Brain Fog, Memory Loss, and Alzheimer’s Risk During Menopause with Dr. Lisa Mosconi

In this episode of unPAUSED, Dr. Mary Claire Haver continues her conversation with Dr. Lisa Mosconi, neuroscientist and associate professor of neuroscience in neurology and radiology at Weill Cornell Medicine, New York Presbyterian Hospital. Dr. Mosconi directs the Alzheimer's Prevention Program, including the NIH-funded Women's Brain Initiative and the Alzheimer's Prevention Clinic, and was recently named director of the $50 million Program in Women's Health, Cutting Alzheimer's Risk Through Endocrinology. She is also the author of the bestselling book The Menopause Brain. Dr. Mosconi and Dr. Haver go deeper into why brain fog, memory lapses, and cognitive changes in midlife are not just frustrating. They are biologically significant, and for some women, they may signal an inflection point for Alzheimer's risk. The conversation covers the statistics women are rarely given starting at age 45, a woman has twice the risk of Alzheimer's as a man of the same age. Women are also twice as likely to be diagnosed with anxiety or depression, three times more likely to develop an autoimmune disorder affecting the brain, four times more likely to suffer from migraines, and more likely to be killed by a stroke after menopause. Guest links: Lisa Mosconi https://www.lisamosconi.com/ Lisa Mosconi https://www.instagram.com/dr_mosconi/?hl=en (Instagram) Lisa Mosconi https://www.facebook.com/lisamosconiphd/ (Facebook) Lisa Mosconi Bio https://wellcomeleap.org/lisa-mosconi-bio/ (LEAP) Books: “The Menopause Brain: New Science Empowers Women to Navigate the Pivotal Transition with Knowledge and Confidence https://www.amazon.com/Menopause-Brain-Transition-Knowledge-Confidence/dp/0593541243,” by Lisa Mosconi “The XX Brain: The Groundbreaking Science Empowering Women to Maximize Cognitive Health and Prevent Alzheimer's Disease https://www.amazon.com/Brain-Groundbreaking-Empowering-Cognitive-Alzheimers/dp/0593083113/ref=tmm_hrd_swatch_0?_encoding=UTF8&dib_tag=AUTHOR&dib=eyJ2IjoiMSJ9.xATDzwdasYSPmgiM-QUxSk1OuLss6xj1tlff-8-ja3e9HQtWrqwUegJ1PwgD9vCDe3uJ9CKC19h4ns0GJOh-jDC2X1TPqkd-w6tHJP6D84ad5TOzUFeXMQNkfTOyBSZEaTJ86el25Xq-hb1XwWx-FRXljYw47SzXkL83sjQin-y69zz3OR4yoGTc7EAt25p1LFelxhyKPvX0asHo_ej6Mals4EmjVUTf-lk4jJHVUgI. IxukrUD8UkV8yXlW0c8Vcf3KEtpBaEQBvVx11YpoppQ,” by Lisa Mosconi “Brain Food: The Surprising Science of Eating for Cognitive Power https://www.amazon.com/Brain-Food-Surprising-Science-Cognitive/dp/0399573992/ref=tmm_hrd_swatch_0?_encoding=UTF8&dib_tag=AUTHOR&dib=eyJ2IjoiMSJ9.xATDzwdasYSPmgiM-QUxSk1OuLss6xj1tlff-8-ja3e9HQtWrqwUegJ1PwgD9vCDe3uJ9CKC19h4ns0GJOh-jDC2X1TPqkd-w6tHJP6D84ad5TOzUFeXMQNkfTOyBSZEaTJ86el25Xq-hb1XwWx-FRXljYw47SzXkL83sjQin-y69zz3OR4yoGTc7EAt25p1LFelxhyKPvX0asHo_ej6Mals4EmjVUTf-lk4jJHVUgI. IxukrUD8UkV8yXlW0c8Vcf3KEtpBaEQBvVx11YpoppQ,” by Lisa Mosconi “The New Perimenopause,”⁠ https://thepauselife.com/pages/the-new-perimenopause-book by Dr. Mary Claire Haver <a href="https://www.amazon.com/New-Menopause-Navigating-Through-Hormonal/dp/059379625X/ref=sr_1_2?adgrpid=190238689390&dib=eyJ2IjoiMSJ9.djG88jtefTqLpTg36Li8QMNmXkpzLIfbFdY438Vro2vit_rKymy65UpF10hk_VTrxmazFUemwk7ywlmqHYY80j-V3LaeSD824-02PCtdlS8Fzp1XPcZs68nYHCL4V_ZdZBTJya---9Ng5PtKdOf-U3ENtuDXbDw68ULSk2wNk6Lt6mEhIPkuLM7FhztUzBJZ0wNBUQCSs6Pk1ZhoV2JDlzRapnMjnZgOq7PBA7Wy2KM._ZZSn21KJ43AyMvvSvI9_Hs3q74tpMBoCJ2zwi9enkc&dib_tag=se&hvadid=779626799212&hvdev=c&hvexpln=0&hvlocphy=9004331&hvnetw=g&hvocijid=16430100151400627515--&hvqmt=e&hvrand=16430100151400627515&hvtargid=kwd-2465259580440&hydadcr=15551_13558570_10211&keywords=perimenopause+book+mary+claire&mcid=ab159bad5384301d948e659e4b52f68d&a ...

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  So sadly, almost two thirds of all Alzheimer's patients are women.

• 0:05Dr. Mary Claire Haver?

  Mm hmm.

• 0:06Speaker 00

  And for a really, really long time, the notion was that women live longer than men and Alzheimer's is a disease of old age. Therefore, at the end of today, more women than men end up with Alzheimer's. That was actually the pushback that I, the first one on my list of pushbacks that I got when I was a PhD student because I wanted to look at sex differences in Alzheimer's and people were telling me it's a waste of your time because it's just aging, it's just longevity, it's just that women live longer than men.

• 0:47Dr. Mary Claire Haver?

  The views and opinions expressed on UnPaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment. In our last episode of UnPaused, Dr. Lisa Moscone helped us name something women had felt for decades but were rarely believed. Menopause doesn't just change your body, it changes your brain. And Dr. Moscone didn't bring opinions. She brought scans. She brought data. She brought a scientific explanation for that moment so many women described with one sentence, "I just don't feel it myself."

• 1:32Dr. Mary Claire Haver?

  In this episode, we go deeper into the why. Dr. Moscone, the author of The Menopause Brain and a neuroscientist and leading researcher in the menopause Alzheimer's connection, shares what we now understand about the biology of Alzheimer's, including the long silent phase that can begin in midlife and the real reasons women develop this disease more than men. And then we look forward. Dr. Moscone explains the work underway to finally treat women's brain health as preventative medicine with better tools, better research, and ultimately, risk calculators and real world clinical pathways that help women protect their brains long before symptoms begin.

• 2:19Dr. Mary Claire Haver?

  Okay, let's jump back in. I'm Dr. Mary Claire Haver, a board-certified obstetrician and gynecologist and certified menopause practitioner. I'm also an adjunct professor of obstetrics and gynecology at the University of Texas Medical Branch. Welcome to UnPaused, the podcast where we cut through the silence and talk about what it really takes for women to thrive in the second half of life.

• 2:56Dr. Mary Claire Haver?

  So, your PhD?

• 2:58Speaker 00

  Yeah.

• 2:58Dr. Mary Claire Haver?

  Is in what?

• 2:59Speaker 00

  I have a dual PhD in neuroscience and nuclear medicine, which is a branch of radiology. So I do a lot of brain imaging.

• 3:07Dr. Mary Claire Haver?

  Your family history, is this what drove you to get this particular PhD?

• 3:11Speaker 00

  I graduated from university and then I had a year of training mandatory in the neurology and nuclear medicine because I wanted to study nuclear medicine. I wanted to look at the brain. I wanted to use brain scanners. I grew up with brain scanners, with scanners. My mom used to work at the accelerator at the CERN in Geneva. So I was very familiar with those concepts and I just really wanted to apply them to biology, which is what nuclear medicine does. And so I went to university and from day one, I was in my first exam was neuroscience. Neuroscience won and I never stopped. And it's only at the end of this five year, four,

• 3:55Speaker 00

  I graduated in four, but it's at that point that my grandmother started showing signs of cognitive decline. And then when I was deciding on my PhD, I knew that I was going to do a PhD in neuroscience, in nuclear medicine, but the topic became Alzheimer's because of that.

• 4:15Dr. Mary Claire Haver?

  Okay. So what was the prevailing thought?

• 4:19Dr. Mary Claire Haver?

  At the time, as to the pathophysiology or the causes of Alzheimer's.

• 4:25Speaker 00

  Yes, you know, it was really, really still in its infancy.

• 4:29Dr. Mary Claire Haver?

  Okay.

• 4:29Speaker 00

  We were just moving away from a diagnosis-based framework where people felt that Alzheimer's was inevitable. That it was.

• 4:41Dr. Mary Claire Haver?

  Aging.

• 4:42Speaker 00

  The consequence.

• 4:42Dr. Mary Claire Haver?

  You live long enough, your brain will.

• 4:44Speaker 00

  Aging or genetics or both. And people were just starting to appreciate that actually that was not the case and that the process of Alzheimer's disease is more like a continuum over time, that you don't just suddenly wake up one day and boom, you have dementia. But rather that Alzheimer's is a slow and silent progressive disorder that takes many, many years to unfold. And that speaks to how powerful our brains are.

• 5:18Dr. Mary Claire Haver?

  Uh huh.

• 5:19Speaker 00

  Because if this progressive deterioration takes years, it also means that the brain is able to withhold and to really withstand the pathology at least for a certain amount of time until the damage is too severe for the brain to be able to function normally. And that's when we start seeing the first signs of cognitive impairment. The only way to know if the marks, the biological signature of Alzheimer's.

• 5:48Dr. Mary Claire Haver?

  Which are?

• 5:49Speaker 00

  Present or not, which are amyloid beta plaques.

• 5:52Dr. Mary Claire Haver?

  Uh huh.

• 5:53Speaker 00

  Or Alzheimer's plaques and neurofibrillary tangles. So the plaques are between neurons and impair communication between neurons, whereas the tangles are inside neurons and damage the neurons from the inside. So we have the plaques that damage the neuron from the outside and the tangles from the inside. And all that creates inflammation that then leads to neuronal apoptosis or death.

• 6:21Dr. Mary Claire Haver?

  So death.

• 6:22Speaker 00

  Yes.

• 6:23Dr. Mary Claire Haver?

  Okay.

• 6:24Speaker 00

  So now we can actually measure that as you walk in the door. Because we have the tools to do that. Back then, we could not. So the only way to measure these lesions, these markers was a postmortem.

• 6:39Speaker 00

  But that is Alzheimer's disease.

• 6:41Dr. Mary Claire Haver?

  Uh huh.

• 6:41Speaker 00

  The disease is the biology. Plagues and tangles. Alzheimer's dementia is the symptoms. Is the memory loss, is the attention deficit. It's the impairment in language. Is the inability to conduct your regular activities. So the disease starts first. And we and others have shown that it can start as early as in the 40s and 50s.

• 7:08Dr. Mary Claire Haver?

  Wow.

• 7:08Speaker 00

  But having the lesions does not mean that you're going to develop the dementia. There are many individuals who do have plaques and tangles and never show symptoms of Alzheimer's.

• 7:23Dr. Mary Claire Haver?

  Do we know why?

• 7:24Speaker 00

  We're looking into why. And that is what is driving the field of Alzheimer's prevention. Because now we understand that even though you may have these lesions in your brain, some people, for whatever reason, do not develop inflammation and do not lose neurons because of that. Yes, other people do. And so we're looking at all the different factors that can lead down one pathway or the other. And we and others, I mean, the field, obviously, has identified multiple risk factors for Alzheimer's that together or in isolation can modulate your odds of, number one, developing the plaques and tangles.

• 8:07Speaker 00

  But most importantly, I think, number two, to determine whether or not the plaques and tangles will be harmful to your brain.

• 8:17Dr. Mary Claire Haver?

  Okay.

• 8:18Speaker 00

  In a way that will impact.

• 8:20Dr. Mary Claire Haver?

  It makes sense of osteoporosis, like.

• 8:21Speaker 00

  Yeah, yeah, exactly. Heart disease.

• 8:23Dr. Mary Claire Haver?

  So not everyone's going to have a heart attack who has atherosclerotic plaques.

• 8:26Speaker 00

  Right, does that make sense?

• 8:28Dr. Mary Claire Haver?

  You, in your book, The Menopause Brain.

• 8:30Speaker 00

  Hmm.

• 8:30Dr. Mary Claire Haver?

  Okay.

• 8:31Speaker 00

  Yes.

• 8:31Dr. Mary Claire Haver?

  Um, write, "Menopause is one of the best-kept secrets in society."

• 8:36Speaker 00

  It was, until you came along.

• 8:38Dr. Mary Claire Haver?

  Do you still? I was like, do we still say that, Ali? Is that still a thing?

• 8:41Speaker 00

  I, I.

• 8:42Dr. Mary Claire Haver?

  What made you write that at that time?

• 8:45Speaker 00

  You know, this was really interesting. I, I was studying. Menopause, together with Dr. Robbie Brinter, Robert D. Diaz. She was my mentor for many years and now she's one of the best friends and colleagues that I could ever hope to work with. I have learned so much from her.

• 9:01Dr. Mary Claire Haver?

  Yeah.

• 9:01Speaker 00

  I started working with Robbie, who is a pioneer in the field of menopause and Alzheimer's connection.

• 9:07Dr. Mary Claire Haver?

  Because that wasn't a thing, right?

• 9:09Speaker 00

  Oh, my God, no.

• 9:10Dr. Mary Claire Haver?

  You guys got laughed at.

• 9:11Speaker 00

  Oh, yeah, yes.

• 9:15Speaker 00

  Yeah, that's a nice way to put it. Yes, yes, yes. So I've always looked at sex differences in Alzheimer's. Since my PhD, that was the first thing I've ever done. Doesn't matter if you're a man or a woman in terms of genetics, response to genetics. And we started looking at mitochondrial DNA. So something that perhaps people are not aware of is that we all have two different types of DNA, three technically. But the first is our typical DNA with the chromosomes, the 23 chromosomes and the X and Y. But we also have a mitochondrial DNA that is completely separate from our chromosomal DNA.

• 9:55Speaker 00

  And what's specific about mitochondrial DNA is that, number one, it impacts energy production. Mitochondria are the powerhouse of the cell. Yes, the powerhouse of the cell. But also is 100% maternally inherited in humans. And so that, I thought, that could be an interesting way by which Alzheimer's risk is inherited from the mother to the children. Because we do know that if you have a maternal history of Alzheimer's, your risk is a little bit higher than if your father is affected. And if you have both parents affected, your risk is higher than having just one parent affected. Risk does not mean that anyone is getting sick, right?

• 10:38Speaker 00

  It just means that relative to another person, your risk is a little bit higher.

• 10:42Dr. Mary Claire Haver?

  Okay.

• 10:43Speaker 00

  But that was my PhD, my doctorate. This is which has now been replicated and people are talking about it and doing more work on. So that was genetics and Robbie loved that work. And she approached me at a conference. And we just started talking and she said, you know, I love your work about maternal inheritance and the risk of Alzheimer's for women, which really nobody talks about.

• 11:09Dr. Mary Claire Haver?

  Even though we are.

• 11:11Speaker 00

  We are now.

• 11:12Dr. Mary Claire Haver?

  Two thirds more likely, like, why is this important? Because a lot of women, a lot of our listeners may not understand that you're much more likely to get Alzheimer's if you're a woman.

• 11:22Speaker 00

  Yes, so sadly, almost two thirds of all Alzheimer's patients are women. And for a really, really long time, the notion was that women live longer than men. And Alzheimer's is a disease of old age. Therefore, at the end of today, more women than men end up with Alzheimer's. That was actually the pushback that I, the first one on my list of pushbacks that I got when I was a PhD student, because I wanted to look at sex differences in Alzheimer's and people were telling me it's a waste of your time. Because it's just aging, it's just longevity, it's just that women live longer than men.

• 12:02Dr. Mary Claire Haver?

  I, we hit this while still in cardiovascular disease and yeah, you know.

• 12:06Speaker 00

  Doesn't matter.

• 12:07Dr. Mary Claire Haver?

  Yeah, muscular skeletal disease, like, why are you looking at sex differences? Like, you're just, everyone's a human and we all, you know, I'm like, okay.

• 12:17Speaker 00

  I know. And so that was my PhD is the reason I moved to New York. Because I, I moved, so I transferred to NYU Medical. And I started working with Dr. Moni De Leon, who is a pioneer in the early detection of Alzheimer's disease and Alzheimer's prevention. So he was doing brain imaging and biomarkers on individuals in their thirties and forties, when everybody else in the field was still working with patients with Alzheimer's in their seventies, eighties and nineties. Because it was a complete switch of framework that I thought was brilliant. And what we have shown since and other people have shown is that Alzheimer's is not a disease of old age.

• 12:59Speaker 00

  It is a disease of midlife with symptoms that start in old age. So the idea is this disconnection between Alzheimer's disease and Alzheimer's symptoms of Alzheimer's dementia. Where the disease starts in midlife for many people, not all people, but it tends to start in midlife. That's when we see the plaques and tangles forming.

• 13:24Dr. Mary Claire Haver?

  Begin.

• 13:24Speaker 00

  When we do brain scans. But then it keeps progressing over time, usually for decades, until the plaques and tangles reach a certain threshold, after which brain performance is no longer maintained. And then we see the changes in memory, attention, language, and whatnot. So that completely changed the question and the conversation finally.

• 13:50Dr. Mary Claire Haver?

  Right.

• 13:51Speaker 00

  For us, because if Alzheimer's disease is not a disease of old age, but it's a disease of midlife, and women have a longer, have a higher long-term lifetime risk of Alzheimer's relative to men, starting in midlife, which we now know to be the case, starting at age forty-five, the woman has twice the risk of Alzheimer's as respect, relative to a man of the same age. Then the real question is, well, what happens to women in midlife? Right? What happens to women in midlife that does not happen to men in midlife? And that could potentially explain the higher long-term risk.

• 14:32Dr. Mary Claire Haver?

  And that thing is menopause. So wasn't until the nineties.

• 14:36Speaker 00

  Yes.

• 14:37Dr. Mary Claire Haver?

  That we discovered that estrogen impacts the brain.

• 14:40Speaker 00

  Yes, and that is ridiculous. The first study showing that estrogen is not just a reproductive factor, but is also a brain hormone, was published in nineteen ninety-two. And it was only replicated in nineteen ninety-four, nineteen ninety-six. When do we get to the moon?

• 14:58Dr. Mary Claire Haver?

  Yeah.

• 14:59Speaker 00

  Right?

• 14:59Dr. Mary Claire Haver?

  C C C R.

• 15:00Speaker 00

  Right? Men landed on the moon like thirty years, twenty years before.

• 15:07Speaker 00

  We were all made aware of the fact that reproductive hormones, sex hormones in quotes, are actually brain hormones too. So in other words, we know more about space.

• 15:18Dr. Mary Claire Haver?

  Than we do about the female brain.

• 15:20Speaker 00

  The Women's Health Initiative, when did they start writing it?

• 15:23Dr. Mary Claire Haver?

  They started the grant in ninety one. They started, yeah.

• 15:27Speaker 00

  Yeah.

• 15:27Dr. Mary Claire Haver?

  They started writing the grant.

• 15:28Speaker 00

  Before we even knew how estrogen worked in the brain. And then we just say they did it wrong. I'm like thinking, they did something incredible, incredible. When no one was talking about prevention.

• 15:42Dr. Mary Claire Haver?

  Uh huh.

• 15:42Speaker 00

  They just went for it. So I think that is very commendable than the way that the results were estimated.

• 15:48Dr. Mary Claire Haver?

  Right. We can't demonize the study because it was groundbreaking.

• 15:52Speaker 00

  It was incredible.

• 15:52Dr. Mary Claire Haver?

  And we still use the data today for prevention.

• 15:55Speaker 00

  Sadly.

• 15:55Dr. Mary Claire Haver?

  You know? So you've said, and you've walked me through the story. And I think it's important for the listeners because I think it's fascinating about estrogen and estrogen receptors in the brain. So you're like newly minted PhD. You're on fire. You're ready to study this. And you're like, what we didn't scan, we didn't see.

• 16:14Speaker 00

  Yes.

• 16:15Dr. Mary Claire Haver?

  You know, like if we don't look for it, it's not there.

• 16:17Speaker 00

  Yes.

• 16:18Dr. Mary Claire Haver?

  Right? And so you go and decide, I want to study estrogen in the brain, but there was a problem.

• 16:23Speaker 00

  Oh, there were plenty. So there were two sets of problems. The first set is that nobody had done it before, which I don't know because I assumed that since menopause is something that impacts all women. I would find a lot is universal. All women got willing, if you live long enough, you'll go through menopause. And we all know as women that menopause is not nothing, right? There are neurological symptoms, but evidently the idea that some of the symptoms that can occur during menopause are neurological in nature was not a well-known or common understanding.

• 17:03Dr. Mary Claire Haver?

  I still get pushback in 2026. No, no, no, no, no. This is just aging. No, no, no, no, no. You know, come on, it's hot flashes. I'm like, the neurotrans, you know, like, the vasomotor symptoms are in the brain.

• 17:17Speaker 00

  Yes, they come from the brain. They're neurological in origin. And that was the first problem. The second problem, so, and then we, we set out to do the studies, right? And that is, those are the brain scans you mentioned before, where, that was back in 2015, when I was like, well, I've been studying midlife women for the risk of Alzheimer's, but I also have information of menopause. Right? And so we went back and we, we talked to all the women in the study. And that was so helpful because what we were finding was this, that if you, in my hands at least, but it's been replicated increasingly.

• 17:58Speaker 00

  If you look at brain scans of midlife women and midlife men, the women, and, and this is very, very important. We work with women who have either a family history of Alzheimer's or an APoE4.

• 18:11Dr. Mary Claire Haver?

  So they're high risk.

• 18:12Speaker 00

  So they're, they're high risk relative to people who don't have these markers. But if we compare these groups, the women consistently and significantly show more red flags for Alzheimer's in their brains relative to men of the same age. And this is very consistent with preclinical work and animal studies as well. But we couldn't find an explanation for that other than sex. But what is it about sex that is driving this, right? Which factors and what other parameters could be involved? And we were looking, I promise, everything. We were looking at family history, of course, APoE4, genotype, we were looking insulin resistance, diabetes, heart disease risk factors.

• 18:56Speaker 00

  And we could not quite really explain the difference. And then we looked at menopause. And we worked with OB-GYN department, of course. That was wonderful, actually, to work with colleagues who had never thought about Alzheimer's. We had never thought about menopause. It was, it was lovely. And we classified, they classified the women as pre-menopausal, regular menstrual cycle, peri-menopausal, irregular menstrual cycle, post-menopausal, no menstrual cycle for twelve months or longer. And then we matched them with men of the same age, because post-menopausal women are a little bit older. Pre-menopausal women and men, no differences. Peri-menopausal women and men of the same age,

• 19:41Speaker 00

  you can see the red flags popping. Mild, but you do see an increase. Post-menopausal stage, men of the same age, really significant difference.

• 19:54Dr. Mary Claire Haver?

  Wow.

• 19:55Speaker 00

  Yes, that was back in twenty seventeen. And we published it. And no one has seen those brain scans before. And that was menopausal stage. So we had a group of women who were pre-menopausal, peri-menopausal, post-menopausal. And we could show how the Alzheimer's plaques are nowhere to be seen.

• 20:16Dr. Mary Claire Haver?

  In pre-menopause.

• 20:17Speaker 00

  In pre-menopause, you can start seeing them in, in my studies, always in the frontal cortex. In peri-menopause, and then they're a little bit everywhere after menopause. But still very mild, right? They're not within the Alzheimer's impaired range, but, but they're there. You can see them, that's why I say red flags. But what was most striking was the difference in brain glucose metabolism, which is something that Robbie has shown, um, time and time again, in rodents, in animal models of menopause and Alzheimer's combined. And what we have shown, and these are brain scans that are all over the internet at this point, you can see the difference in those first images,

• 21:00Speaker 00

  where the pre-menopausal brain is nice and bright, the peri-menopausal brain gets a little bit darker, and the post-menopausal brain is much darker in the same brain regions that are typically hypometabolic or impacted in clinical Alzheimer's patients.

• 21:19Speaker 00

  And quantitatively, that is a thirty percent difference. Now, that was cross-sectional, pushback immediately.

• 21:27Dr. Mary Claire Haver?

  Right.

• 21:27Speaker 00

  But that, you know, this is just-

• 21:28Dr. Mary Claire Haver?

  And this, we're talking about glucose uptake.

• 21:30Speaker 00

  Yes, it's glucose uptake and those two the way it's metabolized, it's glycolysis.

• 21:34Dr. Mary Claire Haver?

  Okay.

• 21:34Speaker 00

  Yes, but we've also done spectroscopy studies to look at ATP production, where ATP is the cellular energy. And we do show the same kind of imbalance. So glycolysis is the very top of the glucose metabolism chain. ATP is at the very end. So we know that the entire metabolic pathway is disrupted.

• 21:56Dr. Mary Claire Haver?

  So for our listeners, we're talking about the Krebs cycle, if everyone remembers from biology in high school.

• 22:01Speaker 00

  Yes.

• 22:02Dr. Mary Claire Haver?

  And you basically start with glucose and we break it down through several steps until we get energy or ATP.

• 22:07Speaker 00

  Yes.

• 22:07Dr. Mary Claire Haver?

  At the end. So what she's saying is, I'm trying to take it down for the laypeople.

• 22:11Speaker 00

  The ATP is not there.

• 22:12Dr. Mary Claire Haver?

  Is we are disrupting that pathway.

• 22:14Speaker 00

  Yeah.

• 22:18Dr. Mary Claire Haver?

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• 23:31Dr. Mary Claire Haver?

  Now, we need to talk about something that went viral. When Robbie testified at the FDA.

• 23:36Speaker 00

  Oh, God, yes, it did.

• 23:37Dr. Mary Claire Haver?

  She talked about, in her studies, that we see. Now, help me, walk me through this so that the basic listener can understand. The brain will start utilizing some of its own white matter for fuel.

• 23:52Speaker 00

  Yes.

• 23:53Dr. Mary Claire Haver?

  In menopause, because glucose metabolism is impaired.

• 23:56Speaker 00

  Yes.

• 23:56Dr. Mary Claire Haver?

  So, meaning, it will turn around and grab whatever it can for energy. The brain will protect itself. And white matter is kind of the insulation, so that's fatty material that lines our neurons. And that got twisted into the brain eats itself somehow, which went viral, of course, on social media. Can you kind of explain what that is?

• 24:15Speaker 00

  Yes. One of the many functions of estrogen is that when it binds to estrogen receptors, that activates the glycolytic pathway, which means the brain starts burning glucose to make energy. The brain is always burning glucose to make energy. The brain runs on glucose for women until menopause, right? And that is wonderful, because neurons need a lot of energy to just function correctly. What happens when estrogen declines or fluctuates is that the estrogen receptors are not activated the same way. And that has a negative feedback effect on the way that the brain uses or not uses

• 24:59Speaker 00

  glucose to make energy. And when estrogen is very low after menopause, but even prior, what happens is that the brain starts glitching, because it can't get all the energy that it needs from glucose. And because the brain is an exceptionally intelligent organ, of course, doesn't just sit there and decide that we're all going to develop dementia, it switches tracks. So it says, okay, if I can't burn glucose for energy, because the mechanisms are not working, I'm going to go hybrid. I'm going to start burning other sources of energy. At first, it switches to amino acids.

• 25:37Dr. Mary Claire Haver?

  Okay.

• 25:38Speaker 00

  It's an easy switch.

• 25:39Dr. Mary Claire Haver?

  Uh huh.

• 25:39Speaker 00

  Very chemically. But the problem is that the brain also needs amino acids to make neurotransmitters. So that could backfire. So then the brain says, well, no, no, no, no, no. I need the amino acids for a number of different functionalities. So I'm going to start burning fat. And that is called beta oxidation. And in the entire body, when you go into a state of very low glucose, the body starts burning fat, which is one of the principles of diet. There you go. The same thing can happen in the brain. So the brain starts burning fat to produce ATP. What happens then? Well, the brain is a very fatty organ. There's a lot of fat, good fat, that, like you said, insulates neurons. Yeah.

