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

- So let's laugh, like, what is brain fog? Like, when should someone be worried? - Yeah, it's one of the reasons that actually, scientists, 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 Alzheimer's prevention clinic at Wal-Cornette Medicine, New York Presbyterian, which everyone comes to us because of brain fog. In mid-life, 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. (upbeat music) - The views and opinions expressed 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 ants all developed 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? Which struck me the most, is that Dr. Moscone

has never shied away from those hard questions.

She has 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 Wil 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 a rector of the $50 million program in women's health, cutting Alzheimer's risk through inocrinology,

“a groundbreaking initiative placing hormones and midlife”

at the center of dementia prevention. She's also the author of a number of bestselling 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 unpaused, the podcast where we cut through the silence

and talk about what it really takes for women to thrive in the second half of life. So welcome to unpaused. Thank you for having me. I'm so glad we were good at it. 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 relevant in Santa Monica. And you stood up and started showing images of the brain of women and premenopause and premenopause and postmenopause and the differences in glucose uptake

and what's happening. And I stood there in the audience. At was I was before or after ever blooming in Carol, had like this mantle, the WHO. And my mind was so blown that day.

And then you're talking about how women's brains change through menopause.

And I'm like, no, we never told me this.

No, whenever ever, ever in all of my training talked to me about the structural changes and the biological and then that menopause was in neuroindocrine event.

You know, my understanding. But let's back to you. So let's talk about our grandmothers.

“Let's talk about 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. And 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 as 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

inevitableity. There are things that we can do. You're young enough to get ahead of this. Absolutely. Tell me about your family.

My family has also been negatively impacted by Alzheimer's in dementia. And that for me, it was involved in 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 and nuclear physicists. They're professor and nuclear physics, both of them. And they're not like the stereotypical nuclear physicists.

They're more they open highmen. I, John, no one's out with me. No one's out with me. But they did 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.

Like you mentioned hallucinations, which is usually a kind of mixed dementia, with some new 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 a red 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 did 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 old 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 obviously do research. But my mom is also really, really participatory and so isn't the father. And we have changed a lot of little things. In terms of lifestyle, we know everything about prevention,

whatever we know at this point in the field about prevention, we do. And we'll dig into that. So yes, that sent me down the rabbit hole of trying to understand first genetics, right?

What was the gene known or is so at the time?

“So at the time, which is now 25 years ago, that was a lot of time.”

We did understand that there are genetic mutations, the cause of Alzheimer's disease. So there are mutations in at least three non genes, which are the APP, the analog precursor protein, and the precineally one and two genes. You feel have an autosomal dominant genetic mutation, one of these three genes, that directly causes Alzheimer's disease.

And what happens is that you run in fiamal is genetic transmission, but this highly penetrant, that also is somal 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 inherited, penetrants is almost complete. And for our listeners, penetrants means the chance that you will express the disease.

So it's so strong.

It's the most always they're going to develop it if they look close to 100%.

Well, that actually starts in the 40s. So that's the type of Alzheimer's that is called early onset. Okay.

“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. Wow, certainly before age 65. Now, the sort of good news is that those genetic mutations are exceptionally rare. Okay. They are found depending on the country in on average 2% of all Alzheimer's patients.

So if you look at the entire population is actually even less, right? 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 will not 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 and Brella, 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 the 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 in familial.

So 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. It's sporadic means to just one person.

To run their cases of Alzheimer's in the family. And the risk is obviously different to the children and grandchildren. 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 order to science in nuclear medicine, which is a branch of radiology. So I do a lot of brain imaging. So three quarters of women, 75%. Yes, we're going to have brain symptoms during this chaos, during this transition. Yeah, brain fog memory lapses, anxiety depression.

“So we've got the mental health and what is brain fog?”

So it's like layered up, like what is brain fog? Like when should someone be worried? Yes, one of the reasons that actually scientists started to look into menopause as the 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 Walkernet Medicine, New York Presbyterian, which I've run, come to us because 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 brain fog is a genetic term as a colloquial term that people use to describe what we

hard time doing things cognitively, you have to explain.

Yeah, especially the ones who are 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, your people who use numbers are really struggling. Yeah, it's exactly that, it's cognitive fatigue in front of a cognitive effort.

It's like things that used to be easy and just seamless, no 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,”

you brain just won't turn on. There's this feeling of not being yourself, but also almost being poisoned. If you make 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 mental positive close to it, so I don't have no experience that,

but I had one experience of brain fog was part of them. Okay, one of our last virginic state, yes. And with breastfeeding and whatnot, that I just could not remember where my child was.

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. Go in the way, not because the baby was within any. But I had no idea what they 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 voice 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 when the research, so 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 connective functional connectivity of the brain is altered in women with brain fog relative to those without. Okay, we have looked at the molecular mechanisms that may be involved. And what we have shown is that the, to be technical, but the ratio of phosphocreatine,

creatinine, creatinine, creatinine. Yeah, creatinine. To ATP is increased. I mean, there is more creatinine, 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 ratio. Whereas 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, what have no data to back this up, I probably should pull the studies that creatinine supplementation could be helpful with brain fog. Is there, is there any data to really support that? There is small scale, study is observational mostly. I'll creatinine supplementation for cognition. I think we're not quite there. Yeah, given everything I know about the biology of creatinine,

“how important is for brain health in the form of phosphocreatine. I think that that is really”

something that's worse starting in part because the rest of creatinine are lower in women than in men and if they are lower in muscle and body, there's also a chance that they're lower in brain to start. Right? And these bigger muscle, the more likely to have higher brain volume, did I read that correctly? Yeah, that's not so, you know. Also, this model, you're feet, and then your risk of all the time is sometimes we find good relations with it, you just see, 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 creatinine data mostly comes from muscle, right, and the bodybuilders, but I think Abysmith Ryan and those people out in North Carolina are starting to look and doing the great cognitive work. Great doing some measurement. Right. So, I think it's something really worse looking into it. There are so many things that become a little bit trendy before the research

spin down. Yeah, but that doesn't mean it's not helpful. It could be helpful. It could be. Well,

This episode of Unpause is brought to you by Aloy 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 too. I first heard about

Aloy through a close friend who is a dermatologist. She shared how few products truly address hormone level skin changes. Once I understood that Aloy'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. Aloy'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 your skin is changing, your skin care should change too. With Aloy, you counsel with a doctor and receive

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

code MCH20 that's MCH20 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 seven to ten years before your period stopped. 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 "don't feel like myself anymore" began. 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. You deserve care before burnout, and you deserve a clear roadmap for a transition that medicine 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 ThePasLife.com. We always recommend Shopify. It took us from an idea to a real business.

“We got set up, I think, in less than a day. With very little effort, we could just focus on”

the supply chain to the product development. Shopify gives us the ability to customize without the complexity. We can change something without introducing fragility or having to pay a developer. Well, thirsty total, and we leveled up our business with Shopify. Start your free trial at Shopify.com/AU. 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 this sandwich area. What's happening? Is it the same bio-mechanical process that's happening that's leading to the emotional changes?

Yes, so this is really imparted at least reflective of the architecture of menopause in the brain. So estrogen receptors are a little bit everywhere, but they're more prevalent. They're more abundant in very specific brain regions and especially in the most primitive parts of the brain. And these we know most different animal studies, but we also now see with the brain scans. They were just looked at, which is the first time in humans and they saw it. It was really fascinating.

They are most expressed in the memory centers of the brain, like the hippocampus and the middle temporal lobes, but also in the emotion control centers of the brain, especially when region does 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

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 hyposalamus and the pituitary gland, which is predominantly reproductive regions,

“but the hyposalamus also feels 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 is not activated correctly. And then you don't consolidate memories and you feel like you have ADHD. Yes, we see all the tensions 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? What is the amount of holes? Or both? Or both? We don't know if we're going to ask something that we're imaging. Exactly, for a long or a long time. Yes, I mean, Della, full of estrogen receptors. Yeah,

“and if estrogen starts fluctuating, what is not there, the amygdala will glitch in regulating emotions.”

Right. So you may feel anxiety and fear when there's no reason for it. You may, it's not just the amygdala, it's the whole network, right? But just to explain the anatomy. You may get the rage, right? If you haven't slept because the estrogen has 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 respond, 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, renovation. So Robbie actually says that 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 a 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 in the same age. So we have a better brain function than men up to a certain activity. Yeah. And then this is what happens at the period menopause of stage. They're basically no differences. And this, you're going to love this. Whoa, yes, I love that. Well, this is postmenopause of women and it's better than before. Wow, yes. So it remodels. It remodels. It remodels. It remodels connect better.

Definitely from before. So these parts of the brain are, this is a cross sectional study. We're now doing the same analogy. Analyzes was known to tune in only over time. It takes a long time to map the transition because it takes many, many years, 17 years and you got to go postmenopausals. They took it out of 15 years. They're going to take a minute. But we do have six years. They turn out so we're doing that. But these suggests, this is a cross sectional study. Lots of people kind of like

“give me like a wrinkle nose when something is then cross sectional, but you have to start”

cross sectional because you don't want to waste your time. Don't do too, definitely. If there's no differences, there's a suggestive of a change. These suggests that there are differences to start with no differences when we're perimenopausal. And more differences at the postmenopausal stage, nobody here is taking hormone therapy. So that suggests that you should change. They 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 postmenopausal women, the grandmothers, were the wisdom keepers that traditionally, if they

how that played out. I think it's beautiful. And I think what we're thinking is the 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. They're 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 really the spring cleaning. All this stuff I no longer need is best if I discard it.

That's my personal own interpretation, but I think this is what happened. And this is the renovation

process where the connectivity is changed, right? 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 of manopause, to the glitches. And unfortunately to a lot of discomfort for a certain amount of time. But it's for we're hoping, of course, a good reason. Right? So when something that is genetically programmed

and expected to happen happens, that is not a pathology. Yeah. And that's important to say. Manopause 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 our brains with the tools and chemicals that it needs to support us and go through a gentler. Yeah, Manopause.

I love that. And there's a long-term risk a lot of time is in the anxiety and depression. And Parkinson will not. So for someone who's listening, who's having the brain fog or having the anxiety, 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 a value-rated?”

Well, I would go to guardless because you want to have a baseline. For me, at least in this day and age, we do have the tools. We have the technology. We have the possibility. We have the access often. I think it's a good idea to have a baseline of your own brain, 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 Manopause. If you do notice that your period is changing and this 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 period. And 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 lot of time. It's unfortunate a lot of time, but it should get better. But we can support it. We can support it.

We can, yes, through the transition. Exactly. In our clinic, we offer hormonal therapy in these cases, and they usually do very well. And there's more research coming, and there are more options.

“So that is really important to know that health is available. And there are therapies and other”

things also lifestyle. You're really good. Oh yeah. Let's get into that. Let's do that. The 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 a lot of people come to us to get cognitive tests in that. And we do

cognitive testing. And you can see that, for instance, this test is called the MMC that we always

do as a screening with the scores go from 0 to 30. And most people might age your age with score 28 to 30. Right. If you are a 30, and menopause brings you down to 28, to you, that is a catastrophe. To ask you are within normal brain for women, your age, and educational level. And that is a huge relief to hear. That yes, we understand. You are experiencing a change in cognitive performance that we refer to clinically subject the cognitive decline, because you feel it,

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 the problem. You need to go get about you. That's”

okay. All right, let's talk about our brain plan, our game plan for midlife, because there's so much hope here. Yes, yes. You know, there's so much we can do. Like Mary Claire's nursing home prevention program is what I like to call it. But for many, you know, for many of us, you process as much easier for me, you know, to deal with. Then how do I hang on to my brain function as long as I possibly can. And so that I really, I won't know the difference. You know, I'll be frustrated, but I don't want

to do this to my kids. 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 to 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 what we're going to start with sleep.

“Yes, I think that's probably one of the most important things in it. I've heard sleep is called”

as the wash cycle. Yes. So what does that mean? What that means is that the brain minute after

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

memorising, feeling is very, very easy. But also supervising the rest of the body. Okay. Even heart rate, amazing. 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 effective like a car wash. There's like fluid. There starts moving throughout the brain, removing toxins, removing waste, removing Alzheimer's plaques. That's when a lot of clearance mechanisms are activated. The oxidative stress is removed. The inflammation is flushed out. All the mess you accumulated through the day. All the things that, yeah, well, it's an organ.

Maybe 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. You lose that window of sleep. That over time has consequences because then all the toxins will not be cleared out, right? They will accumulate in the brain. Alzheimer's plaques will stay in the brain. The inflammation may stay in the brain. So sleep hygiene and sleep protection is a very important and just recently

discovered protective factor for brain health and Alzheimer's disease. Whereas sleep deprivation is a risk factor for Alzheimer's. So now sleep is now in cardiovascular disease, now characterized as a risk factor. How much sleep do we need? And why don't these middle of the night wake-ups, which a lot of my patients complain of? Yes. So one potential mechanism is related to manifolds. And, of course, a stress and anxiety that is a different story, but for women who are

going through manifolds, there can be a hormonal component to sleep disruption. And what can happen is that all this different hormones work together. It's a hormonal system that is in

a flux. We're always talking about estrogen and progesterone, but other hormones also are impacted.

And in particular, stress hormones and sleep hormones, 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. So if you super stress 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. Women who really, really stress out may experience”

more severe symptoms of menopause because you have less available. The pregnant one gets eaten in support. Yes. The hormone started on the other side. You may remember. Yes.

in your body, that's suppressed as melatonin production. So what happens is that usually melatonin

“peaks around the time of night, but that before they want to 3 p.m. window, but then you've”

remains in the system unless you're super stressed out in which case cortisol kicks in. They're on to 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 with 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, meditation journaling, you know, but are there supplements? Are there, you know,

cortisol? Yeah. None of the time I wear all. Okay. A lot of claims out there. Yeah. Take this and we'll lower your cortisol. Oh, God. All kind of internet claims. Oh, you know, I am a supplement and I'll lower your cortisol if you're not aware of any supplements that can directly lower cortisol. What is that here? What has been shown to lower cortisol levels is like you said. It's meditation, stress reduction. If you can sleep, that should also lead to a reduction in stress

“hormone levels. So prioritize and sleep. So so really important. And this is more than a”

daughter of that anything else, but magnesium glycine. May be helpful and do not ask me for clinical exercise. We can't do clinical trials for everything, but at least for for several women. Magnesium glycine in particular can help relax the musculature and help you fall asleep in stay asleep, which then has a differential effect on the cortisol pathway, melatonin can help you sleep and stay asleep and that also may help lower cholesterol. So all the things that help

you sleep, in other words, may also have a lowering effect on the insulin. Okay. So I'll direct, I was saying more indirect, but my DNA in the body. Yeah, it's just exercise. That's my next question. Yes, I mean, who are fit in my life? Yes, whatever fit is defined as, have a 30% lower dementia risk. Does there be women who have the highest level of cardiovascular fitness? Okay, in in 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 nutrients 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. It came out in science that when muscles contract as part of exercise, they produce a peptide that is called erasin from like a product of the brain, but which is very pretty. And eradine can cross the blood

brain barrier, right? And once the cross is the blood brain barrier, it supports like estrogen. It supports bdnf production and reduces the amount of proinflammatory cytokines directly in neurons. So that's a beautiful way that exercise can directly support brain health. And look, this is, um, this is when it comes to Alzheimer's disease. You're not satisfied. I was looking for this the other day. Okay, here we go. Oh, good. All right. So this is what we can't

constantly know about the modifiable risk factors for Alzheimer's disease, which cumulatively account for over 40% of all Alzheimer's cases. Okay. These are all lifestyle based. And I specify what percentage of risk they each account for. And if you look, exercise, actually, physical inactivity, which can be obviously offset by exercise, account for over 2%. Of all Alzheimer's cases globally. And then we have things like excessive alcohol consumption,

which excessively means more than 2 glasses a day. We have social isolation. We have the pressure in midlife, more of an issue for women than for men. We have air pollution. We have low. This is a lower education is more like low intellectual stimulation. Right. I would say rather than just ears of schooling, although that is a factor as well. Hearing and vision loss, if untreated, so glass is hearing aids are becoming important for Alzheimer's prevention as well.

risk factors are 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. Anyone can do any of all these things, to reduce the risk of Alzheimer's. And now we're looking at other things like sleep. Very important diet and nutrition, obviously important. What a lot of people do. Everyone's having a meal. No, no, no, no. No, yeah, no, yeah. "Bos da voideur für alle zum Aldi preis. Milsani Milchnek, 10 mal 28 gram,

01, 09, 70 or Dr. Etka Vitalis Müsli, up 516 gram, 02, 02, 02, 02, Aldi. "Botes für alle."

“All right, well, let's talk about food. Is it what I love?”

In your books, is that you spend a lot of time talking about nutrition?

I love chemistry and nutrition is effectively by your chemistry and my daughter's undergrad before med school, Katherine's a 30-med student, and so her undergraduate is Nutrition Science, but she was a biochemistry program, not the cooking for a thousand people program. Nutrition Science goes two ways, you know, and she absolutely loved it, and I think it's such a strong foundation for her for school. It's so good. I also, I do not study Nutrition at school,

but I am kind of self-taught. At some point I was okay, just get me every chemistry book, because all the things I'm learning about brain health, all the potassium pumps, you know, serotonin is made of trip to fain, and these are all nutrients that come from food. They're not

“made by the brain. They are imported. So I loved it. I spent a lot of time. So that's what you”

really eat 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, okay? It's not even more of a picky either relative to other organs, and it loves predominant needs, predominately 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 predominately from fish nuts and seeds, and some marine algae, if you wish. And we're not really interested. That's where the fish get the omega-3 as they eat the algae. Yeah. So it's part of the food chain. So you can't tolerate fish or you're allergic, you can get the algae based. Yeah, absolutely. And obviously glucose is very important. But within reason, you don't need to eat a ton, but a little bit is important for brain function. Also for

the synthesis of glutamate. So a lot of people just look at glucose as a sugar, right? The glucose is a number of functionalities, and for the brain is they build in block of glutamate, which is the most prevalent glutamate in the entire brain. And it's needed to synthesize GABA, which is the prevalent inhibitory glutamate. So glucose is not just, and then thinking, when the keto diets come out, it was a little bit like, whoa, because it's important, not just for

energy, but also just synthesize. Okay, the most abundant glutamate transmitters ever have. Why are ultra-processed foods so bad for brain health? They're bad indirectly. So those kind of foods in nutrients should not be able to cross the blooddream 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 are bodies are just not equipped to handle, which then leads to oxidated stress and inflammation in 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 much every organ we have. Are there any supplements you

“think are high or are realistic for brain health? Yeah. I wish we had more data. I think there are”

some nutrients for the supplements that are clearly beneficial for brain health. And it makes sense that if you are deficient or subclinicaly deficient is some nutrients, then supplementation

because as we get a little bit older, it becomes more difficult to absorb in,

from the foods that we eat. And almost all elderly individuals are B12 deficient and just don't know that. So it's important to have them. Which are B12 levels and all of our, yeah, as a solid B6, because it's a really important brain vitamins as well. Clinical trials have shown mixed results. I think that supplement that we have the best evidence for is omega-3 fatty acids. And I am 100% partial to anti-oxidants. Full disclosure. I have no confidence of interest. I don't

sell anything. I love anti-oxidants because I think that the brain is exceptionally prone to oxidative

stress. It's actually the major cause of cellular and neuronal aging. And the brain is completely

“powerless against oxidative stress. The only way to counteract the effects is by”

importing vitamin A, C, E, Selenium and the anti-oxidant minerals through the diet. And very few people eat enough fruit and vegetables and some nuts and seeds to really ensure adequate levels. And then it depends and they do believe in a precision medicine approach and all 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, a few out of former smoker, which this is one of the biggest regrets in my life. Same. I quit at 23. Same. Me, too. You know, initially I was growing up there in every

“body. My body was coming out 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 a variant 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? Entry oxidants. So I understand that people won't clinical trials or 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 an antioxidant be just for our list? Vitamin C. Yeah. That's the number one. Even Dr. Pauling, you know, who's the one who discord by them in C and then won the Nobel Prize for the discovery. He took very hard doses of like I'm not saying anyone should try to do this and tell them to do it until the day he died. And he was just held there 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. Cleats good enough. All right. So elephant in the room, lots of talk worries, the metabolic side 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 the thing

“both are really important. And this is 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. There 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 the specifically tested hormone therapy, which in this case is high dose, oral, conjugated equine estrogen and MPA as the projecting,

withered without an MPA and placebo. And they followed this women first to the number of years

and what they showed is two things. Number one, they could not use Alzheimer's disease as the end point because two few women developed Alzheimer's disease. So they had to switch their end point to dementia.

to male disparity. The other forms of dementia that the women in the women's health initiative

memory started 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 the 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 women who were taking only the estrogen, there was a 50% increased risk that was not significant.

These results are not generalizable to meet life women because these patients were much older. Yes, and as we were talking about before, the system may no longer be there. The estrogen receptor binding may not be working the way that it does once you steal or reproduct it once you're still

“transitioning to your non-reproductive life. When you're 20 years passed, it may just not work.”

You're bouncing off of a closed door. Yes, that's the way to put it. And also those are different formulations to what the women would use now. And the new one, the newer formulations

have never been tested this way. So we cannot generalize and we also cannot generalize to Alzheimer's

because that was not the endpoint. All right, please, if I gave you a billion dollars. Right now, what study would you? What would be 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 meat life are going through manopause and they're taking hormone therapy, especially after that micronized astrodial and progesterine which are closer to whether bodies naturally

produced, those using brain scans so that you can know what kind of those 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 tangled 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 sorts 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 fifty million.

But let me show you the observational research. Because we have 20 years worth of evidence from preclinical studies that hormone therapy started around the time of manopause is brain protective. And 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, with a hysterectomy and/or upherectomy. Whereas estrogen with a progesterone, we can't yet separate, like progesterone, I was already progesterone to progesterone, we observational data, but there's still a trend towards the risk reduction. This does not mean that every woman needs to take hormones to reduce the risk of Alzheimer's

in means that we do need to do the research. And something that we show 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 the studies show a protective effect. Northern Europe is red, not protective, not protective. Why? We don't know. But there's

something there. It could be the kind of hormonal formulation that was used to diagnose the criteria 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

you need to go on hormonal 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 hormonal therapy prevents this was said at a national meeting just a month ago. Oh, yeah. I heard it on social media actually. It could be me's interpreted. It's kind of saying the same thing that we need to do the research,

“or need to do the work. But what people understand, I believe correct me, English is my”

third language, but what I would understand is that the right research has been done and there was no benefit. This is what I understand. There is no evidence that it works. Well, we could say that I think it's 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 the scenty we can test. For instance, we can check whether it works for some women or not others. We can check if it works

genetic. 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 protected 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 and know”

combined. And just because the women's health initiative didn't work out, it does not mean that we can't stop all financial research in menopause. So for a woman who's sitting in home right now, listening to us and feel scared, what do you want to say to her about her brain health and moving forward? I would say that we all have more power, not over our brains, but we do have the power to support the health of our brains. And that if you make the right choices in life, it takes consistency,

it takes work, but really the benefits are for life. There are also new studies done specifically on menopause showing that the symptoms can be milder, the experience can be gentler if you take care of yourself. So I would encourage everyone to think more of their brains that can muscle. There are things that you can do to support the 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 meat life 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 what was most women really have no time for

“themselves, but I think it's really important to take a step back and say I also need time for me.”

Right? Self-care is not selfish. You want to take care of yourself so that you can give so much more to your family, to your job, to your friends, and to yourself as well. Well, this feels like this

has been a life-changing conversation. Always every conversation I have with you and I am so

excited for our listeners to hear this episode. 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 thepausedlife.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

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 in opinions expressed on pause are those of the talent and guests alone

and are provided for informational and entertainment purposes only.

“Make the gants just like this, and when they are done, they will catch it.”

-That's right. -Safe. Like this?

Hold it down. Now it's time to look. Now it's time to look for the news.

“No part of this podcast or any related materials are intended to be a substitute for professional”

medical advice, diagnosis, or treatment.