the most

00:00:46.400 requested listener questions covering some of our most popular topics, including brain health,

00:00:51.880 optimal exercise programming, and body composition strategies. Specifically, we discuss modifiable

00:00:58.320 and non-modifiable risk factors for dementia and how exercise, sleep, alcohol, hearing,

00:01:04.740 oral hygiene, supplements, and cholesterol levels influence brain health, how to implement zone

00:01:10.200 two training, why it matters, how to lactate test if you choose to use it, combining cardio modalities

00:01:16.800 and special considerations for peri and post-menopausal women, talk about strategies for

00:01:23.240 how to increase VO2 max, including optimal interval length when shorter HIIT workouts can help and why

00:01:29.800 power or rate of perceived exertion is preferable to heart rate training or heart rate targets during

00:01:36.480 these efforts, the benefits of light movement after meals for glucose control and why exercise-induced

00:01:42.500 glucose spikes are expected and harmless, finding the right mix of strength and stability work,

00:01:48.280 adjusting for workouts, for sore or sensitive backs, and weighing the pros and cons of lifting

00:01:53.580 heavy weights that press down on the spine. Talk about exercise's role in maintaining fat loss programs,

00:02:00.760 debunking the slow metabolism myth, and setting daily protein targets, and managing the lean mass

00:02:07.520 versus body fat trade-off over time. If you're a subscriber and want to watch the full video of

00:02:13.340 this podcast, you can find it on the show notes page. And if you're not a subscriber, you can watch

00:02:17.960 a sneak peek of our video on our YouTube page. So without further delay, I hope you enjoy AMA number 73.

00:02:29.920 Peter, welcome to another AMA. How are you doing?

00:02:33.620 Doing great. Thank you for having me back.

00:02:35.180 I really sense that greatness and that tone of your voice right there. I think you really sold

00:02:41.240 people on it. Before we start, for those watching and for those listening, do you want to explain the

00:02:46.740 t-shirt that you're rocking today? Normally, you are the one that designs all of our t-shirts.

00:02:53.540 This is the first time I've designed a t-shirt. I'm really happy about this. I guess for those who

00:02:58.900 can see it, it's got f of x equals a big fluffy sheep. And then d by dx of f of x equals a big

00:03:08.340 pile of fluffy wool. And then d2 dx squared of f of x is a wool sweater, which I just think is so

00:03:16.880 great. And I made it so that my daughter would have something to look forward to when she got to high

00:03:23.560 school calculus. Yes. And as someone who's never taken high school calculus, I still don't quite

00:03:29.660 know what the letters mean, but I did understand the pictures. So I have that going for me. Today's

00:03:35.860 AMA, nothing to do with math or sheep. Instead of focusing on one topic, what we did is a little bit

00:03:42.420 more of a rapid fire style where we're going to have a variety of questions. And so we went to the

00:03:47.460 audience on social media, through the website, through the AMA portal, gathered some of the most

00:03:52.360 common questions we're asked, the questions we see come through all the time. And also some of the

00:03:57.580 questions on topics that we know are interesting to people, which is brain health, exercise, body

00:04:03.340 composition. For today, we'll cover questions around all the different variables, interventions

00:04:09.000 people can do in order to prevent cognitive and neurological decline, obviously of interest for

00:04:15.700 anyone who has a brain and hopes to keep it intact. We'll dive into the most common exercise

00:04:20.460 questions, which are a lot around zone two, including questions around if females should

00:04:26.140 be doing zone two training, as well as some VO2 max training questions. And then we'll look

00:04:31.060 at some body composition and diet questions, which kind of focus a little bit on exercise,

00:04:35.720 but also around losing fat mass, building lean mass, the role of protein. With all that said,

00:04:41.420 anything you want to add before we get rolling?

00:04:43.940 Take it away.

00:04:44.700 You think you're going to be able to work your math into it throughout that?

00:04:47.300 If there's a way to get a first or second derivative into this, I will find it.

00:04:51.460 A story for a different day, but a throwback for people who have listened to you for a while.

00:04:55.180 I didn't even put together till just now. The t-shirt also fits when you're at parties and you

00:05:01.500 explain to people what you do for a living, which is a shepherd.

00:05:04.240 You don't think that wasn't deliberate, my friend?

00:05:07.920 This is now your social gathering t-shirt. So, oh, nice to meet you. What do you do?

00:05:13.100 Oh, let me tell you about my shirt. Smart. It's well played.

00:05:16.460 This is what I do.

00:05:17.980 Yeah, that's good. I'm really kind of disappointed in myself that I didn't put that together till just

00:05:23.460 now. It's probably why I didn't take calculus. With that, let's roll. So, questions around cognitive

00:05:29.500 neurological health. Mainly what we see a lot in this comes through is preventing cognitive decline.

00:05:35.600 It's something people care a ton about. We did a previous AMA on it, AMA 46, which we went into a lot

00:05:41.360 of detail. We're not going to go into that detail. This will kind of be a primer, answer some questions

00:05:46.020 at a high level. But if anyone wants to dive deeper, that's a great resource. But I think a

00:05:51.460 place to start that's really helpful for people is understanding what even puts someone at a higher

00:05:56.660 risk for dementia cognitive decline.

00:06:00.020 I guess there's different ways one could think about this. I do like to think of it through the

00:06:03.640 lens of modifiable and non-modifiable things. So, we can just briefly, briefly touch on non-modifiable

00:06:10.040 things and say very little about them, frankly, because they're not modifiable, but they're

00:06:14.940 worth acknowledging. Age, sex, genes are not modifiable, and yet they all play a role in the

00:06:22.740 risk of dementia. And I think people who are not strangers to this podcast will know exactly

00:06:28.200 what each of those things imply. So, obviously, as age rises, so too does the risk of cognitive

00:06:33.820 decline, inclusive, of course, of all forms of dementia. That rise is monotonic, meaning it

00:06:38.740 never abates and it just keeps going up and up and up. We also see this profound discordance

00:06:43.540 between men and women, where women have twice the risk of Alzheimer's disease to men. There

00:06:50.520 are lots of theories as to why that's the case, but it is not solely explained by the slight

00:06:56.780 gap in life expectancy between men and women. We've explored this in great detail in other

00:07:01.060 podcasts, so I don't want to say too much more on it here. My personal point of view is that

00:07:05.040 much of that risk is probably explained by sudden estrogen withdrawal during menopause,

00:07:10.000 which, of course, would suggest that HRT might be a way to close that gap, but it's too soon

00:07:14.080 to tell. And then, of course, we have the genetic risks, and the most notable of these is, of

00:07:19.240 course, the APOE4 genotype, but, of course, there are many other genes that are associated

00:07:24.700 with that. Okay, so let's put the non-modifiable risks off to the side, and let's talk about

00:07:29.860 modifiable risks. So when we talk about modifiable risks, what we are talking about is metabolic

00:07:35.040 disease, specifically obesity type 2 diabetes, talking about hypertension, and we're talking

00:07:40.940 about dyslipidemia. All of those things factor heavily into the development of dementia and

00:07:47.140 Alzheimer's disease specifically, and they are all modifiable, which is the good news. I think

00:07:51.780 I could spend the entire discussion on those things, but we've done that elsewhere, so I just

00:07:56.000 kind of want to give a couple of the high points. So obesity is associated with about a 60% increase

00:08:01.020 in the risk of dementia. That means in any given year, an individual who is obese compared to

00:08:07.840 somebody who is not is going to have a 60% relative increase in risk. So at a young age, that doesn't

00:08:13.100 mean anything because the absolute risk is so low, but as you get older, this number gets higher.

00:08:17.420 For every one millimole per liter increase in LDL cholesterol, which is about a 40 milligram

00:08:24.840 per deciliter increase, that's about an 8 to 10% increase in all-cause dementia. And so the added

00:08:33.300 risk for dementia with type 2 diabetes or hypertension is actually similar to that of obesity. Diabetes

00:08:38.800 increases the risk by about 50%, and hypertension increases by about 60%. In other words, having diabetes

00:08:46.440 for a longer period of time increases the risk. We see that, of course, when we see that for every

00:08:53.100 five years that a person is diagnosed with type 2 diabetes, their risk increases by almost 25%. So

00:09:00.520 again, it's kind of like one of these area under the curve problems, not to keep bringing it back to

00:09:04.780 calculus. There's some other nuance to this, which again, may be deeper than we want to go into it for

00:09:10.280 kind of a rapid fire, but it turns out that if you're an APOE4 carrier, you become even more

00:09:15.740 susceptible to these modifiable risk factors. In other words, if you take an APOE4 carrier versus

00:09:23.980 a non-E4 carrier, both of whom have diabetes, there's a significant increase in risk for the

00:09:31.400 APOE4 carrier, and it's about a five to five and a half fold risk difference between these two

00:09:37.100 individuals. So all of this is to say, if your objective is to prevent cognitive decline, which

00:09:42.620 obviously would be everyone's objective, you want to manage what is manageable. You want to be

00:09:48.020 normotensive to blood pressure, 120 over 80 and below. You want lipids as low as possible,

00:09:53.900 although we'll talk about where that plateaus out. You want to be as metabolically healthy as possible

00:09:58.840 and be as insulin sensitive as possible. One follow-up there, which since you brought up math

00:10:04.020 is another math problem, is you ran through obesity, diabetes, hypertension. What do we know on,

00:10:11.000 do those cause dementia or are they just correlated with dementia?

