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

long time, the notion was that women live longer than men and Alzheimer's is a disease

“of all age. Therefore, at the end of the day, more women than men and 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. The views and opinions expressed on on-post 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 Unpost, Dr. Lisa Musconi helped us

name something women have felt for decades but were rarely believed.

“Menopause doesn't just change your body. It changes your brain.”

And Dr. Musconi 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. In this episode, we go deeper into the why. Dr. Musconi, 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. Musconi 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 unpause. 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. , Dr. Musconi, a board certified obstetrics and gynecologist,

a board certified obstetrics and gynecologist, a board certified obstetrics and gynecology, a board certified obstetrics, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

“a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,”

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

“a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,”

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology,

a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, a board certified obstetrics and gynecology, because now we understand that even though you may have these lesions in your brain, some people, for whatever reason, do not develop inflammation, 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, 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 be harmful to your brain. Okay, in a way that immediately makes kind of osteoporosis, like, yeah, yeah, you know, like heart disease, so not everyone's going to have a heart attack who has athletic plaques, right? Does it make sense? You in your book, the menopause brain. Okay. Yes. Right, menopause is one of the best kept secrets in society. It was, and did you say my dog? I was like, do we still say that, I mean, is that still a thing?

I, and what made you write that at that time? You know, this was really interesting. I, I, I was starting menopause together with Dr. Robbie Grintor, Robert, that he has, 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. Yeah. 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. You guys got laughed at. Oh, yes. Yes. Yes. Yes. Yes. Yes. So I've always

looked as sexy differences in Alzheimer's. Since my PhD, there was the first thing I've ever done,

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 a chromosome, so the 23 chromosomes and the X and Y. But we also have a mitochondrial DNA that is completely separate from our chromosome of the N.A. 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% maternity 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. If you have both parents affected, your risk is higher than having John's one parent. In fact, risk does not mean that anyone is getting sick, right? It just means the relative to another person, your risk is a little bit higher. Okay. But that was my PhD. My doctorate. This is which is now being 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 to talk and she said, "You know, I love your work about maternity inheritance and the risk of Alzheimer's for women, which really nobody talks about." Even though we are now two thirds more likely. Why is

“this important? Because a lot of our listeners may not understand that you're much more likely to”

get Alzheimer's if you're a woman. 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 all 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 we haven't lived longer than men. We get this while still in cardiovascular disease. Yes. And yeah, you know, that's a matter. Yes, my skill is a little 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. I don't know. And so there was my PhDs. The reason I moved to New York because I moved, so I transferred to NYU medical. And I started working with Dr. Moni De Leon, who's 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 Alzheimer's in their 70s, 80s and 90s,

whereas there 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 all-day. It is a disease of midlife. We symptoms that start in all-day. So the idea is this connection 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, again, 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 we're not. So that completely changed the question and the conversation

finally right for us because if Alzheimer's disease is not, it is is of all-dayage. But it's a

disease of midlife. In 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 in age 45. The woman has twice the risk of Alzheimer's, as respect relative to a minor at 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

impacts the brain. Yes, and that is ridiculous. The first study is showing that estrogen is not just

“the reproductive factor, but is also brain hormone was published in 1992. And it was only replicated”

in 1996. When do we get to the moon? Yeah. Right. Man landed on the moon like through the years, 20 years before we were all made aware of the fact that reproductive hormones are sex hormones, even quotes, and actually brain hormones too. So in other words, we know more about space. Then we do about the other brain. The women's health initiative, when did this start right in it? They started the grant in 91. They started, yeah,

they started writing the brain. We even knew how estrogen worked in the brain. And then we just

say they did it wrong. They did something incredible. Incredible. When no one was talking about

prevention, it was just one for it. So I think that is very commendable. Then the way that the results were semi-right. We can't demonize the study because it was groundbreaking. It was incredible. It was still used the data today for preventive. Exactly. So you 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 meant to PhD, you're on fire, you're ready to study this. And you're like, what we didn't scan, we didn't see. Yes. You know, like if we don't look for it, it's not there. Yes. Right. And so you go and decide, I want to study estrogen and the brain, but there was a problem. 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 centered in impacts all the women. I would find that a lot is universe. So all women go wheeling if you long enough, you'll go from menopause and we all know as women. That menopause is not nothing. Right. There are neurological symptoms. But evidently, the idea that someone the symptoms that can occur during menopause and neurological in nature was not a well known or common understanding. I still get pushed back in 2026. No, no, no,

