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

Summary

Podcast Summary: unPAUSED with Dr. Mary Claire Haver
Episode: Brain Fog, Memory Loss, and Alzheimer’s Risk During Menopause with Dr. Lisa Mosconi
Date: March 24, 2026

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Episode Overview

In this episode, Dr. Mary Claire Haver sits down with Dr. Lisa Mosconi—world-renowned neuroscientist, author of The Menopause Brain, and a leading researcher on the menopause–Alzheimer’s connection. Their bold, data-driven conversation dives deep into how menopause uniquely impacts women’s brains, the biology behind increased Alzheimer’s risk in women, and groundbreaking research that’s rewriting our understanding of cognitive aging. Dr. Mosconi details why Alzheimer’s is not merely a disease of old age, how brain energy metabolism changes during the menopausal transition, and what new international studies could mean for women’s preventative brain care.

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Key Discussion Points & Insights

1. Why Are Women at Greater Risk for Alzheimer’s?

• Nearly two-thirds of Alzheimer’s patients are women.

  "Sadly, almost two thirds of all Alzheimer's patients are women. ... For a really, really long time, the notion was that women live longer than men and Alzheimer's is a disease of old age. ... But that's not the whole story." – Dr. Lisa Mosconi (00:00, 13:01)

• Old beliefs attributed this difference only to longevity, but new science points to biological sex differences and the role of menopause.

2. Moving Beyond Age as the Sole Factor

• Alzheimer's is a process, not an event: Pathology develops silently over decades; lesions (plaques and tangles) may begin accumulating in the 40s and 50s, while symptoms show much later. (06:23–09:03)

  "Alzheimer's is a slow and silent progressive disorder that takes many, many years to unfold... the disease is the biology, plaques and tangles. Alzheimer's dementia is the symptoms..." – Dr. Lisa Mosconi (06:23)

3. The Menopause–Alzheimer’s Connection

• Menopause and elevated risk:

  “If Alzheimer's disease is not a disease of old age, but it's a disease of midlife, and women have a higher long term lifetime risk of Alzheimer's relative to men starting in midlife... what happens to women in midlife that does not happen to men?” (15:12)

• Estrogen’s brain role:
  • Only since the 1990s has science recognized estrogen as a driver for brain health—not just a reproductive hormone. (16:19)
  • Estrogen acts on brain energy metabolism; menopause is now known to trigger brain changes.

    “The first study showing that estrogen is... also a brain hormone was published in 1992.” – Dr. Lisa Mosconi (16:19)

4. Groundbreaking Brain Scans & Energy Metabolism

• Using brain imaging, Dr. Mosconi’s team found that:
  • Premenopausal women have bright, active glucose metabolism in the brain.
  • Perimenopausal brains show a visible decline.
  • Postmenopausal brains show a 30% reduction in glucose metabolism in Alzheimer’s-vulnerable brain regions—mirroring patterns seen in diagnosed Alzheimer’s. (21:33–23:13)

  “Pre-menopausal brain is nice and bright, perimenopausal brain gets a little bit darker, and the post-menopausal brain is much darker...” (21:33)

[TIMESTAMPS]

• 13:01 – Why “women live longer” isn’t the full story
• 21:33 – Brain scan imagery and glucose metabolism differences
• 23:35 – Disruption describes entire metabolic pathway: "The entire metabolic pathway is disrupted." – Dr. Mosconi

5. “The Brain Eats Itself” – Fact vs. Myth

• Dr. Mosconi clarifies viral misinterpretations of her work: following menopause and loss of estrogen, the brain may begin using white matter (fatty insulation) as an alternate fuel. This is not “autoimmunity” or “eating itself” but an energy-adaptive, compensatory mechanism—seen in animal models, not (yet) fully proven in humans.

  “The brain starts glitching because it can’t get all the energy that it needs from glucose... it goes hybrid, starts burning other sources of energy...” (28:52) “When you look at MRI scans… that’s white matter, which means fat... the brain starts utilizing a little bit of this white matter as a source of energy.” (30:36)

6. Adaptation & Compensation

• Not all brain changes are harmful:

  “We do see that the metabolic changes are progressive in some brain regions, not all... we also find evidence of compensation. Some parts of the brain ramp up... so overall cognitive performance is preserved.” – Dr. Mosconi (34:18–34:21)

• Menopause does not cause Alzheimer’s directly; it may unmask underlying vulnerabilities.

7. Statistics: The Broader Picture of Women’s Brain Health

• After age 40:
  • Women are twice as likely (vs. men) to be diagnosed with anxiety, depression, or Alzheimer’s.
  • Three times more likely to develop autoimmune brain disease.
  • Four times more likely to have migraines or headaches. (36:41)
• These numbers highlight that prevention and vigilance are necessary.

8. Estrogen, the Brain, and the Search for Better Treatments

• There’s a crucial distinction between natural estradiol from ovaries and exogenous hormone therapy. (43:13–46:56)
• Dr. Mosconi’s lab was the first to document upregulation of estrogen receptors in the human brain across menopause—a compensatory mechanism to low hormone levels, not a decline as seen in animals. (48:27–54:06)

  “What we found was more estrogen receptor density, rather than less... an attempt to just grab every little bit of estrogen... It’s also a bit of a distress signal.” (52:37–54:06)

[TIMESTAMPS]

• 48:27 – Discovery of upregulated estrogen receptors in human brains
• 52:37 – Brain’s compensatory mechanisms to low estrogen
• 55:05 – Brain continues trying to compensate up to age 65

9. Prevention, Empowerment, and the Future of Women’s Brain Health

• Prevention is “on the table”—lifestyle, exercise, sleep, stress management, and possibly early hormone therapy may all help.

  “We have a lot of power to make the right choices and protect our bodies and brains.” – Dr. Mosconi (37:37)

• Dr. Mosconi’s new, unprecedented research collaboration, CARE (Cutting Alzheimer’s Risk through Endocrinology), is building risk calculators and clinical tools for women.

  “The question is: Can we realistically halve the risk of Alzheimer's disease for women by the year 2050?” (60:37)

  • Includes 70+ scientists, 17 sites, and aims to assess data from 100 million women globally.
  • Will produce the largest-ever examination of women’s health and Alzheimer’s risk by leveraging a biomarker-based, personalized approach for prevention.

[TIMESTAMPS]

• 59:31 – $50 million global research project: scope and goals
• 60:37 – “Can we halve Alzheimer's risk for women by 2050?”
• 62:45 – CARE: Cutting Alzheimer’s Risk through Endocrinology

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Notable Quotes & Memorable Moments

• "Alzheimer’s is a disease of midlife with symptoms that start in old age." – Dr. Lisa Mosconi (15:12)
• "We know more about space than we do about the female brain." – Dr. Mosconi (16:40)
• "Menopause does not cause Alzheimer’s. ... It unmasks a vulnerability." – Dr. Mosconi (34:20)
• "The choices you make today directly affect your brain health tomorrow and you have more power than you think." – Dr. Mary Claire Haver (58:08)
• “What we found was more estrogen receptor density... which is likely an attempt to just grab every little bit of estrogen that's present in the circulation. It's also a bit of a distress signal." – Dr. Mosconi (53:30–54:06)
• “Can we realistically halve the risk of Alzheimer's disease for women by the year 2050... and how do we do that?” – Dr. Mosconi (60:37)

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Resources, Further Reading & Guest Info

• Dr. Lisa Mosconi’s latest book: The Menopause Brain
• Follow Dr. Mosconi: Instagram @rmosconi | Website: lisamosconi.com
• CARE project: Cutting Alzheimer’s Risk through Endocrinology (details in episode)
• Host: Dr. Mary Claire Haver | Instagram @drmaryclaire | thepauselife.com
• Preorder Dr. Haver’s upcoming book: The New Perimenopause

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Conclusion

This episode offers a comprehensive, hopeful, and sometimes surprising look at the relationship between menopause and brain health, toppling myths and highlighting the urgent need for research that treats women’s brains as both unique and worthy of attention—well before symptoms develop. Dr. Mosconi’s research is ushering in a new era of early detection, prevention, and individualized care, aiming to ensure women not only live longer, but live well.

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For those interested in understanding how menopause really affects their brain—and what the future of prevention looks like—this is a must-listen.

Transcript

[Dr. Lisa Mosconi]

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.

[Dr. Mary Claire Haver]

The views and opinions expressed on Unpaused are those of the talent and guests

[Podcast Narrator/Host]

alone and are provided for informational and entertainment purposes only.

[Dr. Mary Claire Haver]

No part of this podcast or any related materials are intended to be a

[Podcast Narrator/Host]

substitute for professional medical advice, diagnosis or treatment.

[Dr. Mary Claire Haver]

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 describe with one sentence,

[Podcast Narrator/Host]

I just don't feel it myself.

[Dr. 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. 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. Unpaused is supported by Claude from Anthropic Midlife comes with questions that deserve more than surface level searching. Maybe you're trying to make sense of conflicting research on hormone therapy, or you've got a stack of lab results and want to understand what your numbers mean in context. Not just whether they're in range, but but what the patterns might suggest over time. Claude is an AI that thinks through those questions with you. It doesn't just hand back a summary, it helps you dig into the research, pushes back when the evidence is mixed, and cites its sources so you can see the receipts and where the info was pulled from. You can now even connect your Apple health data to Claude, which means Claude can help you understand fitness patterns, track progress towards goals, and visualize trends with native charts. So when you're prepping for an appointment or just trying to figure out why your sleep has been so off the past week, Claude has the full picture,

[Podcast Narrator/Host]

not just the first Google result.

[Dr. Mary Claire Haver]

Try Claude for free at Claude AI Unpaused and see why problem solvers choose Claude as their thinking partner. This episode is brought to you by Peloton Break through the busiest time of year with the brand new Peloton Cross Training Tread plus. Powered by Peloton iq. With real time guidance and endless ways to move, you can personalize your workouts and train with confidence, helping you reach your goals in less time. Let yourself run, lift, sculpt, push and go. Explore the new peloton cross training Tread [e-mail].

[Podcast Narrator/Host]

So your PhD?

[Dr. Lisa Mosconi]

Yeah.

[Podcast Narrator/Host]

Is in what?

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

I graduated from university and then I had a year of training mandatory and I did 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 1. And they never stopped. And it's only at the end of this five year four. 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.

[Podcast Narrator/Host]

Okay, so what was the prevailing thought at the time as to the pathophysiology or the causes of Alzheimer's Yes.

[Dr. Lisa Mosconi]

You know, it was really, really still in its infancy. We were just moving away from a diagnosis based framework where people felt that Alzheimer's was inevitable, that it was aging. They concentrated.

[Podcast Narrator/Host]

You live long enough, your brain will

[Dr. Lisa Mosconi]

detect 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. 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 is present or not, which are amyloid beta plaques 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 over time. Yes. Okay, 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 or these markers was postmortem. But that is Alzheimer's disease. The disease is the biology, plaques and tangles. Alzheimer's dementia is the symptoms, is the memory loss, is the attention deficit, it's the impairment in language, it's the inability to cope, 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. 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.

[Podcast Narrator/Host]

Do we know why?

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

Okay.

[Dr. Lisa Mosconi]

In a way that makes heading of osteoporosis like. Yeah, yeah. Heart disease.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Right. Does it make sense?

[Podcast Narrator/Host]

You in your book, the Menopause Brain.

[Dr. Mary Claire Haver]

Okay.

[Dr. Lisa Mosconi]

Yes.

[Podcast Narrator/Host]

Write. Menopause is one of the best kept secrets in society.

[Dr. Lisa Mosconi]

It was until you came along.

[Podcast Narrator/Host]

I was like, do we still say that? Is that still. Still a thing? What made you write that?

[Dr. Lisa Mosconi]

At that time, you know, this was really interesting. I was starting menopause together with Dr. Robbie Brinto. Roberta 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.

[Podcast Narrator/Host]

Yeah.

[Dr. Lisa Mosconi]

I started working with Robbie, who is a pioneer in the field of menopause and the Alzheimer's connection, because that wasn't a thing. Oh, my God. No.

[Podcast Narrator/Host]

You guys got laughed at.

[Dr. Lisa Mosconi]

Oh, yes. Yeah. That's a nice way to put it. 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 then 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. So the 23 chromosomes and the X and Y. But we also have a mitochondrial DNA that is completely separate from our chromosomal DNA. And what's specific about mitochondrial DNA is that, number one, it impacts energy production. Mitochondria are at the powerhouse of the cell, factories of the cells. Yes, the powerhouses 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 effect. Risk does not mean that Anyone is getting sick. Right. It just means that relative to another person, your risk is a little bit higher.

[Podcast Narrator/Host]

Okay.

[Dr. Lisa Mosconi]

But that was my PhD, my doctorate thesis, 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, even though we are. We are now two thirds more likely.

[Podcast Narrator/Host]

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.

[Dr. Lisa Mosconi]

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.

[Podcast Narrator/Host]

I. We hit this while still in cardiovascular

[Dr. Lisa Mosconi]

disease, and, yeah, you know, doesn't matter. Yes.

[Dr. Mary Claire Haver]

Musculoskeletal disease.

[Podcast Narrator/Host]

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, I know.

[Dr. Lisa Mosconi]

And so that was my PhD is the reason I moved to New York, because I moved. So I transferred to NYU Medical, and I started working with Dr. Moni D. 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 30s and 40s when everybody else in the field was still working with patients with. With Alzheimer's in their 70s, 80s, and 90s. 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. 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 when we do brain scans. But then it keeps progressing over time, usually for decades, until the plaques and tangles reach a certain threshold and 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 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 45, a 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.

[Podcast Narrator/Host]

And the thing is menopause. So it wasn't until the 90s that we discovered that estrogen impacts the brain.

[Dr. Lisa Mosconi]

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 1992 and it was only replicated in 1994. 1996. When do we get to the moon?

[Podcast Narrator/Host]

Yeah, right, right.

[Dr. Lisa Mosconi]

Men landed on the moon like 30 years, 20 years before we were all made aware of the fact that reproductive hormones as sex hormones in quotes are actually brain hormones too. So in other words, we know more about space than we do about the female brain. The Women's Health Initiative, when did they start writing it?

[Podcast Narrator/Host]

They started the grant in 91. They started?

[Dr. Lisa Mosconi]

Yeah, yeah. They started WR before we even knew how estrogen worked in the brain. And then we just say they did it wrong, like thinking they did something incredible. Incredible. When no one was talking about prevention, they just went for it. So I think that is very commendable. Then the way that the results were disseminated. Right.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

It was incredible.

[Podcast Narrator/Host]

Still use the data today for, for prevention, sadly. You know, so you've said and you've

[Dr. Mary Claire Haver]

walked me through the story.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

and you're like, what?

[Podcast Narrator/Host]

We didn't scan, we didn't see.

[Dr. Lisa Mosconi]

Yes.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Yes.

[Dr. Mary Claire Haver]

Right.

[Podcast Narrator/Host]

And so you go and decide, I want to study estrogen in the brain. But there is a problem.

[Dr. Lisa Mosconi]

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.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

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 on menopause. Right. And so we went back and 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. If you look at brain scans of midlife women and midlife men, the women, and this is very, very important. We work with women who have either a family history of Alzheimer's or an APOE 4. So they're high risk allele, so 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, and we could not quite really explain the difference. And then we looked at menopause and we worked with ob GYN department, of course. So 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 premenopausal, regular menstrual cycle, perimenopausal, irregular menstrual cycle, postmenopausal, nomenstrual cycle for 12 months or longer. And then we match them with men of the same age because postmenopausal women are a little bit older. Premenopausal women and men, no differences. Peri, menopausal women and men of the same age. 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.

[Podcast Narrator/Host]

Wow.

[Dr. Lisa Mosconi]

Yes. That was back in 2017 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 premenopausal, perimenopausal, postmenopausal, and we could show how the Alzheimer's plaques are nowhere to be seen in pre menopause. You can start seeing them in my studies, always in the frontal cortex in perimenopause. 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 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 sent to the rabi, has shown 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 where the premenopausal brain is nice and bright, the perimenopausal brain gets a little bit darker, and the postmenopausal brain is much darker in the same brain regions that are typically hypometabolic or impacted in clinical Alzheimer's patients. And quantitatively, that is a 30% difference. Now, that was cross sectional pushback immediately. But that, you know, this is just.

[Podcast Narrator/Host]

We're talking about glucose uptake.

[Dr. Lisa Mosconi]

Yes, it's glucose uptake in those two ways metabolized. So it's glycolysis.

[Podcast Narrator/Host]

Okay.

[Dr. Lisa Mosconi]

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.

[Podcast Narrator/Host]

So for our listeners, we're talking about the Krebs cycle. If everyone remembers from biology in high school, and you basically start with glucose and we break it down through several steps until we get energy or ATP at the end. So what she's saying is, I'm trying to take it down for the lay people.

[Dr. Lisa Mosconi]

The ATP is.

[Podcast Narrator/Host]

We are disrupting that pathway.

[Dr. Lisa Mosconi]

Yeah.

[Dr. Mary Claire Haver]

This episode of Unpaused is brought to you by Alloy Health.

[Podcast Narrator/Host]

We talk a lot about hormones affecting

[Dr. Mary Claire Haver]

mood and energy, but they also play a major role in your skin. Collagen, hydration, elasticity. And in midlife, when hormone levels start to shift, your skin changes too. I first heard about aloe through a close friend who is a dermatologist. She shared how few products truly address hormonal skin changes. Once I understood that aloe's approach is rooted in hormone science and physiology, I decided to try it myself. It changed the way I think about how skin care is at this stage of life. Alloy's M4 line includes the M4 face cream, M4 face serum and M4 eye cream. These are prescription strength formulas made with Estriol, the gold standard hormone your body stops producing naturally, and they are backed by clinical research. Women are seeking smoother looking skin, improved firmness and a brighter, more even tone. If your skin is changing, your skin care should change too. With Alloy, you consult with a doctor and receive expert guidance and have your treatment delivered right to your door. Head to myalloy.com and use code MCH20. That's MCH20 to get $20 off your first order. Perimenopause is not early menopause. It is its own distinct biological phase and it has been largely ignored. My new book, the New Perimenopause, is about the seven to 10 years before your periods stop a transition that is anything but gentle. Hormones fluctuate wildly, and for many women, this is when the anxiety, brain fog, sleep disruption, weight changes, mood shifts, joint pain, and that unsettling feeling of I don't feel like myself anymore begin long before anyone says the word menopause. Perimenopause often starts quietly. It shows up in the brain first, then the body, then everywhere else. And too often, women are told nothing is wrong. I wrote the new perimenopause because you deserve answers before things spiral, you deserve care before burnout, and you deserve a clear roadmap for a transition that Medicine has ignored for far too long. The new perimenopause is now available for pre order everywhere. Books are sold. Learn more and pre order your [e-mail] Many of you know I've spent my career pushing for better medical standards for women. MIDI Health is on that same mission, delivering the kind of care women have always deserved. For too long, women have been told to just deal with perimenopause and menopause symptoms. Your labs are normal. This is just a part of aging. Eat less, work out more. That approach failed us. And it's exactly why both my work and Mitti's exist. Midlife and menopause aren't the beginning of the end. They're a critical window of opportunity. But education is only half the battle. Women need access to clinicians who actually understand the science of female aging. That's the gap MITI was built to close. Mitti is focused on health span, not just lifespan. That means looking at your metabolic health, bone density, cardiovascular risk and cognitive function. It's the kind of proactive, evidence based care I've always believed women deserve. And it's exactly what MITI delivers. And here's what matters most. Women in all 50 states can access this care covered by insurance with clinicians trained in the latest menopause and longevity science. Because your zip code should never determine your access to quality menopause care, book your virtual visit today@join midi.com that's join midi.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Oh God, yes I did.

[Podcast Narrator/Host]

She talked about in her studies that we see. And 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 in menopause because glucose metabolism is impaired. 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?

[Dr. Lisa Mosconi]

Yes. One of the many functions of estrogen is that when it binds to estrogen receptors, that activates the glycolithic 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. 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 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 a exceptionally intelligent organ, of course, doesn't just sit there and decides 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 and birds. It switches to amino acids. It's an easy switch chemically, but. 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, then, like you said, insulates. Insulates, yes. 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 trigger the brain eats itself, which is called catabolism, anabolism. When you're building tissue catabolism, you're breaking it down. It does sound unpleasant.

[Podcast Narrator/Host]

Yeah, it was kind of scary. The brain eats itself, but I know

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

Yes, it's remodeling.

[Dr. Lisa Mosconi]

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 progress to white matter degradation and then neuronal loss. But this is in rodents. We need to consider, then. Female rats tend to die quite soon after the end of the reproductive life. So reproductive senescence for animals is a little bit like the end of the line. Right. So their lifespan matches their reproductive span.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Exactly.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Yes. So women live at least another 20.

[Podcast Narrator/Host]

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 sort of.

[Dr. Lisa Mosconi]

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. 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 on women, but we can apply those findings to see if similar mechanisms or patterns are present in women. 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 also have published and we're doing longitudinal studies where we're following women over time. And we do see that the 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.

[Podcast Narrator/Host]

Not others.

[Dr. Mary Claire Haver]

Yeah.

[Dr. Lisa Mosconi]

But we also find evidence of compensation.

[Podcast Narrator/Host]

Okay.

[Dr. Lisa Mosconi]

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 are 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 and how that could reflect an inflection point for Alzheimer's risk for some women. Menopause does not cause Alzheimer's. What we are understanding more and more is that it kind of unmasks a vulnerability or multiple vulnerabilities Right. It's when some women develop anxiety or depression is when some women have more severe symptoms of multiple sclerosis. That's when the risk for stroke increases. There's like a cellular aging accelerator, I guess, if you have an underlying vulnerability, that becomes more evident. Right. And it's important to study that because then we can offset that the risk, which is really hard to do. Right.

[Podcast Narrator/Host]

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 when you start having symptoms. So women are twice as likely as men to be diagnosed with an anxiety disorder or depression. 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 and then we double that.

[Dr. Lisa Mosconi]

Yeah.

[Podcast Narrator/Host]

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 and to treat vasomotor symptoms. But we do see a doubling. So we go from 10 to 20% after age 40, and then we go to 25% at age 65. 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, including multiple sclerosis. Four times more likely to suffer from migraines or headaches.

[Dr. Lisa Mosconi]

Yes.

[Podcast Narrator/Host]

And then more likely to actually be

[Dr. Mary Claire Haver]

killed by a stroke after menopause.

[Podcast Narrator/Host]

And that's a ratio that's 2 to

[Dr. Mary Claire Haver]

1 or even higher.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Me neither.

[Podcast Narrator/Host]

So this is all kind of new information.

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

I pulled these stats from your book.

[Dr. Lisa Mosconi]

Yes. I figured this is a research that we had to do kind of from scratch by pulling information 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. Yeah. And that 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 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 and brain health and that there are many things that we can do.

[Dr. Mary Claire Haver]

Sometimes you don't need a whole new outfit. You just need the right finishing touch. And for me, that's Jenny Bird. You know that moment when you look in the mirror and you think, okay, this works. But then you add one piece of jewelry and suddenly it's like, yes, there it is. That's the Jenny Bird effect. It honestly feels like all my Jenny Bird pieces work together. So getting dressed is effortless. I can mix and match without thinking about it and, and still feel completely put together. The pieces are lightweight and easy to wear. Perfect for looking polished without spending forever accessorizing. Everything is designed to pull together instantly in a way that feels elevated but not overdone. And honestly, every time I wear it, someone asks where it's from. Every single time. From their iconic hoops to their bracelets and bangles, there's truly something for every style. And they just launched a new fine jewelry collection that feels modern, elevated, and really special. If you've been thinking about elevating your everyday look, this is your sign. You can get 20% off your first order with Jenny Bird by visiting jenny-bird.com and using the code unpaused at checkout. If you're a woman navigating menopause, you know sleep can suddenly feel complicated. Over half of postmenopausal women report significant sleep disruption. And hot flashes are one of the leading causes. In fact, more than half experience sleep disorders during this stage of life. And it's not just about falling asleep. It's about staying asleep when night sweats, temperature swings and neck or back discomfort keep interrupting those deeper sleep cycles. That's where cooperation sleep goods come in. Their Cool plus pillow is made to help dissipate excess heat during hot flashes. With cooling gel infused memory foam, 50% more breathability, and a cool to the touch cover that feels crisp and refreshing. Plus, the adjustable fill lets you customize the loft and firmness to support proper spine alignment. Whether you're a side, back, stomach or combination sleeper, let Coop help you show up feeling rejuvenated and ready to go. Get 20% off your first order and try Coop risk free with 100 Night Sleep Better Guarantee at coopsleepgoods.com unpaused that's coopsleepgoods.com Unpaused Eczema is unpredictable, but you

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[Podcast Narrator/Host]

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 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.

[Dr. Lisa Mosconi]

Yes.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Yeah.

[Podcast Narrator/Host]

And we're not. And the, the Common theme in this. We're not. Seems to be perimenopause. There's an inflection point. I love the way you describe it.

[Dr. Mary Claire Haver]

So walk our listener through, in general,

[Podcast Narrator/Host]

what is happening to our brains before menopause, you know, perimenopause and then postmenopause

[Dr. Lisa Mosconi]

from a brain perspective, it's a really good question. And I think we need to do more research to really be conclusive and talk about old 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. That's shocking to me. It's not that shocking. You know, menopause is now on people's minds, but it was not until recently. Well, 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 is a hormonal organ that responds to the action of sex hormones from the ovaries, which are predominantly estradiol and progesterone. And. And at the same time, the brain uses hormones to communicate back with the ovaries. And these hormones are called gonadotropine. So they're usually 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 confused. The reason being. So actually, this is a very important thing that I was hoping we would talk about that. When I talk about estrogen being neuroprotective, I'm really talking about estrogen, the endogenous hormone, estradiol, coming from the ovarium, the endogenous hormone that the ovaries make because of this feedback loop. I'm not talking about estrogen therapy, but a lot of people make the assumption they're the same. Yes. Especially now that people use this term of bioidentical hormones, it's even more confusing because you're thinking, well, if the estrogen I make is neuroprotective and I can take the same estrogen from a patch or a pill, then that estrogen also needs to be neuroprotected. It's assumed to be neuroprotected. Not so easy. We would wish. Right. That would be 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 acid diffusion and also potentially transport mediated channels that are being investigated now. And then it goes in the cell and looks for estrogen receptors. Estrogen will bind to an estrogen receptor. It's like a key that needs to open a lock. Actually, it's like a key that needs to get jammed inside the 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 ere, estrogen receptor element that is in the promoter part of the DNA. So it directly triggers 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.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

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 a certain thing. So what can estrogen with the receptor do? Well, for instance, can make more bdnf, brain derived neurotrophic factors.

[Podcast Narrator/Host]

And that is a very good thing.

[Dr. Lisa Mosconi]

That's wonderful. It's a protein that really supports synaptic plasticity and growth. It keeps your neurons healthy, which is why we say that estrogen is neuroprotective. By activating these pathways, you, 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 turning TNF alpha, stop making Interleukin 6. Right. So it turns off the pro inflammatory, the inflammatory response. So that's why estrogen is. Estrogen is so important for brain health. And we are now able to measure that using brain scans, which again is the first time ever.

[Podcast Narrator/Host]

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 upregulate the estrogen receptor.

[Dr. Lisa Mosconi]

You have to look at it. Yes, yes.

[Dr. Mary Claire Haver]

Okay.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

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. But that needs to be proven. Right. So 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. I was like, so you had no

[Podcast Narrator/Host]

way to study estrogen in the brain because there was no tracer available.

[Dr. Lisa Mosconi]

There was no tracer.

[Podcast Narrator/Host]

So tracer is something they use in radiology.

[Dr. Mary Claire Haver]

Explain what a tracer is.

[Dr. Lisa Mosconi]

A tracer. In our case, we do positron emission tomography, or PET imaging, which is that kind of technique when you look at the brain and some parts are red, blue, green. So that's positive an emission, just like here. 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. It's a very, very low dose radioactivity. But what is so special 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. 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.

[Podcast Narrator/Host]

You light up on the sky.

[Dr. Lisa Mosconi]

You light up. Yes. It's like a GPS or it.

[Podcast Narrator/Host]

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.

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

But there was nothing available for esthetic.

[Dr. Lisa Mosconi]

There was nothing. No, sadly, 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 whatever traces, the brain protects itself.

[Podcast Narrator/Host]

There's a blood brain barrier, and it's very protective.

[Dr. Lisa Mosconi]

Yes. 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.

[Podcast Narrator/Host]

So walk everybody through the images.

[Dr. Lisa Mosconi]

Yes. So these are three brain scans of three different women. One is premenopausal, one is perimenopausal in the middle, and the last one is postmenopausal, early postmenopausal 52. 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 hotspots. In a way, what we were looking for, based on animal studies, was a reduction in estrogen receptors. Because, like we were saying before, the brains of female rodents are not well suited to outlive menopause. And so what happens that soon after the end of the reproductive span, the brain stops making estrogen receptors and you can see the downregulation. It really just. They, they, they disappear.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

The opposite. So, and I drove my students insane. It was like, you've done it wrong. They're like, no, I haven't. It's like, go back. I just could not believe it. And we just kept enrolling participants because it was like, maybe it's just a fluke. 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 perimenopausal 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. Is that part of the brain that is actually talking to the ovaries and sending down the fsh and LH saying, I need more Estrogen. 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 65. And people thought I was crazy when I said we're going to go all the way to 65 because I wanted to map the curve, right? And they thought, it's too late. It's too late to just do 15 years.

[Podcast Narrator/Host]

The brain is trying.

[Dr. Lisa Mosconi]

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 the hor. 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 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.

[Podcast Narrator/Host]

That is amazing. And then after age 65 ish, we see this signal attenuate.

[Dr. Lisa Mosconi]

We haven't yet. We're doing it now. Look, as of now, I think until 65 team doing this.

[Podcast Narrator/Host]

Amazing.

[Dr. Lisa Mosconi]

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 development to new brain tracers for estrogen. But 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, this was stunning when, when we found it and, you know, the response that we got and people just don't.

[Podcast Narrator/Host]

Couldn't believe it.

[Dr. Lisa Mosconi]

Did not believe it.

[Dr. Mary Claire Haver]

Repeat the study.

[Podcast Narrator/Host]

Yeah.

[Dr. Lisa Mosconi]

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

[Dr. Mary Claire Haver]

Now it's time for the medi 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 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 2 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. And arguably most importantly, I protect my sleep and manage my stress daily. 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

[Podcast Narrator/Host]

what your body and brain need.

[Dr. Mary Claire Haver]

Right now, that's exactly what MIDI is built for. Go to join midi.com J-O-I-N-M-I d I.com and connect with one of their clinicians today.

[Podcast Narrator/Host]

So what are you most excited about right now?

[Dr. Lisa Mosconi]

I am super excited that I started working with Dr. Regina Dugan, who is 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 Wellcome Leap, which is an independent subsidiary of the Wellcome Trust, which is based in London, one of the world's largest philanthropic organization. So welcome. Leap takes after darpa, which means that they sponsor high risk, high reward, three years research programs.

[Podcast Narrator/Host]

And this is not nih.

[Dr. Mary Claire Haver]

This is.

[Dr. Lisa Mosconi]

This is not nih. It's independent of nih. Fully independent.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

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,

[Dr. Mary Claire Haver]

which I was like, oh, my God, is it Christmas?

[Dr. Lisa Mosconi]

It's got to be Christmas. And what I really love about this is that 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 relaxed.

[Podcast Narrator/Host]

Silo. Because you're fighting for the same research process.

[Dr. Lisa Mosconi]

We're fighting for the same. Yeah. So the same part of money is 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 17 sites with over 70 leading scientists from all over the world.

[Podcast Narrator/Host]

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

[Dr. Lisa Mosconi]

Well, the question is, can we realistically half the risk of Alzheimer's disease for women by the year 2050 in the next 25 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 the next three years potentially for, then we can expect to reduce the risk of Alzheimer's disease for an estimated 330 million women all over the world and given current conversion rates to Alzheimer's, hopefully prevent 55 million 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 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 that can be.

[Podcast Narrator/Host]

We have them for breast cancer, we have them for cardiovascular.

[Dr. Lisa Mosconi]

Exactly.

[Podcast Narrator/Host]

We have a VAR osteoporosis.

[Dr. Lisa Mosconi]

Exactly.

[Podcast Narrator/Host]

Yeah.

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

I mentioned and CARE stands for.

[Dr. Lisa Mosconi]

CARE stands for cutting Alzheimer's risk through endocrinology. Wow. So when I made this slide, we had 67 leading scientists. We now have 70 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 100 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.

[Podcast Narrator/Host]

Amazing.

[Dr. Lisa Mosconi]

Congratulations. Thank you. I am so happy.

[Podcast Narrator/Host]

I think your new position is less

[Dr. Lisa Mosconi]

stressful than surprisingly enough, it is.

[Dr. Mary Claire Haver]

You're doing the work you're born to

[Podcast Narrator/Host]

do now, you know, like without the.

[Dr. Mary Claire Haver]

This episode was sponsored by MIDI Health, the first virtual clinic created for women by women for the treatment of menopause. Don't let anyone tell you menopause is something you have to suffer through alone. MIDI can help. Visit joinmidi.com to learn more.

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[Dr. Lisa Mosconi]

How quick?

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[Podcast Narrator/Host]

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.

[Dr. Lisa Mosconi]

Yes, you know, oh, this is.

[Podcast Narrator/Host]

Build your program, here's the money. Let us know how it works out,

[Dr. Lisa Mosconi]

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

[Podcast Narrator/Host]

Well, congratulations.

[Dr. Lisa Mosconi]

Thank you.

[Podcast Narrator/Host]

And I'm so glad you came. So glad to see that all the paper's coming, so it's going to be amazing. As a reminder to our audience, you can follow Dr. Moscone on Instagram Rmosconi.

[Dr. Mary Claire Haver]

Her book the Menopause Brain is available

[Podcast Narrator/Host]

now through her [e-mail] youm can find full episodes of Unpaused on YouTube at Dr. Maryclaire. I'd love to hear from you about this topic and anything else that's on your mind. You can follow me on Instagram rmaryclaire and get honest and accurate information on health, fitness and navigating [e-mail] 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.

[Dr. Mary Claire Haver]

So if this podcast has helped you feel seen, understood, or supported, hit follow

[Podcast Narrator/Host]

right now so you never miss an episode.

[Dr. Mary Claire Haver]

Thank you for being here with me. Let's keep going.

[Podcast Narrator/Host]

Unpaused Unpaused is presented by Odysee in conjunction with pod people.

[Dr. Mary Claire Haver]

I'm your host, Dr. Mary Claire Haver. The views and opinions expressed on Unpaused are those of the talent and guests

[Podcast Narrator/Host]

alone and are provided for informational and entertainment purposes only.

[Dr. Mary Claire Haver]

No part of this podcast or any related materials are intended to be a

[Podcast Narrator/Host]

substitute for professional medical advice, diagnosis, or treatment.