The Alzheimer's Prevention Plan for Women: Hormones, Sleep, and Nutrition with Dr. Lisa Mosconi

25:41Dr. Mary Claire Haver:Spell B-A-B-B-E-L dot com slash listen. Rules and restrictions may apply.

25:51Dr. Mary Claire Haver:Let's talk about the emotional side of it. So, you know, the occasional outburst in a lot of my patients, they come in and they're completely worried because of rage and fear and paranoia and severe anxiety and anger. And, you know, it's affecting relationships. And at the same time, it is a hard time of our lives for a lot of us with aging parents and teenagers. You know, we're kind of in this sandwich area. So what's happening? Is it the same biomechanical process that's happening that's leading to the emotional changes? Yeah. So this is really in part at least reflective of the architecture of menopause in the brain.

26:32So estrogen receptors are a little bit everywhere, but they're more prevalent. They're more abundant in very specific brain regions. And especially in the most primitive parts of the brain. And these we know mostly from animal studies, but we also now see with the brain scans that we just looked at, which is the first time in humans and they thought it was really fascinating. They are most expressed in the memory centers of the brain, like the hippocampus and the medial temporal lobes, but also in the emotion control centers of the brain. Like especially one region that's called the amygdala that sits right on top of the hippocampus and is connected to the rest of the brain, of course, and kind of regulates emotions, including fear, but also empathy.

27:24So it's very complex. And then the estrogen receptors are present in the frontal cortex, which is in charge of thinking and reasoning and inhibition. Very important. And the posterior cingular cortex and precunias, which are more about autobiographical memory, which is the memory of places you've been and things you've done. Yes. And then in the brainstem, where we find all the nodes for sleep and wake, the sleep cycle, but also stress. And then, of course, we have the hypothalamus and the pituitary gland, which is predominantly reproductive regions, but the hypothalamus, also both regions, actually both glands, play an important role in autonomic function, which is like control of blood pressure, heart rate.

28:11So all the most primitive functionalities are effectively influenced by the presence of estrogen and the way it works with the receptors, which means if estrogen starts fluctuating and is all over the place, then the hippocampus is not activated correctly. And then you don't consolidate memories and you feel like you have ADHD. Yes. We see. All the time. Patients complain constantly of that. Yes. They become aware that they can't memorize things and they have a hard time paying attention to things. Is it ADHD or is it menopause? Or both.

28:49Dr. Mary Claire Haver:Or both. Do we unmask something we were managing before? Exactly. of vulnerability yes amygdala full of estrogen receptors yeah and if estrogen starts fluctuating what is not there the amygdala will glitch in regulating emotions right so you may feel anxiety and fear when there's no reason for it you may it's not just the amygdala it's the whole network right but but just to explain the anatomy you may get the rage right if you haven't slept because the estrogen hasn't been activated. Your sleep cycle and your melatonin is completely out of whack. That will make it worse. And if your frontal cortex is impacted, you're going to have a harder time inhibiting this response, this strong response that is not you.

29:38It's your brain transitioning to work mostly without estrogen. So the same brain regions that were supported by the presence of estrogen before are now finding themselves in a state of remodeling. Yeah, renovation. Yes. So Robbie actually says that menopause is a renovation project on the brain. I want to show you one slide if I find it. So here we are looking at differences between premenopausal women and age-controlled men when the women in all those fiber tracts inside the brain show more positive markers of connectivity. So there's more diffusivity, there's more, it's just the brain is basically better connected in those specific parts of the brain relative to men at the same age.

30:35So we have better brain function than men up to a certain... Connectivity, yeah. And then this is what happens at the perimenopausal stage, there are basically no differences. And this, you're going to love this. Whoa. Yes. Oh, I love that. Whoa. This is postmenopausal women and it's better than before.

30:58Dr. Mary Claire Haver:Wow. Yes. So it remodels. It remodels to make us connect better. Differently from before. So these parts of the brain are, this is a cross-sectional study. We're now doing the same analysis longitudinally over time. It takes a long time to map the transition because it takes many, many years. Seven to 10 years and then you got to go post-menopausal. So you're looking at a 15-year... It's going to take a minute, but we do have six-year data now. So we're doing that. But this suggests, this is a cross-sectional study. Lots of people kind of like give me like a wrinkled nose when something is done cross-sectionally.

31:38But you have to start cross-sectionally because you don't want to waste your time longitudinally if there's no differences that are suggestive of a change. This suggests that there are differences to start with, no differences when we're perimenopausal, and more differences at the postmenopausal stage. Nobody here is taking hormone therapy. So that does suggest a U-shape change that we find with other modalities as well. Brain aging is not linear in women. And that is something that is difficult to model and study, but we are doing it. We're doing deep phenotyping and increased sampling. And we're trying to map it really, really carefully now.

32:25But I thought this was brilliant.

32:26Dr. Mary Claire Haver:It's amazing. It's amazing. Women have been the wisdom keepers in their older age. The postmenopausal women, the grandmothers, were the wisdom keepers. And that, you know, traditionally, if they live long enough, you know, they were they carried their traditions. They taught the younger, you know, it's kind of beautiful how that played out. I think it's beautiful. And I think what when we're thinking as a field is that this remodeling is essential. It's very important because the link between the brain and the ovaries is a very is a very big pathway in the body. and it's very expensive to maintain.

33:06So once women are no longer reproductive, it makes no sense to keep all these connections and all these mechanisms that are necessary to trigger ovulation and to potentially make your body able to host a pregnancy. A lot of what happens in the pregnancy actually comes from the brain, right? And once you no longer have the ability to be pregnant, it's really cost effective for the brain to say, you know what? It's really the spring cleaning. All this stuff I no longer need is best if I discard it. That's my personal own interpretation. But I think this is what happened. And this is the renovation process where the connectivity is changed, right?

33:48We're preparing for a non-reproductive phase of life, which needs to remain productive. So the brain rearranges itself. but at the same time that is tricky to do right right and that can lead to the symptoms of menopause to the glitches and unfortunately to a lot of discomfort for a certain amount of time but it's for we're hoping of course a good reason right so when something that is genetically programmed and expected to happen happens that is not a pathology yeah and that's important to say. Menopause is no walk in the park. It's certainly no picnic for so many women, but there's a reason for it and their brains and bodies are equipped to go through it.

34:39What we can do is to support them during the transition, to provide our brains with the tools and chemicals that it needs to support us and go through a gentler menopause with a lower long-term risk of Alzheimer's and anxiety and depression and Parkinson's and whatnot.

35:00Dr. Mary Claire Haver:So for someone who's listening, who's having the brain fog or having the anxiety, you know, especially on the cognitive side, but when should the brain fog or the cognitive symptoms be a red flag? When should you worry and say, I need to go get evaluated? Well, I would go regardless because you want to have a baseline. For me, at least in this day and age, we do have the tools, we have the technology, we have the possibility, we have the access often. I think it's a good idea to have a baseline of your own brain and your own cognitive performance when you're relatively young because you are the best reference for you when you are a little bit older.

35:38Now, there is no reason usually to get alarmed if brain fog tends to emerge during the transition to menopause. If you do notice that your period is changing and it's getting more irregular and you also experience brain fog, that is most likely to be part of the hormonal transition. Once obviously you go to your GP, it should get better. It should resolve within two to six years of the final menstrual period, which I know it's a lot of time. It's a long time. It's unfortunately a long time, but it should get better. But we can support that. We can support it.

36:17Dr. Mary Claire Haver:Yes. Through the transition. Exactly. In our clinic, we offer hormone therapy in these cases and they usually do very well. And there's more research coming, you know, there are more options. So that is really important to know that help is available and there are therapies and other things. Also lifestyle. You would be. Oh yeah. Yeah. Let's get into that. I'm excited. Let's do that. Brain fog gets worse, right? And if you don't remember where you put your keys, that is not Alzheimer's. If you can't remember what your keys are for, that is a problem. I will use that again. That is excellent. But then again, a lot of people come to us to get cognitive testing done.

36:58And we do cognitive testing. And you can see that, for instance, there's this test that's called the MMSE that we always do as a screening, where the scores go from zero to 30. And most people, my age, your age, will score 28 to 30. Right. If you are at 30 and menopause brings you down to 28, to you, that is a catastrophe. To as you are within normal range for women, your age and educational level. And that is a huge relief to hear that, yes, we understand you are experiencing a change in cognitive performance that we refer to clinically as subjective cognitive decline. Because you feel it, you're aware of it, is not measurable using standardized cognitive tests, which means you do not have dementia.

37:52at this stage.

37:53Dr. Mary Claire Haver:I love that. If you can't remember where you put your keys, but if you don't know what the keys are for, you need to go get evaluated. That's a problem. Okay. All right. Let's talk about our brain plan, our game plan for midlife because there's so much hope here. Yes. Yes. You know, there's so much we can do. Like Mary Claire's nursing home prevention program is what I like to call it. You know, preventing getting osteoporosis is much easier for me, you know, to deal with than how do I hang on to my brain function as long as I possibly can. And so that I really, I won't know the difference, you know, I'll be frustrated, but I don't want to do this to my kids.

38:32Dr. Mary Claire Haver:You know, I don't want them to have to go through this like gut-wrenching decision-making that my family and my husband's family is going through and how to best help our parents, you know, as they traverse this. So menopause is a neurological transition, not just a reproductive one. Yes. But what can women actually do to protect their brains? So let's talk about the key lifestyle factors involved in brain health. Yes. So we're going to start with sleep. Oh, yes. Yes. I think that's a problem for a lot of us, isn't it? I've heard sleep is called as the wash cycle. Yes. So what does that mean? What that means is that the brain, minute after minute, is always busy supervising the rest of the body.

39:14The brain is constantly either thinking, memorizing, feeling, is very, very busy. For sure, misremembering. But also supervising the rest of the body. Even heart rate and breathing and moving, all of that needs to be active at all times. The only time in the day that the brain can actually take care of itself is during sleep and specifically during slow wave sleep or deep sleep, which is when your body is completely still. You are not moving, just breathing very quietly. The brain can let go of everything else and activate a system that is called the glymphatic system, which is like effectively like a car wash.

40:04There's like fluid that starts moving throughout the brain, removing toxins, removing waste, removing Alzheimer's plaques. That's when a lot of clearance mechanisms are activated. The oxidative stress is removed. The inflammation is flushed out. All the mess we accumulated through the day. All the things that, yeah, well, it's an organ. There's a lot of activity going on. So if you don't sleep, if your sleep is fragmented and you sleep, especially your deep sleep is impacted and you lose that window of sleep, that over time has consequences because then all the toxins will not be cleared out, right?

40:50They will accumulate in the brain. The Alzheimer's plaques will stay in the brain. The inflammation may stay in the brain. So sleep hygiene and sleep protection is a very important and just recently discovered protective factor for brain health and Alzheimer's disease, whereas sleep deprivation is a risk factor for Alzheimer's.

41:10Dr. Mary Claire Haver:So now sleep is now in cardiovascular disease, now characterized as a risk factor. How much sleep do we need? Well, that's a really good question. And why do these middle of the night wake-ups, which a lot of my patients complain of, including me? So one potential mechanism is related to menopause. And of course, stress, anxiety, that is a different story. But for women who are going through menopause, there can be a hormonal component to sleep disruption. And what can happen is that all these different hormones work together. It's a hormonal system that is in a flux. We're always talking about estrogen and progesterone, but other hormones also are impacted.

41:53And in particular, stress hormones and sleep hormones. Cortisol. Cortisol and melatonin. Okay. So for cortisol, the relationship is well characterized in that the body needs a common precursor, which is pregnenolone, to make both sex hormones and cortisol, the stress hormone. If you're super stressed out, the body is going to have to use most or more of the pregnenolone to make the cortisol. And that means it cannot make as much of the sex hormones. Wow. Yes. That's why stress sinks your hormones. And women who are really, really stressed out may experience more severe symptoms of menopause because you have less availability.

42:40The pregnenolone gets eaten up. Yes. It gets shifted on the adrenal pathway to make cortisol. Yes. And for melatonin is a similar problem where if stress and cortisol, say cortisol is high in your body, that suppresses melatonin production. So what happens is that usually melatonin peaks around that time of night, but that before day one to 3 p.m. window, but then you've remains in the system unless you're super stressed out, in which case cortisol kicks in around two in the morning. Wow. And so it's a whole mechanism. You know, when the sex hormones are disrupted, the stress hormones are disrupted, the sleep hormones are disrupted.

43:22So you can start any of these nodes.

43:24Dr. Mary Claire Haver:The internet is full of all of these wellness cures, you know, some and I have no data, you know. Right. How do we lower cortisol? I know we can do, you know, stress reduction, meditation journaling, you know, but are there supplements? Are there, you know... For cortisol. Yeah. Not that I'm aware of. Okay. A lot of claims out there to say to take this and we'll lower your cortisol. Oh God, all kind of internet claims. Buy my supplement and I'll lower your cortisol. I'm not aware of any supplements that can directly lower cortisol. Good to hear. What has been shown to lower cortisol levels is like you said, is meditation, stress reduction.

44:06If you can sleep, that should also lead to a reduction in stress hormone levels. So prioritizing sleep is also really important. And this is more anecdotal than anything else, but magnesium glycinate may be helpful. And do not ask me for clinical trials. We can't do clinical trials for everything, but at least for several women, magnesium glycinate in particular can help relax the musculature and help you fall asleep and stay asleep, which then has a differential effect on the cortisol pathway. Melatonin can help you sleep and stay asleep, and that also may help lower cholesterol. So all the things that help you sleep, in other words, may also have a lowering effect on cholesterol.

44:58It's not direct. I would say it's more indirect. Indirect, right. But mediating. Relaxing the body.

45:03Dr. Mary Claire Haver:Yeah. Exercise. Exercise. That's my next question. So women who are fit in midlife, whatever fit is defined as, have a 30 % lower dementia risk. Those are the women who have the highest level of cardiovascular fitness in midlife. Yes. So moderate to high intensity. What's what's exercise doing to the brain? Exercise supports brain health through multiple pathways. And the most interesting ones, I believe, are the direct pathways. So the first one is by increasing blood flow to the brain. That is very, very important because that supports oxygenation and nutrient transmission. So you're effectively feeding your brain.

45:43Exercise is also anti-inflammatory and reduces oxidative stress, which the brain is very sensitive to. And then there was a really super interesting discovery just a couple of years ago. It came out in science that when muscles contract as part of exercise, they produce a peptide that is called iridesin from the Greek goddess of the rainbow, which is very pretty. And iridin can cross the blood-brain barrier, right? and once it crosses the blood-brain barrier, it supports like estrogen, it supports BDNF production and reduces the amount of pro-inflammatory cytokines directly in neurons. So that's a beautiful way that exercise can directly support brain health.

46:33And look, this is when it comes to Alzheimer's disease. I love this slide. I was looking for this the other day. Okay, here we go. Oh, good. All right. So this is what we currently know about the modifiable risk factors for Alzheimer's disease, which cumulatively account for over 40 % of all Alzheimer's cases. Okay. These are all lifestyle-based. And I specified what percentage of risk they each account for. And if you look, exercise, actually physical inactivity, which can be obviously offset by exercise, accounts for over 2 % of all Alzheimer's cases globally. And then we have things like excessive alcohol consumption, which excessive means more than two glasses a day.

47:23We have social isolation. We have depression in midlife, more of an issue for women than for men. We have air pollution. We have low, they say low education is more like low intellectual stimulation. Right. I would say rather than just years of schooling, although that is a factor as well. Hearing and vision loss if untreated. So glasses, hearing aids are becoming important for Alzheimer's prevention as well. Traumatic brain injury, especially with loss of consciousness. Smoking and then the heart disease risk factors. So obesity, diabetes, hypertension and high LDL cholesterol. Those are 14 and have been formalized as risk factors for Alzheimer's disease that can be modified, right?

48:08Right. Anyone can do any of all these things in society to reduce the risk of Alzheimer's. And now we're looking at other things like sleep, very important. Diet and nutrition, obviously important. What about GLP-1? We're not there yet. Everyone's asking yet. No, no, no, no, no. Not yet. Not yet.

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50:56Dr. Mary Claire Haver:All right, well, let's talk about food because what I loved in your books is that you spend a lot of time talking about nutrition. I love chemistry and nutrition is effectively biochemistry. Well, my daughter's undergrad before med school. Catherine's a third year med student. And so her undergraduate is nutrition science. But she went to a biochemistry program, not the cooking for a thousand people program. The nutrition science goes two ways, you know. Yeah. And she absolutely loved it. And I think it's such a strong foundation for her for medical school. It's so good. I also, I did not study nutrition at school, but I'm kind of self-taught.

51:34At some point it was, okay, just get me every chemistry book because all the things I'm learning about brain health, all the sodium potassium pumps, you know, serotonin is made of tryptophan. And these are all nutrients that come from food, right? They're not made by the brain. They are imported. So I loved it. I spent a lot of time studying nutrition. So what should we be eating for our brains? The brain is an interesting organ. And if you eat healthy for your brain, you're also eating healthy for the body, not necessarily the other way around. So the brain is more specific. It's a little bit more of a picky eater relative to other organs.

52:15And it needs predominantly antioxidants like vitamin A, C and magnesium and vitamin E. specific amino acids especially the essential amino acids which come from many different foods and omega-3 fatty acids which are predominantly from fish nuts and seeds and some marine algae if you wish and that's where the fish get the omega-3 is they eat the algae yes so it's part

52:45Dr. Mary Claire Haver:of the food chain so if you can't tolerate fish or you're allergic you can get the supplement the algae-based supplement. Yes, absolutely. And obviously glucose is very important for brain health. But within reason, you don't need to eat a ton, but a little bit is important for brain function. Also for the synthesis of glutamate. A lot of people just look at glucose as a sugar, but glucose is a number of functionalities. And for the brain, it's the building block of glutamate, which is the most prevalent neurotransmitter in the entire brain and is needed to synthesize GABA, which is the prevalent inhibitory of neurotransmitters.

53:25So glucose is not just, and I'm thinking when the keto diets came out, it was a little bit like, whoa, because it's important not just for energy, but also to synthesize the most abundant neurotransmitters that we have. Why are ultra-processed foods so

53:41Dr. Mary Claire Haver:bad for brain health? They're bad indirectly. So those kinds of foods and nutrients should not be able to cross the blood-brain barrier, but they do increase inflammation in the rest of the body and they do have almost like a sort of toxic effect in your gut for sure that then leads to widespread negative effects throughout the body and brain. There are a lot of chemicals that are used in the synthesis and making of ultra processed foods that our bodies are just not equipped to handle, which then leads to oxidative stress and inflammation and those sort of medical issues really that then also negatively impact brain health.

54:24What's good for your heart is good for your brain. What's bad for your heart is bad for your brain. And ultra processed food is bad for pretty much every organ we have.

54:34Dr. Mary Claire Haver:Are there any supplements you think are hype or are realistic for brain health? Yeah. I wish we had more data. I think there are some nutrients for the supplements that are clearly beneficial for brain health. And it makes sense that if you are deficient or subclinically deficient in some nutrients, then supplementation might help. I'm thinking B vitamins. So we do know, especially B12, is an issue for a lot of people because as we get a little bit older, it becomes more difficult to absorb it from the foods that we eat. And almost all elderly individuals are B12 deficient and just don't know that.

55:20So it's important to have that measured. We check B12 levels in all of our patients. Yes, folate, B6, those are really important brain vitamins as well. Clinical trials have shown mixed results. I think that the supplement that we have the best evidence for is omega-3 fatty acids. And I am 100 % partial to antioxidants. Full disclosure, I have no conflicts of interest. I don't sell anything. I love antioxidants because I think that the brain is exceptionally prone to oxidative stress. It's actually the major cause of cellular and neuronal aging. And the brain is completely powerless against oxidative stress.

56:02The only way to counteract the effects is by importing vitamin A, C, E, selenium, and the antioxidant minerals through the diet. And very few people eat enough fruit and vegetables and some nuts and seeds to really ensure adequate levels. And then it depends. And I do believe in a precision medicine approach.

56:27Dr. Mary Claire Haver:you know you do too but not everyone has access to that so like for the lady on the couch in ohio listening you know who just has a primary care doctor who's gonna do standard you know like what can we tell her well for instance if you are a former smoker which this is one of the biggest regrets of my life same i quit at 23 same me too you know in italy i was growing up there and everybody was smoking. Everyone smoked. Oh my God. And so did I. And I really wish I hadn't. But I did. I'm aware. And we know that smoking is a major risk for ovarian function and for brain health. How do you counteract the negative effects of reactive oxygen species that are caused by smoking and the possible epigenetic modifications that then lead to more oxidative stress being produced.

57:27Antioxidants. So I understand that people want clinical trials of supplements. I'm not sure how feasible that is financially and in terms of commitment. But I would say if you are a former smoker, there is no downside to using antioxidant supplements. For example, what would an antioxidant be? Just for our listeners.

57:48Dr. Mary Claire Haver:Vitamin C. Vitamin C. Yeah, that's the number one. And even Dr. Pauling, you know, who's the one who discovered vitamin C and then won the Nobel Prize for the discovery. He took very high doses of vitamin C. I'm not saying anyone should take high doses. He should take high doses and tear their stomach up. He did. Until the day he died. And he was as healthy as anyone can be. Now, that's one person. Nobel Prize. Let's say one person. I would say a regular amount of vitamin C, especially liquid. Liquid vitamins are really good in terms of being absorbed. Absorption. It's good to know. All right.

58:23Dr. Mary Claire Haver:So elephant in the room. Lots of talk, worries. The Menopause Society meeting had a whole section on this. Let's talk about hormone therapy and dementia. Yes. What do we know? What do we know and what we do not know yet? And I think both are really important. And this is the perfect situation to talk about the fact that language matters. If it's okay. Absolutely. In both directions. Yes. So what do we know? We know that we have not done all the work that we could have. That is a fact. There is only one clinical trial that ever looked at hormone therapy for dementia prevention, which is the Women's Health Initiative that we mentioned before.

59:10They were way ahead of their time. Fantastic study in women who were postmenopausal by decades. There's a part of the Women's Health Initiative that is called the Women's Health Initiative Memory Study, where they specifically tested hormone therapy, which in this case is high dose oral conjugated equine estrogen and MPA as they're progestin with or without an MPA and placebo. and they followed these women first to the number of years. And what they showed is two things. Number one, they could not use Alzheimer's disease as the endpoint because too few women developed Alzheimer's disease. So they had to switch their endpoint to dementia.

1:00:01Now, dementia is not Alzheimer's. Right. Alzheimer's is the only form of dementia that shows the female to male disparity. The other forms of dementia that the women in the Women's Health Initiative memory study developed was predominantly vascular, where there is a lower hormonal component relative to Alzheimer's, as far as we know. And some had mixed dementia. So that was an important finding. Nonetheless, when they looked at the rates of how many women develop dementia, they found in the conjugated equine estrogen and MPA group, there was an increased rate, double the rate of dementia in women who were taking the hormones as compared to placebo.

1:00:48The absolute difference in cases was more, was about 12 more women than in the placebo group. in the group of women who were taking only the estrogens, there was a 50 % increased risk that was not significant. These results are not generalizable to midlife women. Right. Because these patients were much older. Yes. And that's what we were talking about before, that the system may no longer be there, right? The estrogen receptor binding may not be working the way that it does once you still are reproductive, once you're still transitioning to your non-reproductive life. When you're, you know, 20 years past, it may just not work.

1:01:34You're bouncing off of a closed door. Yeah, that's a good way to put it. And also those are different formulations to what - Right, the one we'd use now. Yes, and the new one, the newer formulations have never been tested this way. So - Right, so we cannot generalize. And we also cannot generalize to Alzheimer's because that was not the end point.

1:01:57Dr. Mary Claire Haver:The end point. All right, Lisa, if I gave you a billion dollars right now, what study would you, what would be the study? I would redo the Women's Health Initiative memory study. I would do it using biological markers of Alzheimer's where we work with women who are in midlife, are going through menopause and they're taking hormone therapy, especially micronized estradiol and progesterone, which are closer to what their body is naturally produced. dosed using brain scans so that I can know what kind of dose you actually need, not just for symptom relief, but for brain health and support. And I would use biological markers of Alzheimer's because that I can track as you get treated.

1:02:45What is a biological marker? So these are... It's the brain scan. So we can look at plaques in the brain. We can look at tangle formation in the brain, we can look at estrogen and how the therapy modifies estrogen binding in the brain. What's your hypothesis of this study? Your hypothesis is? But my hypothesis is optimistic, of course, but I would also have a sort of plan B in place because there is a chance that they may not work out, but I think we need to give it a fair chance because why don't you have a billion dollars for this study? I have 50 million. But let me show you the observational research because we have 20 years worth of evidence from preclinical studies that hormone therapy started around the time of menopause is brain protective.

1:03:36And we have observational data showing something similar. And observational data cannot prove cause and effect. You need to have clinical trials, which is what we are missing. But nonetheless, we do see that estrogen-only therapy is associated with a 30 % reduced risk of Alzheimer's disease among women with a hysterectomy and or oophorectomy. Whereas estrogen with a progesterone, we can't yet separate progesterone to progestin with observational data. But there's still a trend towards a risk reduction. This does not mean that every woman needs to take hormones to reduce the risk of Alzheimer's.

1:04:21It means that we do need to do the research. And something that we showed just recently that I think is really interesting is that that also was replicated. There's a strong effect of geographic location. So if you look at all the studies, like in North America, everything is blue. It means that the vast majority of studies show a protective effect. Northern Europe is red. Not protective. Not protective. Why? We don't know. But there's something there. It could be the kind of hormonal formulation that was used, the diagnostic criteria. It could be a number of reasons. But the studies in North America are consistently protective in Canada, which really suggests that we need to look at what different people are doing clinically when they use these formulations.

1:05:09So good. I just want to say this. when people say blanket statements like, you need to go on hormone therapy to prevent dementia. We don't know. We need to do the research. But when people say, which I hear, there is no evidence that hormone therapy prevents. I believe this was said at a national meeting just a month ago. Oh, yeah? I heard it on social media, actually. It could be misinterpreted. It's kind of saying the same thing, that we need to do the research. We need to do the work. But what people understand, I believe, correct me, English is my third language, but what I would understand is that the right research has been done and there was no benefit.

1:05:51This is what I understand. There is no evidence that it works. What we could say that I think is more accurate is that we have not done the right research yet. We don't know if it works, but we also really don't know that it doesn't. And that's important because it's something we can test. For instance, we can check whether it works for some women and not others. We can check if it works by age. Genetics, thank you. And now we have the brain scans as well, which we never had them before. We give women therapeutic standardized doses of estrogen that are for symptom reduction. We don't give women doses of hormones that are brain protective because we don't know what doses would be.

1:06:43So this is what we're trying to do now. We need to have more visibility. We need to have a better understanding of the brain dynamics. We need to do more work. We need to do work. But I think it's important to do the work. I think it's important to maintain an open mind. and just because the Women's Health Initiative didn't work out, it does not mean that we can't find... We stop all meaningful research in menopause. Exactly.

1:07:09Dr. Mary Claire Haver:So for a woman who's sitting at home right now, listening to this and feels scared, what do you want to say to her about her brain health and moving forward? I would say that we all have more power, not over our brains, but we do have the power to support the health of our brains and that if you make the right choices in life, it takes consistency, it takes work, but really the benefits are for life. There are also new studies done specifically on menopause showing that the symptoms can be milder, the experience can be gentler if you take care of yourself. So I would encourage everyone to think more of their brains like a muscle.

1:07:56There are things that you can do to support your brain health. Like when you exercise your muscles, right? When you eat carefully to promote your cardiovascular fitness or your fitness overall, the same principles apply to brain health. You can feed your brain properly. You can exercise your brain properly. You can take care of your brain properly and your brain will just perform so much better for you. And it's really, it's a long-term insurance policy. And you want to start as soon as you can, because there's always the idea that it doesn't matter how old you are. If you start taking care of yourself, it will show, you will feel it.

1:08:35But the sooner you start, the better. Because midlife really is a big turning point for a woman's health, not just today, but for the rest of your life. So this is the time where most women really have no time for themselves. but I think it's really important to take a step back and say, I also need time for me, right? Self-care is not selfish. You want to take care of yourself so that you can give so much more to your family, to your job, to your friends and to yourself as well.

1:09:09Dr. Mary Claire Haver:Well, this feels like this has been a life-changing conversation. Always, every conversation I have with you and I'm so excited for our listeners to hear this episode. As a reminder to our audience, you can follow Dr. Moscone on Instagram at Dr. Underscore Moscone. Her book, The Menopause Brain, is available now through her website at lisamosconi.com. 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 follow me on Instagram at Dr. Mary Claire and get honest and accurate information on health, fitness, and navigating midlife at thepawselife.com.

1:09:51Dr. 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 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.

1:10:39Dr. Mary Claire Haver:No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment.