Understanding Your Brain Through Perimenopause and Menopause with Dr. Louisa Nicola

Let me tell you for every woman listening, and by the way, women represent 70% of all Alzheimer's disease cases. So two out of three cases are female of Alzheimer's disease. The small percentage that isn't is like Betty. If you have been given a, you've got a genetic mutation in three genes, the presenilin one, presenilin two, and the amyloid precursor protein, that's only like two to 3% of population. Very percent. Okay. Small percent. So the other 95%, why are they getting it? It's through lifestyle interventions, life's the way that you live your life. So we know that we have agency over it. So the 70% and then the rest of, you know, there's another very small portion that then has to care for their becoming caretakers. So really women are at the mercy of this disease. The views and opinions expressed on Unpaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment. As many of you know, I am obsessed with the science of women's midlife health. But there's one piece that keeps women up at night more than anything else. the fear of losing themselves, the fear of cognitive decline, and the fear of dementia. The facts are shocking. Around 50 to 55 million people worldwide are living with Alzheimer's disease today, and we expect that number to triple by the year 2050. But the part that rattles me the most is that only three to five percent of those cases are caused by genetic mutations, which means 95% or more of Alzheimer's disease is influenced by something else. Women ask me constantly, what can I do now to protect my brain? And my guest today, Louisa Nicola, is one of the clearest, most compelling voices in neuroscience, helping us understand the answers to this question. Louisa is a neurophysiologist and Alzheimer's expert on a mission to eradicate this destructive disease. She is the founder and head performance advisor of NeuroAthletics, a human performance education platform that has certified over 2,000 coaches and also a former world champion triathlete. I'm Dr. Mary Claire Haver, a board-certified obstetrician and gynecologist and certified menopause practitioner. I'm also an adjunct professor of obstetrics and gynecology at the University of Texas Medical Branch. Welcome to Unpaused, the podcast where we cut through the silence and talk about what it really takes for women to thrive in the second half of life. Women in midlife face questions that don't come with easy answers. Conflicting research on hormone therapy, financial decisions, relationship shifts, questions about your own health that require real thought, not just a quick search. Claude is an AI built for that kind of thinking. When you're trying to understand why experts disagree or work through something personal and complicated, Claude doesn't give you a quick answer and move on. It sits in the complexity with you, asks follow-up questions, helps you think through the trade-offs. And Anthropic, the company behind Claude, has committed to keeping Claude ad-free. Claude's responses will not be shaped by advertisers or third parties. When you're making decisions about your life, that integrity matters. Try Claude for free at claude.ai slash unpaused to see why problem solvers choose Claude as their thinking partner. This podcast is supported by FX's love story, John F. Kennedy Jr. and Carolyn Bessette. The new limited series from executive producer Ryan Murphy. It explores the complex courtship of the iconic couple considered to be American royalty, whose love story captured the attention of the nation. Their fairytale romance would unfold in front of the public eye, where their private love would also become a national obsession. FX's love story, John F. Kennedy Jr. and Carolyn Bessette. Watch now on FX, Hulu, and Hulu on Disney Plus for bundle subscribers. Dr. Nicola, welcome. Hi. To Unpaused. I'm so excited to be here. Walk me through your training. You grew up in Sydney, Australia. Well, I actually, well, I grew up in Australia, two hours north of Sydney. So my training, I did an undergraduate degree. I actually became a high school teacher. Really? Yes. So I was- That was like my backup plan. Really? Well, I did that because I was an elite triathlete and I was training six hours a day. In high school? I was training in high school and then after high school. I wanted to compete and go to the Olympics. And my mother said, the best way to do that is to become a high school teacher. You get your degree and you can do casual hours. And so I did. I ended up becoming a math teacher. So I was teaching senior boys. I went on to do a master's of mathematics and I was actually looking at neuron signaling. So I was doing algorithmic work with neuron signaling. I became fascinated by the human brain. I couldn't believe the trillions of cells that were communicating with each other during that time. And there's a mathematical equation for it. And I then went on, I did a master's of medicine and then further into a PhD. So quite extensive, but very analytical. And I love what I do because I have both clinical and a research side. So I work half of my week in neurosurgery, which gives me a really broad overview of looking at patient cases from tumors to, I'm in neuroplastic neurosurgery. So looking at reconstruction of skulls. And then I have the research side of my... So how did you end up in the US? Well, I came here because I wanted to work with the world's best neurosurgeons. And in Australia, we've got a population of 25 million. It's not the same as the US. And I thought I could broaden my understanding by coming here. What made you particularly interested in this area? So I'm looking at right now, I'm really an Alzheimer's disease researcher, and this comes from being a neurophysiologist. So that is my... Okay, for our listeners, what is a neurophysiologist? So it's a subspecialty of neurology. So it's somebody who is looking at the brain, but a specific area of the brain. You would see a neurophysiologist if you've had, maybe you're suspected of having multiple sclerosis or epilepsy. If you've had a seizure, you'll go and see a neurophysiologist and what they'll do is they'll scan your brain using an EEG. And it's one of those caps that you put on your head with all the wires that come out of it and it assesses the functionality of the brain. And so that's primarily what I've done. I've done thousands, thousands of thousands of EEG scans ranging from epilepsy, sleep study scans. And then I was put just by chance, and this was in 2017, I was put to primarily scan the brains of mild cognitive impairment patients. And for our listeners, what is mild cognitive impairment? So mild cognitive impairment is a pre-dementia state. We're going to talk a lot about dementia. And so I was tasked with, hey, Louisa, we've got all these patients coming in with memory complaints and they're having all of these difficulties with words and I was like okay so I started to scan their brains which was very new to me and we were able to come up with a clinical diagnosis of mild cognitive impairment okay combining an EEG and a QEEG and over that time in 2017 I had so many questions I kept asking my superior who was a double board certified neurologist and neurophysiologist, every time I asked him, why do we have so many women getting mild cognitive impairment compared to the men? And he said, it's just how it is. No one gave me answers. I didn't have the answers. I didn't know what caused Alzheimer's disease. And how old were these patients in general? The one who really changed the course of my career was 52, but most of them ranged from 50s to 80s. But I was really dumbfounded. I couldn't understand why we were getting 50-year-olds. And I used to think that this was a disease of your 70s and 80s, which is what I was being told in a hospital setting, in a neurology clinic, which is what I was being told. But when I was looking at these scans and you were looking at the demographics, you know, very like high socioeconomic status females getting this, having these complaints. And when you talk to them, and I'll give you the example of, let's call her Betty, 52 year old female, mother, three kids. She saw me over the course of two years and she went from saying, hi, Louisa, to over two years asking me if I'm her daughter. And that was a very, very fast progression into early onset Alzheimer's disease. so she did have a genetic mutation in the pre-senilin one gene but that's what really formulated okay this is i need to research this is what my phd will be on everything amazing yeah so when you went to your thesis advisor you know i guess that's how that works for the phd with this idea of i want to study i guess sex specific sex specific differences in alzheimer's Did you get pushback or were they excited? No, I got a lot of pushback. My mentor and advisor is a male, but he's phenomenal. There was just not a lot of work being done. 2017, you know, I knew actually about Lisa Moscone. I read a lot of her work and we didn't really understand sex specific differences in really any broad category, whether it was pharmacokinetic, any broad category. Cardiovascular disease. Exactly. It's just like multiple things. Yeah, but as the years went on, we started to accumulate all of this, all of these research papers that showed that 70% of all Alzheimer's disease cases were women. And that just kept like really knocking me, knocking me, knocking me. So you, you know, have this advanced, incredible degree in neuroscience and you are hitting the clinical floor. You doing scans as part of your job. Suddenly you get put on a project where you're doing early cognitive decline and noticing they're all, it's just dumbfounding to me that less than a decade ago, that, you know, you were shocked by this. I was shocked by this. And every time I asked for answers as to what causes Alzheimer's disease, what is dementia? What is the difference? Are there different forms of Alzheimer's? Like, what are we doing for these women? Now let's go back to Betty. When you interview Betty and you ask her about her lifestyle, she was never asked. She didn't know about, she didn't know if she was in menopause or not. as she had never in her life had a doctor ask her for her genetic profile. So she never checked her genetic profile. She rarely did blood tests, maybe once a year at her PCP annual. It wasn't deep, the biomarkers were just skimming the surface, vitamin D, metabolic panel, wasn't going deep into cholesterol panel. She had the standard American diet because that's what she was told. She was doing what she was told as per government guidelines. And she still ended up in this position. Wow. Where she was given, by the way, the end diagnosis of Alzheimer's disease is comparable to end stage cancer. And that's quite scary. And people don't see it that way still today in 2025. And my mom has Alzheimer's. I don't know if you knew this. And she's in her 80s. Her mother most likely had it. There was no diagnosis back then. she just was an old lady who laid in a bed for at least five years, you know, completely bedridden, yelling out, having lots of hallucinations and just drooling on herself, you know, at the very end and extremely frail. And then my mom, I think just kind of considered it her turn, you know, and now she's in a memory care, like we have better options. She's in memory care, but again, thought she heard my father, um, calling her in the middle of the night on New Year's Eve, got out of bed, fell and broke her hip, you know, then went through the surgical repair and she's never walked again. And so it's just as a family member and, you know, my sister's the primary caretaker because she's a nurse and logistically she's closer to mom. I live out of state and like, it is, it's life-changing and it's devastating and it is not what my mother would have wanted. And so I love these conversations because I can't wait to dig into this more because I am refusing for this to be the future for my children. I have two daughters and they're 21 and 25. I don't want this to be their future. No, and this is the disease, the only disease that robs you of who you are. Yeah. You know, you spend your whole life, I keep thinking about it. You spend your whole life getting to know yourself, getting to know your children and having that all taken away from you. Isn't life's greatest gift to really understand who you are. And finally, once you get there, it takes a very long time. I can only imagine. Once you finally get there and you're okay with who you are, it's taken away from you. One of the most painful things for me to watch is that it leaves her, not just her memory is gone, right? She's angry. She's, of course, she's, she's, you know, paranoid. She's in this horrible state of mind most of the time that seems like her brain is torturing her. Yeah. You know, and she's, she's, she's, she's, she's, she's, she's, she's, she's, she's, she's, just unhappy. It's downsized. Her brain has downsized because it's basically at a point where she's like, I've, the brain has said, we've given up, we give in now we're going in and that's it. Uh, and it's, you know, I'd love to just ask, did you check your status? So we're negative where there's no genetic component. Um, she did have flax. So that's how they made the diagnosis. She's in her eighties and, um, lifestyle like had to have had a huge part of this, you know, When my father died about six years ago, she really kind of gave up on healthy habits. And she was dealing with grief, I think, through excessive alcohol ingestion. Most of her caloric intake probably in the last year as she was at home was from alcohol. And so, you know, my sister and I talk about these are the things we have to avoid so that we cannot do this to our children. Absolutely. And it's a long progression, which is why people don't really pick up on it. And when it's too late, it's too late. So when you're given the diagnosis, there is no reversal, although some doctors claim there is. I don't believe there is. There is no reversal of the disease. There's no backtracking. And there's no real prevention other than lifestyle. Our audience is filled with mostly women. Our listeners are mostly women. Though we do have about, you know, we have several men that listen. But, you know, this caring for aging parents, are you seeing this in your population? My patients are coming in with the usual brain fog, and we'll talk about that, but they are looking at what's happening to their mothers, especially with their mental health and their cognitive changes in their parents and saying, okay, absolutely not. This is not what I want. How can we get ahead of this? And you're saying in your work, we're figuring out the path to decrease this risk. Correct. And let me tell you for every woman listening, and by the way, women represent 70% of all Alzheimer's disease cases. So two out of three cases are female of Alzheimer's disease. The small percentage that isn't is like Betty. If you have been given a, you've got a genetic mutation in three genes, the presenilin one, presenilin two, and the amyloid precursor protein, that's only like two to 3% of the population. Very percent. Okay. Small percent. So the other 95%, why are they getting it? It's through lifestyle interventions, life's the way that you live your life. So we know that we have agency over it. So the 70% and then the rest of, you know, there's another very small portion that then has to care for their becoming caretakers. So really women are at the mercy of this disease. Let's talk about brain fog. Yeah. And how is it different than dementia? Like when should someone be worried? So first of all, let's just do some terms. Dementia is the umbrella term that's used to describe the, you're starting to have a decline in your cognition. So your cognition is your thinking, your reaction time, your information processing speed. This starts to decline, which a lot of your listeners, if they're in their, maybe their mid forties, early fifties, they kind of feel like, you know, that's what brain fog really is. It's like a, it's like a mismatch in, oh, memory, you know, memory, it's like what's short-term memory. Like what was his name? What was that thing, you know, in the surgical, in the OR could be, could you pass me that thing? The long one with the handle. Yeah, the long one with the handle. You're starting to forget that's all brain fog, right? And it's exasperated through the loss of estrogen. We'll get there in a second. So dementia is the umbrella term. How do we diagnose dementia? This is a medical diagnosis. This is a medical diagnosis. Now you're not going to get dementia per se. You're going to get Alzheimer's dementia, dementia with Lewy bodies. So we have to really figure out which one it is. The reason why we know Alzheimer's disease is because most of the cases of dementia is Alzheimer's disease. So there's Alzheimer's disease, then underneath it is vascular dementia. Okay. Okay. So I've got different forms of dementia. So if you get diagnosed, you're getting diagnosed with vascular dementia and Alzheimer's disease is made up of two proteins. This is how you'll see it on pathology and on a report. You'll do a CSF, like a spinal tapping. you'll see that you've got accumulation of amyloid beta and tau proteins. If you've got vascular dementia, you've got a problem with the vessels in the brain. Or you might get Parkinson's dementia. Maybe first you had Parkinson's disease, it's exasperated and caused some form of dementia. So that's how you're diagnosed. You're usually needing urologists to do that through imaging. And then how is this different than brain fog? So brain fog is a symptom. Now brain fog is, like I mentioned to you, it doesn't mean that you have dementia. It's a cognitive complaint. It could be exasperated by stress, right? So what we know is that we have estrogen receptors that flood the frontal part of the brain. The frontal part of the brain is where we hold our executive functions, thinking, processing speed. When those estrogen receptors die, because there's no circulating estradiol, we don't have enough estrogen, what happens? Well, our thinking is not the best but it can also happen in a hypercortisol state so if you are severely stressed you may not have your short-term memory but that could also be brain fog as well so it doesn't mean that you have alzheimer's disease or dementia just because you have brain fog it's just a symptom and we can fix that you've said that alzheimer's doesn't suddenly appear at 70 no that it is actually starts quietly in our 30s and 40s so walk our listeners through you know What is actually happening in the brain? So we've got this 30 year projection, right? And Alzheimer's disease, if we think about it, it's really starts in the 30s because what tends to happen? Well, this is when our brain has fully formed. We're already there. So the only thing evolutionarily is okay great I I formed and now it time for me to decompress And what tends to happen just due to the natural brain aging process we get thinning of the gray matter So we got gray matter and white matter. And if we don't look after our brains, we get little lesions in the white matter of the brain. And as we're getting older, we've got more things, time is of the essence. We don't have, we're not looking after ourselves as much. So all of the things that we're meant to be doing that builds a high-performing brain and that stave off Alzheimer's disease, we're not engaging in these activities. We're not exercising. We're sleep deprived, whether that's due to kids, whether that's due to work-related, stress-related, all of these things. So we're not doing the things that are there to serve and protect our brain. And over the course of 20 years, if we don't do that, what happens in the brain, these plaques, these amyloid beta proteins and these tau tangles, they start to build up and they compound and you don't realize it in your 30s. I may scan your brain right now and I could scan my brain. We've probably got amyloid built up in the brain and some tau residue. We probably have because I don't know if you're sleep deprived, but we're in New York City. There's a lot of toxins in the air and then we wash it out at night. But if we don't do that, if we don't sleep every night and we don't wash out those amyloid beta proteins, they compound, they accumulate, they start to take over the brain. It causes losses of synapses and that over time causes Alzheimer's disease. Is there a threshold? How much accumulation do you need before you start having, this is Alzheimer's? So amyloid beta, okay, we'll talk about it. It was demonized as this toxic protein. We know now it's not a toxic protein. I was taught bad, bad, bad. Yes, because we used to think of Alzheimer's disease as the amyloid cascade hypothesis. That's what it was, right? But we know that that's not it. Okay. Amyloid is actually a protective molecule, right? It actually is served to protect your brain. So when we activate our innate immune system, when we get stressed, the neurons start releasing amyloid as a way to shield the neurons to protect them. but what happens is we have to have a good clearance system at night which is when we go into deep sleep to clear it out that's amyloid beta it lives outside of the neurons okay in the cerebral spinal fluid and then we have tau proteins now i don't think you i don't know if you know this but the one of the reasons that i hypothesize that 70 percent of women have alzheimer's disease is because we are more predisposed to tau proteins than men okay yeah walk me through this So tau protein lives in the microtubules. Let's neuroanatomy right now, we have around 87 billion neurons. Okay. Each neuron has around 15,000 connections. I think of neuron as a star with a long tail and a little star at the bottom. There you go. I love that. So that star, I can think about it like a tree. Okay. So that star is the neuron cell body and then you've got the axon. Okay. So that's the trunk and that axon within that live these highways, if you will. and this is where we send information, information processing speed goes up, that conduction velocity. That's where the microtubules live and that's where tau protein lives. Now tau protein, once it is phosphorylated, it breaks off the microtubules and it starts to aggregate. And when it starts to form clumps in that part of the brain, that's when we get collapses of the axon. This is really interesting. So there is an enzyme responsible, GSK3 beta. It's an enzyme that actually phosphorylates the tau protein. So it causes it to become hyperphosphorylated within that. And when it becomes hyperphosphorylated, it causes the collapse of the axon. Get this. Estrogen, progesterone, and prolyctin. I was going to say, like, does hormones have anything to do with this process? Yes. Estrogen, progesterone, and prolactin inhibit that enzyme. So it shuts it off. So estrogen and progesterone and prolactin actually stop the phosphorylation of that tau. Okay. So what happens during perimenopause? We don't have the support of the estrogen. So we are now hyperfixated on that. So we have an increased risk of getting hyperphosphorylated because we don't have the support anymore. And does the sleeping, the glymphatic system, the nightly washout, does it clear the tau proteins or just the amyloid? Just the amyloid because during sleep, we activate the glymphatic system. We've got a lymphatic system in our body, but what happens is the glial cells, that's where it comes from. Now glial cells comes from the Greek word glue. They stick between neurons and they shrink in size during deep slow-wave sleep. So when they shrink, what happens we can get all of the cerebral spinal fluid to wash through the brain and clear out the amyloid so it clears out the amyloid but it doesn't clear out the tau this is what i'm hypothesizing right now i'm doing a meta-analysis which you can understand is a really really big statistical analysis of all of the available evidence but i'm hypothesizing that this tau protein that we accumulate more so than men has something to do with the fact that 80 of all autoimmune diseases are female. Because if you think about autoimmune diseases, let's talk about multiple sclerosis, for example. What is that? It's a demyelinating disease. And I have done a lot. We do AMG studies. So for our listeners, demyelonization. So the myelin sheath is the insulation around the neurons and allows the more insulation you have, the faster the electrical impulses travel between neurons. Okay. When we demyelinate, we remove the insulation and There's an autoimmune disease that will cause that to happen. And then those nerve transduction times will slow down. So people with MS will have these physical defects, you know, or they can't feel or they're struggling. They get foot drop or ptosis in the eye. And what we see on an EMG is conduction slowing or complete conduction block. And I always think, and if that's happening... And what's an EMG for the listeners? Electromyography. So it's a needle which you'll stick into one of the nerve fibers and we can check the speed of impulses. And is that how we diagnose MS? Yeah, it is. And other neuroimaging studies. And I hypothesize that this is something, you know, because we still don't know why. Why are 80% of all autoimmune diseases women, we still don't know why. Why do you think that is? Well, this is one of my hypotheses. It hasn't been, this is just me speculating. No, why haven't we studied it to the point that we would know the answer? Because women are understudied, underresearched, because they have a hormonal cycle, which is... Makes them hard. Yes, makes them hard to deal with. So we've got the accumulation of tau and amyloid beta in the brain. And so there's several mechanisms too. So then you think, okay, well, is the whole process of Alzheimer's disease not getting it just to stop the amyloid and tau protein? Well, no, because what happens in Alzheimer's disease, that amyloid, when it builds up, it stops the connections between neurons. Okay, so that's what Alzheimer's disease really is. You've got these connections in the neurons and these connections go from 15,000 connections to 5,000. And those connections are responsible for everything we do, your actions, the way that you feel, the way that you think. And that causes memory complaints, short-term memory loss. And the first area to go in Alzheimer's disease is the hippocampus, which is this seahorse shaped structure. We all have one. It's deep in the temporal lobes, just behind the ears. And it got the name, it's a Latin name for seahorse because that's what it looks like. And that holds our memories, memory formation, memory consolidation. And that is the first thing to go as we get older, but also during the disease. Hormones affect more than how you feel. They affect your skin, too. As estrogen drops in midlife, your skin can lose collagen, hydration, and elasticity. That's where Alloy Health comes in. Alloy makes evidence-based menopause care accessible, connecting women with menopause experts. And now they're redefining skincare with M4, their prescription line made with estriol, a form of estrogen that only works on the skin. It started with the M4 Face Cream RX, and now Alloy's added two game changers, the M4 Face Serum RX, and the M4 Eye Cream RX. Getting started is easy. Head to myalloy.com. That's M-Y-A-L-L-O-Y dot com. Answer a few quick questions, and a licensed physician will review your info. Use code MCH20. That's M-C-H-2-0 for 20 bucks off your first order. Your personalized skincare ships right to your door. No appointments, no pharmacy lines. Because your skin's changing, and your routine should too. Visit myalloy.com and use code MCH20. That's MCH20. So a lot of the naysayers, when we talk about the possible connection with mental health and especially in cognitive decline, will try to negate hormones having anything to do with this and say, this is just aging. No, dementia and Alzheimer's disease is not part of the natural brain aging process. you can get to 100 years old and have your cognitive functions intact. It is possible. It is hard, but it is possible. Hormones are one factor. There are many pathways to getting Alzheimer's disease if you're a type 2 diabetic. Men get it, but men are more protective. They have greater cognitive reserve. They go through andropause at a much later stage, slower rate, But they also have more testosterone and testosterone aromatizes into estrogen. And estrogen is protective. And estrogen is very protective. So walk me through a premenopausal brain, a perimenopausal brain, and a postmenopausal brain. So the premenopausal brain has everything functioning adequately, right? Depending on lifestyle, but let's just say you're living just, you know, a really great, healthy life. Your brain is getting fed with estrogen. that's the first one, progesterone, prolactin, and testosterone. These are, I wouldn't say they're like fertilizer for the brain, but they are mediating many pathways. So you've got proper glucose metabolism in the brain. The brain's primary fuel source, it's a hungry organ. Okay. 2% of your total body weight, but consumes 20% of the total energy that you take in. It's fascinating to me. Why is that? Because it takes so much to power. It's going 24-7. It's such a hungry organ. so it needs fuel where does it get its fuel from it uses glucose estrogen helps mediate glucose that's in your that's in your blood get into the neuron so we can use it get into the cell body and what happens as we so we can use so that means we have our cognitive functions intact we've got a lot of energy we can go out and in our 20s and and and write ourselves off and wake up and do a marathon the next day. I know I did that at 22. So when we start to see this dip in estrogen, that means our brain isn't as supported as what it once was. Okay. So our glucose metabolism isn't working as well. In the brain. In the brain. Or actually in all parts of the body. Some women get hot flashes at night, which is waking them up during the night. And therefore, you get sleep disruption which is also accumulating amyloid beta we have higher we have a lower tolerance to stress okay because of hormones and then when we get to that stage like you've all you've said it yourself and it's not my wheelhouse but you said that we've got a window of opportunity to intervene and when i look at the studies especially for apel e4 carriers which represents 20% of the population, homozygous, these are the women who are most vulnerable to that window of opportunity. That study came out of Scandinavia, right? Yes, it did. Yeah. Which showed that women who have one copy of ApoE4 have a two to four fold increase in getting Alzheimer's disease. And then what did the HRT do for them or the estrogen replacement do for them? Well, it lowered their risk. And that's only during that window of opportunity. Then what is the window? Early? It's early. It's like 10 years prior to menopause. And then this is shown in cardiovascular data. We knew for observational studies for years, and the WHI did prove this for the younger patients. We have a cardiovascular window of opportunity too, where it is preventative for the plaque accumulation calcification. if you get it started before the plex form. Yeah. It's not really helpful to the plex once they're already formed, as far as we understand. Yeah. Basically, think of your brain like a Formula One car, right? And if you're not fueling the Formula One car with proper gas and you're doing the cheap gas and then eventually it just stops working, you just don't put the gas in anymore, it's not going to go efficiently. When we're talking about estrogen and estrogen replacement therapy and hormone replacement therapy. What you're doing is, I don't call it, it's not a miracle. It's an adjunct to help you do other things that are necessary for the brain. It's going to help you go to the gym. Okay. Push more. It's going to help with bone mineral density. It's going to help with lowering fat mass. It's going to help lower inflammation. All of these things that if are heightened can exasperate neural inflammation and Alzheimer's disease. Okay. So like a secondary. Correct. Yeah. Yeah. Many of our listeners know what hot flashes are, you know, and understand that and mood swings, but they don't understand really why cognitive function shifts. So you've talked about the nerves and nerve conduction. Where do neurotransmitters play here? Oh my God. So this is actually really fascinating. I'm not sure if you've heard of this. Did you know that the hypothalamus has a cluster of neurons called candy neurons? Keep going. Yeah. So K-I-N-D-Y, but it's pronounced candy and it stands for kispeptin, neurokinin 6 and dynorphin. Okay. I've heard of neurokinin only because the new neurokinin receptor agonists that have come out, phenophilia, as in stuff to treat hot flesh. So this cluster of neurons actually are, they help regulate reproduction and temperature. So what happens when we have low estrogen during perimenopause and menopause, estrogen actually regulates these. So when we don't have any estrogen there, these candy neurons, I love the name by the way, these candy neurons, they're hyperactive. They don't know what's going on. There's no one. Estrogen's not there. Estrogen's not there to control it. So these neurons, these clusters start going crazy. They go, oh, and this is why we get hot flashes. This is one of the hypotheses as to why we can't regulate temperature correctly. And when we get hot flashes, we get a rush of blood because your brain is also, by the way, glucose metabolism also plays a role. When the brain is starved of glucose and it doesn't know what to do, many things happen. We know that we start to metabolize fats, but in relation to hot flashes, we get a rush of blood that goes through our body because the brain is sensing, oh my God, I'm starving. I don't know what to do. So we get this rush of blood, which ends up becoming a hot flash. They showed on fMRI studies that the brainstem lights up just before a hot flash happens. The brainstem is responsible in that area for temperature control regulation, but also this is where it controls breathing and sleep. So this is probably why a lot of women are having these hot flashes during sleep. Then we get this sleep disruption, which is where the cascade of problems happen. Yeah. And then talk to me about serotonin, norepinephrine, these, these little chemicals that, you know, signals from neuron to neuron. Yeah. So when our brain cells are communicating with one another, we use something called a sodium potassium pump. Yeah. So it releases these, these neurotransmitters, which are just chemicals, that are responsible for many things, happiness, serotonin, dopamine, motivation, it's a neuromodulator. Funnily enough, they live in two areas, but most predominantly in the frontal lobe. And what's the frontal lobe predominantly filled with? They're out where our estrogen receptors are, and also the hippocampus. So when we see a decline in that, we see a decline in the inefficiency of the neurons to communicate with one another. Okay. And can you talk a little bit about the mental health changes we're seeing. I see this in clinic acutely. The SSRI is being prescribed. So in my clinic, you know, and the data holds this up, actually it's a great data coming out of Australia that looked at using HRT in perimenopause for new onset anxiety or depression and seeing how well those patients were doing much better than putting them on an SSRI. But most doctors haven't learned how to prescribe hormone therapy or uncomfortable doing it because they were never taught. And as a default, they are prescribing a lot of SSRIs to treat hot flashes. Hopefully we can get everybody educated and get some better options out there. But the fact of the matter is about 10% of women in the US are getting their prescriptions filled for an SSRI up until about age 40. And then across the perimenopause transition, that doubles. Yes, doubles. And then at 65, it goes up another 5%. When you're saying that it could be replaced or monitored better if maybe they got on hormone replacement therapy. There is at least for a new onset mental health change in perimenopause or someone who was previously well controlled on her medication and now suddenly is not manageable. Adding in and starting on HRT or adding in HRT to that regimen will probably benefit her better than adding in a second SSRI or starting her new start. I think what's important to understand is that when your brain doesn't function adequately, the way that it's supposed to, meaning like the both structural and functional changes and the white matter lesions that we discussed earlier, it can cause an array of different issues. If your brain doesn't know how to function properly, it starts to think to itself. You've got to think evolutionarily. Okay. Well, I'm under attack, sympathetic nervous system out of control, neural inflammation, which is literally the inflammation that you see in your body, but it's in the brain and it starts to inflame your brain. And this is what's causing depressive like symptoms. And they can be confused if they're not downregulated by hormone replacement therapy or other forms of therapy as well. Exercise is a great mediator, by the way. Creatine is a fantastic media, which we'll go into. So if you're not taking care of that thing, yes, you could be mistaken to just have an SSRI and let's just calm you down. Just garden variety. Yeah. Depression. Let's go back to sleep. Yeah. The girls are not sleeping. Like my patients don't sleep. And so they almost, not universal, but oh gosh, I would say 70% are coming in with some kind of a sleep disruption. If it's hot flashes that are disrupting their sleep, we can fix that, you know? But even if we have their vasomotor symptoms controlled, women are still struggling. There's still that 2 a.m. They're going to bed okay, it seems like, but they having that 2 a 3 a wake up Yeah And it consistent You know everybody gonna do that once in a while but you know walk me through why do you think this is happening And that interesting because I actually seen a lot of female patients getting prescribed amitriptyline in replacement of poor sleep, which I think is crazy because it's a tricyclic antidepressant. And so insomnia is occurring for a number of different reasons, but what tends to happen is the reason why you're waking up more often is because you've run out of melatonin. And that is what Andrea Matsumura, who's a sleep medicine specialist, says. And so your brain wakes you up and this could be a disruption in your circadian rhythm. Where did the melatonin go? Like, why, why don't we not have melatonin? The pineal gland is just disrupted and it's just waking you up. And then what happens is you can't get back to sleep. You've got the racing thoughts. And then we've got a really big one is because the loss of progesterone, which is activating GABA. And GABA is the chief inhibitory neurotransmitter. So oftentimes what you see is women have got two complaints. I'm having trouble falling asleep. I'm having trouble staying asleep. Okay. One may be a temperature control problem. One may be racing thoughts. If it is the racing thoughts at night, I'm having trouble falling asleep. That is okay. It's progesterone. I know that progesterone therapy helps, but also gamma amino butyric acid, GABA in the form of a supplement could help as well. Oh, good. Yeah. And I think this is where maybe cognitive behavioral therapy. Cognitive behavioral therapy could help. But let's go and switch to the fact that we actually need our core body temperature in order to fall asleep and stay asleep. Our core body temperature needs to drop at least two degrees. A lot of women don't understand this. We throw out the word sleep hygiene. Like it's candy and everybody can do it, but this is hard. Yeah. To drop your core body temperature? Oh, it's very hard. And so I've got a number of different techniques, but in order to fall asleep, so what is happening is your body can be raising its core body temperature and waking you up. So what happens is our cortisol rises according to the sun. Okay. So if the sun, okay, our core body temperature rises and that's what actually wakes us up. Cortisol wakes us up in the morning. But if you're waking up at 2am, then we have to think, is it cortisol? Is it the activation of your sympathetic nervous system? Or is it core body temperature? Because the moment that your body senses that it's getting warmer, it'll wake you up. And a lot of women do struggle with getting hot at night. So to cool the body down, there's many things you can do. Really easy hack is having your feet outside of the sheets at night. I was self-regulating doing that without thinking that one leg out of the, out of the, like I would do it without thinking. I'd wake up and one leg would be out of the bed. Cause now we have the mattress that cools automatically. But it's very expensive and not everyone can afford this. So yeah. And you don't have to. Okay. Funnily enough, having a hot shower prior to going to bed raises your core body temperature really high. And then in order to compensate, it brings your core body temperature really like plumbers it down to the point that you cool off. oh that's amazing that's another hack that you can do but that may be one reason why you're waking up and i have to say if you are waking up at 2 a.m definitely don't look at your phone it's so hard yeah yeah yeah it is really hard i'm like at least i just want to check the time and then of course the rabbit hole opens and i fall in yeah sometimes yeah how much sleep is enough so there was a really phenomenal study printed in pnas which showed that even one night of sleep deprivation can raise amyloid beta circulating levels in the brain, which is crazy, right? Because how many new mothers are getting sleep deprived? So, I mean, I get sleep deprived, okay? And they showed that it was six hours. Wow. A lot of women feel like six hours is enough. Yes, it's not. From all of the data that I've seen, I boil it down to seven hours and 30 minutes. Okay. Between seven, I usually, The reason why we say eight hours is to give you that 30 minute buffer time of falling asleep and, you know, waking up as well. So I think you definitely want to be asleep for at least seven to seven and a half hours every single night. Do you feel like women are going to bed too late? Well, so that's another thing. So what we're seeing in the sleep studies is one of the biggest ways to stave off all cause mortality that is dying of any cause like hypertension, getting hit by a bus, whatever that is. is actually sleep regularity. Going to sleep at the same time every day and waking up at the same time every day is actually more important than sleep time itself. And that is because that dictates our circadian rhythm. And remember, what is your brain like? It likes safety, it likes rhythm, and it likes a schedule. So I know that we're not robots. So a good rule of thumb is to think of sleep regularity as 80% of the week to give you a buffer time of like two nights a week. Yeah. So one of the things that I made the choice to do, which was hard because this was a profession I went into on purpose. Like I went in with eyes wide open was obstetrics. I've given up obstetrics as part of my medical practice, not because I don't love the process of taking care of pregnant people and delivering babies. I mean, I just, I miss it so much, but the hours were literally killing me. Yeah. And I realized it. And as this new research was coming out and I'm reading, I'm like, I am constantly sleep deprived because of my job. I'm tearing years off of my life because I'm not able to, because I'm on call three nights a week, you know, able to get into a sleep pattern that's going to keep me healthy. And because it's, sleep doesn't just represent how good you feel the next day. It's actually something that is going to help you get up in the morning, go to the gym, and you've got this flow on flow effect. So if you're sleep deprived, you accumulate those amyloid beta plaques, you get up late, you are more insulin resistant. So you're hungrier, leptin, ghrelin out, you know, it's going crazy. You eat more, then you go to, then you're disrupted going to sleep that night. You've got the accumulation of amyloid beta that you haven't cleared out. That amyloid beta actually prevents you from going to sleep. This is why maybe your mother and people with mild cognitive impairment and Alzheimer's disease actually have trouble falling asleep because of the accumulation of amyloid beta. So it's this cycle that just keeps going and going. I hear a lot about the sleep hygiene and the wind down routine. How important is that? Wind down routine is so important because you want to start down regulating and getting your brain primed to sleep. So generally we start to see a secretion or a release of melatonin at around 8 p.m. according to when the sun goes down wherever you live. And you have to understand that our brain senses that we're awake via this little area in the brain called the suprachiasmatic nucleus. And that is activated via the cells on the bottom of our retina. So if they sense any type of light, any type of light, at the end of the day, they're very susceptible to light because they're weaker, because they've been open all day working. So if you're watching the television, it senses light. It senses that you're awake. So it sends a signal to that area of the brain. It tells the brain, hey, we're awake. Stop the melatonin, increase cortisol. So you're getting all of this cortisol throughout the night and you're not down regulating. And this is why we're having trouble falling asleep. So wind down routines that involve dimming the lights at night, not looking at your email, trying not to respond or having heavy conversations with your partner or whoever that is. What about reading? I'd love to read? I love to read too, but it excites me. So it gets me all worked up. Sometimes I'll be so into a novel and all of a sudden it's one in the morning and I can't go to bed. Yeah. I don't know if this is the placebo effect or not, but I wear really great blue light blocking glasses. Okay. Okay. They're orange. What about red light therapy? Red light therapy is phenomenal. I have a red light panel as well. Everybody's different. Okay. I've got some women soaking their feet in warm water just to calm them down at night. So I was gifted a sauna blanket. Oh, good. Like a sleeping bag. That is a red light sauna. And that is when I'm home, which I've been traveling a lot lately, that is part of my routine at night is to get in that thing for 20 minutes. Whatever calms you down is what you should, no one should stick to the same wind down routine. Okay. Yeah. Find out what works for you. Correct. Keep experimenting. What do you do? I take a sleep stack of supplements to 20 minutes before bed. But my wind down routine is really like dark house. I wear my red light blocking glasses. I actually have this incredible device that I place on my abdomen. It wraps around, it vibrates and it's got red light therapy on it. Amazing. Yeah. It's so insane. And then 20 minutes prior to sleep, I'm having magnesium L3 and 8. I'm having GABA because I've got a racing mind. Sometimes when I travel, I do have two milligrams of melatonin. I'm not against it. I think it's fantastic, especially as it relates to immunity. I'm in bed at 10. Non-negotiable. Non-negotiable. Lights out is 10 PM. And we know that the hours prior to midnight are really what counts when it relates to sleep as well. That's when I deep sleep. Yeah. Is in the early part of the night. Exactly. Yeah. Deep, slow wave sleep. So I try and be asleep by 1030. How do you feel about sleep trackers or, you know, nearables and wearables? Love them, but I know that they're not 100% reliable. I have an Oura ring and I wear that religiously and I check my data and you do too. What I'm checking for is regularity and I'm checking for patterns. So, and the most noticeable pattern is your heart rate variability. If it is a certain amount. Please. Yeah. What is heart rate variability? I know. Why does it matter? Yeah. So basically it's the variation between your sympathetic nervous system and your parasympathetic nervous system. And what are those? So your sympathetic nervous system is that fight or flight. So it gets activated in response to a threat. Evolutionarily, it was to run away from the tiger and hunt and do what we needed to do. It shuts down all of the blood flow to the organs. It sends it to the brain and makes us really focused, right? There's some pluses and minuses to that, right? Pluses is we become super focused. Minus is we increase the amount of inflammation in our body. The other one, the parasympathetic nervous system is the rest and digest one, the one that we want. Our heart rate variability. We don't want to be all day in sympathetic or in parasympathetic. We want a really high variation of the two. We want to be in sympathetic nervous system. We also want to be in parasympathetic nervous system. So if you have a high heart rate variability, it means that you have really great flexibility of going from sympathetic to parasympathetic. You know, I'll get dinged on my ring from having low heart rate variability from time to time. Like, how do you fix that? Well, alcohol plummets your HIV and it also plummets your REM sleep, right? So one of the worst things you can do is drink alcohol, okay? but I have a standard rule for anyone that I work with and that is I will promise you that I will increase your heart rate variability by at least 10 points right how do you do that the best known way is resonance frequency breathing or breath work really I want you to try it if you try and you know you have to do it part of my wind down like oh if you do training if you do 20 minutes a day. Usually if you do 40 minutes a day, that's great. Separated by two by two. But if you do 20 minutes a day of breath work, I don't care which one, just do breath work. You will see a change in your heart rate variability tomorrow. Okay. You'll see it. So that's one of the best ways to increase it. I know the way is really quick, quick and simple breath work routine. Okay. One of the best ways, just close your eyes and you do want to do breath. You want to do the four in and then the four out. You can do four by four. You can do box breathing. I do box breathing. But it's not about that. It's about the time. So you want to do it consistently for at least 20 minutes. Okay. Yeah. Amazing. Best way to increase your heart rate variability. Okay. Have you ever stood in front of your closet and feel like you have nothing to wear? That's where Daily Look comes in. It's the number one highest rated personal styling service for women, delivering a curated selection of pieces right to your door. Here's the best part. Each customer is paired with a dedicated stylist who picks pieces based on your body, your preferences, and your lifestyle. The stylist is a real person, not an algorithm, and you work with the same stylist for every box. Each delivery includes up to 12 premium pieces to try on at home. You keep what you love and return the rest. Shipping is free both ways. Plus, you can schedule deliveries every 30, 60, or 90 days, whatever works for you. 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So the weather's cool every year for about 15 years, our knees started getting as we hit our fifties. So, but you know, that was kind of our thing. And every fall we'd start training and run together. And that kind of like led into what else can we do? And so we started doing these small triathlons that were actually in Galveston. And so I'm not a great swimmer, you know, swimming was the hardest leg for me. And I bought my first triathlon was with like a Schwinn, like my daughter's bike with a basket on it. And then I got a tri bike, you know, and so, but I was never like hardcore, but I did it. And it was fun. That's phenomenal. Oh my God. Yeah. No, I lived and breathed it all through my twenties. So yeah. Amazing. Yeah. And three legs, people think you have to be the best in three legs. So I was the best at swimming. I was first out of the water. I was great on the bike. What let me down was my run. I love running, but I was heavier than the other girls. So they would just fly past me. But people don't realize that it's actually four legs because we consider the transition as an actual leg as well. Yeah. And you're a performance coach on top of everything else you do. Well, I was, I mean, right now. So I've got some clients as well that when I say performance, I'm doing everything from blood work. I'm doing EEG scans. I'm trying to get people to their absolute peak and everyone's peak is different. Amazing. Okay. Back to exercise. Yes. So, cause you are the expert women aren't really connecting. I think I'm doing a lot of messaging on social media right now about the importance of muscle health, because that is definitely one thing I never, never, never, never, never, never, never thought about those times. I only thought about my weight and the weight was to be as small as possible and as thin as possible and muscle weight a lot. So why on earth would I want that? So all of my time in the gym, was aerobics. I mean, I grew up in the eighties, you know, doing step aerobics and doing all this cardio, which is great for my heart health, running marathons in my forties, never picked up a weight seriously until 50 something. The Jane Fonda era. Yeah. Yeah. And so walk me through exercise and brain health. Oh my God. It is so beautiful. Okay. And this is what I published. I was the first author for this really beautiful narrative review, which looked at exercise and mild cognitive impairment. But let's think, you know, I honestly think that the biggest reason why muscle is so good for longevity and brain health is because of the process that it takes to get the muscle. So it is the muscle itself, yes, because it's a storage sink for glucose, but I think it's the process. So exercise is by far the best elixir for your brain. Did you know that women who have a high peak respiratory fitness as measured by a VO2 max test can lower their risk of getting dementia by 80%. I did not know that. So the fitter you are, ladies, the greater that you will stave off all cause dementia and Alzheimer's disease. So how do you improve your VO2 max? And what is VO2 max? So let's talk about exercise. Okay. And I'm going to split it into two categories. We've got resistance training. Okay. That's your strength training. And then we've got your cardio metabolic So I'm seeing all of this drama, all of the internet. Don't do cardio. Yes, do cardio. I know it's- Lift weights, da, da, da, da. What should women be doing? It doesn't have to be that hard either. So let's talk about aerobic fitness and what that does for the brain. So when we're engaging in long runs, you've probably heard of it, it's your zone too, right? That's around 60% of your maximum heart rate. Your maximum heart rate is as hard as you can go until your heart rate reaches its maximum, okay? To the point where you may pass out afterwards. so 60% of that which looks like you and I going for a depending on how fit you are a brisk walk or a light jog and we can hold a conversation what you're doing in that zone is you are getting a massive release of something called BDNF brain-deriving neurotrophic factor and some you know back in the early 2000s neuroscientists would call this fertilizer for the brain but what it's actually doing is once it's in the blood it goes up to the brain it crosses the blood brain barrier and it actually can create new neurons grow new neurons in the hippocampus of the brain that area that goes during alzheimer's disease in fact there was one study this is actually what propelled me into studying this it was a study done by erics ericsson et al which showed that you can decrease your risk of Alzheimer's disease by at least 40% by engaging in aerobic physical activity. And not just that, he found that you can grow the hippocampus by 2%. 2%, a 2% growth and the hippocampal sub-regions from aerobic physical activity. Only 30 minutes. That's all you need. Yeah, I was like, how much are we talking? Marathon training? You only need 30 minutes to get that massive release. three times a week. Wow. Okay. So that's not much, right? When you engage in aerobic physical activity, you are having an effect on 13 types of cancer. So aerobic exercise at 30 minutes, this is 30 minutes a day, can decrease your risk of 13 types of cancer. So many women have only heard about exercise as a way to master some number on the scale. And talking about it, I think there's some lady, I always talk about our little sweet lady on the couch in Ohio, who is listening to this saying, because to me, you know, using exercise, one, it was social, doing the training with my girlfriends. That was great. But you know, really it was like, I want to be a certain body type. I want to look a certain way. And when you're not seeing the results, it's very demotivating that I'm not thin and I'm not this and I'm not that. But then when you're thinking about it, I'm decreasing my risk of dementia. Yeah. I'm growing bones and muscles. You know, I am. You are growing the hippocampus of your brain. And not just that. So my narrative review showed that what we can do is we can actually have an effect on the white matter portion of the brain Wow And what is white matter for our listeners again So we got white matter and gray matter The gray matter is the cortex on the brain the outside of it. The white matter is the myelinated neurons, which is involved. It's the fat. And actually 70% of the brain is myelinated, right? So it's the fatty portion of the brain. So what happens is we get women, especially during the perimenopause stage, but also as we age, we get something called white matter lesions. These little lesions on the white matter. What we showed was that exercise can improve those white matter lesions. So what exercise in this study were your patients doing? We primarily looked at the... Oh, this was more resistance training. Okay. So let's move on to resistance training. By the way, I do want to point out something that is not happening right now. Women are anxiously afraid of zone five. I call it the death zone. It's that high pace. It's that 90% of your maximum heart rate. And this is so, so, so important. In my opinion, it's actually even more important. For brain health. For brain health. And it doesn't take much, right? Well, what you're really primarily engaged in is something called the four by four principle. Okay. This is to predominantly increase your VO2 max. Okay. So zone five, we should be training and you only need to train in it 20 minutes a week. what you're doing in that zone is you're producing lactate, right? We used to think that lactate or lactic acid was the burning. Yeah. And it's not causing that burning sensation in your muscles, okay? That's not what lactic acid buildup is. Lactate is a by-product of working out at that really hard zone. Lactate is fuel for your brain, okay? We need it. Your brain prefers lactate as a source over glucose. It's such a miracle molecule. I'm obsessed with lactate. It's so amazing, but we can only get it when we're working out at that hard intensity. So what does that look like? It looks like going to the gym or doing anything really hard out for four minutes. Four minutes on, four minutes off, repeat that four times. You will increase or maintain your VO2 max by going at that hard stage. Okay. All right. So what else do we need to do? We need to resistance train. Okay. Resistance training at least three times a week. Okay. When we do resistance training, we release something called myokines. Okay. They're muscle-based proteins that live inside the muscle. And when they go into the bloodstream, we have receptors for them. Just like we have estrogen receptors, we have myokine receptors all over our body and in our brain. and they can improve the functioning of your frontal lobe, improve your executive functions. So you can actually, this is one of the best ways of staving off neurodegeneration is by resistance training. And this is what we found in our study, which is from, if you combine resistance training with cognitive training, okay, doing something cognitively, maybe you're throwing, doing reaction training drills, three times a week is all that's needed. So what would that look like? Getting a tennis ball, okay? Throwing a tennis ball to the wall 20 times, okay? Throwing it like left and right, left, right, left, right, maybe standing on one leg. Because what you're doing there is you've got to think about it. You're doing reaction time. You're doing balance, cerebellum. You're doing spatial processing, visual, yeah, hand-eye coordination, visual processing. You're doing so much and your brain is having to think at the same time. I've got to think where's the ball, what's it look like, move back further. It's hard, it's challenging. your brain needs stimulus and it needs supply. So stimulate your brain. You've got to do hard things or it won't grow and it won't adapt. What is neuroplasticity? Neuroplasticity is the way that the brain wires together. When neurons wire together, they wire together, meaning that you can learn something new by doing it repetitively. See, I was always under the impression and probably taught, and was wrong, that we have our neurons in the brain and we can't grow more. Correct. We can't. Adult neurogenesis doesn't exist. To destroy them with alcohol and smoking and bad things, but you can't grow new nerves. But that doesn't mean you can't change the brain. Correct. And rewire the brain. That's the functioning of the brain. So yeah, so those connections I spoke about, you can't grow new neurons, but you can grow new synapses. Okay. So you have to think every time you see something new for the first time or do something challenging, you've created a new synapse. You've created a new pathway for the brain to connect. Your brain needs hard stimulus in order for it to grow and repair. Okay. So adult neurogenesis doesn't exist, but it doesn't mean through neuroplasticity that you can't help and grow new synapses. Okay. Yeah. The functioning of the brain exists. Global functioning, 80% of brain gray matter is modifiable by physical activity. There's a study that shows the hearts of 50-year-olds can look 20 years younger. Oh, yeah. After two years of cardiovascular training and that it literally remodels the heart. And why is this important for the brain? The brain is like a mini heart. Did you know that we've got 43,000 neurons in the adult heart? No. Yeah. Yeah, we've got these clusters and they're actually sensory neurites. So they're responsible for sensing things, which is why you sense something in your heart and it translates to your brain. But this was a study done by Ben Levine where he took a group of 50-year-olds and he took photos of their heart, really did all these images and looked at their hearts. Then he put them under a two-year intense protocol of vigorous intensity exercise around that 80% to 90% of your maximum heart rate. He exposed them to that five times a week, which was a rigorous exercise. But what he found over the course of two years, he scanned their hearts again and found that they looked 30 years old. So he reversed the age-related decline in their heart by 20 years. Wow. Yeah. So if you have a better performing heart, stronger chambers, you have more blood that is being able to be delivered to the brain. Your brain is the most vascular rich organ in the entire body. It's comprised of vessels such as veins, arteries, capillaries. The capillaries are the first things to go in hypertension. But what do all these vessels do? They supply the brain. They bring things to the brain and they take things away. Nutrients, oxygen, exactly. So if you've got a better performing aorta, we've got branching off the aorta, we've got the vertebral arteries, the carotid arteries, that's what supplies the brain with blood. When these are working well, the pump is working well and our chambers of the heart is working better, more efficiently, what happens? What happens is we have more blood that goes into the left ventricle that can go throughout the body and into our brain. Okay. Yeah. Amazing. So back to exercise a little bit, a lot of chatter and myself included talking about estrogen and it's loss of estrogen, loss of sex hormones in general, and their effects on muscle, and we know the effects on bones, you know, that resistance training might be the single best thing that they can do. The single best thing that you can do for bone health, for bone health, for overall longevity is exercise. You know, we're so worried about supplements and we're so worried about all these, these little gimmicks that what can I do? You know, can you do a jump squat? Can you do a box squat? Can you, you know, can you do plyometrics? These are arguably the most important thing. And I'll tell you what, if you want to focus on one thing, focus on lower body strength, because one of the things that we lose as we get older, especially if it's more pronounced in women is we lose power first. Okay. So the ability to, uh, lift force, you know, in a certain amount of time. So really fast, that's what power really is. And they showed this in a twin study. Okay. They tracked twins, okay? They got many sets of twins and they, you know, same genetic makeup and they got, they put one- Identical twins. Identical twins, okay? And they put one twin under a lower body training session, okay? Over the course of, I think it was like a few years. And they found that the twin who had larger leg muscles, okay? And more lower body power, especially in their legs, they had larger brains. So the larger the legs, the larger the brain. All right, let's go to nutrition. Everyone's dying to know. If you're on the interwebs, you are bombarded with nutrition advice and it's often conflicting. What is your clear message to our listeners? Nutrition is just information and I see nutrition as biomarkers. So we've got wars happening on Instagram, vegan versus carnivore, and it doesn't have to be that way. The best known diets for brain health and cognitive impairment is the MIND diet, the Mediterranean Interventional DASH diet, which consists of little amounts of meat, poultry, fish, and large amounts of fiber, fruits, vegetables, et cetera. I don't see it that way. That is really good for the brain, but why? It's because that we really want to lower our ApoB and LDL cholesterol. So if you're maintaining a really good LDL, right, your brain doesn't want to be filled, the arteries in the brain don't want to be filled with cholesterol, okay, and these plaques. If you've got that, then you can have your steak, okay? But I look at nutrition as instead of what should you take out, you should be thinking about what aren't you having? You know, do you have adequate green leafy vegetables? Because that contains magnesium, okay within the chlorophyll are you having omega-3 fatty acids are you having enough protein because these are the things that we need to be focusing on instead of just subscribing to a certain diet because somebody on the internet told you to and what about supplements do they have any effect or omega-3 fatty acids probably the best thing that you can take for your brain we have we have receptors on the outside of our brain that allows for dha and epa to pass through it and they get leaky during the brain when we're inflamed or during the brain aging process. But it turns out that most of the fat in our brain, about 70% of the total fat composition in our brain is made of DHA, which comes from fatty fish. So feeding our brain with at least two grams of DHA per day and EPA is phenomenal. So how much fish would that be? Well, it's a lot of fish. Okay. So if you've seen that documentary, Seaspiracy, you'll see that if we're eating fish, we're probably stripped of all the nutrients. So I actually like to think about it. It's probably like three or four salmon steaks a day. We can't do that. So you should be supplementing. Okay. Yeah. So you would recommend supplementation here? Yes. 100%. I recommend supplementation with EPA DHA. How would someone find a good supplement? You're sending someone off to, Where would they buy it? What are they looking for? There is, I'm not affiliated, but there is a really great app called SUPP.co. S-U-P-P dot C-O. And that is the only place I know that actually does all of the quality control testing. And they give all of the brands a score. So you can go in there and you can type creatine. And it comes up with the best creatine on the market. And it gives you a link to go and buy that from a certain brand. That's good advice. Yeah. Do you test omega indexes? Yeah. Omega-3 index, which is the measure of omega-3 fatty acids inside the red blood cell. I check it every year in January. It's like a new year thing I do. This year I got 11.3%. And what's a good level? So in the US alone, most women are actually below 4%, which is raising your risk of all-cause mortality and sudden cardiac death, by the way. So you want to get at least an omega-3 index of at least 8% or more. And you can get from 4% to 8% just by supplementing with two grams of EPA and DHA a day. Any other supplements that you would consider? Creatine. Creatine. Yes, 100%. Tell me about creatine. Creatine helps with cell energy metabolism. We naturally produce it, but we don't produce enough of it. And we used to think of it... And is that an age-related decline? No, it's not age-related. It's just that men and women, we don't produce enough of it. And we used to think that it was a bodybuilding supplement, but we now have substantial evidence to show that women can greatly benefit from taking creatine. But here's the thing. We used to think that five grams a day of creatine was enough, but five grams of creatine just saturates the muscle. Okay. So once the muscle takes up, that's where 95% of the stored creatine that we have lives inside the muscle, around 5% lives inside of the brain. So the muscle soaks up all of the creatine that you take, right? So five grams, it's taken it all. So now we need more, okay? We need more in order to raise our brain creatine levels. Let me tell you something. The best times to take creatine is times of sleep deprivation and high stress. I've heard that, I've heard that, like when you're traveling overseas, like when you, they're doubling on their, you know, the creatine experts are doubling on their dose when they're in sleep deprived, you know, from travel usually. You can eliminate a lot of the symptoms that occur and all the devastating effects that occur from sleep deprivation by supplementing with creatine. How much? Caveat, it is 20 grams. That's a lot. Yes. But this is where it also affects. It really affects with giving you more energy, cell energy metabolism. We know that there's There's hypometabolism in these mental health disorders. And a lot of people are worried about kidney function though. It's not going to damage your kidneys. It's not going to make your hair fall out. It doesn't degrade in hot water. So you can have it with your coffee. It doesn't taste bad. I've even seen people are worried because they have a history of breast cancer or they're high risk for breast cancer. Look, everything's on the internet. The latest study that came out this year, it's phenomenal. They're now showing the effect of creatine on cancer to showing that it's actually down-regulating the effect. Yeah, so you can actually help cancer diagnosis from creatine. Wow, okay. Yeah. What are the three most important things that a woman today can do to decrease her risk of dementia or improve her brain health? First thing is get tested. I know that some people may tell you not to, but you want to know where you are. 20% of the population does have the APLE4 gene, the risk gene. go and get tested so you know where you're at where would they go get tested you can ask your your your doctor and just push for it or you can go and there's blood work that you can do everywhere okay really go and get tested the second thing so it's a blood test it's a blood test sorry yes okay uh lipid control you really want to maintain a low ldl and a low apo b the next thing is i don't know what is going to get you off the couch but if you are not exercising you are doing yourself and your future self a disservice. Is walking helpful? Walking is great. Get your 10,000 steps a day, but that should just be incidental. But what if you're sedentary? Is walking helpful? So say she's on the couch. Okay. If you go from sedentary, completely sedentary to walking, then yes, you're going to see a huge increase. But the thing is, it's going to stop right there because you're not getting the release of the BDNF and the myokines. You want to get into a habit of first get yourself a personal trainer if you have to. If not, anything. Just start calisthenics, body weight exercises, and then move into weights. There's so much available on YouTube with just basic body weight exercises that you can start there. You start where you are. Just raise that heart rate. Okay. Okay, stimulate it. From there, you want to go into good sleep hygiene. fix your sleep because if you don't fix your sleep, everything else will just come falling down. The next thing is start to look at the nutrition. Eliminate anything ultra processed. You don't want to be having processed foods, a lot of fruits, a lot of vegetables. And if you can, try supplementing with EPA, DHA, and creatine. Okay. Do you use fish oil for that typically? Yeah. It actually says EPA, DHA on the bottle. Okay. Awesome. One last thing I want to touch on is social connection. Oh, yeah. I don't know if you've read it yet, but the gerontologist, she's on Instagram. I just love her, Carrie Burnbright. And she wrote Joy Span. Yes. And really, so she takes care of the super ultra geriatric population and has done studies on what makes these people function better. And her mother's like the best example. She's 96. She's independent. She's beautiful. You know, she's aging, but she still has her brain. you know, she's incredible. She has friends and they, social connection is so important. So important for the brain and not just that. Um, yes. So what she found, it was a, it was an 80 year follow-up study and they found that those with the greatest brain health benefits at the, the greatest functioning brain with those ones who maintained a good social connection. Okay. And that doesn't mean, um, romantic partners, right? It could mean close friends. Okay. Okay. So maintaining good, close friendships, but also there's an amazing study that shows that being kind to yourself can decrease your risk of mortality and dementia. And what would that look like? So, and it was a really beautiful study. I'll have to put it up on Instagram. It basically showed that if you are kind to yourself and you're not telling yourself bad things and you're, you could be in the form of affirmations or journaling, you sense to your brain that you are safe and it down regulates cortisol and it makes you just happier and it actually makes you appreciate your day to day. So you're more likely to go to bed, not stressed, eat well for yourself. So being kind to yourself is actually physiology. Well, thank you so much for sharing all of your incredible knowledge with our audience. And I'm sure you're going to change some lives today. Thank you so much for having me. you can find Louisa on Instagram at Louisa Nicola and on YouTube at Louisa Nicola and you can listen to her podcast the neuro experience wherever you get your podcasts you can find full episodes of unpaused on YouTube at Dr. Mary Claire I'd love to hear from you about this topic and anything else that's on your mind you can find me on Instagram at Dr. Mary Claire and get honest accurate information on health, fitness, and navigating midlife at thepawslife.com. My upcoming book, The New Perimenopause, is available for pre-order on Amazon. If you're loving this podcast, I have an important request. Please take a moment to follow Unpaused on your favorite podcast app. Following and listening is what pushes this information forward to more women who need it. So if this podcast has helped you feel seen, understood, or supported, hit follow right now so you never miss an episode. Thank you for being here with me. Let's keep going. Unpaused. Unpaused is presented by Odyssey in conjunction with Pod People. I'm your host, Dr. Mary Claire Haver. The views and opinions expressed on Unpaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment.