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

What is brain fog? So let's clear it up. Like, what is brain fog? Like, and when should someone be worried?

Yeah, it's one of the reasons that actually scientific brain scientists started to look into

manopause as a risk factor for Alzheimer's disease. And still today, the vast majority of patients who

come to us at the Alzheimer's prevention clinic at Wal-Connate Medicine, New York Presbyterian,

which have run, come to us because of a brain fog in midlife that can be so severe to really

trigger concerns about early onset dementia. So it's really important to clarify what is brain fog

and what is Alzheimer's and how one thing could lead to concerns about the others because it's

really legitimate to be scared.

The views and opinions expressed on on pause 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.

When I first heard Dr. Lisa Moscone speak, she showed brain imaging that followed a woman

from premenopause into postmenopause. The changes were distinct and undeniable. We literally

rewire our brains through menopause. I remember sitting there floored because in my training and

practice, no one had ever shown me this before. To see a woman's brain transition captured on a

scan was both validating and life changing. It was proof of what so many of my patients had told

me over the years. I just don't feel like myself anymore. Dr. Moscone showed us that this isn't

just a feeling, it's biology and it needs to be taken seriously. And then I learned her personal

story. She grew up watching her grandmother and two great aunts all develop dementia while their

brother did not. That heartbreaking pattern became her life's work. She turned grief into purpose,

asking the question no one else was asking why are two thirds of all Alzheimer's patients women

and what role does menopause play in that risk? What struck me the most is that Dr. Moscone

has never shied away from those hard questions. She is pushed against the old dogma that ignored

women's brains and in doing so, she's opened up an entirely new conversation about women's health.

She's shown us that menopause is not just an ovarian story, it's a brain story. Dr. Lisa Moscone

PhD is a neuroscientist and associate professor of neuroscience in neurology and radiology at Will

Cornell Medicine, New York Presbyterian Hospital. She is the director of the Alzheimer's

Prevention Program, which includes NIH funded women's brain initiative, the award winning

Alzheimer's Prevention Clinic, and the newly launched Alzheimer's Prevention Clinical Trials Unit.

Most recently, she was named director of the $50 million program in women's health,

cutting Alzheimer's risk through endocrinology, a groundbreaking initiative placing hormones and

midlife at the center of dementia prevention. She's also the author of a number of best selling

books, including the menopause brain. What I admire most is that Dr. Moscone is not only advancing

science, she's changing the conversation. 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 Unpost,

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. Unpost is supported by Claude from Anthropic. Midlife comes with questions

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So welcome to Unpost. Thank you for having me. I'm so glad we got to do this.

So we have been friends for a long time. I want to say the first time I saw you

was on stage at my first well event in Santa Monica, and you stood up and started showing images

of the brain of women in pre-menopause and perimenopause and post-menopause, and the differences

in glucose uptake and what's happening. And I stood there in the audience. I was before or after

Avron Blooming and Carol had like this manaled the WHO. My mind was so blown that day.

And if you're talking about how women's brains change through menopause, and I'm like,

no one ever told me this. No one ever ever ever in all of my training talked to me about the

structural changes and the biological and you know that menopause was a neuroendocrine event.

And you opened that door for me, and so I'll forever be grateful in my understanding.

But let's back to you. So let's talk about our grandmothers.

You share a similar story to mine in that my grandmother who died in her early 90s, mid 90s,

spent the last. I didn't know what to call it back then. Of course I was in early college,

maybe starting med school, and she was bedridden at the end. And I know now that she had

dementia-likely Alzheimer's and was very, very frail and was probably the last two to three years

in a bed. She was very sweet, but then became very confused and would like call out and thought

people were in the room. She was having a lot of hallucinations at the end. It was just really

painful to watch. My mom now has been formally diagnosed with Alzheimer's. She's in her 80s.

She's in a facility specifically for memory care. And it's really one of the most painful things

I've ever had to do is watch her deteriorate. And sorry, it's not. It comes and goes. So we have

our good days and we have our days where I think oh she's doing better and then she'll say something

so outrageous, you know, or talk about my dad being in the room. He passed away seven years ago.

And I just realized I don't want this. And so I just kind of grew up thinking this is inevitable

for me, but it's not. No. And you are the one teaching me that. So you're the first person to even

say that this is not your inevitability. There are things that we can do. You're young enough to

like. Absolutely. Get ahead of that. So like tell me about your family. My family has also

been negatively impacted by Alzheimer's and dementia. And that for me also involved my grandmother

who, I mean, she was exceptional, extremely intelligent. You remember her without dementia?

Oh, yes. Oh, I grew up with my grandmother mostly. My parents are nuclear physicists.

They're professor on nuclear physics, both of them. And they're not like the stereotypical

nuclear physicists. They're more the open-heimer type person. No, that would be.

But they do work a lot when I was growing up. So your grandmother took on the care taking.

Yes, effectively, I was almost always with my grandmother. And I remember her just being my

grandmother. And then at some point when I was about to graduate from university and start my PhD,

she started showing signs of cognitive decline. That was shocking because she was always a sharp

as attack. But that led to at least a decade of dealing with progressive cognitive decline

Alzheimer's symptoms, dementia symptoms, acumencin hallucinations, which is usually a

mixed dementia with some Louis body components, which was the case for my grandmother as well. And

she ended up spending at least years, her final years in bed clearly not enjoying her life. And

that was the most heartbreaking part. You know, the helplessness. And for my mother, who was the

primary caregiver, I was already in the United States at that point. That was brutal for the whole

family because we do not have the kind of health and support that is available today.

Even more shocking to us as a family was that my grandmother was one of four siblings,

three sisters and one brother. She was the oldest. So she was the first one to develop Alzheimer's.

And then a few years later, the middle sister also started showing the same kind of deterioration

and more progressive memory loss and then ended up with dementia. And then the third one,

the youngest sister also had exactly the same fate. Whereas the brother do not, even though they all

lived to the same age. So that was alarming because one person alone, you may be like,

but when three women expressed the same genetic vulnerability, that does hit you hard.

So my mom and I have been just so up to speak with the research. I always do research, but my mom

is also really, really participatory and so as my father and we have changed a lot of leader

things in terms of lifestyle. We know everything about prevention, whatever we know at this point

in the field about prevention. We do. We'll dig into that. So yes, that sent me down the rabbit hole

of trying to understand first genetics, right? What causes Alzheimer's as well? Was it known? Was

that genome or at the time? So at the time, which is now 25 years ago, it was a long time. We

did understand that there are genetic mutations, the cause of Alzheimer's disease. So there are

mutations in at least three known genes, which are the APP, the amylo precursor protein,

and the precenele one and two genes. If you have an autosomal dominant genetic mutation, one of

these three genes that directly causes Alzheimer's disease and what happens is that it runs in

the family's genetic transmission, but it's highly penetrant, an autosomal dominant, which means

that if you do inherit the mutation, number one, you have a 50-50 chance. Again, in the mutation,

if you do inherit it, penetrance is almost complete. And for our listeners, penetrance means

the chance that you will express the disease. So it's so strong. Almost always they're going to

develop, but if they live long enough, that actually starts in the 40s. So that's the type of Alzheimer's

that is called early onset. I think this is important because a lot of people think that early

onset is 60s, but early onset, when we talk about early onset Alzheimer's is 40s and 50s.

Certainly before age 65. Now, the sort of good news is that those genetic mutations are

exceptionally rare. They are found, depending on the country, in an average 2% of all Alzheimer's

patients. So if you look at the entire population, it's actually even less. But if you look at all

patients with Alzheimer's, no more than 2% carry this kind of genetic mutations that cause Alzheimer's

directly for everybody else. So the 98% of people don't have a genetic mutation. They now have a

genetic mutation. So what is it? Right. So in that case, we talk about risk. And we do understand

that Alzheimer's is now classified. So first of all, we look at early onset versus late onset.

Early onset before, I'm going to say 60, late onset after age 60. Now, in the late onset Alzheimer's

umbrella, some people do develop the symptoms of Alzheimer's when they're closer to 60.

And a lot of individuals refer to that as early onset. It's early by any standards, but the

right term is earlier, because early in absolute terms for these 60s, earlier, yes, it's 60,

it's horrible. But the good news is that it's not genetically induced. Okay. And then most people

develop dementia around the age of 72 on average. And that is late onset. Then we have sporadic

Alzheimer's cases and familial Alzheimer's cases. So like in my grandmother's case,

we talk about familiarity because it's not just my grandmother, but also her sisters.

So that is familial late onset. It's not a genetic mutation, but it does run in the family,

same for you. sporadic means to just one person. No other cases of Alzheimer's in the family.

And the risk is obviously different to the children, immigrant children. So this is what we talk

about when we discuss Alzheimer's disease in terms of characterizing which type of Alzheimer's

one has. So your PhD is in what? I have a dual PhD in neuroscience and nuclear medicine,

which is a branch of radiology. So I do a lot of brain imaging. So three quarters of women,

75% are going to have brain symptoms during this chaos during this transition. Brain fog memory

lapses, anxiety depressions. So we've got the mental health and and what is brain fog? So let's

like clear it up. Like what is brain fog? Like when should someone be worried? Yeah, it's one of the

reasons that actually scientific brain scientists started to look into menopause as a risk factor for

Alzheimer's disease. And still today, the vast majority of patients who come to us at the Alzheimer's

prevention clinic at Walconat Medicine, New York Presbyterian, which have run come to us because

of brain fog in midlife that can be so severe to really trigger concerns about early onset

dementia. So it's really important to clarify what is brain fog and what is Alzheimer's and how one

thing could lead to concerns about the others because it's really legitimate to be scared. So

brain fog is a generic term is a colloquial term that people use to describe what we

inrology refer to as cognitive fatigue or mental fatigue, which is this having a really hard time

doing things cognitively. My patients plan like, yeah, especially the ones who were like cognitive

high functioning at work, teachers, attorneys, you know, they're quitting their job, some of them

because they don't feel like they can complete the tasks that they used to it was mindless for them

and accountants, you know, people who use numbers, yeah, are really struggling. So yeah, it's exactly

that. It's it's cognitive fatigue in front of a cognitive effort is like things that used to be

easy and just seamless now require a huge amount of effort and it's I think one of our patients

described it as this feeling that no matter what you do, your brain just won't turn on.

There's this feeling of not being yourself, but also of almost being poisoned. If it makes sense

like if anyone has ever had a bacterial infection, right, I had it once and I could not find my

energy, my mental energy. And I think that's I don't I'm not a manopausal close to it. So I don't

I have no experience that, but I have I had one exam, one experience of brain fog was part of

okay, one of our estrogenic state, yeah, yes. And with breastfeeding and whatnot that I just

could not remember where my child was. I was a complete panic. I just, first of all, I knocked

on the door of the fridge before opening the fridge and that was already like, oh my god.

And then I found myself outside with the stroller empty going away. Not because the baby was within

any, but I had no idea what I was doing. And that was the only time in my life I could not count

on my brain. And that was absolutely petrifying, petrifying. So if my mental post is anything like

that, oh my gosh. And they completely sympathize. And that's why we're really trying to help

women who come to us and also, but doing the research. So what we and others have found

is that there is an association at this point with brain fog and alterations in brain energy

levels. And other people have used FMRI function MRI to show that the connectivity, the functional

connectivity of the brain is altered in women with brain fog relative to those without.

We have looked at the molecular mechanisms that may be involved. And what we have shown is that

it's a bit technical, but the ratio of phosphocreatine, creatine,

creatine, yeah, like creating to ATP is increased, meaning there is more

creatine phosphocreatine than ATP being made. So phosphocreatine is what the brain uses to make

energy is the buffer, right? But what you want is ATP. So you want them to be in the one-to-one

where as the ATP production is suppressed in some of the same brain regions that are

affected by Alzheimer's disease. Now, I've seen on the internet,

we'll have no data to back this up. I probably should pull the studies that

creatine supplementation could be helpful with brain fog. Is there is there any data to really

support that? There are small scale studies observational mostly of creatine supplementation

for cognition. I think we're not quite there. Given everything I know about the biology of

creatine, how important it is for brain health in the in the form of phosphine creatine, I think

that that is really something that's worth starting in part because the rest of water of creatine

are lower in women than in men. And if they are lower in muscle and body, there's no

switchance to their lower in brain to start with. And these bigger muscles, the more likely to have

higher brain volume. Did I read that correctly? Yeah, that's the answer. You know, also the smaller

your feet and the risk of Alzheimer's sometimes we find good relations so that you just say, I don't

know. I don't know. But I would love to see those studies. Yeah, I would like that. I think

they're doing some observational stuff. The creatine data mostly comes from muscle,

right? Yes. And the bodybuilders. But I think Abysmith Ryan and those people out of North Carolina

are starting to look and doing the good cognitive work. Great doing some measurement there.

I think something really worth looking into it. There are so many things that

become a little bit trendy before the research has been done. Yeah, but that doesn't mean

it's not helpful. It could be helpful. It could be. Well, you just don't know yet.

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Let's talk about the emotional side of it. The occasional outburst in a lot of my patients,

they come in and they're completely worried because of rage and fear and paranoia and

fear anxiety and anger and it's affecting relationships. At the same time, it is a hard time of

our lives for a lot of us with aging parents and teenagers. We're kind of in the sandwich area.

What's happening? Is it the same biomechanical process that's happening that's leading to

the emotional changes? This is really important, at least, reflective of the architecture

of menopause in the brain. Estrogen receptors are a little bit everywhere but they're more prevalent,

they're more abundant in very specific brain regions and especially in the most primitive parts

of the brain. These we know most different animal studies but we also now see with the brain scans.

We just looked at which is the first time in humans and they thought it was really fascinating. They

are most expressed in the memory centers of the brain, like the hippocampus and the

medial temporal lobes but also in the emotion control centers of the brain, like especially

one region that's called the amygdala, this sits right on top of the hippocampus and is connected

to the rest of the brain of course and kind of regulates emotions including fear but also

empathy. So it's very complex and then the estrogen receptors are present in the frontal cortex

which is in charge of thinking and reasoning and inhibition, very important and the posterior

single cortex and precunios which are more about autobiographical memory which is the memory of

places you've been and things you've done. Yes and then in the brain stem where we find all the

nodes for sleep and wake, the sleep cycle but also stress and then of course we have the

hypothalamus and the pituitary gland which is predominantly reproductive regions but the

hypothalamus also really both regions actually both glands play an important role in autonomic

function which is like control of blood pressure, heart rate. So all the most primitive

functionalities are effectively influenced by the presence of estrogen and the way it works

with the receptors which means if estrogen starts fluctuating and is all over the place

then the hippocampus does not activate it correctly and then you don't consolidate memories

and you feel like you have ADHD. Yes we see all the time patients complain constantly of that.

Yes they become aware that they can't memorize things and they have a hard time

paying attention to things. Is it ADHD or is it manopause or both?

Or both. We don't have any masks, something that we are managing. Exactly.

It's all over the place. Yes, amygdala, full of estrogen receptors.

Yeah and if estrogen starts fluctuating or it's not there the amygdala will glitch in regulating

emotions, right? So you may feel anxiety and fear when there's no reason for it.

You may, it's not just the amygdala, it's the whole network, right? But just to explain

they're not on me. You may get the rage, right? If you haven't slept because the estrogen hasn't

been activated, you sleep cycle and your melatonin is completely out of whack that will make you worse

and if your frontal cortex is impacted you're going to have a harder time inhibiting.

This response, this strong response that is not you, is your brain transitioning to work

mostly without estrogen. So the same brain regions that were supported by the presence of estrogen

before are now finding themselves in a state of remodeling. Yeah, renovations.

Yeah, so Robbie actually says that manopause is a renovation project on the brain.

I want to show you one slide if I find it. So here we are looking at differences

between premenopause of women and age-controlled men. When the women in all those fiber

tracks inside the brain show more positive markers or connectivity. So there's more diffusivity,

there's more, it's just the brain is basically better connected in those specific parts of the

brain relative to men at the same age. So we have a better brain function and men up to a certain

connectivity. Yeah. And then this is what happens at the premenopause stage. They're basically

no differences. And this, you're going to love this. Whoa. Yes. Oh, I love that. Wow. This is

postmenopause. And it's better than before. Wow. Yes. So it remodels, it remodels to make us

connect better differently from before. So these parts of the brain are desecrasectional study

we're now doing the same analysis longitudinally over time. It takes a long time to map the

transition because it takes many, many years, seven to ten years. And then you got to go postmenopause.

So you're talking at a 15 year, you're going to take a minute. But we do have six year data now. So

we're doing that. But this suggests that this is a cross section of study. Lots of people kind of

like give me like a wrinkled nose when something is then cross sectionally. But you have to start

cross sectionally because you don't want to waste your time longitudinally. If there's no

differences that are suggestive of a change, these suggests that there are differences to start

with. No differences when we're pyrimenopause and more differences at the postmenopause

stage. Nobody hears taking hormone therapy. So that does suggest a usual shape change that we find

with other modalities as well. Brain aging is not linear in women. And that is something that

is difficult to model and study. But we are doing it. We're doing deep phenotyping and increase

sampling. And we're trying to map it really, really carefully now. But I thought this was brilliant.

It's amazing. It's amazing. Women have been the wisdom keepers in their older age. The postmen

oposal women, the grandmothers were the wisdom keepers and that traditionally if they live long

enough, they carried the traditions they taught the younger. It's kind of beautiful how that

played out. I think it's beautiful. And I think what we're thinking as a field is that this

remodeling is essential. It's very important because the link between the brain and the ovaries

is a very big pathway in the body and it's very expensive to maintain. So once women no longer

are no longer reproductive, it makes no sense to keep all these connections and all these mechanisms

that are necessary to trigger ovulation and to potentially make your body able to host a

pregnancy. A lot of what happens in the pregnancy actually comes from the brain. And once you no longer

have the ability to be pregnant, it's really cost effective for the brain to say, you know what?

It's the latest print cleaning. All this stuff I no longer need is best if I discard it. That's

my personal own interpretation. I think this is what happened. And this is the renovation process

where the connectivity is changed. We're preparing for a non-reproductive phase of life which needs

to remain productive. So the brain rearranges itself. But at the same time, that is tricky to do,

right? And that can lead to the symptoms, the menopause, to the glitches. And unfortunately,

to a lot of discomfort for a certain amount of time. But it's for we're hoping, of course,

a good reason. Right. So when something that is genetically programmed and expected to happen

that is not a pathology. Yeah. And that's important to say, menopause is no walk in the park.

It's certainly no picnic for so many women. But there's a reason for it. And their brains and

bodies are equipped to go through it. Okay. What we can do is to support them during the transition,

to provide their brains with the tools and chemicals that it needs to support us and go through a

gentler. Yeah. Menopause. I love that explanation. And over long-term risk of Alzheimer's,

and anxiety, and depression, and Parkinson's and whatnot. So for someone who's listening,

who's having the brain fog or having the anxiety, you know, especially on the cognitive side.

But when should the brain fog or the cognitive symptoms be a red flag? When should you worry and say,

I need to go get evaluated? Well, I would go to Godless because you want to have a baseline.

For me, at least in this day and age, we do have the tools, we have the technology, we have the

possibility to have the access often. I think it's a good idea to have a baseline of your own

brain, your own cognitive performance when you're relatively young because you are the best

reference for you when you are a little bit older. Now, there is no reason usually to get alarmed

if brain fog tends to emerge during the transition to menopause. If you do notice that your

period is changing and is getting more irregular and you also experience brain fog, that is most likely

to be part of the hormonal transition. Once, obviously, you go to your dream, right? It should get

better. It should resolve within two to six years of the final menstrual period, which I know,

it's a lot of time. It's a long time. It's unfortunately a lot of time, but it should get better.

But we can support that. We can support it. Yes, through the transition.

In our clinic, we offer hormone therapy in these cases and they usually do very well.

And there's more research coming. There are more options. That is really important to know that

health is available and there are therapies and other things also lifestyle. You would be

okay. Let's get into that. Let's do that.

If brain fog gets worse, and if you don't remember where you put your keys, that is not Alzheimer's.

If you can't remember what your keys are for, that is a problem. I will use that again.

That is. But then again, a lot of people come to us to get cognitive testing done.

And we do cognitive testing. You can see that, for instance, there's this test that's called

the MMSE that we always do as a screening where the scores go from zero to 30. And most people,

my age, your age was score 28 to 30. If you are a 30, and menopause brings you down to 28,

to you, that is a catastrophe. To us, you are within normal brain for women, your age and educational

level. And that is a huge relief to hear. Yes, we understand. You are experiencing a change

in cognitive performance that we refer to clinically as subjective cognitive decline,

because you feel it, you're aware of it, is not measurable using standardized cognitive tests,

which means you do not have dementia at this stage. I love that. If you can't remember where

you put your keys, but if you don't know what the keys are for, that is a problem. You need to go

get a value. All right, let's talk about our brain plan, our game plan, for midlife,

because there's so much hope here. Yes. Yes. There's so much we can do. Like Mary Claire's

nursing home prevention program is what I like to call it.

For many of you know, preventing osteoporosis is much easier for me to deal with than how do I

hang onto my brain function as long as I possibly can. And so that I really, I won't know the

difference. You know, I'll be frustrated, but I don't want to do this to my kids. You know,

I don't want them to have to go through this like gut-wrenching decision-making that my family,

and my husband's family is going through and how to best help our parents, you know, as they

traverse this. So, menopause is a neurological transition, not just a reproductive one,

but what can women actually do to protect their brains? So, let's talk about the key lifestyle

factors involved in brain health. Yes. So, we're going to start with sleep.

Yes. I think that's probably one of the most important things. I've heard sleep is called as

the wash cycle. Yes. So, what does that mean? Would that mean that the brain minute after minute

is always busy supervising the rest of the body? The brain is constantly either thinking,

memorising, feeling is very busy, but also supervising the rest of the body,

even heart rate and breathing and moving. All of that needs to be active at all times.

The only time in today that the brain can actually take care of itself is during sleep,

and specifically during slow wave, sleep or deep sleep, which is when your body is completely still.

You are not moving, just breathing very quietly. The brain can let go of everything else

and activate a system that is called the glimphatic system, which is like effectively like a car wash.

Does that fluid just start moving throughout the brain, removing toxins, removing ways,

removing Alzheimer's plaques? That's when a lot of clearance mechanisms are activated.

The oxidative stress is removed, the inflammation is flushed out. All the mess we accumulate

it through the day. All the things that, yeah, well, it's an organ. There's a lot of activity going on.

So if you don't sleep, if your sleep is fragmented and you sleep, especially your deep sleep

is impacted and you lose that window of sleep, that over time has consequences because then all

the toxins will not be cleared out. They will accumulate in the brain. The Alzheimer's plaques

will stay in the brain. The inflammation may stay in the brain. So sleep hygiene and sleep

protection is a very important and just recently discovered protective factor for brain health

and Alzheimer's disease, whereas sleep deprivation is a race factor for Alzheimer's. So now sleep

is now in cardiovascular disease, now characterized as a risk factor. How much sleep do we need?

Really good question. And why do these middle of the night wakeups, which a lot of my patients

complain of, including the one potential mechanism is related to manopause. And of course,

stress, anxiety, that is a different story. But for women who are going through manopause,

there can be a hormonal component to sleep disruption. And what can happen is that the

all these different hormones work together is a hormonal system that is in a flux. We're always

talking about estrogen and progesterone, but other hormones also are impacted. And in particular,

stress hormones and sleep hormones. Cortisol. Cortisol and melatonin. Okay. So for cortisol,

the relationship is well characterized in that the body needs a common precursor, which is

pregnant alone, to make both sex hormones and cortisol, the stress hormone. If you're super

stressed out, the body is going to have to use most or more of the pregnant alone to make the

cortisol. And that means it cannot make as much of the sex hormones. Wow. Yes. That's why stress

sinks your hormones. And women who really, really stressed out may experience more severe symptoms

and manopause, because you have less availability. The problem when you get to eat is support. Yes.

You're a hormonal therapist. You don't have to worry about yourself. Yes. And for melatonin is a

similar problem where if stress and cortisol, say, cortisol is high in your body, that suppresses

melatonin production. So what happens is that usually melatonin peaks around the time of night,

but that before they want the 3 p.m. window, but then you've remains in the system unless you're

super stressed out, in which case cortisol kicks in around 2 in the morning. Wow. And so it's a whole

mechanism. You know, when the sex hormones are disrupted, the stress hormones are disrupted,

the sleep hormones are disrupted. So you can start any of these nodes. The internet is full of all

of these wellness cures, you know, some, and I have no data, you know. Right. How do we lower

cortisol? I know we can do, you know, stress reduction, and meditation, journaling, you know,

but are there supplements? Are there, you know, cortisol? Yeah. No, there's a lot of claims out

there to take this and we'll lower your cortisol. Oh, God, all kind of internet claims.

Oh, you know, I'm my supplement and I'll lower your cortisol. I'm not a way of any supplements that

can directly lower cortisol. What has, what has been shown to lower cortisol levels is like you said,

is meditation, stress reduction. If you can sleep, that should also lead to a reduction in

stress hormone levels. So prioritizing sleep, so it's really important. And this is more than

a daughter, anything else, but magnesium glycinate may be helpful and do not ask me for clinical

trials. We can't do clinical trials for everything, but at least for, for several women,

magnesium glycinate in particular can help relax the musculature and help you fall asleep and stay

asleep, which then has a differential effect on the cortisol pathway. Milatoning can help you sleep

and stay asleep, and that also may help lower cholesterol. So all the things that help you sleep,

in other words, may also have a low weighting effect on the rest of the room.

It's not direct. It was there's more indirect, but it's relaxing the body. Yeah, it's just exercise.

Exercise. That's my next question. Yeah, women who are fit in middle life, whatever fit is

defined as, have at 30% lower dementia risk. Does there are the women who have the highest level

of cardiovascular fitness in their life? Yes. So what is exercise doing to the brain? Exercise

supports brain health through multiple pathways, and the most interesting ones I believe are the

direct pathways. So the first one is by increasing blood flow to the brain. That is very, very

important because that supports oxygenation and nutrient transmission. So you're effectively feeding

your brain. Exercise is also anti-inflammatory and reduces oxidative stress, which the brain is

very sensitive to. And then there was a really super interesting discovery just a couple of years

ago, I came out in science, that when muscles contract as part of exercise, they produce a peptide

that is called irisin, from the brain, which is very pretty. And iridin can cross the blood

brain barrier, right? And once it crosses the blood brain barrier, it supports, like estrogen,

it supports BDNF production and reduces the amount of pro-inflammatory cytokines directly in

neurons. So that's a beautiful way that exercise can directly support brain health. And look,

this is, this is when it comes to Alzheimer's disease. I was looking for this the other day.

Okay, here we go. All right. So this is what we currently know about the modifiable risk factors

for Alzheimer's disease, which cumulatively account for over 40% of Alzheimer's cases. Okay.

These are all lifestyle based. And I specified what percentage of risk they each account for.

And if you look, exercise, actually physical inactivity, which can be obviously offset by exercise,

accounts for over 2% of Alzheimer's cases globally. And then we have things like excessive alcohol

consumption, which excessive means more than two glasses a day. We have social isolation,

we have depression in midlife, more of an issue for women than for men. We have air pollution,

we have low, say low education is more like low intellectual stimulation, right? I would say rather

just ears of schooling, although that is a factor as well, hearing and vision loss if untreated.

So glasses, hearing aids are becoming important for Alzheimer's prevention as well.

Tomato brain injury, especially with loss of consciousness, smoking. And then the heart disease,

risk factors, obesity, diabetes, hypertension, and high LDL cholesterol. Those are 14 and have been

formalized as risk factors for Alzheimer's disease that can be modified. Right? Right.

Anyone can do any of all these things, you need to decide to reduce the risk of Alzheimer's.

And now we're looking at other things like sleep. Very important diet and nutrition obviously

important to include? What about you, everyone? We're not there. Everyone's there. Yeah.

No, no, no, no, no, no, no, no, no, no, no.

Oh yeah, oh yeah.

No, no, no, no, no, no, no, no, no, no, no, no, no, no.

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No, no, no, no, no, no, no, no, no, no, no, no, no.

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Let's talk about food because of what I love in your books is that you spend a lot of time

talking about nutrition. I love chemistry and nutrition is effectively biochemistry and my daughters

undergrad before med school, Catherine's a third year med student and so her undergraduate is

nutrition science, but she went to a biochemistry program, not the cooking for a thousand people

program. The nutrition science goes two ways, you know, and she absolutely loved it and I think

it's such a strong foundation for her for medical school. It's so good. I also, I do not study

nutrition at school, but I'm kind of self taught. At some point it was okay, just get me every

chemistry book because all the things I'm learning about brain health, all the sodium potassium

puns, you know, serotonin is made of triptophane and these are all nutrients that come from food,

right? They're not made by the brain, they are imported. So I loved it. I spent a lot of time

at that time. So what should we be in for our brains? The brain is an interesting organ and if you

eat healthy for your brain, you're also eating healthy for the body, not necessarily the other way around.

So the brain is more specific, it's a little bit more of a picky either relative to other organs

and it loves predominant needs, predominantly antioxidants like vitamin A, C, and magnesium,

and vitamin E, specific amino acids, especially the essential amino acids which come from many

different foods and omega-3 fatty acids which are predominantly from fish nuts and seeds

and some marine algae, if you wish. And we're not really sure. Obviously, that's where the fish get

the omega-3 is, they eat the algae. Yeah, so it's part of the food chain. So if you can't tolerate

fish or you're allergic, you can get the algae based supplements. Yeah, absolutely. And obviously

glucose is very important for brain health. But within reason, you know, you don't need to eat a ton,

but a little bit is important for brain functional. Also for the synthesis of glutamate. A lot of

people just look at glucose as a sugar. Right. A glucose is a number of functionalities and for the

brain is they build in block of glutamate, which is the most prevalent neurotransmitter in the entire

brain and is needed to synthesize GABA, which is the prevalent inhibitory neurotransmitter. So glucose

is not just in them thinking when the keto diets came out, it was a little bit like whoa,

because it's important not just for energy, but also to synthesize. Okay, the most abundant neurotransmitters

there we have. Why are ultra processed foods so bad for brain health? They're bad indirectly. So

those kinds of foods in nutrients should not be able to cross the blood drain barrier, but they do

increase inflammation in the rest of the body and they do have almost like a sort of toxic effect

in your gut for sure that then leads to widespread negative effects throughout the body and brain.

There are a lot of chemicals that are used in the synthesis and making of ultra processed foods

that our bodies are just not equipped to handle, which then leads to oxidative stress and inflammation

and those sort of medical issues really that then also negatively impact brain health.

What's good for your heart is good for your brain. What's bad for your heart is bad for your brain

and ultra processed food is bad for pretty much every organ we have.

Are there any supplements you think are hype or most realistic for brain health?

Yeah, I wish we had more data. I think there are some nutrients for the supplements that are

clearly beneficial for brain health and it makes sense that if you are deficient or some

clinically deficient with some nutrients, then supplementation might help. I'm thinking

be vitamins. So we do know, especially B-12 is an issue for a lot of people because as we get

a little bit older, it becomes more difficult to absorb it from the foods that we eat and almost

all elderly individuals are B-12 deficient and just don't know that. So it's important to have

them as B-12 levels and all of our patients as a solid B-6. It's a really important brain

vitamins as well. Clinical trials have shown mixed results. I think that the supplement that we

have the best evidence for is omega-3 fatty acids and I am 100% partial to antioxidants for

disclosure. I have no conflicts of interest. I don't sell anything. I love antioxidants because

I think that the brain is exceptionally prone to oxidative stress is actually the major cause

of cellular and neuronal aging and the brain is completely powerless against oxidative stress.

The only way to counteract the effects is by importing vitamin A, C, E, selenium and the

antioxidant minerals through the diet. In very few people eat enough fruit and vegetables and

some nuts and seeds to really ensure adequate levels. And then it depends and they do believe

in a precision medicine approach and what you do too. But not everyone has access to that.

So like for the lady on the couch and Ohio listening, you know, who just has a primary care doctor

who's going to do standard, you know, like what can we tell her?

Well, for instance, if you are a former smoker, which this is one of the biggest regrets in my life.

Same. I quit at 23. Same. Me too. You know, in Italy, I was growing up there and every body was

every week's smoke. Oh my god. And so did I. And I really wish I hadn't. But I did. I'm aware.

And we know that smoking is a major risk for ovarian function and for brain health.

How do you counteract the negative effects of reactive oxygen species that are caused by

smoking in the possible epigenetic modifications that then lead to more oxidative stress being

produced antioxidants. So I understand that people want clinical trials of supplements. I'm not

sure how feasible that is financially and in terms of commitment. But I would say if you are

a former smoker, there is no downside to using antioxidants. For example, what would any

antioxidant be just for our list? Vitamin C. Vitamin C. Yeah. That's the number one. Even Dr.

Pauline, you know, who's the one who discovered vitamin C and then won the Nobel prize for the

discovery. He took very high doses of, I'm not saying anyone. Until the day he died and he was

as healthy as anyone can be. Now that's one person. Nobel prize. That's the one person. I was a

regular amount of vitamin C, especially liquid. Liquid vitamins are really good in terms of

being absorption. It's good to know. All right. So elephant in the room. Lots of

talk worries. The medical society meeting had a whole section on this. Let's talk about

hormone therapy and dementia. Yes. And what do we know? What do we know? And what we do not know yet?

And I think both are really important. And this is the perfect situation to talk about the

fact that language matters. If it's okay. Absolutely. Both direction. Yes. So what do we know? We

know that we have not done all the work that we could have. That is a fact. There is only one

clinical trial that ever looked a hormone therapy for dementia prevention, which is the Women's Health

Initiative that we mentioned before. They were way ahead of their time. Fantastic study

in women who were postmenopausal by decades. There's a part of the Women's Health Initiative

that is called the Women's Health Initiative Memory Study, where they specifically tested hormone

therapy, which in this case is high dose oral, conjugated equine estrogen and MPA as the

progestin, with or without an MPA and placebo. And they followed these women for the number of

years. And what they showed is two things. Number one, they could not use Alzheimer's disease

as the endpoint, because two few women developed Alzheimer's disease. So they have to switch

their endpoint to dementia. No, dementia is not Alzheimer's. Right. Alzheimer's is the only form

of dementia that shows the female to male disparity. The other forms of dementia that the women

in the Women's Health Initiative Memory Study developed was predominantly vascular, where there is

a lower hormonal component relative to Alzheimer's as far as we know. And some had mixed dementia.

So that was an important finding. Nonetheless, when they looked at the rates of how many women

developed dementia, they found in the conjugated equine estrogen and MPA group, there was an increased

rate double, the rate of dementia in women who were taking the hormones as compared to placebo.

The absolute difference in case it was more was about 12 women than in the placebo group.

In the group of women who were taking only the estrogen, there was a 50 percent increased

risk that was not significant. These results are not generalizable to meet life women.

Right. Because these patients were much older. Yes. And as we were talking about before,

the system may no longer be there. Right. The estrogen receptor binding may not be working the way

that it does once you still are reproducted, once you're still transitioning to your non-reproductive

life, when you're, you know, 20 years past. Right. It may just not work. You're bouncing off

of a closed door. Yeah. That's a good way to put it. And also, those are different formulations

to what the women would use now. Then, yes. And the new one, the newer formulations have never

been tested this way. So, right. So, we cannot generalize. And we also cannot generalize to Alzheimer's

because that was not the end point. The end point. All right. Please, if I gave you a billion dollars.

Good right now. What study would you? What would be the study? I would redo the Women's

Health Initiative Memory Study. I would do it using biological markers of Alzheimer's where we

work with women who are in midlife, are going through manopause. And they're taking hormone therapy,

especially, estrogen, that micronized, estrogen, and progesterone, which are closer to

whether body is naturally produced. Dozed using brain scans so that I can know what kind of

dose you actually need, not just for symptom relief, but for brain health and support. And I would

use biological markers of Alzheimer's because that I can track as you get treated. What is a

biological marker? So, these are the brain scans. So, we can look at plaques in the brain. We can

look at tangle formation in the brain. We can look at estrogen and how the therapy modifies

estrogen binding in the brain. What's your hypothesis of this study? Your hypothesis is, but my

hypothesis is optimistic, of course, but I would also have all sort of plan B in place because

there is a chance that they may not work out, but I think we need to give it a fair chance because

why don't you have a billion dollars for the study? I have 15 million.

But let me show you the observation of research because we have 20 years worth of evidence from

preclinical studies that hormone therapy started around the time of manopause is brain protective.

We have observational data showing something similar. And observational data cannot prove cause

and effect. You need to have clinical trials, which is what we are missing. But nonetheless,

we do see that estrogen only therapy is associated with a 30% reduced risk of Alzheimer's disease

among women with a hysterectomy and or uferectomy. Whereas estrogen with a progesterogen, we can't

yet separate progesterogen or sorry progesterone to progesting we observational data, but there's still

the trend towards a risk reduction. This does not mean that every woman needs to take hormones to

reduce the risk of Alzheimer's. It means that we do need to do the research and something that we

showed just recently that I think is really interesting is that that also was replicated.

There's a strong effect of geographic location. So if you look at all the studies like in North

America, everything is blue. It means that the vast majority of studies show a protective effect.

Northern Europe is red. Not protective. No protective. Why? We don't know. But there's something there.

It could be the kind of hormone formulation that was used to diagnose the criteria. It could be

a number of reasons, but the studies in North America are consistently protective in Canada,

which really suggests that we need to look at what different people are doing clinically

when they use these formulations. So good. I just want to say this when people say blanket statements

like you need to go on hormone therapy to prevent dementia. We don't know. We need to do the

research, but when people say, which I hear, there is no evidence the hormone therapy prevent this

was set at a national meeting just a month ago. Oh yeah. I heard it on social media actually.

It could be misinterpreted. It's kind of saying the same thing that we need to do the research. We

need to do their work. But what people understand, I believe correct me English is my third language,

what I would understand is that the right research has been done and there was no benefit.

This is what I understand. There is no evidence that it works. What we could say that I think is more

accurate is that we have not done the right research yet. We don't know if it works, but we also

really don't know that it doesn't. And that's important because essentially we can test. For

instance, we can check whether it works for some women or not others. We can check if it works

by age, genetics. Thank you. And now we have the brain scans as well, which we never had

them before. We give women therapeutic standardized doses of estrogen that are for symptom reduction.

We don't give women doses of hormones that are brain protective because we don't know what

doses would be. So this is what we're trying to do now. We need to we need to have more visibility.

We need to have a better understanding of the brain dynamics. We need to do more work. We need

to do work. But I think it's important to do the work. I think it's important to maintain

an open mind. And just because the women's health initiative didn't work out, it does not

mean that we can't stop all medical research in menopause. Exactly. So for a woman who's

sitting at home right now listening to this and and feel scared, what do you want to say to her

about her health, her brain health and moving forward? I would say that we all have more power

not over our brains, but we do have the power to support the health of our brains.

And that if you make the right choices in life, it takes consistency, it takes work,

but really the benefits are for life. There are also new studies done specifically on menopause,

showing that the symptoms can be milder, the experience can be gentler if you take care of yourself.

So I would encourage everyone to think more of their brains that can muscle.

There are things that you can do to support your brain health. Like when you exercise your muscles,

right, when you eat carefully to promote your cardiovascular fitness or your fitness overall,

the same principles apply to brain health. You can feed your brain properly, you can exercise

your brain properly, you can take care of your brain properly and your brain will just perform

so much better for you. And it's really it's a long term insurance policy and you want to start

as soon as you can because there's always the idea that it doesn't matter how old you are. If you

start taking care of yourself, it will show you will feel it, but the sooner that you start

the better because midlife really is a big turning point for the woman's health, not just today,

but for the rest of your life. So this is the time when most women really have no time for themselves,

but I think it's really important to take a step back and say, I owe you any time for me, right?

Self-care is not selfish. You want to take care of yourself so that you can give so much more

to your family, to your job, to your friends, and to yourself as well.

Well, this feels like this has been a life-changing conversation.

Always every conversation I have with you and I'm so excited for our listeners to hear this episode.

As a reminder to our audience, you can follow Dr. Musconi on Instagram at Dr.

underscore Musconi. Her book, The Menopause Brain, is available now through her website at

LisaMusconi.com. You can find full episodes of Unposed on YouTube at Dr. Mary Claire.

I'd love to hear from you about this topic and anything else that's on your mind.

You can follow me on Instagram at Dr. Mary Claire and get honest and accurate information

on health, fitness, and navigating midlife at ThePauseLife.com. My upcoming book, The New 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 Unposed on your favorite podcast app. Following and

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Thank you for being here with me. Let's keep going. Unposed. Unposed is presented by Odyssey

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