• 26:24Speaker 00

  So actually, when you look at MRI scans, you leave a little bit of gray around the brain. That is the gray matter, but everything else is white, right? That's white matter, which means fat and other things. So what is the easiest accessible source of fat to burn? The white matter. And so the brain, at least in animal models, starts utilizing a little bit of this white matter as a source of energy. In rodents, very specific Alzheimer's models, that long term turns into the word that triggered the brain eats itself, which is called catabolism.

• 27:07Dr. Mary Claire Haver?

  Uh huh.

• 27:08Speaker 00

  Anabolism, when you're building tissue. Catabolism, you're breaking it down. It does sound unpleasant.

• 27:15Dr. Mary Claire Haver?

  Yeah. It was kind of scary, you know?

• 27:17Speaker 00

  Yeah, I understand.

• 27:18Dr. Mary Claire Haver?

  The brain eats itself, but I knew.

• 27:21Speaker 00

  It is not an autoimmune disorder. It is not an autoimmune reaction. It is not phagocytosis. It's an adaptive response.

• 27:30Dr. Mary Claire Haver?

  It's remodeling.

• 27:31Speaker 00

  It's more like energy preservation in that case. I would say that in rodents, backfires if it doesn't stop after a certain amount of time. And if it just doesn't stop, it will lead

• 27:44Dr. Mary Claire Haver?

  Progress eventually.

• 27:45Speaker 00

  To white matter degradation and the neuronal loss. But this is in rodents. We need to consider that female rats tend to die.

• 27:56Speaker 00

  Quite soon after the end of the reproductive life. So reproductive senescence for animals is a little bit like the end of the line.

• 28:07Dr. Mary Claire Haver?

  Mm hmm.

• 28:07Speaker 00

  Right, so their lifespan matches the reproductive span.

• 28:11Dr. Mary Claire Haver?

  Right, most mammals don't have a protracted menopause like humans.

• 28:14Speaker 00

  Exactly.

• 28:14Dr. Mary Claire Haver?

  There are a few, but we're really the.

• 28:17Speaker 00

  Yes, so women live at least another twenty.

• 28:19Dr. Mary Claire Haver?

  So and there's not a great menopause model, other than taking out ovaries. We don't have a perimenopause model, you know, you don't.

• 28:26Speaker 00

  So, you know, if there are some female rats that live quite long, some specific strains, and then Robbie uses them to look at the natural menopausal transition. But still, still, it it does not really replicate brain aging in humans.

• 28:43Dr. Mary Claire Haver?

  Okay.

• 28:43Speaker 00

  And that's why translation of research is so important. That's why Robbie reached out to me and we've been working together ever since because she can probe the mechanisms, doing experiments, which we will never be able to do.

• 28:56Dr. Mary Claire Haver?

  On humans.

• 28:56Speaker 00

  On women.

• 28:56Dr. Mary Claire Haver?

  Mm hmm.

• 28:57Speaker 00

  But we can apply those findings to see if similar mechanisms or patterns are present in women.

• 29:05Dr. Mary Claire Haver?

  Okay.

• 29:05Speaker 00

  Very often they do, but sometimes they do not. That we have shown by following women over time, and this is actually not published yet, but it's hopefully soon, we have shown evidence for adaptation as part of menopause. So definitely there are changes in, now I can say changes because we're also have published and we're doing longitudinal studies where we're following women over time. And we do see that metabolic changes are progressive in some brain regions, not all brain regions. We do find that the gray matter is reduced in some regions and not others.

• 29:41Dr. Mary Claire Haver?

  Not others, yeah.

• 29:42Speaker 00

  But we also find evidence of compensation.

• 29:44Dr. Mary Claire Haver?

  Okay.

• 29:45Speaker 00

  Some parts of the brain ramp up their metabolic activity as other brain regions decline. So overall cognitive performance is preserved. And I think this is very, very important to say because I know that our work has perhaps not been fully understood. And the notion is that if you have these things, then you have a disease or a pathology. Whereas we're always saying, no, no, no. What we're trying to do is really understand how the brain, women's brains respond to a very significant transition, not just from a reproductive perspective, but also from a neurological perspective.

• 30:26Speaker 00

  And how that could reflect an inflection point for Alzheimer's risk for some women. Menopause does not cause Alzheimer's. What we're understanding more and more is that it kind of unmask a vulnerability or multiple vulnerabilities, right? It's when some women develop anxiety or depression is when some women have more severe symptoms, multiple sclerosis, that's when the risk for stroke increases. It's like a cellular aging accelerator. I guess if you have an underlying vulnerability, that becomes more evident, right?

• 31:10Speaker 00

  And it's important to study that because then we can offset that, the risk, which is really what we're trying to do.

• 31:16Dr. Mary Claire Haver?

  Right, we can intervene earlier, see who's at risk and provide hope. Well, let's talk about the statistics that a lot of women aren't familiar with, and I'm not fear mongering here. I think it's important that our listeners, especially younger listeners who are like, is this, you know, oh, my God, I don't want to get older. This sounds terrible. But I think if you know, then you can prepare yourself and you're not so blindsided.

• 31:40Speaker 00

  Yeah.

• 31:41Dr. Mary Claire Haver?

  When you start having symptoms. So, women are twice as likely as men to be diagnosed with an anxiety disorder or depression.

• 31:50Speaker 00

  Yes.

• 31:51Dr. Mary Claire Haver?

  And so when I looked at the data on SSRI prescription, you know, use, so that's a marker for how many women have depression or anxiety because these are the medications we use to treat. We have about a 10% use before perimenopause.

• 32:03Speaker 00

  Mm hmm.

• 32:04Dr. Mary Claire Haver?

  And then we double that.

• 32:05Speaker 00

  Yeah.

• 32:06Dr. Mary Claire Haver?

  Now, part of that is because a lot of practitioners are not comfortable prescribing hormone therapy and will default to giving a patient an SSRI. To treat a hot flash.

• 32:15Speaker 00

  Yes.

• 32:15Dr. Mary Claire Haver?

  And to treat visomotor symptoms, but we do see a doubling. So we go from ten to twenty percent after age forty. And then we go to twenty five percent at age sixty five.

• 32:24Speaker 00

  Mm hmm.

• 32:24Dr. Mary Claire Haver?

  And then women are twice as likely to develop Alzheimer's, three times more likely to develop an autoimmune disorder, including those that attack the brain.

• 32:33Speaker 00

  And multiple sclerosis.

• 32:34Dr. Mary Claire Haver?

  Including multiple sclerosis. Four times more likely to suffer from migraines or headaches.

• 32:39Speaker 00

  Yes.

• 32:40Dr. Mary Claire Haver?

  And then more likely to actually be killed by a stroke after menopause. And that's a ratio that's two to one or even higher.

• 32:47Speaker 00

  Mm hmm.

• 32:47Dr. Mary Claire Haver?

  No one taught me this, you know, when I was in training in medical school.

• 32:50Speaker 00

  Uh, me neither.

• 32:51Dr. Mary Claire Haver?

  So this is all kind of new information.

• 32:54Speaker 00

  Yeah. Yeah, I I looked it up when I was writing the XX Brain.

• 32:58Dr. Mary Claire Haver?

  Mm hmm.

• 32:58Speaker 00

  And I was like.

• 32:59Dr. Mary Claire Haver?

  I pulled these stats from your book.

• 33:01Speaker 00

  Yes, I figured. This is all research that we had to do kind of from scratch by pulling information from from different fields to really. I think it's important to have a big picture. You know, like a high level understanding of what your risks may be. And how to protect yourself against those risks. And I think it's really important to know that prevention is on the table.

• 33:27Dr. Mary Claire Haver?

  Yeah.

• 33:27Speaker 00

  And we have a lot of power to to make the right choices and protect our bodies and brains. I think, I think because we can't see our brains, we we really don't have some kind of direct line of access to our brains. They feel so foreign, almost like I can't touch them, they can't really, they don't quite, it doesn't quite belong to you, your brain, until you have symptoms, right? Then you realize, oh, my God, I do have a brain, how can I take care of my brain? But I think it's becoming more and more commonplace to pay attention to mental health.

• 34:00Dr. Mary Claire Haver?

  Yes.

• 34:01Speaker 00

  And brain health. And that there are many things that we can do.

• 34:14Dr. Mary Claire Haver?

  What I'm seeing in my patients in clinic and definitely when people, you know, sharing their stories on social media is the cognitive and the mental health

• 34:23Speaker 00

  Yeah.

• 34:24Dr. Mary Claire Haver?

  changes that are really acutely happening where we build a life for ourself, right? We build a family, we build a job, we build this wonderful, beautiful life that is messy and complicated and, you know, all the things, you know, that all the jobs and the hats we wear as women.

• 34:40Speaker 00

  Yes.

• 34:41Dr. Mary Claire Haver?

  And we've got it, we've got it managed. We have good days, we have bad days, but, you know, we are in control of our lives.

• 34:46Speaker 00

  Yeah.

• 34:47Dr. Mary Claire Haver?

  And then, we're not. And the common theme in this "we're not" seems to be perimenopause. There's an inflection point. I love the way you describe it.

• 34:57Speaker 00

  It's a disruptor.

• 34:58Dr. Mary Claire Haver?

  So walk our listeners through, in general, what is happening to our brains? Before menopause, you know, perimenopause, and then postmenopause.

• 35:06Speaker 00

  From a brain perspective?

• 35:08Dr. Mary Claire Haver?

  Mm-hmm.

• 35:08Speaker 00

  It's a really good question, and I think we need to do more research to really be conclusive and talk about all women. As far as I know, we are still one of the very few teams that are looking into it at this point in time, and we are learning more and more.

• 35:26Dr. Mary Claire Haver?

  That's shocking to me.

• 35:28Speaker 00

  It's not that shocking. You know, menopause is now on people's minds, but it was not until recently. What happens is this, that hormones are starting to change, and the pattern of hormones is starting to change. And what we have learned, and we're learning more about, is that the brain is in part a neuroendocrine system, it's a hormonal organ that responds to the action of sex hormones from the ovaries, which are predominantly estradiol and progesterone. And at the same time, the brain uses hormones to communicate back with the ovaries. And these hormones are called gonadotropin, so they're usually

• 36:13Speaker 00

  FSH and LH that we focus on most. So as long as estrogen and progesterone are flowing up, and FSH and LH are flowing back down, the brain has a very clear plan with the ovaries. When the ovaries start glitching, and they're running out of follicles, and their sex ovarian hormones start to fluctuate, the brain gets...

• 36:37Speaker 00

  Confused. The reason being, so actually, this is a very important thing that I was hoping we would talk about, then when I talk about estrogen being neuroprotective, I'm really talking about estrogen, the endogenous hormone. Estradiol, coming from the ovary. The endogenous hormone that the ovaries make because of this feedback loop. I'm not talking about estrogen therapy. Right. But a lot of people make the assumption. The same. Yes, especially now that people use this term of bio-identical hormones, it's even more confusing because you're thinking, well, if, if the estrogen I make is neuroprotective

• 37:21Speaker 00

  and I can take the same estrogen from a patch or a peel, then that estrogen also needs to be neuroprotective, it's assumed to be neuroprotective. Not so easy. We would wish, right? Right. Fantastic. But the point is that estrogen alone doesn't quite matter. Can we talk about the biology of estrogen? Yes. Okay, good. The way that estrogen works, and let's just look at the brain, is that estrogen is able to cross the blood brain barrier by passive diffusion and also potentially transport mediated channels that are being investigated now. And then it goes in the cell and looks for estrogen receptors.

• 38:02Speaker 00

  It by, estrogen will bind to an estrogen receptor, it's like a key that needs to open a lock, or actually, it's like a key that needs to get jammed inside a lock. And together, they go inside the nucleus of the cell. They look for DNA and they bind to a specific part of DNA that's called the E R E, estrogen receptor element, that is in the promoter part of, of the DNA. So it directly triggers.

• 38:34Speaker 00

  Transcription, which means protein synthesis and cell function. So hormones alone, if you don't have the receptor and if the system is not responsive, the hormones alone don't do anything.

• 38:47Dr. Mary Claire Haver?

  Don't do anything. They have to bind to something.

• 38:49Speaker 00

  Yes, they need to bind to the receptor. And the binding needs to be functional. It needs to be able to get to the DNA, speak to the DNA and tell the DNA what to do. The things that can happen is either we're telling the DNA to make more of certain things or we're telling the DNA to make less of certain things. So what can estrogen with the receptor do? Well, for instance, can make more BDNF, brain-derived neurotrophic factor.

• 39:18Dr. Mary Claire Haver?

  And that is a good thing.

• 39:19Speaker 00

  That's wonderful. It's a protein that really supports a synaptic plasticity and growth. It keeps your neurons healthy, which is why we say that estrogen is neuroprotective. By activating these pathways, it supports brain protection. Things that we want to make less of, for instance, pro-inflammatory cytokines. We say that estrogen is anti-inflammatory, reduces oxidative stress because it goes through the DNA and say, stop making TNF-alpha, stop making interleukin-6, right? So it turns off the pro-inflammatory response. So that's why estrogen is so important for brain health.

• 40:03Speaker 00

  And we are now able to measure that using brain scans, which again is the first time ever.

• 40:09Dr. Mary Claire Haver?

  And your research, one of the things that fascinated me was you were the first or your team to document that across the transition, we actually up-regulate the estrogen receptor.

• 40:21Speaker 00

  Do it to look at it.

• 40:21Dr. Mary Claire Haver?

  Yes. So for those of you who are listening on our YouTube, we will have the images for you to see. And we'll get the images and they'll be linked in the show notes as well.

• 40:31Speaker 00

  Great. So back to 2019, we had been studying menopause for a bit. And the assumption was that the differences that we were seeing between women at different menopausal stages, but also at that point over time, were directly caused or associated with changes in estrogen function.

• 40:55Speaker 00

  But that needs to be proven, right? So I went to, I went to my radiochemistry department and I said, I need a tracer to use with brain imaging to look at estrogen in the brain, 2019, right? And they said to me, well, we don't have it. And I said, hmm, that doesn't sound so good to me.

• 41:15Dr. Mary Claire Haver?

  So you had no way to study estrogen in the brain? Cause there was no tracer available?

• 41:20Speaker 00

  There was no tracer.

• 41:21Dr. Mary Claire Haver?

  So tracer is something to use in radiology. Explain what a tracer is, so.

• 41:25Speaker 00

  A tracer, in our case, we do positron emission tomography or PET imaging, which is that kind of technique, you know, when you look at the brain in some parts of red, blue, green, so that's positron emission tomography. Yeah. And what we do is that in this case, we take estradiol and we just attach a fluorine 18 molecule to the estradiol. Fluorine 18 is a radioactive isotope, is a very, very low dose radioactivity. But what is so special about it is then that becomes a tracer or a ligand. And you just inject it in the bloodstream and it behaves exactly like estrogen. So it's lipid soluble, so it gets right through inside the brain.

• 42:09Speaker 00

  And then it looks for the estrogen receptors and it binds to the estrogen receptors. But we have this teeny tiny little thing attached to it that emits gamma rays, which means it shoots out light.

• 42:22Dr. Mary Claire Haver?

  It will light up on the scan.

• 42:23Speaker 00

  Yes, it's like a GPS.

• 42:25Dr. Mary Claire Haver?

  Or it, very similar to when we do thyroid studies. Lots of women have had this, a tracer that picks up thyroid hormone and they're looking for activity for different autoimmune thyroid diseases.

• 42:36Speaker 00

  Yes, we use it for all sorts of things, for breast cancer, we use it for heart.

• 42:41Dr. Mary Claire Haver?

  But there was nothing available for estrogen?

• 42:43Speaker 00

  There was nothing, no, no. So this tracer was available, this is called fluoroestradiol. And we have been using this tracer for breast cancer for a very long time, but that's from the neck down. It's really hard to get stuff in the brain unless the brain accepts.

• 43:01Speaker 00

  Whatever traces.

• 43:02Dr. Mary Claire Haver?

  The brain protects itself. There's a blood brain barrier and it's very protective.

• 43:05Speaker 00

  Yeah, which is great, right, for us as humans. Not so great if you're trying to see what's happening. But this tracer actually crosses and it binds especially to that structure in red.

• 43:18Dr. Mary Claire Haver?

  Okay, so walk everybody through the images.

• 43:21Speaker 00

  Yes, so these are three brain scans of three different women. One is pre-menopausal, one is perimenopausal in the middle, and the last one is post-menopausal, early post-menopausal fifty-two. And what we're looking at is the way that the estrogen tracer binds to estrogen receptors in the brain. What's important to know is that estrogen receptors are everywhere in the brain, but they're more abundant in some regions than others. So we are looking for the hot spots in a way. What we were looking for, based on animal studies, was a reduction in estrogen receptors. Because, like we were saying before,

• 44:05Speaker 00

  the brains of female rodents are not well-suited to outlive menopause. And so what happens is that soon after the end of the reproductive spin, the brain stops making estrogen receptors. And you can see the downregulation, it really just, and they disappear.

• 44:23Dr. Mary Claire Haver?

  You expected this to happen in humans? Like when women go through menopause, they'll just stop making estrogen receptors. But what did you find?

• 44:30Speaker 00

  The opposite. So and I drove my students insane and was like, you've done it wrong. They're like, no, what happened? I was like, go back. I just could not believe it. And we just kept enrolling participants because it was like, maybe it's just.

• 44:46Dr. Mary Claire Haver?

  A fluke.

• 44:46Speaker 00

  Yes, some kind of abnormalities, but it really holds. And now we have hundreds of women in the study and we still see this. So pre-menopause, we're looking at women who are at the peak of ovulation. So we have a lot of estradiol, endogenous estradiol in the brain. So all the estrogen receptors are taken. So you don't see any binding, basically. Everything is kind of bluish, greenish. But then at the peri-menopausal stage, when estrogen is actually, this is late period, so the estrogen is kind of down. We start seeing the red blob in the middle of the brain. That is the pituitary gland. It's that part of the brain that is actually talking to the ovaries and sending down the FSH and LH, saying, I need more estrogen.

• 45:31Speaker 00

  And what we found was in more estrogen receptor density, there are more estrogen receptors rather than less, which was expected in peri. But there are even more after menopause, up to age sixty-five. And people's always crazy when I said we're going to go all the way to sixty-five because I wanted to map the curve, right? And they thought, it's too late, it's too late.

• 45:56Dr. Mary Claire Haver?

  So for fifteen years, the brain is trying.

• 45:59Speaker 00

  The brain is trying. This is how I read it. This is the brain's attempt to compensate for the fact that estrogen is very low. So usually, hormones and receptors work in balance. When you have a physiological level of hormone, you only need these many receptors. If you have a lot of hormone, then you need fewer receptors, which is a conservative, right? It takes energy to make the receptors, so it's good to kind of like, sit back and relax. But if the hormones go down, that is an upregulation that is likely an attempt to just grab every little bit of estrogen that's present in the circulation. It's also, in a way, a bit of a distress signal.

• 46:43Speaker 00

  Because what's happening in the pituitary, you can see it, is that the FSH and LH levels are increasing, right? So it's the brain telling the ovaries, I still want it. I'm still here.

• 46:58Dr. Mary Claire Haver?

  That is amazing. And then after age sixty-five-ish, we see this signal attenuate.

• 47:04Speaker 00

  We haven't yet. We're doing it now. Look, as of now, I think we're the only team doing this.

• 47:11Dr. Mary Claire Haver?

  Amazing.

• 47:12Speaker 00

  As far as I know, we are the only team with an active IND, with the permission from the FDA to use this tracer for the brain. I'm hoping that more and more people will start doing it. At the same time, I'm directly sponsoring developmental new brain tracers for estrogen, because this is, this is good enough for the pituitary, which is very interesting. But we want to be able to measure more and to get more information out of the brain scans. And the other thing we're doing now is that we're looking at hormone therapy and what kind of effect it has on these receptors. But this was, it was stunning when, when we found it and you know, the response that we got, the people just don't, did not believe it.

• 47:53Dr. Mary Claire Haver?

  Couldn't believe it.

• 47:54Speaker 00

  Did not believe it.

• 47:55Dr. Mary Claire Haver?

  Repeat the study, yeah.

• 47:56Speaker 00

  Or don't, don't waste money. I was told, do not waste money.

• 48:02Dr. Mary Claire Haver?

  Now it's time for the Midi Pause. I'm Dr. Mary Claire Haver, host of the podcast UnPaused, bringing you a word from Midi Health. Let's talk about something that I think about a lot and something I know many of you lie awake worrying about, dementia. Here's what I want you to know. The choices you make today directly affect your brain health tomorrow. And you have more power than you think. As a 57-year-old woman, I am taking small steps daily to protect my brain, like staying active, eating well, and managing my stress. These are things I find work for me, but they may not be right for everyone. Every woman deserves the conversation, and that's why Midi Health is dedicated to changing

• 48:45Dr. Mary Claire Haver?

  the way menopause is treated with a personalized approach to each woman's specific needs. I personally lift weights two to three times a week. Resistance training is important because having more muscle is directly linked to better cognition and brain health. Strong body, strong mind. It's all connected. In my workouts, I try to do at least 150 minutes of cardio per week, zone two training usually, at a moderate pace where you can still hold a conversation. Your heart, lungs, and brain all benefit. I also eat to fight inflammation, whole grains, healthy fats, lean protein, colorful fruits and vegetables, and prioritize protein, at least 30 grams per meal.

• 49:27Dr. Mary Claire Haver?

  And arguably, most importantly, I protect my sleep and manage my stress daily.

• 49:34Dr. Mary Claire Haver?

  Sleep is when brain clears waste and consolidates memory, and chronic stress speeds up brain aging. By getting quality sleep and setting boundaries, you're putting your health first and getting ahead of any dementia symptoms. It may not be right for everyone, but every woman deserves the conversation. Women who start hormone therapy early in menopause have shown lower rates of dementia, stronger bones, and lower heart disease risk. You deserve a conversation. If you want a clinician in your corner who understands what your body and brain need right now, that's exactly what Midi is built for. Go to joinmidi.com, J-O-I-N-M-I-D-I dot com, and connect with one of their clinicians today.

• 50:23Dr. Mary Claire Haver?

  So what are you most excited about right now?

• 50:26Speaker 00

  I am super excited that I started working with Dr. Regina Dugan, who's the former director of DARPA. DARPA is the Advanced Research Program Agency for Defense, which is basically the research arm of the US military. In other words, she's the first woman to ever run DARPA, and she is brilliant, and she is a powerhouse. She's magnificent. And she launched Welcome Leap, which is an independent subsidiary of the Wellcome Trust, which is based in London, one of the world's largest philanthropic organizations. So Welcome Leap takes after DARPA, which means that they sponsor

• 51:10Speaker 00

  high-risk, high-reward, three-years research programs.

• 51:15Dr. Mary Claire Haver?

  And this is not NIH?

• 51:16Speaker 00

  This is not NIH.

• 51:17Dr. Mary Claire Haver?

  Independent.

• 51:18Speaker 00

  It's independent of NIH, fully independent.

• 51:21Dr. Mary Claire Haver?

  And so this is where you got the $50 million?

• 51:24Speaker 00

  Yes, so they asked me to serve as program director, which is a huge honor, and I was able to design my own program of research. They gave me a $50 million budget, which I was like, "Oh, my God, is this Christmas? It's got to be Christmas." And what they really love about this is then they didn't just give me. That money to do the work. They sponsor global international coalitions of scientists who then all work together to address a question that none of us can realistically hope to answer alone. So they really promote collaboration between scientists, whereas usually we're very reluctant.

• 52:09Dr. Mary Claire Haver?

  Silo, because you're fighting for the same research dollars.

• 52:11Speaker 00

  We're fighting for the same, yes, the same pot of money. It's terrible. And in this case, instead, we now have, I'm trying to find this slide that I want to show you. We now have seventeen sites with over seventy leading scientists from all over the world.

• 52:28Dr. Mary Claire Haver?

  And what is the question you're trying to answer?

• 52:30Speaker 00

  Well, the question is, can we realistically have the risk of Alzheimer's disease for women by the year 2050, in the next twenty-five years? And how do we do that? We have estimated, we have done all sorts of calculations and projections, but we have estimated that if we're able to do all the work that I designed, all the work that I said we needed to do in the next three years potentially, then we can expect to reduce the risk of Alzheimer's for an estimated three hundred and thirty million women all over the world. And given current conversion rates to Alzheimer's, hopefully prevent fifty-five million

• 53:15Speaker 00

  new Alzheimer's cases among women by the year 2050. What we're doing specifically is that we are looking at menopause and hormonal aging throughout a woman's life. We're looking at pregnancy, we're looking at puberty, we're looking at birth control, we're looking at all the female-specific risk factors that are mainly neuroendocrine-based, but also everything else that impacts a woman's life, everything we have talked about today. And we're going to try and firmly position at least some of these factors as predictors of Alzheimer's risk in women using brain scans and biological markers. And then we're going to test whether hormone therapy can offset the risk of Alzheimer's by using a modern.

• 54:00Speaker 00

  Biomarker based approach, which is what I think is missing in the field right now. And then we're going to use all the knowledge to develop sort of like online risk calculators for women.

• 54:12Dr. Mary Claire Haver?

  Yeah, we have them for breast cancer. We have them for cardiovascular disease. We have a verosiparous.

• 54:17Speaker 00

  Exactly.

• 54:18Dr. Mary Claire Haver?

  Yeah.

• 54:18Speaker 00

  We don't have them for Alzheimer's, especially for women. And we are targeting an easy to use tool that can be implemented in Epic and become point of care for women. I must show you this slide. We have now data through CARE, so we have all these scientists that I mentioned.

• 54:37Dr. Mary Claire Haver?

  And CARE stands for?

• 54:38Speaker 00

  CARE stands for Cutting Alzheimer's Risk Through Endocrinology.

• 54:44Dr. Mary Claire Haver?

  Wow.

• 54:44Speaker 00

  So when I made this slide, we had sixty seven leading scientists. We now have seventy investigators from all over the world. These are all the data that we have access to from all over the planet. Six continents, all major continents except Antarctica. And we're going to leverage data from one hundred million women, estimated, if all the data sets come through, which makes CARE, this program of research, the largest ever global examination of women's health and Alzheimer's risk ever attempted.

• 55:18Dr. Mary Claire Haver?

  Amazing. Congratulations.

• 55:20Speaker 00

  Thank you. I am so happy.

• 55:21Dr. Mary Claire Haver?

  I think your new position is less stressful than.

• 55:25Speaker 00

  Surprisingly enough, it is.

• 55:28Dr. Mary Claire Haver?

  You're doing the work you're born to do now. You know, like without the, what, you know, our listeners don't understand is, is the way that research has been set up historically is very difficult and so many hoops to jump through and that you basically were given the gift of a lifetime for a researcher.

• 55:46Speaker 00

  Yes.

• 55:46Dr. Mary Claire Haver?

  You know, build your program. Here's the money. Let us know how it works out.

• 55:51Speaker 00

  Yes. And really, you know, with all the pushback and all the, all the things that people have said to me ever, ever since I started being a scientist, just hearing, I believe that you know what you're doing.

• 56:07Dr. Mary Claire Haver?

  Mm hmm.

• 56:07Speaker 00

  You know, it's like, oh, yeah, we do know what we're doing.

• 56:11Dr. Mary Claire Haver?

  Well, congratulations.

• 56:12Speaker 00

  Thank you.

• 56:13Dr. Mary Claire Haver?

  And I'm so glad you came.

• 56:15Speaker 00

  So glad to hear.

• 56:16Dr. Mary Claire Haver?

  Can't wait to see that all the papers coming. So it's gonna be amazing.

• 56:21Dr. Mary Claire Haver?

  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 thepauselife.com. My upcoming book, The New Perimenopause, is available for preorder on Amazon. If you're loving this podcast, I have an important

• 57:00Dr. Mary Claire Haver?

  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 Podpeople. I'm your host, Dr. Mary Claire Haver. The views and opinions expressed on UnPaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or

• 57:41Dr. Mary Claire Haver?

  any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment.