Welcome to the Dr. Gabrielle Lyon show where cutting edge science meets innovation for practical application for everyone. In today’s episode, I sit down with my dear friend, Louisa Nicola. We discuss exercise, specifically resistance exercise and cardiovascular training and its influence on Alzheimer’s and cancer. I hope you enjoy this episode as much as I do. Now let’s jump into the show.

 (Upbeat Music)

 Louisa Nicola, welcome to the show. I’m really excited to have you back in studio in Houston. Great to see you. It’s so nice to see you again. Almost two years from the date that we first recorded. Your episode did so well that obviously I had to bring you back. Yeah. You’re a wonderful scientific educator and I really appreciate that. You recently wrote a paper, we co-authored a paper. You are first author and it is, “Does resistance training in older adults lead to structural brain changes associated with a lower risk of Alzheimer’s dementia?” A narrative review.

 Now you speak about dementia, specifically Alzheimer’s dementia. I’m gonna give you some statistics.

 2019, an estimated 57.4 million individuals worldwide were living with dementia.

 This number is expected to increase to as much as 152.8 million people.

 Alzheimer’s disease and Alzheimer’s is a kind of dementia, accounts for 60 to 80% of dementia and is considered the primary cause of dementia worldwide. Yeah, it’s a scary statistic. In fact, we’ve got around eight million people, seven to eight million people in the US that have Alzheimer’s disease. That number’s going to triple. It’s around 55 million people worldwide.

 I want everybody listening to think about someone you know with dementia.

 It is not uncommon. It is a leading cause of death and it is devastating.

 I know that you really want to change the world. I’m trying to and when you look at these diseases, Gabb, which you’re a physician, you’ve probably seen a lot of people maybe administered some end of life medication at some point. And you have my scholarship in geriatrics. There we go, yes, exactly. When you think about the four horsemen of diseases, you’ve got cancer, we’ve got heart disease, we’ve got Alzheimer’s disease.

 Alzheimer’s disease is the only one where you literally lose who you are. You forget your name, you forget your children’s names. You look in the mirror and you don’t recognize yourself and that is so scary. And the fact that it is 2024 and we have no cure, that’s not okay with me. We’ve made multiple strides in cancer, in cardiovascular disease. We’ve even gone to what we’re gonna be living on Mars soon and yet we still can’t find a cure. We’re not even close to finding a cure for this disease.

 That is terrifying. But one of the things that I think is so valuable, a lot of these things we might not be able to have lifestyle interventions for. But Alzheimer’s dementia is related to metabolic health.

 You know, when I was doing my fellowship, we looked at body composition, brain function. And if we want to move the needle, then we have to be able to leverage what we can.

 Which leads me to exercise’s role in cognitive health, cognitive impairment, Alzheimer’s, please tell us. Yeah, well, I think it’s really important to first differentiate and we can, you know, let’s talk about what dementia is. Dementia is the umbrella term that’s used to describe a set of cognitive decline symptoms. And when we look specifically at different forms of dementia, we can see Parkinson’s dementia. We can see dementia with Lewy bodies, Alzheimer’s disease, frontotemporal dementia, which Bruce Willis has currently been diagnosed with. But then you’ve got the most prominent one being Alzheimer’s disease. And Alzheimer’s disease is, it used to be this acetylcholine hypothesis. Now we’ve moved into what we call the amyloid cascade hypothesis. That’s where we’re at right now. We still don’t know what is causing it, but we do know this. It’s a multiproteinopathy. So there’s two proteins right now that we know of that are interfering with the brain. And one of them is amyloid beta. And this is a sticky protein that lives outside of the neuron cell body. And then we’ve got tau protein. And the tau is located and built up and phosphorylated in the axon, in the neurofibrillium axon. Of the cells. So we’ve got two things happening here. We’ve got an inside cell function catastrophe. And then we’ve got the outside amyloid beta that it’s interfering with the connections.

 Now, when we look at the brain, it’s around two pounds of heart. You think about it, it’s like Jello, right? A bit thicker than Jello. You’ve probably been in surgery. You’ve probably seen one before.

 It’s around a hundred billion neurons, approximately. Each neuron having 5,000 connections. So if you think about the math on that, you’ve got over 50 trillion, 500 trillion, if I’ve done my math correct, connections.

 In my opinion, Alzheimer’s disease is a connection problem. You are having, and that’s what dementia is. The loss of cognitive, you know, the cognitive decline is the inability of the neurons to connect to one another. So we have to take a step back and we have to think why are we focusing on a cure? If this is a degenerative disease, and by the way, most, you start off by becoming asymptomatic. You then move into mild cognitive impairment, and then it’s a straight line down to Alzheimer’s disease. So Alzheimer’s disease, you might be diagnosed in your 70s, but your symptoms have been starting. And these proteins have been accumulating in your 30s, in your 40s, and in your 50s. And I actually have a problem with the word mild cognitive impairment, to be honest. Why? Because there’s nothing mild about it. You don’t say, what is the end stage of cancer? It is stage one, stage two, you’ve got metastasis. Nobody says you are in stage three mild cancer. That’s a very good point. Yeah, there’s nothing mild about it. When you start to forget names, and that’s what it starts with, your episodic memory starts, you start to forget names, forget where you put your keys. That’s not mild, that’s scary. Sometimes you get into your car, people with mild cognitive impairment get into their car, they don’t know where they’re going. And can you mention the difference between episodic, executive function, so that people can kind of get a sense, because typically, in dementia, numbers don’t go first. People will experience difficulties in short-term memory versus long-term memory. Yeah, and so when we think about executive functions, these are a set of cognitive functions that live in our frontal lobe. We’ve all heard of the prefrontal cortex, the CEO of our brain, and these are responsible for things such as information processing speed, our ability to think, make sound decisions. Memory is also involved in the frontal lobe of the brain as well, but it’s also located in the hippocampus, and that’s actually the first part of the brain to go during Alzheimer’s disease, these seahorse-shaped structures deep in the temporal lobes. You’ve got your long-term memory, and surprisingly, this doesn’t, that’s not the first thing to go, so let’s just say you’re R70, 75, and you’ve got Alzheimer’s disease, there are chances you will still remember maybe your wedding day, if you will. It will come back to you, but that short-term memory, that episodic memory is the first thing to go. You know, and I’m sure people are listening to this thinking, I can’t remember where I put my keys or my glasses, that is not what we’re talking about. We all live very busy lives, potentially. People are not paying attention, but before individuals get concerned, they do have to recognize that there are lifestyle factors that play a huge role. Is there a reason, so you mentioned amyloid, beta, and tau proteins, is this a normal process? Would, for example, these things be metabolites in a normal functioning brain? Is there a problem with the ability to remove them, to manage them? Oh my gosh, I love this question.

 Amyloid is an antimicrobial peptide. It is part of the innate immune system. We need this. This is the first line of defense. Every time you activate that innate immune system, albeit from our diet, albeit from stress, albeit from sleep deprivation, what’s happening is you’re activating the innate immune system.

 Amyloid precursor protein is that molecule which is the precursor of amyloid. Amyloid precursor protein, it gets cleaved at two sites. Once it gets cleaved, we produce amyloid. And amyloid is basically, it is a protective molecule. That’s what I want everyone to know. We demonize amyloid. I’m not sure why. It’s like we’re just trying to find a cure, I guess, for our lack of dietary interventions, if you will.

 Once that gets cleaved and it becomes amyloid, amyloid’s there to protect you. But what happens is if we keep activating it through stress and lifestyle, that amyloid builds up. We can remove the amyloid in small doses during sleep, during the activation of the glymphatic system. We activate our glymphatic system when we run. We can help when we exercise. We can help the clearance of it through dietary modifications. But what happens is if we don’t, it accumulates. And I mentioned earlier that it’s on the outside of the cells. It’s sticky. It is a sticky protein. It’s going to stick to things and not allow cerebral spinal fluid to move through. Blood flow, imperative for brain health. But also, I don’t know, you probably do know this, it actually binds to insulin receptors.

 So tell me more, yes. You become more insulin resistant. So that’s an even bigger player here. You know, when I was doing my fellowship, one of the things that we always spoke about was Alzheimer’s dementia is type 3 diabetes of the brain. Yes. You also mentioned something else, the rate of disposal of these amyloid proteins. You mentioned exercise. I did not know that. I did not know that exercise impacts amyloid proteins until I started learning from you. Oh yes, and we’ll go into that specifically.

 Do you feel that there is not a cure, but very specific actions people can take, just because someone has an ApoE4 gene,

 do you believe that there are interventions that can happen that are meaningful, meaningful interventions regardless of your genetics? 100%, because when you see the amount of people that have Alzheimer’s disease around 97, that’s actually me being very lenient. I would say that 99% of the cases are driven through lifestyle factors. Do we know certain populations that don’t seem to have Alzheimer’s dementia? Yeah, when you look at this, there was a study done in Nigeria. I’ll be really careful with what I say, because when this was done in Nigeria, they saw that the population had, they were positive for the two alleles of ApoE4. You get one from mom, one from dad. They had a very big population of people who had two alleles. And yet their rate of getting Alzheimer’s disease was far lower.

 Do they know why? Do you think it was activity, was it diet? Yeah, it’s my understanding that it has a lot to do with the way they’re living. You know, I wasn’t very big on this whole micro toxin exposure, but now I’m looking very deep into it through another research paper that I’m doing, and I’m finding that toxic mold exposure is another big sector. I’m so, you know, we were chatting before this, but obviously I’m having my home remediated at this time. I will tell you, we’ve been seeing patients, I mean, I’ve been seeing patients for almost two decades, and we are seeing environmental factors really affect cognition. And the evidence just is, you know, the body of evidence isn’t fully there yet, just because I think it’s so foreign that individuals would think there would be sick building syndrome. Yep. Was there something that happened that made you become very interested in the microbial antimicrobial effect? It was when I realized that amyloid is not the demon. It is an antimicrobial peptide, so it is there to protect you. And what Alzheimer’s disease is, it is your brain’s way of saying, “I give up. You have put me under attack for the past 20 years. I’ve tried to help you by building up amyloid. And when I build up amyloid in your brain to protect you, Louisa, you don’t give me a break. You don’t sleep well, you don’t eat well. You’re far too stressed. Your lipids are through the roof, so I give up. Here is a brain full of amyloid, around 4.5 grams, by the way, of amyloid accumulates in these brains.” And it’s just there, and it’s saying, “It’s now time to decompress.” Gosh, and is there, from my understanding, there is not a way to, I mean, and I say this loosely, regenerate. Because there is, you know, BDNF can help with neurogenesis, but from what we know now, or in the current literature, is there a way to regenerate the brain? We’ve seen, and this is the work of Dr. Dale Bredesen. He has seen, yeah, and he’s wonderful. We were talking just last week, actually, and he’s seen patients where they’ve come in with a mocha score of 18. It’s at the Montreal Cognitive Assessment score, very standard. I think everyone should do it. It should be aiming for a score of 30. It is a free test that everyone can do. He’s seen people come in with a score of 18, and under his protocol, go to a score of 30. Now, I will do 30. Yeah, it’s out of 30. So you would do the test, you’d most likely get 30. No, that is very questionable.

 I do a test, I get 30. You are actually mild cognitive impairment, stay if you get 18, for example. Now, the interesting thing here is you can have a head full of amyloid, but still preserve your cognitive functions. What does that mean? That means that it is a connectivity issue.

 Your neurons have these little legs that come off them, they’re called dendrites, comes from the Greek word tree. And they’re like little branches, and they connect to the other neurons, and they produce our synapses, how we think, how we produce actions. Once they die off, we don’t get the connections anymore, and that’s what results in cognitive decline.

 But then you can also have a brain full of amyloid, and still have your cognitive functions at play. Is it because, so if someone were to say, “Okay, I’m going to create a plan for myself to prevent Alzheimer’s.” The majority of Alzheimer’s is not genetic. I think is it 1% that’s actually genetic? Of course, there’s vascular dementia, which is different, relates to vasculature. And then Alzheimer’s dementia,

 which seems to be metabolic in nature, is that true, or is it metabolic, environmental? Are there other influences? Yeah, there’s many stages and many things at play. You do have metabolic.

 What do we look at when we see metabolic? We see you’ve got what we’re eating. Sugar is a huge factor to point out right now. Why? Because you’re looking at the mitochondrial function of the cell, you’re looking at insulin sensitivity.

 And it’s funny when I was doing research on this,

 chocolate was actually brought into the United States, candy from Hershey. He was the one that realized, we don’t have chocolate in this country. I think it’s only in the other, I think it was Denmark, don’t get me wrong. And he brought it in here because he noticed that people enjoyed sweets, and that was the rise of- Really? Yeah, and so that’s when it came into play. So now we’ve got this problem happening. And I also think it is the interventions part as well. And then there’s also another part which we’ll get into, which is the trophic factors. Your brain needs trophic support, which come from hormones such as estrogen and testosterone. And this is actually a reason why two out of three Alzheimer’s disease cases are women. And- Say that again, two- Two out of three Alzheimer’s cases are women. I was looking up the funding. Do you know that 12% of NIH funding goes towards women focused dementia?

 More cases of Alzheimer’s disease are diagnosed in women. More cases of multiple sclerosis are diagnosed in women. And we still don’t know why due to the lack of funding. Isn’t that wild? You know, we’re starting to see more and more research with hormones, hormones, estrogen, playing a role in dementia. And if we were to build a healthy brain, let’s just say I’m gonna go on a brain optimization program for myself. Yes. What would that look like? So we have, in our brain, we have a supply and demand issue. We need supply, adequate supply to the brain. That comes from blood, that comes from oxygen, trophic factors such as hormones.

 It comes from our mitochondria. Then we have a demand issue, right? Every single day, your brain is under attack. So it needs the supply to meet the demand. If the demand is too high, you don’t have enough supply, that’s when we see a problem. So we need to think about, okay, well, what are the things that are in our control?

 I do believe, I am a proponent of getting an APOE4 genetic test. Some people are scared to get one. We always get them in our patients. Yes, correct. And if you do, at any chance, feel like you may be worried, there’s counseling, there’s genetic counseling involved. Somebody talks to you about what that may look like. But if you do, even if you are APOE positive for two alloys, you still don’t have to get our sinus disease. Isn’t that wild? There’s a genetic propensity, which again, but if two thirds of the women, there’s again, it’s going to be 152.8 million people that have Alzheimer’s dementia by 2050, what are the influences? So for, according to the CDC, when we talk about exercise, which I think is really important work, we always talk about muscle health and exercise as it relates to looking good, being jacked, but it is so much more valuable than that. And probably nothing creates more influence. 50% of Americans do not work out, 50%. That’s a lenient number too. Yeah, they completely agree. And roughly 72% do not meet the standards of the baseline recommendations, which are five days a week or 150 minutes of moderate to vigorous activity, plus two days a week of doing some kind of resistance training.

 What impact does exercise have on the brain? And is there a difference between cardiovascular exercise or resistance training? Because if we already know that the majority of the population isn’t even meeting the baseline recommendations. Yeah, and this comes into public health policy, which is something I’m advocating strongly for. Let’s look at why, let’s categorize exercise into three buckets. You’ve got aerobic training, you’ve got resistance training, and then you’ve got cognitive training. We’ll go into all of them. We have seen in the last 30 years, we’ve seen a huge push for cardiovascular training. Why is that? Well, first and foremost, it’s easy. It’s the first interventions to be studied and funded in mice back in 1960, when we first realized the role of BDNF, which we’ll go over. I also think that it’s so much more accessible to people. Cardiovascular activity. Cardiovascular activity, because you can just get outside, you can run. I think the nomenclature around resistance training becomes very intimidating, especially among women. I mean, you and I don’t fall in this category. I’ve been weight training my entire life, so I’m never worried at the gym, but I do know that there are many women who are intimidated to go to the gym and lift weights. If you were to pick one thing, if you were to say, okay, I, and this is a hard question, and we don’t have to pick one thing, but if you were going to choose between cardiovascular activity, resistance training, high intensity interval training, what would you say seems to be the most efficacious for brain function? Oh, yeah, you’re putting me in such a bad spot. I mentioned that I’m currently doing my doctorate, and it is really much focused on resistance training and cognitive decline. However, I would definitely not consider HIIT training in that. I would strongly look at minimum four hours a week of aerobic, and at minimum three days a week of resistance training.

 And have you thought about the mechanisms as to why? Yes, so let’s look at cardiovascular training. There’s so many benefits here. What’s the first thing that your brain needs to survive?

 It needs adequate blood flow, correct? How do we get blood flow to the brain? Well, we know that every time we push blood through our aorta, we’ve got the carotid arteries, which supply the frontal part of the brain with blood. We’ve got the vertebral arteries supplying the back end or the posterior part of the brain. So your brain needs blood flow to survive. We get this predominantly from aerobic training, because every time we move our body, we’re pushing blood. But not just that, you’re getting the cardiac remodeling. And a lot of people, I guess when we talk about, we talk to neurologists and cardiologists and they’ll fight. The brain’s more important, no, it’s the heart. Imagine what happens when you talk to the urologist. Oh gosh. And you know what’s most important to them. Yeah, and you’ve got this synergistic relationship between the two, what’s good for the heart is good for the brain. Because when you remodel the cardiac system, when we improve left ventricular, or the left ventricle of the heart, which supplies the body with blood, you’re getting a better profusion of blood. You’re becoming more efficacious with your blood flow. It becomes more efficient, you become stronger. Therefore, as you get older, and we see these age-related defects in the heart, we get left ventricular stiffness, we get stiffening of the arteries. You can actually change that, remodel the heart, so it is fitter and it is stronger and you can pump more blood to the brain. So you do like cardiovascular training, which is wonderful. And obviously it’s very well studied. Very well studied. Does it matter the intensity? Someone is increasing the blood flow and is there a dose-dependent relationship? So you said four hours of aerobic activity. Is that pretty safe to say?

 It could be less if the intensity is higher, or is there a time component, like a dose-dependent component? Yeah, in fact, the studies, and this is what I found in the paper that we collaborated on, it said that minimum three hours, I lobby against that. I lobby against the CDC guidelines all the time, which are recommending 150 minutes to 300 minutes of moderate to vigorous physical activity. If you were to tell my mother that, she’d say, “What are you talking about?” Absolutely. So the nomenclature needs to change. Now in exercise physiology, we learn about zones. We’ve got zone one, which is where sitting down right now in zone one. Zone two is where I think we should all be training at. I can’t see actually why we need to dip into the zone four for more than 35 minutes a week. There are so many people right now I’m seeing on social media, hitting the gym, doing HIIT training, getting into zone four, zone five, whatever zones you wanna work in. Zone four, let’s just call that your maximum. They’re beating at zone four every single day and they’re seeing diminishing returns. You don’t like that? No, I don’t see why you need to do that. However- What is there any downside? Well, I mean, you’re over training. You’d probably, you’ve got the mental component where you feel like, “Oh my God, it’s just too hard to get up every day.” You know this with your patients. What’s the biggest behavior change? It’s something that someone can put into place every day.

 If we’re gonna get behavior change, we need to fit it to something, a protocol or administer something where somebody can do it every single day.

 Not just that, the only reason why I think

 this is problematic.

 Let’s talk about the positives of it. So maximal aerobic exercise.

 Dr. Ben Levine, he’s a cardiologist, phenomenal, phenomenal physician.

 He did a study where he took 53 50-year-olds

 and he subjected them to maximal aerobic activity. I think it was around three to four hours a week. He measured their heart. He did EKGs. He looked at their entire heart, looked at what was happening. Now, I mentioned earlier that as we age, we see a stiffness in the arteries. We also see left ventricular hypertrophy. So the left ventricle, it becomes thicker. So if that becomes thicker, there’s a smaller space for the heart to pump blood to the rest of the body. The right ventricle supplies the lungs with deoxygenated blood.

 So what he saw over the course of two years, he reversed the age-related decline in the heart. He saw that these 50-year-olds that came in with a 50-year-old heart once scanned again after that protocol with just two years, he reversed the heart-related decline by 20 years. So these 50-year-olds had 30-year-old hearts. And do they just define that with stroke volume, blood pressure? Stroke volume, blood pressure, left ventricular hypertrophy decreased. So he was opening up the left ventricle. Interesting, okay. You should see the actual MRI. Yeah, that’s interesting. Yeah. And how long did that take? Two years. Took two years. Yep. Of maximal training. That seems like a lot, three to four hours. It is. Three to four hours a week. Yep. For two years. For two years. 50-year-olds. At, yep, at that zone four. And by the way, for everybody listening, when I talk about zone four, I’m generally talking at around 85 to 90% of your maximum heart rate. That’s hard, right? Sounds like a good time to me. Now, what are you not getting? Have you done a VO2 max test? No, my husband has. I’m gonna have to, we’re gonna have to do one. But what you see is people who are less metabolically efficient will get on a treadmill.

 And once they start running, they go from zone one, obviously set entry. Those who are less metabolically efficient go from zone one to zone three, to zone four. They skip zone two. So, zone two is the sweet spot. And this is a spot that is so easy. It’s that 65% of your maximum heart rate, it’s actually defined as two millimoles below, two millimoles if you take a lactate test, which we do as well, and it’s really easy to do.

 That’s where you wanna be training. It’s basically when you’re walking really fast or running, depending on how fit you are, but you can hold a conversation with another person.

 So there’s two things we wanna discuss right now. The effects of cardiovascular training on the brain. And then I wanna talk to you about immunology and the effects of cardiovascular training on cancer.

 Beautiful, beautiful work. So let’s talk about cardiovascular training on the brain. Well, when we’re engaging in this zone two training, 65% of aerobic capacity, we are releasing trophic factors. We’re releasing hormones, we’re releasing molecules that are really responsible for the regeneration and growth of the connections of these neurons. So remember how I said earlier, that with Alzheimer’s disease and cognitive decline, we lose the connections. The 5,000 connections per cell go down to 2,000, 1,000, then there’s no little dendrites left. And then what do you have? Yeah, I pretty much have a dead cell. So we grow new connections with a molecule called BDNF, brain derived neurotropic factor. In fact, Marianne Diamond back in 1960s, early 1960s was the first one to discover this. She, obviously she got rats and she subjected the rats one to an environment that was really depressing in a room where they had no wheels to run and not an enriched environment. Then she took the mice and put them in an enriched environment. Wheel running, they had little stairs to climb. And what she saw was that over the course of her study, she saw that when these mice are placed in an enriched environment, they grow the connections. That’s what we’re looking for. They grow the connections. They also grow the hippocampal volume. Okay, so you’re growing bigger hippocampi. You’re also growing new neurons. So BDNF is responsible for this. Is there a time where you are not growing new neurons? This makes me think about my children and children.

 They probably need to be, I sent you a video yesterday. My daughter in jujitsu and she’s not even five. Granted at this time, that’s not zoned to training in kind of any extended period of time, but have you looked at the literature of children and is it valuable for them to be training? Will it potentially increase their IQ, help inoculate them against metabolic dysfunction later on in life for their brain?

 So you want to put them in an enriched environment because when you look at, I love using the homunculus. It’s a beautiful little figure. If you guys look it up, you’ll see this weird looking man, small body, big hands. And basically it’s a representation or a map of your brain. And so if every single area of the brain is responsible for something different, whether it’s vision, hearing, touching, sensation, perception, you want to preserve these as we get older. So you want your child to be in an enriched environment, getting as many activities as possible. Multiple domains, jujitsu, gymnastics, all of these things. I’d be really interested in studying the difference between rural areas, kids, you know, for myself, I grew up in Australia. I was swimming, I was running, I was outdoors. Now I live in New York city and I meet people, you know, I’ve got friends now who say to me, oh no, I was born in an apartment, raised in an apartment, I never did extracurricular activities. And I would love to see what the difference in their brain structures were. Yeah, and probably, you know, follow them over time. Yeah, but yes, so it’s really important for your kids up until the age of, you know, 25. But I want to point out that you’re fixed with these neurons. There is no, so adult neurogenesis does not exist. It’s not like we can just go out and grow new connections. Are we born with the amount, for example, a woman is born with a certain amount of eggs. Yes. Are we born with a certain amount of neurons? Yes. And then there is, depending whether it’s cognitive reserve, these things decline. Yes. And are people born with different amounts of neurons? That’s an interesting question. You know, it brings me back to, I was doing some Parkinson’s disease research once and we came across, I think it’s the only person in the world who was actually born without a cerebellum.

 So, but to answer your question, I don’t, I probably would say that there is a certain amount of people.

 This comes down to Charles Darwin, actually, and how he measured the brains of a female and a male brain. And that’s when we got this whole notion that female brains are smaller, but they’re not. They’re actually proportional to your head size. So without understanding that fully, I don’t think that. I wonder if it’s a, and this is just a thought, I don’t know if this has any relationship to do with IQ or smarts, if the actual amount, you know, if an individual just needs however many, 50 trillion billion and anything above that really isn’t helpful, but it might preserve memory, it doesn’t necessarily make you smarter. Well, you’ve got to think about it as cognitive capacity and cognitive load. Now I know you talk about this, let’s build, you talk about building a stronger body, more muscle mass, because the rate of decline after the age of 40 is huge in both muscle mass and strength. That’s the way we need to think about it for our brain. You need to build up as much cognitive reserve, cognitive capacity, so you can withstand what we call insults. Now I’ve had many people actually, I use that word a lot, it’s used in neurology. It is, and geriatrics. Exactly, so we use that, and insult is pretty much an attack to your brain. We have cerebral insults, which is classified as a stroke, for example, you can have insults, or even an insult such as a head trauma, that’s what I mean. You want to be able to protect yourself against these insults as you get older. The more cognitive reserve that you have, it’s basically saying, okay, we are armed. I love that.

 Exercise, resistance training, let’s circle back to BDNF.

 The neurons are formed, your adult brain is formed at 25? Yep, 25 to 30. BDNF is then, is that almost as if someone was watering a garden? Yeah, and so many neuroscientists call it fertilizer for the brain, I don’t like to say that, it is a trophic factor, it supports it, yes. It supports the growth and proliferation of neurons. Now, you can’t grow new neurons in the brain of humans, you can in mice.

 What we see in the studies is that if we grow new neurons in the hippocampus, and the hippocampal volume increases, that is not directly proportional to cognitive health. So what does that mean? So if I can grow new neurons, it’s kind of confusing because then what do we need the BDNF for? Connections. For connection. Yes, 5,000 connections per cell, they die off, so we need those branches to be, you know, we’re in Gab’s place right now, she’s got a beautiful olive tree. Those branches, you know, the leaves that are coming off it, that’s what it is. Imagine we cut those down, it’s just the stick. I see, so BDNF is required, it’s one of the trophic factors required for brain connectivity. Yes. And if someone was not doing exercise, whether it’s cardiovascular exercise or resistance training, one is not stimulating BDNF. That is correct, yeah. Are there other ways to stimulate BDNF? Yes, you can do it through cold water immersion. Can you really? Yeah, we can stimulate BDNF through cold water immersion. Is that documented in humans?

 Not yet, it’s pretty clinical studies, I’ve seen it in mice, yeah. My husband would say that’s why seals are smarter. Yeah, but– Because of winter how weak? There is just so many other things at play here with cardiovascular training, and this brings me into the whole immunology section, and I’m going to credit Benta Pedersen for this. Ah, my favorite. You know, I’ve tried to get Bente on the podcast, I’m working on it. I’m actually thinking about flying to Copenhagen, I have ripped her, you know– I will go with you. Yeah, she is phenomenal, I’ve ripped every single one of her books and her studies apart, and she was the one that actually coined the term myokine. It’s a really beautiful, it’s really beautiful. So she’s an MD, an immunologist I believe, and she was working on, she got bored in the lab and she was working, you know, on the immune system, the innate immune system, and she came across this aisle six, okay? Interleukin six, part of the interleukin family, it’s a pro-inflammatory cytokine, which she knew of. But then she found that during exercise, she wanted to study exercise, she loved exercise at the time, she found that exercise robustly releases aisle six acutely, now– From muscle cells. Well, then she found that it came from muscle cells, and it became many things, it became an anti-inflammatory cytokine. So then that raises the question then of,

 well, if this is now an anti-inflammatory cytokine, what is that having, how is that having an effect? So she kept digging deeper, and it was with her lab partner, who actually surprisingly passed away of cancer, they both became obsessed with finding out, well, how does aisle six play in cancer, cancer metastases? They started working with tumors of the prostate. And what they found was that when you exercise, you release other cytokines, natural killer cells, these natural killer cells get shunted into the tumor site, and that then shrinks the tumor. And not just that, when you have a tumor at a specific site in your body, let’s call it stage one prostate cancer. The reason why cancers end up becoming stage two, and obviously detrimental is because they lead to metastasis. Now what happens is they break off little pieces of these tumor cells, break off, and they go through the bloodstream, and then they’re called circulating tumor cells.

 Through exercise, we can call it aerobic training, or even maximal exercise. You are ameliorating these circulating tumor cells. So you can actually, they did studies on patients who were recently diagnosed with cancer, and they found that they’ve downregulated the tumors. So going from stage two back to stage one. I have to ask you a question. Yeah. Do you think cancer is in part a disease of sedentary behavior?

 In part, I am, depending, obviously let’s take your headaches. I mean that’s a very heavy question. It is. But think about that. Yeah. If what you’re saying is true, which it is, it’s in the literature, then obviously there is some kind of genetic mutation that happens. It would make one think, and I’m sure Dr. Joe Zundell has a comment or an opinion on this. Is it that sedentary behavior and lack of interleukins that are released from muscle cells, not from macrophages or other cells, but because they’re pleiotrophic,

 could that contribute to the onset of cancer? And or potentially could it be part of a treatment protocol that we are totally missing?

 100%, and I’ll tell you why. And this is looking at her human randomized control trials. What she found was that people who exercise at least 30 minutes a day have a decreased risk in 13 types of cancer. Are those all metabolic cancers? Correct, yes.

 Likely she also found that if people start to exercise after a cancer diagnosis, their survival rate increases. She found this in three cancers, breast cancer, prostate cancer, and colon cancer. And this one in prostate cancer is phenomenal because it was published in Cell Press, a high stringent journal. They also took into account the other myokines that go in and inhibit the growth of tumor cells. You also have to remember tumors have a blood supply. They’re hungry, so they are there and they are hungry to produce more blood supply to allow it to grow. So then they can be like, we are strong enough guys, let’s go and find other nests, which is metastases. You need to cut off the blood supply. How do you do that with natural killer cells? Well, how do you get the natural killer cells in there? It’s via exercise.

 It is extraordinary. So exercise is medicine. It’s preventative medicine and it’s curable medicine. Does the cardiovascular exercise versus resistance training have a different myokine release and or impact on these various challenges, health problems like cancer? More so involved in brain health and dementia. We’ve got hundreds of documented myokines. Now– I heard there’s one called Luisa Nicole, LN. There will be one very soon, I assure you. We need a few more samples. (Laughing) Taking our applications friends. We’ve got Iresin.

 Actually, why don’t we just talk about what the study that we collaborated on found, because there’s two notable studies. Yeah, this was a review article, everybody, which is, it takes all of the current literature that is available through human randomized control trials. Extremely well done review, Luisa. Thank you. And I’ll just repeat the title. This was published in Aging Research Reviews July, 2024. The title of this paper that we collaborated on is does resistance training in older adults lead to structural brain changes associated with a lower risk of Alzheimer’s dementia, a narrative review. So let’s look at the two studies that I think are most prominent. We have the brain power study. That’s when they took 155 healthy women and they subjected them to two times a week of resistance training. They got another group, subjected them to once per week resistance training, and then they took a sham group.

 Overall findings were improvements in two domains. We’ve got cognitive functions. By the way, I should have stated earlier, when we talk about the brain, we talk about structural parts of the brain, then we talk about functional parts. Now, I’m a neurophysiologist. I’m primarily involved in the functional part of the brain. That is how the brain cells function. So that’s the functional part. Then the structural part is the gray matter and the white matter of the brain, the lobes, if you will. So we saw an improvement in executive functions measured via a STROOP test. STROOP tests are great for anybody that’s wanting an extra challenge, just YouTube STROOP test, and you’ve got it on there.

 They saw memory improvements, and this is in the twice weekly resistance training.

 They saw some changes in both gray matter volume and white matter integrity. I just wanna focus on that. So your brain is made of both gray and white matter. Basically what that means is the cell body of the neuron is classified as the gray matter. The white matter is the myelinated part of the neuron. It’s called the axon. It’s why, you know, we’ve got actually some neurons or axons that can be as, depending on how tall you are, can be as long as like two meters, right? Imagine the bronze, right? Goes from your head all the way down to your foot. And so you’re having an effect on the gray matter. Now, people get this confused.

 There was a really great study that came out back in 2016, which stated that 80% of brain gray matter is modifiable by physical activity. While that is true, I wanna make note that doesn’t mean you’re growing new neurons in cell bodies. You are growing greater connections. The connections are on the cell body, which means that the gray matter is quote unquote thicker. And you know, one of the things that I think that the listener or viewer has to understand is you are making a very important case for the fact that you are not going to grow a new brain. You are not going to regenerate. And your overarching message is to keep the brain that you have healthy and robust. Correct. So I think it’s a very valuable component to the conversation because we can intervene early. Can intervene early. And it also makes you a much smarter consumer because if you see products marketed at enhancing neurogenesis, you know that that might be a trick. So what else did we see in the brain power study? Well, we saw white matter volume. So it had thicker cortical white matter and improved gray brain matter. That was a great study. I think there was a lot of limitations. However– But were a few, do you remember any of the limitations? Yeah, I think that, you know, first of all, they took it on healthy women. Yeah, so that’s– It was only on women. So that’s actually what I was just thinking, okay. What I did like was the fact that it was, they were aged 65 to 75. So that’s a great age to be looking at this. You probably know hormone treatment. They were, that stuff, yeah. Now let’s look at the other study, which is called the SMART study, where they took– Hallmark study.

 Yes. The Hallmark study, yes. Correct. They took 100 men and women aged 55 to 87 with mild cognitive impairment. So these people had pre-dementia states. So this is what I was interested in, which I really love.

 Participants were assigned to what we call progressive training combined with cognitive training.

 So they had resistance training, and they were also doing some form of cognitive training. This may look like doing squats and performing a task called serial seven. Oh, that’s so hard. It is so hard. It’s basically you’re doing squats, but you have to count down from 100 by seven. Which is– I could not do that if I was squatting or not squatting. Now the way that we do it at NeuroAthletics is we’ll get you to perform a drill, but also think about other tasks. Like tell me all of the words you can think of starting with the letter T. And you would know that when we look at Alzheimer’s disease patients, you see a reduction in their language processing. So it’s a really great tool for everybody to come by. The second group was just resistance training, and that’s it. And the third group was just cognitive training, and that’s it. This is where it gets interesting. They had improvements in their cognitive functions, streuptests and other different functions, and improvement in executive functions. They were able to remember things better. They were able to pick up on other information, but process information better. But this is where the beauty of the study came in, the structural changes. Remember how I mentioned hippocampus.

 They saw an improvement in the left hippocampus. We’ve got two lobes of the brain, so you’ve got two structures of everything. It resulted in a slower rate of atrophy in the left hippocampus.

 It was statistically significant and meaningful. Yes, they saw an increased cortical thickness in the posterior cingulate cortex, which by the way, that area of the brain is probably so much profound when it comes to goal setting, when it comes to dopamine, when it comes to obviously brain performance.

 And then last but not least, resistance training reserved the progression of white matter lesions.

 White matter lesions are these little structural changes that occur in the white matter of the brain. Now I mentioned earlier that you’ve got the white matter of the axon. This is where– They saw improvements in the white matter or just they stopped. A slower progression of white matter lesions. White matter lesions is a risk factor for Alzheimer’s disease. And by the way, a lot of people are doing brain imaging, Pernova scans.

 Typically you might see, if you’re 50, you might see one white matter lesion. They seem to accumulate per decade.

 It’s considered a normal part of aging, which is fascinating. That upsets me so much. And potentially, maybe it is, maybe it’s not, but exercise might influence that. Dementia is not part of the normal brain aging process. I wanna be really clear on that. Now, we didn’t just see a slowing of the progression. We actually saw a 3.4 regression of these white matter lesions. So regression, like reversing. That’s wild. Yeah. That’s wild. And a 3% progression in the non-resistance training group. So now we have to think about this. We are affecting the rate at which we process information. When you go and see a neurophysiologist or a neurologist, and let’s just say they, because I did a lot of, when I was practicing, a lot of EMGs, electromyography, where we would pick up on what we call conduction velocity. This is for people who we suspect may have multiple sclerosis. You’ll see an MRI, you’ll see all these white dots and be like, okay, great, we need to conduct an EMG. When we see an EMG, we are picking up what we call complete conduction block or a decreased conduction velocity. That means that the rate of impulse down that neuron axon body is slowed or impaired.

 We can reverse this. I’m not saying, by the way, this has nothing to do with multiple sclerosis. However, we can actually get an increase in our conduction velocity. So we can have a faster rate of processing speed. I’m gonna ask you a question. And this is just a thought. I mean, maybe there is no direct evidence for this or not. Do you think that there is a correlation between skeletal muscle mass and cognitive function? 100%.

 The bigger the leg muscles, the greater the brain volume. Don’t quote me on that. That’s just a layman’s way of saying that more muscle mass, improved cognitive function, larger brain. We see preservation of brain volume. We see preservation of functional capacity. We know that with more strength and with more muscle, we have more mitochondria, better insulin sensitivity. If we look at the top of the hierarchy of what could be causing all of these, all the attack of the amyloid, the breakdown of the microtubules due to tau, we see that insulin sensitivity is sitting at, I would say almost the top and the forefront.

 It’s wild. It’s wild.

 The, do you think that there will be dose recommendations to exercise and disease? Well, this is what I’m trying to lobby for in terms of public health initiatives. Right now, the recommendations are too low. What we’ve seen in the study is that, yes, at minimum, at minimum, we need the 150 minutes to 300 minutes of aerobic. We need at minimum two days a week of whole body resistance training. By the way, guys, just to preserve, now you know this with muscle mass, what’s the rate of decline of muscle mass and strength? I believe, I did look it up. I wasn’t at like 9.2. So it’s around three to 8% per decade, but I actually. But that accelerates when you get to 50, 60. It does, and I actually think that it has much less to do with aging and much more to do with lifestyle. So the government now is putting out these recommendations to tell you, just do the bare ass minimum. Okay, just do the bare ass minimum just to make you keep afloat, right? Just survive. Just survive, but we’re not talking about that. That’s not what you talk about on this podcast. That’s not what you and I are delving into. We’re talking about how can we become high performing and how can we live a long life, remember our kids and our grandkids at the age of 85, 90, 95 and beyond. And this review, basically the highlights are resistance exercise may protect the brain structures, affect Alzheimer’s disease, structural changes are associated with cognitive benefits, amazing. Protected regions include the cingulate white matter tracks and the hippocampus, and finally dose response studies suggest a minimum of two sessions a week for six months. Can you speak to, do you think the kind of resistance training program matters? Is it, does it matter if it’s squats or a compound movement? Is it just fully the overarching musculature? It’s the overarching musculature, however, you don’t need to body build your way to better health. To a better brain. Yes, basically to a better brain health, I should say. You wanna take into consideration lower body, first and foremost. Now, there was a really fascinating study that correlates leg size to brain volume. And I think that the argument behind this is probably because when you look at the quad muscles, in terms of vector size, you’ve got more muscle cells right in there to play with, right? But every time you are engaging in resistance training, if you are strapped for time, just do as much full body compound movements as possible. Here’s the caveat. It does matter what you’re doing in terms of how much you’re lifting. I think this comes back to public policy. I see a lot of women in the gym lifting small weights and you have to move the needle. You have to put stress upon the system to create an effect. And this comes down to muscle mass, but these myokines, which I really do wanna get into another too, these myokines muscle-based proteins will not be excreted and released if you’re lifting tiny weights. So you have to be lifting at around– Even if you go to failure. If you go to failure, okay, but you do need to be lifting. You’ve gotta think about, you’re contracting the muscle to squeeze out these myokines.

 What the study that we did showed at around six to eight. Six to eight reps. Yeah, but that’s gotta be hard. Around 80% of maximum, of one RM. And most people don’t know they’re one RM. My suggestion would be, figure out the weight that you’re comfortable with and don’t be shy. People are concerned about, I can’t lift that 40 pound weight. My toddler is 40 pounds. And his grandmother wouldn’t think twice about lifting Leo up, but my mother might think twice, and maybe not my mom, but she’s just repping it out. But many, I think women would be intimidated by a heavier weight. And it’s unnecessary intimidation.

 And it’s really doing a public health disservice. Yeah, and this is why I’m a big proponent of personal trainers. Same. So I think everyone, if you can, find a trainer, God, I even have one. I have a squat trainer. You do? I had to like, I’m like, listen, you’re with me just for squats. He’s like, why don’t we, I said, you’re just a squat trainer. That is hilarious. Yeah, he wants to do more than that. And I’m like, no, just squat and dead lifts. But that is there because my form can be off. Sometimes I’m, maybe I’m tired, I’m fatigued. That messes form. It can lead to injury, which can then lead to me being in a bed and not doing anything for two weeks. So it’s important to have a trainer who knows what they’re doing, who can help and guide you through it. Absolutely. But let’s also talk just a bit about the other myokines. Is there anything more about interleukin 6? No. That you want to talk about? Just the correlation between cancer. And that’s probably the most famous interleukin or the most famous myokine is interleukin 6. And you know, we can test it. It’s the first one. Yes. And we can test it in blood tests, but it’s just not valuable yet from an optimization standpoint.

 And you’re laughing. Okay, so Louisa knows this because she’s laughing and I was very interested in taking some of the evidence in the literature and seeing if we could translate that to clinic, which in part is what they’re doing in Copenhagen. But it is so difficult. Here’s what I was thinking. If say Mia, my assistant over there is, I say Mia, okay, because in order to work on my team, you have to train. That is part of in the contract, you work out. That’s what I have for my friends. If you’re going to be in my circle, you have to train. And so I were such great friends. And let’s say Mia came to me and said, you know what, Gabrielle, I am training three days a week and I’m pushing it. I’m like, all right, Mia. I don’t really know if that’s true. Let’s test your interleukin 6. This was my idea because we are giving prescriptions to patients about training.

 Training is much more difficult to assess the efficacy than it is nutrition. I could say, Luisa, I want you to be eating less than 130 grams of carbs. When you do, I can see that your triglycerides drop by 20%.

 But if I say, Luisa, I want to see you squat for eight to 10 reps, I don’t know if number one, you are activating your glutes appropriately. Are we getting the correct stimulus? Maybe you’re using your back. Maybe you’re using your rectus spine and not contracting the muscles that we need to get the myokine release. Exactly. I had this idea that, well, we’re gonna measure myokines. Let me just tell you, it doesn’t work that way. No, I wish. Myokines are released from a tremendous amount of cells for a tremendous amount of reasons, not just exercise. I don’t think anyone would be comfortable with a muscle biopsy, just mid session. I had to do those for two years. Yeah, have you ever had one done? No, I just administered them. Yeah, I’ve never had one done. I’ve administered one in the calf before and it was traumatic for both parties. But you’re correct. How would we ever know? And that’s the limitations right now. I think that there’s more work to be done, but these myokines are like pharmacological agents. And you had mentioned, so you mentioned BDNF, which is a myokine, you mentioned Interleukin 6. I’ve always said irison, but maybe I’m pronouncing it wrong. Irison, yes. Or irison, yeah. So kapsacin, what is– Kapsap Yes, kapsap is your next myokine that you wanted to discuss. Well, so irison is the messenger molecule. So that, by the way, they all do something different. It’s fascinating.

 So irison actually helps with the expression of BDNF. So once BDNF is present in the blood, then irison comes up and basically pushes it and pushes it along and says, express more. We’ve got kapsap B as well, which does the same thing. They all acutely cross the blood brain barrier and they have an effect on our connectivity and our brain function. What I would love to see is, it’s my dream, Gabb, to have a cocktail of interventions that are available for patients with mild cognitive impairment. Prior to mild cognitive impairment, these are the stages. You’ve got asymptomatic. You then move into what we call subjective, cognitive impairment. Subjective lasts around 10 years. You then move into MCI and then Alzheimer’s disease. Which is mild cognitive impairment.

 So it is my dream to have a cocktail of interventions, whether it’s pharmaceutical, right, at a specific stage. We can talk about the new FDA approved LeCatemab, but also there’s really great research that’s now being done on genes.

 And have you ever heard of Clotho? I have not. So Clotho is the fountain of youth gene, if you will. And it was actually named, I’m sorry, I have to say it, after a Greek god of Clotho. For those of you who don’t know, this is Louisa, not just has beautiful skin, but is Greek. Correct, and we always refer to what we’ve done, if you’ve seen my big fat Greek wedding. Lots of Windex in there. Lots of Windex. Do you think, speaking of Windex, which you shouldn’t drink, I know that they had tried administering IV Interleukin-6. Have you seen any evidence that people could take any of these myokines orally? Is that something that could potentially happen? Pharmaceutical industry is banking on this. They are trying to create an IV of BDNF. It doesn’t exist yet. You think it will? Eventually, yes. If we can get to Mars, like, come on. I keep saying that. First of all, who wants to go to Mars? I am telling you they have no Starbucks, this place is going to be extremely dirty. I actually submitted my application. To go to Mars? That was, yeah, two years ago. You’re gonna come back with no muscles, it’s gonna be a whole thing, I’m gonna have to do your hormones. It’s just gonna be a disaster, I think you should stick to Earth. Yeah, but if I did go up there, I think our podcast would hit. Like, yeah. Our podcast is, we have an amazing audience who wants to share this information. And by the way, guys, I just wanna say something. The reason why we can do this for you at no cost is because we take sponsors. Some people have said, “Oh, I’m not gonna listen, “there are ads.” Yeah, it’s so that it can be free. Correct. We have a whole team here. So friends, I appreciate you being patient with the ads because it’s all part of how we can bring this free information.

 So we’ve got Erisun, we’ve got Kithepson B, so we’ve got, look, we’ve got hundreds of them. Soon we’ll have a Louisa that will help inhibit– No, you have to think of a Greek goddess name. Yeah, I will. I don’t know what that would be yet, but, look, it is monumental. I think the work of Bento Pederson and I think it’s just gonna continue. I think we’re gonna move into a new era of actually looking at resistance training. It would be great if we had these interventions in hospital settings. Wouldn’t it be amazing if we had this? But, oh, back to the clotho gene. So I think the future is also looking into how can gene expression and CRISPR potentially help patients with Alzheimer’s disease?

 When you think about tropic, tropic factors, you talked about hormones, you talked about myokines. I don’t know if you wanted to mention any other myokines or we feel good that we’ve covered that.

 On the opposite side, what would be the alternative to a tropic factor, an atropic factor? Yeah.

 A tropic factor. Would something like, and people get very angry about this alcohol or cannabis use, would these things affect the brain? Do we know its effect on the brain from a negative or positive or stimulants? Are there other things that would potentially counterbalance? Let’s say there’s a gym rat, they’re doing tons of resistance training, and then they’re, we’re not talking about sleep because everybody’s talked about sleep. We have talked about sleep till everyone is blue in the face, but other things that are out there that people are commonly doing. Yeah, and remember that all of these other factors, we’ll talk, you know, the UK Biobank released a phenomenal study where they showed that moderate amounts of alcohol in women is seven drinks per week. In men, I think it was around 13 to 14 drinks per week, we saw a reduction in gray amount of volume. We also saw an increase in white matter lesions. Seven drinks, but we will say that the UK Biobank is epidemiology, it’s population-based, and they may be doing other things. Maybe they’re smoking or, right, they could be doing other things. But we know that when you ingest ethanol, which is obviously alcohol, it ends up turning into acetyl aldehyde. And acetyl aldehyde is what? Don’t you put that on weeds to kill them? So it’s actually poison to the brain. But that’s not the, I don’t think that that’s the only issue we’re talking about when we talk about the sugar that we eat and we talk about what are the effects afterwards. Yes, it blocks sleep. Yes, it can upregulate, you know, downregulate immunity, upregulate tumor producing cells, so. Do you think there is a dose that is potentially safe? Oh, let’s hope that no one cuts this. But look, I don’t think that there’s any– I’m sure people will and–

 I’ll make it clear, I don’t think that any form of alcohol is good for the brain. However, I don’t see a problem in if you’re having one drink a week.

 You heard it here. What about cannabis, yes? Cannabis, I don’t know who needs to hear this, but cannabis is not helping you sleep. I think it’s doing more than just affecting the brain. I think that– I agree with you. And I think that the actual studies show that a prolonged period of cannabis use, which is, I would say, you know, 20 years of use can actually lead to an increase in psychosis. Yeah.

 Hormone, hormone replacement therapy. I think, do you wanna share what your thoughts are on that? I can certainly share my– The biggest failure in medicine was the Women’s Health Initiative. Initiative, yeah. And did you wanna– No, I mean, because of the Women’s Health Initiative, many women have not been treated with hormone replacement therapy. It still carries a huge stigma, and even testosterone replacement therapy for men and women. There are estrogen receptors in the brain. Is it that women are having an increased dementia risk because of the declining estrogen levels? There’s a lot of data that still needs to come out, but I believe– And there is that window of opportunity. There is a window of opportunity. But my only concern there is someone could sit back then and say, “Okay, Gabrielle, well, what if I go on HRT? “Do I preserve my cognitive functions “due to the increase or the preservation of estrogen?” It’s important to note that what we produce endogenously as a hormone is not 100% replicated synthetically. So with HRT, whether you’re putting an estrogen gel on, if you’re whatever type of estrogen you have, pharmacologically, when you remember back to pharmacokinetics, the way that they replicate it isn’t 100% identical to the endogenous hormone.

 Will you see an improvement? Yes. And you see that clinically. Yeah. Women that go on estrogen replacement therapy, testosterone and progesterone. I don’t know if there are progesterone receptors in the brain, but I will tell you, and maybe it’s because they’re sleeping better or, I mean, I suppose they’re what increases GABA, but it seems as if these interventions early and often make a difference in outcomes later on. Correct, and I do know that that window of opportunity, you should be going to a very specialized person who can give you the right information at the right time, because once you lose that, then, yeah. Then it’s not, you know, this is a very serious topic. Usually I smile and laugh and make lots of really bad mom jokes, but the mission that you’re on is critical. And we are facing a population, it reminds me of that movie, it’s called “WALL-E”, or is that, was that “WALL-E” where they’re all in chairs, Matt? Oh yeah. Do you guys remember? They’re all in chairs and they are, like, very obese, not moving. Have you seen that movie?

 No, it’s not, no, I haven’t seen it. When you have kids, you definitely will, maybe will play it tonight.

 It is this belief that a sedentary lifestyle, which is a disease state, being sedentary is a disease state. No matter how you cut it, when you look at the data and it says a healthy older individual or a healthy woman or a healthy sedentary person, it is not true. And I think that we are going to see with this increasing sedentary behavior that what we find acceptable is going to be our demise.

 One thing that I want to point out, which is probably controversial, that it is my belief and my opinion that Alzheimer’s disease is now optional.

 It is an optional disease.

 40 years ago, it was not optional. But now, I mean, your kids are probably going to be at the best point because now they’ve got options to either put themselves into a state of attack where we move from connection, as I mentioned, to protection.

 It’s just beautifully stated.

 I have a few questions on oral intakes of things. And I don’t know if you’ve looked at beta hydroxybutyrate or ketones, do you have a perspective on that? I mean, they’re different, two different things.

 First of all, no, there’s been great, that that’s actually one of the supporting factors, ketones. Absolutely. Of brain cells. I’m glad that we both agree on that. However, I will point out that the primary fuel source of the brain is glucose.

 That was my next question. What is a dose you feel comfortable with? For if someone said, “How much carbohydrates can I have? “How much sugar?” I mean, that’s your field. I don’t go, sugar, it would be zero.

 I don’t go into that. I go into more, the studies I’ve looked at are more, what are the nutrients that would support a healthy brain? And I would say for the listener, if someone is on a regular diet or the Lyme protocol, But 100, I was gonna say below. About 100 grams. Because when I look at the nutritional studies, About 100 grams, you can go higher if you earn it. The RDA is 130, do we eat that much? If you’re sedentary, probably not. And of course the body can generate glucose through protein.

 If you were to say there is a handful or your number one thing that really concerns you for brain function, what would that be? Inflammation. Okay. Yeah. And the biggest way to counteract that?

 Exercise, good sleep, proper nutrition, and in fact, your social circle.

 So the amount of support that you have over an 80 year period, it was a followup study of 85 years by Harvard, which showed that those with the best brain function, those who had a close social, the quality of their social relationships. And if you were to think about a protocol, let’s say if you wrote a book, which I’m hoping that you will, what would your protocol, Louisa’s brain protocol be? So I would start with that tree. If we all start, if we think that, well, what’s the cascade that is occurring here? It would definitely start as an inflammatory process. So how do we down regulate inflammation through first and foremost lifestyle factors? It would be, we need to be getting you to sleep well, and we need you to be sleeping,

 if you can, quite robotically at the same time every night and waking up at the same time every day, getting good quality sleep. We then wanna be really honing in really deeply on exercise. I think you should be moving every day. I think you should be working on what we call the base of your system, which is built through zone two cardio training. That can be done long runs, it can be done on a stationary bike. You wanna build up an engine. I want good lung health, I want good capacity, I want a great heart. We wanna be doing 40 minutes, 35 to 40 minutes of maximal exercise per week. And we wanna be as strong as we can. So that is really getting deep into resistance training around three to four days a week. I do have an extra protocol, which is engaging in neuro-athletics cognitive training. If you can do this for five or 10 minutes a day, that’s the sweet spot. I’ll then move up to the pyramid. And instead of talking about, cause this is what you talk about, you talk about in nutrition, what not to have. Let’s talk about what should you have.

 Your brain is made of water, around 70% water, 30% fats.

 The fat component or the lipid component, 20% of the lipids in the brain is made of DHA, which comes from omega-3 fatty acids. You wanna be dosing with this at around four grams a day. If somebody brings up the study that was, that came out six months ago, showing that increased EPA DHA results in AFib. Please tell them to message me because I’ve written an article on how that’s not true. So you wanna be having that. Turns out that your brain loves antioxidants and polyphenols.

 Blueberries are like a super food for your brain. Any berry, really, you’ve got goji berries, blackberries. You wanna have those. You also wanna be having selenium found in Brazil nuts and vitamin E surprisingly. And animal products. Yes, and beta-carotene, correct. So your brain loves that. I do love supporting factors for the brain nutritionally such as creatine, which is, it helps with– 10 grams, 10 to 12 grams for the brain. Oh, 10 to 12, okay. I generally get people to start on five grams. Five for muscle and 10 for brain. Why is that? I don’t know. I don’t know the mechanism of action, but it’s from the work of Darren Kandao and other researchers for creatine to have a cognitive impact. It’s about 10 grams. I believe that that, because he was on my podcast too, and if I think back, I think that’s because of the bioavailability when it crosses the blood-brain barrier and infiltrates the neuron. Plus it becomes neuroprotective against insults. And there’s no way you could eat, I mean, it’d be very difficult to eat 10 grams of creatine. Do you know when you cook meat, it decreases creatine bioavailability? Even liver? Because it’s abundant in liver. But it decreases it. Of course, that’s why. It’s a carny nutrient. Creatine is a carny nutrient, only found in animal products. And isn’t this the same as fish? Like if somebody says, “Well, Louisa, why can’t I eat?” I don’t know, five pounds of fish a day. I think fish actually, I think herring has a robust amount of creatine. Yeah, mackerel, herring, salmon. But if you go and watch that documentary, “Seasppiracy,” you’ll turn your face from that. So you’ve got creatine, omega-3 fatty acids, and then you really want to support the connection of the cells with electrolytes, sodium, potassium, all of these electrolytes that we lose just from everyday thinking, cognitive load.

 And I bet you eventually, probably another layer to that as it comes out is gonna be environment, mold, just other environmental factors, pollution, and very difficult to do things about this, unless you know. Well, that’s what the next part of it is, toxic mold and pollution. But I will say as well with what you’re doing, I’m a huge proponent of meat.

 We want to maintain good arterial health, which we can measure through a basic lipid panel. So as long as you’re keeping your APO-B, your LDL and triglycerides in check, and optimize, there should be no reason as to why you shouldn’t be eating these meats. No, yeah. We definitely talk a lot about nutrition on this podcast. And what I love about this conversation, and I’m so grateful that you’ve taken the time to come on, is that you are paving the way of reframing activity, not just for physical fitness, for looking good naked, for all the other aesthetics, and even the metabolic factors, but very specifically to brain health. Why are you doing this? Yeah, it’s a good question. I’ve had no one personally in my family. In fact, we have had, I’ve lost two people very close to me to cancer, and it was a rapid, very like two week. And that really scared and shocked me, which is why I’m really loving the research on cancer and exercise. I’m doing this because I don’t think it’s right that we don’t have a cure. I don’t think it’s right to, you go to sleep by yourself every night, whether you’re with a spouse or not. You are born alone and you die alone with your thoughts. To have that robbed of you for something that can be completely preventable is not okay with me, it just doesn’t sit well. I’ve exercised my whole life. I’ve been privileged enough to see what exercise can do. I was a competitive triathlete for Australia. I love it. It’s a free intervention. It brings so much happiness and it really is medicine.

 Luisa Nicola, thank you so much for coming on the podcast. Thank you, my friend. (Upbeat Music)