this is just aging. Yes, come on. It's hot flashes. I'm like the neurotransmitter. Yeah. Like the vasimotor symptoms are in the brain. Yes. They come from the brain. They're neurological in origin. And that was the first problem. The second problem. So and then 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 at, 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, increase in me. If you look at brain scans of midlife women in 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 apoeophore to their eyebrows. So they're,

their 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 the

“about sex that is driving these, right? Which factors? And what other parameters could be involved?”

And we were looking, I promise, everything. We were looking in a family history, of course, apoeophore, general taboo, we're 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 a big-eyed 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 lovely.

And we classified, they classified the women as premenopause, regular menstrual cycle, peremenopause, irregular menstrual cycle, postmenopause, no menstrual cycle for 12 months or longer. And then we matched them with menopause, because postmenopause women are a little bit older.

you can see the red flags popping, mild, but you do see an increase, postmenopause stage, men of the same age, really significant difference. Wow. Yes, there was back in 2017. And we published it and no one has seen those brain scans before. And that was menopause stage. So we had a group of women who were premenopause, a peremenopause, a postmenopause, a week ago, how the Alzheimer's plaques are nowhere to be seen in premenopause,

you can start seeing them in my studies, always in the frontal cortex, in peremenopause,

and then they're a little bit everywhere after menopause. It was still very mild. 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 was sent to the Robby, has shown time and time again in rodents, in animal models of menopause and Alzheimer's combined. And what we have shown in these are men scans that are all over the internet at this point, you can see the difference in those first images where the premenopause brain is nice and bright. The peremenopause of brain gets a little bit darker. And the postmenopause

of brain is much darker in the same brain regions that are typically hypomethabolical 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, we're talking about glucose

“uptake. Yes, it's glucose uptake in those two ways metabolized, it's glycolysis. Okay. Yes. But we've also”

done spatroscopy studies to look at ATP production where ATP is the cellular energy. And we do show the same kind of imbalance. So glycolysis is a very top of the glucose metabolism chain. ATP is the very end. And so we know that the entire metabolic pathway is disrupted. So for our listeners, we're talking about the crepes cycle. If everyone remembers from biology and high school.

Yeah. And you basically start with glucose. And we break it down through several steps until we get

energy or ATP. Yes. At the end. So what she's saying is, I'm trying to take it down for the late people. It is not there. It is. We are disrupting that pathway. Yes. This episode of Unposed is brought to you by Alloy Health. We talk a lot about hormones affecting mood and energy. But they also play a major role in your skin. Collagen, hydration, elasticity. And in midlife, when hormone level start to shift, your skin changes to. I first heard about Alloy

through a close friend who is a dermatologist. She shared how few products truly address hormone level skin changes. Once I understood that Alloy's approach is rooted in hormone

“science and physiology. I decided to try it myself. It changed the way I think about how skincare”

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 Estriel. The gold standard hormone, your body stops producing naturally. And they're backed by clinical research. Women are seeking smoother looking skin, improved firmness, and a brighter, more even tone. If you're skin is changing, your skin care should change too. With Alloy, you counsel with a doctor and receive

expert guidance and have your treatment delivered right to your door. Head to m-y-a-l-l-o-y.com

and use code m-c-h-20. That's m-c-h-20 to get $20 off your first order.

Perry menopause is not early menopause. It is its own distinct biological phase. And it has been largely ignored. My new book, The New Perry Menopause, is about the 7 to 10 years before your period stops. A transition that is anything but gentle. Hormones fluctuate wildly. And for many women, this is when the anxiety, rainfall, 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." Perry menopause 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 Perry Menopause because you deserve answers before things spiral.

has ignored for far too long. The new Perry Menopause is now available for pre-order everywhere

“books are sold. Learn more and pre-order your copy at thepauselife.com.”

Many of you know I've spent my career pushing for better medical standards for women.

Many 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 Perry Menopause 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 midi'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 midi was built to close. Midi 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 midi 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 at joinmittie.com. That's joinmidi.com. Now, we need to talk about something that went viral. When Robbie testified at the FDA? Oh, God, yes, it is. 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 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 that lines our neurons. And that got twisted into the brain eats itself somehow, which would viral, of course, social media. Can you kind of explain what

that is? 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. 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 use this 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 exceptionally intelligent, organ, of course, doesn't just see it there and decides they were all going to develop the answer. It's switch is track. 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 is switches to amino acids. Okay. It's an easy switch, right, 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. I need 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. She's one of the people. So diet there. 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 fact, good fat. Then, like you said, insulin later on. Yeah. So actually, when you look at MRI scans, you'll need 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?

of this white matter as a source of energy. In rodents, various specific Alzheimer's models that

long-term turns into the word that triggered the brain itself, which is called catabolism. Anabolism, when you're building tissue, catabolism, you're breaking it down. It that sound unpleasant. Yeah. It was kind of scary. Yeah, it was kind of scary. I understand. The brain eats itself. Yeah, I know. I know. It is not a new disorder. It is not a new reaction. It is not phagosytosis. It's an adaptive response. Yes. It's re-modeling. 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 to grass, totally. When measured the gradation and they're not lost. But this is in rodents. We need to consider that 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 under the line. Right. So their life span matches the reproductive span.

Right. Most mammals don't have a protracted menopause like humans. Exactly. They're a few, but yes. We're really the. Yeah. So women leave at least another 20. So then there's not a great menopause model of it taking out ovaries. We don't have a period in that model. You know, you don't, you know, if there are some female rats that leave quite long, some specific strands. And then Robby uses them to look at the natural menopause transition. But still, still. It does

“not really replicate brain aging in humans. And that's why translation of research is so important.”

That's why Robby reached out to me and working together ever since because she can probe the

mechanisms doing experiments, which we will never be able to do on humans. Women. But we can apply

those findings to see the similar mechanisms or patterns are present in women. Okay. Very often to do of it. Sometimes they do not. They 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. Yes, part of the menopause. So definitely there are changes. 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 the metabolic changes are progressive in some brain regions, not all brain regions. We do find that the brain mother is reduced in some regions and not others. But we also find evidence of compensation. Okay. 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 artwork has perhaps not been fully understood. And the notion is that if you

have these things then you have a disease or a pathology. But as we're always saying, 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. 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 unmasks a vulnerability or multiple vulnerable. Right. It's when some women develop

anxiety or depression is when some women have more severe symptoms of multiple sclerosis that's when to risk for stroke increases. Does that say 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 all set that the risk. Right. We have to do it. Yeah. Can intervene earlier. See who's

“at risk. That's what I hope. 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. The 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

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. Now part”

of that is because a lot of practitioners are not comfortable prescribing hormone therapy and we'll default to giving a patient an SSRI to treat a hot flash and to treat phismotor 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, and multiple sclerosis, for times more likely

to suffer from migraines or headaches. 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. No one taught me this. You know, when I was in training in medical school. No, I mean either. So this is all kind of new information. Yeah, I looked it up when I was riding the XXX brain. And I was like, I pulled these stats from your book. Yes. This is not 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 you've reached maybe 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 we have a lot of power 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 read. They don't quite, it doesn't quite

belong to you. You're 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 pay attention to mental health. Yes. And brain health. And there are many things that we can do. 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 say,

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 a match without thinking about it 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 and 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

JennyDashBird.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 experienced 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 are

back discomfort keep interrupting those deeper sleep cycles. That's where coop 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 a hundred night sleep better guarantee at coop sleep goods.com forward slash unpaused. That COOP sleep goods.com slash unpaused. 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

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. And we've got it, 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. And we're not. And the common theme in this we're not seems to be pairing menopause. There's an inflection point. I love the way you describe it. So walk our listener through in general, what is happening to our brains before menopause, you know, pairing menopause and then

“post menopause 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 menopause is now on people's minds, but it was not until recently. What happens is this, the 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 and neuroendocrine systems is a hormonal organ that responds to the action of sex hormones from the ovaries,

which are predominantly ester diol and progesterine. 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”

the ifestation that lage that we focused on most. So as long as estrogen and progesterine are flowing

up and a facetion that lage 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. Then when I talk about estrogen, being neuroprotective, I'm really talking about estrogen, 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 of 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 the estrogen I make is neuroprotective and I can take the same estrogen from a patch or uphill, 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? The way that estrogen works, let's just look at the brain, is that estrogen is able to cross the blood-dream barrier because of the fusion and also potentially transport mediated channels that are being investigated now and then it goes in the cell and looks for estrogen receptors. Ebi 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 a lock and together they go inside the nucleus of the cell. The 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

and don't do anything. They have to bind to some. Yes, they need to bind to the receptor and the bind they need to be functional, they need 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 or certain things. 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

fact and that is a very good thing. That's wonderful. It's a protein that really supports

is not a protected by activating these pathways is supports brain protection. Things that we want to make less of, for instance, proinflammatory cytokines. We say that estrogen is anti-inflammatory, reduces oxidative stress because it goes through the DNA and say, stop taking TNF alpha, stop

“making into Luke 6. So it turns off the inflammatory response. So that's why 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. 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. Okay. Yes. Okay. 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 we'll be linked in the show notes as well. Great. So back to 2019, we had been studied menopause for a bit. And the assumption was that the differences that we were seeing between women at different menopause 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 the one-to-my-video chemistry department

and I said, I need a tracer to use with brain imaging to locate estrogen in the brain. 2019. Right.

And they said to me, "Well, we don't have it." I said, "Hmm." That doesn't sound so good to me. So you had no way to study estrogen in the brain because there was no tracer of it. There was no tracer. So tracer is something that you use in radiology. Explain what a tracer is. It's tracer. In our case, we do positronimission to ography or pet imaging, which is that kind of technique. You know, when you look at the brain

and some parts of red, blue, green, so that's positronimission. Just like everything. Yeah. And what we do is that in this case, we take estradio and we just attach

a flourine-18 molecule to the estradio. Flourine-18 is a radioactive isotope.

It's 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 injected in the bloodstream and it behaves exactly like estrogen. So it's lipid, soluble. So it gets dry through inside the brain and then it looks for the estrogen receptors. And it binds to the estrogen receptors. But we have this tini-tini-tini-lid-o-thing attached to it that emits gamma rays, which means,

it shoots out light. You light up. You light up. Yes. It's like a GPS. Or it's very similar to when we do thyroid studies. Lots of women have had a tracer that picks up thyroid hormone and they're looking for activity for a different autoimmune thyroid diseases. Yes. So you as if we're also doing things for breast cancer, we used it for heart.

“But there was nothing available for estrogen. So you're not thinking about that?”

No. So this tracer was available. This is called floro estradio. 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 tracer. The brain pertains itself. There's a brain barrier and it's very protective. Yes. Which is great. Right? For us as humans. Not so great if you're trying to see what's happening. But these tracer

actually crosses and it binds especially to that structure in red. Okay. So they block everybody through the images. Yes. So these are three brain scans or three different women. One is premenopauseum. One is peremenopauseum in the middle. And the last one is postmenopauseum early postmenopauseum 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 half spots in a way. What we were looking for based on animal studies was a reduction. In estrogen receptors. Because that we were saying before, the brains of female rodents are not well suited to outlive manopause. And so what happens that soon after the end of the reproductive span, the brain stops making estrogen receptors. And you can see

the downgradulation. It really just. And they they these appear. You expected this to happen in humans.

find the opposite? So and I drove my students inside. I was like, you're done it wrong.

“There's nowhere to happen. It was like, go back. I just cannot 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 setting. We're still seated. So premenopause. We're looking at women who are at the peak of ovulation. So we have a lot of astrodial endogenous astrodial in the brain. So all the estrogen receptors are taken. So you don't see any binding, basically, because everything is kind of blueish greenish. But then at the

pyramid of positive stage, when estrogen is actually this 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 FXH 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 period. But there are even more

after menopause up to age 65. People's always crazy when I said we're going to go all the way to

65, because I want to map the curve, right? And it's always too late. It's too late. It's just too 50 years. The brain is trying. 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 when 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 rate. It takes energy

to make the receptor. So it's good to kind of light it back and relax. But the whole, 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 that the FSH and LH levels are increasing. Right. So it's the brain telling the ovaries. Please. I want it.

I'll see you here. How does it look? Amazing. Yeah. And then after I get you to 65-ish, we see this

“signal at any way. We haven't yet. Oh, okay. As of now, I think we're doing this amazing. 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 the more and more people will start doing it at the same time. I'm directly sponsoring the development of new brain tracers for estrogen. Because 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 we're kind of the fact it has on these receptors. But this was, they was stunning when we found it. And you're not in response to it. Yeah, and people just don't, you don't believe it. Do not believe it. Repeat the study. Yeah. Don't waste money. So it's told. Do not waste money. Now it's time for the Medi-Pause. I'm Dr. Mary Claire Haver, hosted the podcast, Unpause,

bringing you a word from Medi-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 Medi-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 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, color for fruits and vegetables, and prioritize protein at least 30 grams per meal. And are youably, most importantly, I protect my sleep,

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 join MIDI.com,

“J-O-I-N-M-I-D-I.com, and connect with one of their clinicians today. So, what are you most excited about?”

Right now. 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, just magnificent. And she launched a welcome leap, which is an independent subsidiary of the Welcome 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. And this is not NIH. This is not an independent independent independent. It's independent and so this

is where you got the $50 million. Yes, so they asked me to serve as a 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 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 done all the work together to address a question that none of us can really secretly hope to answer alone. So, they really promote collaboration between scientists,

whereas usually we're very relaxed, because you're fighting for the same research. We're fighting for this same, yes, we're in the same power of money, it's just terrible. And in this case, instead, we now have, I'm trying to find this later on to show you, we now have 17 sites

“with over 70 leading scientists from all over the world. And what is the question you're trying to answer?”

Well, the question is, can we realistically have 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 sort of calculations and projections, but we have estimated that we were able to do all the work that I designed, all the work that I said we needed to do the next three years, potential 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 the 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. They're mainly neuroendocrine-based, but also everything else that impacts the

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 in biological markers, and then we're going to test whether hormonal therapy can offset the risk of

“Alzheimer's, but 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 calculator for women. Yeah, we have them for the answer. Yeah, we have them for cardiovascular . We have a porosity process. Exactly. Yeah. 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-to-care, for a women. I must show you this slide. We have now data through care, so we have all this

endocrinology. So when I made this slide, we had six to seven 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 in

“Alzheimer's risk ever attempted. Amazing. Congratulations. Thank you. I am so happy. I think”

your new position is less stressful than surprisingly enough. It is. 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 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. Yes, you know, this is a build your program. Here's the money that let us know how it works out. Yes. And really,

you know, without 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.”

Mm-hmm. You know, is it, oh, yeah, we do know what we're doing. Well, congratulations. Thank you. And I'm so glad you came. So glad you're waiting to lovely that all the papers coming. So it's

gonna be amazing. As a reminder to our audience, you can follow Dr. Masconey on Instagram at

Dr. underscore Masconey. For book, the menopause brain is available now through her website at LisaMasconey.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 the pauslife.com. My upcoming book, the new Perry menopause

“is available for pre-order on Amazon. If you're loving this podcast, I have an important request.”

Please take a moment to follow unpaused on your favorite podcast app. Following and listening is what pushes this information to more women who need it. So if this podcast has helped you feel seen,

understood or supported, hit follow right now so you never miss an episode. Thank you for being

here with me. Let's keep going. Unpaused. Unpaused is presented by Odyssey in conjunction with pod people. I'm your host, Dr. Mary Claire Haver. The views and opinions expressed on unpaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for Professional Medical Advice, Diagnosis, or Treatment.