00:10:15.420 Yeah, always the important question. How would one answer that question? So there are really only

00:10:20.640 two tools we have at our disposal to address causality in humans. And one is the randomized control

00:10:27.820 trial, and that's the gold standard. And then I'd say a slightly lesser standard,

00:10:31.420 and it varies dramatically by indication, is the Mendelian randomization.

00:10:36.700 So when you consider this particular question, we have fairly robust evidence that hypertension,

00:10:44.000 type 2 diabetes, and hypercholesterolemia can cause heightened increase in dementia risk.

00:10:51.620 And we say that because when you look at RCTs that specifically treat those things with a primary

00:11:00.020 outcome being dementia risk reduction, we see those benefits. Now, sometimes those are secondary

00:11:06.740 benefits. So we have trials that are conducted, for example, to address coronary artery disease as the

00:11:12.640 primary outcome, but a secondary outcome is dementia. And you have to be a little bit careful because you

00:11:18.040 don't always have a trial designed exactly to identify all the conditions around secondary findings.

00:11:23.100 But nevertheless, when you have robust and significant volume of RCT datas that are treating

00:11:29.640 constitutive elements within this, and you see benefits, that becomes pretty powerful.

00:11:35.200 You also then have to look at what are the mechanistic reasons why these might be the case. And again,

00:11:39.220 I think in all of these cases, high blood pressure and the endothelial damage that comes from it,

00:11:45.020 hypercholesterolemia and the endothelial damage that comes from that, and type 2 diabetes,

00:11:50.680 you see common things that occur in all of these things. You see inflammation, you see oxidative

00:11:55.300 stress, you see amyloid buildup, you see insulin resistance, and all of these things mechanistically

00:12:01.280 also make sense. So again, all of this is to say that I think we're very confident that there is

00:12:07.780 not just correlation here, but causality. Now, one of the challenges, and this is why I don't find

00:12:13.060 myself memorizing what the risk factors are here and saying, well, gosh, the relative risk here is 60%

00:12:19.780 versus 55%. These things don't travel by themselves. So it's not uncommon that a person

00:12:27.040 with type 2 diabetes often will have hypertension and dyslipidemia. And while statistically we can

00:12:31.900 try to identify the impact of each of those, it does become a bit muddy. And therefore, I think

00:12:37.280 we shouldn't find ourselves worrying about whether it's a 50% increase or a 60% increase. The bottom line

00:12:42.740 is we want to manage these things. Again, I think in the show notes, we'll link to some of the various

00:12:48.200 trials and recommendations around these things. But again, suffice it to say, we have a pretty good

00:12:54.320 sense of the idea that having, for example, systolic blood pressure below 120 millimeters

00:13:00.460 per mercury, even compared to 140 millimeters per mercury, doesn't just lower the risk of dementia

00:13:06.720 over a relatively short timeline, three, four years, but also lowers even mild cognitive impairment.

00:13:13.420 Doesn't seem like a stretch to understand why that's the case when you understand just what

00:13:19.120 kind of capillaries are in the brain and how sensitive they are to anything that disrupts

00:13:25.040 their lining. Similarly, lipid lowering with statins, which by the way, are probably my least

00:13:30.000 favorite way to lower lipids, is still associated with a 20% decrease in the risk of dementia. Again,

00:13:35.700 this is identified in RCT studies where the primary outcomes tend to be cardiovascular disease,

00:13:41.720 but along the ride, you're seeing this. By the way, all-cause dementia, when you look at Alzheimer's

00:13:45.860 disease, that increases to about a 30% reduction in risk. Obviously, you talked about obesity there,

00:13:52.080 and we know things like diet and exercise or lifestyle changes can also impact obesity. Do we

00:13:58.760 know anything specifically around diet and or exercise on can it help prevent cognitive decline,

00:14:06.360 and the risk of dementia? It's a question that we see come through a lot outside of just the obesity

00:14:11.800 piece. Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested

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The Peter Attia Drive - July 14, 2025

#356 - AMA #73： Preserving brain health, optimizing exercise programming, improving body composition, and more

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