Hey everyone, welcome to a sneak peek Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Atia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peteratiamd.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything AMA episode 73. For today's AMA, we're answering a mix of the most requested listener questions, covering some of our most popular topics, including brain health, optimal exercise programming, and body composition strategies. Specifically, we discuss modifiable and non-modifiable risk factors for dementia and how exercise, sleep, alcohol, hearing, oral hygiene, supplements, and cholesterol levels influence brain health, how to implement zone 2 training, why it matters, how to lactate test if you choose to use it, combining cardio modalities and special considerations for peri and postmenopausal women, talk about strategies for how to increase VO2 max, including optimal interval length when shorter hit workouts can help and why power or rate of perceived exertion is preferable to heart rate training or heart rate targets during these efforts. The benefits of light movement after meals for glucose control and why exercise-induced glucose spikes are expected and harmless, finding the right mix of strength and stability work adjusting for workouts, for sore or sensitive backs, and weighing the pros and cons of lifting heavy weights that press down on the spine. Talk about exercise's role in maintaining fat loss programs, debunking the slow metabolism myth and setting daily protein targets, and managing the lean mass versus body fat trade-off over time. If you're a subscriber and want to watch the full video of this podcast, you can find it on the show notes page, and if you're not a subscriber, you can watch a sneak peek of our video on our YouTube page. So without further delay, I hope you enjoy AMA number 73. Peter, welcome to another AMA. How you doing? Doing great. Thank you for having me back. I really sense that greatness and that tone of your voice right there. I think you really sold people on it. Before we start, for those watching and for those listening, do you want to explain the t-shirt that you're rocking today? Normally you are the one that designs all of our t-shirts. This is the first time I've designed a t-shirt. I'm really happy about this. I guess for those who 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 pile of fluffy wool, and then d2 dx squared of f at x is a wool sweater, which I just think is so great. And I made it so that my daughter would have something to look forward to when she got to high school calculus. Yes, and as someone who's never taken high school calculus, I still don't quite know what the letters mean, but I did understand the pictures, so I have that going for me. Today's AMA, nothing to do with math or sheep, set a focus on one topic. What we did is a little bit more of a rapid fire style where we're going to have a variety of questions. And so we went to the audience on social media, through the website, through the AMA portal, gathered some of the most common questions we're asked, the questions we see come through all the time, and also some of the questions on topics that we know are interesting to people, which is brain health, exercise, body composition. For today, we'll cover questions around all the different variables, interventions people can do in order to prevent cognitive and neurological decline, obviously, of interest for anyone who has a brain and hopes to keep it intact. We'll dive into the most common exercise questions, which are a lot around zone two, including questions around if females should be doing zone two training, as well as some VO2 max training questions. And then we'll look at some body composition and diet questions, which kind of focus a little bit on exercise, but also around losing fat mass, building lean mass, the role of protein. With all that said, anything you want to add before we get rolling? Take it away. You think you're going to be able to work your math into it throughout that? If there's a way to get a first or second derivative into this, I will find it. A story for a different day, but a throwback for people who have listened to you for a while. I didn't even put together till just now the T-shirt also fits when you're at parties and you explain to people what you do for a living, which is a shepherd. You don't think that wasn't deliberate, my friend? This is now your social gathering T-shirt. So, oh, nice to meet you. What do you do? Oh, let me tell you about my shirt. It's smart. It's well played. This is what I do. Yeah, that's good. I'm really disappointed in myself that I didn't put that together till just now. It's probably why I didn't take calculus. With that, let's roll. So questions around cognitive neurological health. Mainly, what we see a lot in this comes through is preventing cognitive decline. It's something people care a ton about. We did a previous AMA on it, AMA 46, which we went into a lot of detail. We're not going to go into that detail. This will kind of be a primer. Answer some questions at a high level. But if anyone wants to dive deeper, that's a great resource. But I think a place to start that's really helpful for people is understanding what even puts someone at a higher risk for dementia or cognitive decline. I guess there's different ways one could think about this. I do like to think of it through the lens of modifiable and non-modifiable things. So we can just briefly, briefly touch on non-modifiable things and say very little about them, frankly, because they're not modifiable, but they're worth acknowledging. Age, sex, genes are not modifiable, and yet they all play a role in the risk of dementia. I think people who are not strangers to this podcast will know exactly what each of those things imply. So obviously, as age rises, so too does the risk of cognitive decline, inclusive, of course, of all forms of dementia. That rise is monotonic, meaning it never abates and it just keeps going up and up and up. We also see this profound discordance between men and women, where women have twice the risk of Alzheimer's disease to men. There are lots of theories as to why that's the case, but it is not solely explained by the slight gap in life expectancy between men and women. We've explored this in great detail in other podcasts, so I don't want to say too much more on it here. My personal point of view is that much of that risk is probably explained by sudden estrogen withdrawal during menopause, which of course would suggest that HRT might be a way to close that gap, but it's too soon to tell. And then of course, we have the genetic risks, and the most notable of these is of course the ApoE4 genotype, but of course there are many other genes that are associated with that. Okay, so let's put the non-modifiable risks off to the side and let's talk about modifiable risks. So when we talk about modifiable risks, what we are talking about is metabolic disease, specifically obesity type 2 diabetes, talking about hypertension, and we're talking about dyslipidemia. All of those things factor heavily into the development of dementia and Alzheimer's disease specifically, and they are all modifiable, which is the good news. I think I could spend the entire discussion on those things, but we've done that elsewhere, so I just kind of want to give a couple of a high point. So obesity is associated with about a 60% increase in the risk of dementia. That means in any given year, an individual who is obese compared to somebody who is not is going to have a 60% relative increase in risk. So at a young age, that doesn't mean anything because the absolute risk is so low, but as you get older, this number gets higher. For every 1 millimole per liter increase in LDL cholesterol, which is about a 40 milligram per deciliter increase, that's about an 8 to 10% increase in all cause dementia. The added risk for dementia with type 2 diabetes, your hypertension is actually similar to that of obesity. Diabetes increases the risk by about 50%, and hypertension increases by about 60%. In other words, having diabetes for a longer period of time increases the risk. We see that, of course, when we see that for every five years that a person is diagnosed with type 2 diabetes, their risk increases by almost 25%. Again, it's one of these area under the curve problems, not to keep bringing it back to calculus. There's some other nuance to this, which again, may be deeper than we want to go into it for kind of a rapid fire, but it turns out that if you're an ApoE4 carrier, you become even more susceptible to these modifiable risk factors. In other words, if you take an ApoE4 carrier versus a non-E4 carrier, both of whom have diabetes, there's a significant increase in risk for the ApoE4 carrier, and it's about a five to five and a half fold risk difference between these two individuals. All of this is to say, if your objective is to prevent cognitive decline, which obviously would be everyone's objective, you want to manage what is manageable. You want to be normo-tensive, so blood pressure 120 over 80 and below. You want lipids as low as possible, although we'll talk about where that plateaus out. You want to be as metabolically healthy as possible and be as insulin-sensitive as possible. One follow-up there, which since you brought up math is another math problem, is you ran through obesity, diabetes, hypertension. What do we know on do those cause dementia or are they just correlated with dementia? Yeah, always the important question. How would one answer that question? There are really only two tools we have at our disposal to address causality in humans, and one is the randomized control trial, and that's the gold standard. Then I'd say a slightly lesser standard, and it varies dramatically by indication, is the Mendelian randomization. When you consider this particular question, we have fairly robust evidence that hypertension, type 2 diabetes, and hypercholesterolemia can cause heightened increase in dementia risk. We say that because when you look at RCTs that specifically treat those things with primary outcome being dementia risk reduction, we see those benefits. Now sometimes those are secondary benefits, so we have trials that are conducted, for example, to address coronary artery disease as the primary outcome, but a secondary outcome is dementia. You have to be a little bit careful because you don't always have a trial designed exactly to identify all the conditions around secondary findings. Nevertheless, when you have robust and significant volume of RCT data that are treating constitutive elements within this, and you see benefits, that becomes pretty powerful. You also then have to look at what are the mechanistic reasons why these might be the case. Again, I think in all of these cases, high blood pressure and the endothelial damage that comes from it, hypercholesterolemia and the endothelial damage that comes from that, and type 2 diabetes, you see common things that occur in all of these things. You see inflammation, you see oxidative stress, you see amyloid buildup, you see insulin resistance, and all of these things mechanistically also make sense. So again, all of this is to say that I think we're very confident that there is not just correlation here, but causality. Now, one of the challenges, and this is why I don't find myself memorizing what the risk factors are here and saying, well, gosh, the relative risk here is 60% versus 55%, these things don't travel by themselves. So it's not uncommon that a person with type 2 diabetes often will have hypertension and dyslipidemia, and while statistically we can try to identify the impact of each of those, it does become a bit muddy, and therefore I think we shouldn't find ourselves worrying about whether it's a 50% increase or a 60% increase. The bottom line is we want to manage these things. Again, I think in the show notes, we'll link to some of the various trials and recommendations around these things, but again, suffice it to say we have a pretty good sense of the idea that having, for example, systolic blood pressure below 120 millimeters per mercury, even compared to 140 millimeters per mercury, doesn't just lower the risk of dementia over a relatively short timeline three, four years, but also lowers even mild cognitive impairment. Doesn't seem like a stretch to understand why that's the case when you understand just what kind of capillaries are in the brain and how sensitive they are to anything that disrupts their lining. Similarly, lipid lowering with statins, which by the way are probably my least favorite way to lower lipids, is still associated with a 20% decrease in the risk of dementia. Again, this is identified in RCT studies where the primary outcomes tend to be cardiovascular disease, but along the ride, you're seeing this. By the way, all cause dementia when you look at Alzheimer's disease, that increases to about a 30% reduction in risk. Obviously, you talked about obesity there and we know things like diet and exercise or lifestyle changes can also impact obesity. Do we know anything specifically around diet and or exercise on can it help prevent cognitive decline, the risk of dementia? It's a question that we see come through a lot outside of just the obesity piece. Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members and in return, we offer exclusive member only content and benefits above and beyond what is available for free. 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