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

22:22Dr. Mary Claire Haver: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. I've never heard this. Yeah. 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.

23:01But what happens is we have to have a good clearance system at night, which is when we going to 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 one of the reasons that I hypothesize that 70 % of women have Alzheimer's disease is because we are more predisposed to tau proteins than men.

23:27Dr. Mary Claire Haver:Okay. Walk me through this. So tau protein lives in the microtubules. Let's, neuroanatomy right now, we have around 87 billion neurons. 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. So that star is the neuron cell body, and then you've got the axon. 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.

24:08Now 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. Okay. 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 prolactin. I was going to say, like, does hormones have anything to do with this process?

24:53Dr. Mary Claire Haver: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. 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 hyperphosphorylate because we don't have the support anymore. And does the sleeping, the 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.

25:38Now, 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.

26:18because 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.

26:27Dr. Mary Claire Haver:We do AMG studies. 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...

27:09And 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, 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. Why haven't we studied it to the point that we would know the answer? because women are understudied, under-researched because they have a hormonal cycle, which is - Makes them hard.

27:51Yes, 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.

28:39We 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.

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32:37Dr. Mary Claire Haver: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 a hundred 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.

33:19They go through andropause that are at a much later stage, slower rate, but they also have more testosterone and testosterone aromatizes into estrogen.

33:29Dr. Mary Claire Haver: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. You've got 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.

34:07The 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 blood, get into the neuron so we can use it, get into the cell body. And what happens as we... So we can use... That means we have our cognitive functions intact. We've got a lot of energy. We can go out in our 20s and write ourselves off and wake up and do a marathon the next day.

34:49I 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.

35:07Dr. Mary Claire Haver: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, 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 homocysticis these are the women who are who are most vulnerable to that window of opportunity.

35:46That study came out of Scandinavia, right? Yes, it did. Yeah. Which showed that women who have one copy - So they're high risk. Yeah. One copy of APOE4 have a two to four fold increase in getting Alzheimer's disease.

36:00Dr. Mary Claire Haver: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. Yeah. depending it's like 10 years prior to so menopause when 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 yes to where it is preventative for the plaque you know accumulation calcification if you get it started before the plaques form yeah it's not really helpful to the plaques once they're already formed as far as we understand Yeah.

36:40Basically 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.

37:13It'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.

37:24Dr. Mary Claire Haver: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 functions shift. So you 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, neurokinane 6, and dynorphin. Okay. Okay. I've heard of neurokinin only because the new neurokinin receptor agonists that have come out finitely as in stuff to treat hot flesh.

38:07So 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. Okay. Okay. They don't know what's going on. There's no one. Estrogen's not there. They're looking and estrogen's not there to control it. Right. So these neurons, these clusters start going crazy. They go all, and this is why we get hot flashes. This is one of the, you know, one of the hypothesis as to why we can't regulate temperature correctly.

38:48And 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.

38:55Dr. Mary Claire Haver:Okay. When the brain is starved of glucose and it doesn't know what to do. Many things happen. We know that we start to tablize 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.

39:39Then we get this sleep disruption, which is where the cascade of problems happen. Yeah.

39:44Dr. Mary Claire Haver:And then talk to me about serotonin, norepinephrine, these little chemicals that jump 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 neurotransmitters, which are just chemicals, okay, 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 there out where our estrogen receptors are and also the hippocampus.

40:25So when we see a decline in that, we see a decline in the inefficiency of the neurons to communicate with one another. Okay.

40:32Dr. Mary Claire Haver: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.

41:10Dr. Mary Claire Haver: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 U.S. 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.

41:51Dr. Mary Claire Haver: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.

42:33Okay. 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.

42:57Dr. Mary Claire Haver: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, old, women are still struggling. There's still that 2 a.m. They're going to bed. Okay. It seems like, but they're having that 2 a.m., 3 a.m. wake up. Yeah. And it's, it's consistent, you know, everybody's going to do that once in a while, but you know, walk me through why that you think this is happening.

43:37And that's interesting because I've actually seen a lot of female patients getting prescribed amitriptyline, you know, 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.

44:00Dr. Mary Claire Haver: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.

44:33I'm having trouble staying asleep. Okay. One may be a temperature control problem. One may be racing thoughts. If it is the racing thoughts that I'm having trouble falling asleep, that is okay. It's progesterone. I know that progesterone therapy helps, but also gamma-aminobacteric acid, GABA, in the form of a supplement could help as well. Oh, good.

44:53Dr. Mary Claire Haver: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.

45:31So 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.

46:04Dr. Mary Claire Haver: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. Really? Okay. Yeah. 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. So that's another hack that you can do, but that may be one reason why you're waking up.

46:39And I have to say, if you are waking up at 2am, definitely don't look at your phone. It's so hard.

46:44Dr. Mary Claire Haver: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 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.

47:23Okay. 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.

47:39Dr. Mary Claire Haver: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.

48:16So 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

48:26Dr. Mary Claire Haver: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.

49:08And 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, 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.

49:43This 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 suprachriasmatic nucleus.

50:27And that is activated via the cells on the bottom of our 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.

51:13What about reading?

51:14Dr. Mary Claire Haver: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 like blocking glasses. Okay. Okay. They're orange. What about red light therapy? Red light therapy is phenomenal. Um, 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, um, sauna blanket. Oh, good. Like a sleeping bag.

51:47Dr. Mary Claire Haver: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 help me 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.

52:26Amazing. 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 p.m. 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 10.30.

53:05Dr. Mary Claire Haver: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. It's so insane. 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.

53:42So 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 plus and minuses to that, right? Pluses is we become super focused, minuses 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. Yeah. 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.

54:19We 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.

54:34Dr. Mary Claire Haver: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, you know, you have to do it. It's part of my wind down.

55:13Like, oh, 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. Another way is sleeping earlier. Really quick, quick and simple breath work routine. Okay, one of the best ways, just close your eyes and you do 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.

55:50It's about the time. So you want to do it consistently for at least 20 minutes. Okay. Yeah.

55:54Dr. Mary Claire Haver:Amazing. Best way to increase your heart rate variability. Okay.

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57:52We'll be right back. Rules and restrictions may apply.

58:03Dr. Mary Claire Haver:All right, let's move on to exercise. Okay, great. That's my favorite part. Wait, let's go back to your history. You are a triathlete. Yes. I've done two sprint triathlons. Oh, really? That is all. Yeah. And that is all I will do. What was the time? It doesn't matter. Okay. I finished. I'm so competitive. I finished. You finished it. I started running after there was a big hurricane in Galveston where I live and it kind of wiped out our community. And as I therapy, my girlfriends and I, we're about 40, started jogging together. And that turned into a 5K and 5K turned into a 10K. And then we're like, let's sign up for the Houston half marathon, which we ended up doing.

58:36Dr. Mary Claire Haver:It's in January. 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 uh and I bought my first triathlon was with like a Schwinn like my daughter's bike with a basket on it yeah and then I got a tri bike you know and so but I was never like hardcore but I did it yeah and it was fun that's phenomenal yeah oh my god yeah no I lived and breathed it all through my 20s 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.

59:22I 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.

59:54Dr. Mary Claire Haver: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 this time. 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.

1:00:32The Jane Fonda era.

1:00:33Dr. Mary Claire Haver: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 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%.

1:01:21Dr. Mary Claire Haver: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 training. So I'm seeing all of this drama, all of the internet. Don't do cardio. Yes, do cardio. Lift weights. It doesn't have to be that hard either. So let's talk about aerobic fitness and what that does for the brain.

1:01:55So when we're engaging in long runs, you've probably heard of it. It's your zone two, 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, 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.

1:02:37But 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 Eriksen 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.

1:03:22Only 30 minutes that's what you need. Yeah I was like how much are we talking marathon 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.

1:03:49Dr. Mary Claire Haver:So many women have only heard about exercise as a way to master some number on the scale. Yeah. 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.

1:04:24Dr. Mary Claire Haver:Yeah. I'm growing bones and muscles. You know, I am 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. Okay. And what is white matter for our listeners again? So we've 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, okay. Which is involved, It's the fat. And actually 70 % of the brain is myelinated. 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.

1:05:05These 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? Primarily looked at the smile. This was more resistance training. 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. And it doesn't take much, right?

1:05:44Well, 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 byproduct of working out at that really hard zone. Lactate is fuel for your brain. Okay, we need it. Your brain prefers lactate as a fuel source over glucose.

1:06:26This is, 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. All right. So what else do we need to do? We need to resistance train. Resistance training at least three times a week. When we do resistance training, we release something called myokines. They're muscle-based proteins that live inside the muscle.

1:07:09And 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.

1:07:44So 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, right?

1:08:17So 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.

1:08:34Dr. Mary Claire Haver:I was always under the impression and probably taught it was wrong. that, you know, 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, you know, 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.

1:09:13You've created a new pathway for the brain to connect. Your brain needs hard stimulus in order for it to grow and repair. So adult neurogenesis doesn't exist, but it doesn't mean through neuroplasticity that you can't help and grow new synapses. The functioning of the brain exists. global functioning 80 percent of brain gray matter is modifiable by physical activity

1:09:38Dr. Mary Claire Haver:there's a study that shows the hearts of 50 year olds yeah 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, 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.

1:10:20Then he put them under a two year intense protocol, okay of vigorous intensity exercise around that you know 80 to 90 percent of your maximum heart rate he exposed him to that five times a week which was a rigorous exercise but what he found over the course of two years he scanned their 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.

1:11:01It'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. oxygen. Exactly. So if you've got a better performing aorta, okay, 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.

1:11:42Okay. Yeah.

1:11:43Dr. Mary Claire Haver:Amazing. um so back to exercise a little bit you know a lot of chatter and myself included talking about estrogen and its 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 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?

1:12:20These 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 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.

1:12:59Okay. 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.

1:13:16Dr. Mary Claire Haver: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. right? 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.

1:14:03I don't see it that way. That is really good for the brain, but why? It's because we really want to lower our APOB and LDL cholesterol. So if you're maintaining a really good LDL, your brain doesn't want to be filled. The arteries in the brain don't want to be filled with cholesterol and these plaques. If you've got that, then you can have your steak. 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?

1:14:42Are 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 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.

1:15:21So 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. 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.

1:15:46Dr. Mary Claire Haver:Okay. Yeah. So you would recommend supplementation here? Yes, 100%. I recommend supplementation with EPA, DHA. How would someone find a good supplement? Like what's your, you know, 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. 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.

1:16:26That's good advice.

1:16:27Dr. Mary Claire Haver: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 U.S. 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.

1:17:09Dr. Mary Claire Haver: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 we just, 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.

1:17:43So 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.

1:18:11Dr. Mary Claire Haver: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 hypometabolism in these mental health disorders. And a lot of people are worried about kidney function though.

1:18:48It'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.

1:18:56Dr. Mary Claire Haver:I've even seen people are worried because they have a history of breast cancer or they're high risk for breast cancer. 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.

1:19:3320 % of the population does have the APOE4 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 doctor and just push for it or you can go and there's blood work that you can do everywhere, really. Go and get tested. The second thing is - So it's a blood test? It's a blood test. Sorry, yes. Lipid control. You really want to maintain a low LDL and a low APOB. 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?

1:20:11Walking is great. Get your 10 ,000 steps a day, but that should just be incidental. But what if you're sedentary?

1:20:17Dr. Mary Claire Haver:Is walking helpful? So say she's on the couch. 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, you know, with just basic body weight exercises. Workout, yes. Yeah, that you can start there. You start where you are.

1:20:52Just 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. Okay. The next thing is start to look at the nutrition. Okay. 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.

1:21:20Dr. Mary Claire Haver:Do you use fish oil for that typically? Oh yeah. It actually says EPA, DHA on the bottle. Okay. Yeah. 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.

1:21:58Dr. Mary Claire Haver:She has friends. and social connection is so important. So important for the brain. And not just that. Yes, so what she found, it was an 80-year follow-up study and they found that those with the greatest brain health benefits at the greatest functioning brain were those ones who maintained a good social connection. Okay, and that doesn't mean romantic partners, right? It could mean close friends, 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.

1:22:41I'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.

1:23:10Dr. Mary Claire Haver: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 thepawselife.com.

1:23:49Dr. Mary Claire Haver: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.

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