Why Are Most Alzheimer's Patients Women? - with Dr. Lisa Mosconi | The Empowering Neurologist EP. 94

Well, hello everyone. I'm Dr. David Perlmutter. Welcome again to The Empowering Neurologist. Women get Alzheimer's disease at a rate of 2 to 1 in comparison to men. Why is that? What is unique about a woman and a woman's brain that makes women more susceptible to this type of brain degeneration? Well, there's a lot of differences to look at that may possibly explain this, and a lot of differences that may explain other things like rates of depression, for example, being greater in women. And we're going to explore that today on our program with Dr. Lisa Mosconi. Many of you know Dr. Mosconi. She's been on the program before. Her new book is called The XX Brain. And if you don't know much about genetics, XX is the fact that women have 2 X chromosomes as opposed to XY being what the male chromosomal array would look like, at least with respect to the sex chromosomes. Elise Mosconi has a PhD. She's the director of the Women's Brain Initiative and associate director of the Alzheimer's Prevention Clinic at the Weill Cornell Medical College, where she is an associate professor of neuroscience and neurology and in radiology. In addition, she's an adjunct faculty member at the NYU Department of Psychiatry, and she is the author of the book Brain Food, which I have here, which we have talked about before. She is always a wonderful guest, and in the spirit of our time together today, I've invited to be my co-host today my wife, Liz Perlmutter. So let's get started. Hello, Dr. Moscone.

Hi, thank you for having me.

Well, congratulations on doing the Today Show today, as it were. That's really great that you're getting information out about your amazing book. This is just terrific. I've had the opportunity to review it over the past couple of months, actually, which I'm happy to say, as I think I texted you along the way, a picture of me highlighting your book and telling you how great it was. I

didn't receive that. I didn't see the picture. I didn't—

No, I did, because you answered me.

Oh, well done. There you go.

All right, you're doing all the things in your book, so I know you remember. Anyhow, let's start off with the problem, and then at the end we'll provide the solution. So tell us how big this problem is, and then You know, specifically about women?

I think we do have a problem as related to women's brains. And the problem starts with really the acknowledgement that we never talk about women's brains. Even when we talk about women's health, we don't talk about women's brains. In fact, especially when we talk about women's health, we do not talk about women's brains, which is bizarre in a way because we're talking about their breasts, we're talking about their ovaries, we're talking about their reproductive organs. But brain health is just not part of the conversation. And this is a concern, especially for us as neuroscientists and doctors working in the brain health field, because women's brains are not the same as men's brains. And for a really long time, there was a misconception that women were essentially smaller men with different reproductive organs, which I refer to as bikini medicine. In the book, and we're now learning to appreciate how women's brains are fundamentally different from men's brains. Not in terms of structure or anatomy. It's not like we have some parts of the brain that the men don't have or the other way around, but really in terms of functionality. And these differences are really important for health because I'm now going to answer your question. We have some scary statistics out there. Yeah. So women are twice as likely as men to suffer from anxiety and depression. We're 3 times more likely to develop an autoimmune disorder, including those that attack the brain like multiple sclerosis. We're 4 times more likely to have headaches and migraines. We're much more likely to develop a meningioma, which is the most common form of brain tumors. And we're far more likely, again, to die of a stroke should a stroke occur. And on top of all this, women also have a much higher chance of being diagnosed with Alzheimer's disease, which is the most common form of dementia.

Let's start by just— I mean, the title of your book, The XX Brain. Maybe let's start— let's look at the genetics of this. We know that women, as you just mentioned, have a higher risk for autoimmunity, i.e., there's something involved in the immune system/inflammation. We know that, I don't mean to be too technical, but a similar increase in autoimmunity is seen in, for example, Klinefelter's. So is there something unique about this extra X chromosome or protective about the Y chromosome? What can you tell us?

I think it's really, it's really interesting how genetics play or don't play out in terms of phenotype, right, and the health risks that actually manifest themselves. We do know that the XX genotype is different from the XY. genotype because these chromosomes differ in some ways. Just to start with, the X chromosome is much bigger than the Y chromosome. It's 10,098 genes against the 78 genes of the Y, the tiny Y chromosome. So as soon as a woman is born, she's coming to this world with 1,000 more genes than a man. And many of these genes are actually involved in brain function. And like you mentioned, there are some disorders and conditions that are related to having more chromosomes or fewer chromosomes that are related to a number of problems. Like sometimes there's inflammation, sometimes it's infertility. But I think overall, men's brains and women's brains have unique strengths and capabilities and also unique risk factors that we're starting to understand a little better. And I think we don't yet fully understand what the definitive risks are, but inflammation is definitely a big one for women's brains.

Mm-hmm.

And this seems to be more of a problem for women's brains because our brains are somehow less equipped to really respond to the inflammation. Our microglia, the cells in the brain that are responsible to turn on and off the inflammation, are not as efficient in a woman's brain as much as in a man's brain. So this is also one thing that we need to really consider.

You know, a lot of what you talk about later in the book has to do with lifestyle choices and diet and nutrition, and, you know, I think we should probably finish up there later on, but I was very taken by a lead article in JAMA recently talking about how the focus on brain degeneration is really brain energetics, looking at glucose metabolism, and in fact I recall when you and I lectured some time ago, probably last year, I actually used some of your images that showed changes post-menopause in glucose and sugar utilization in the brain. And we know that is sort of a harbinger for future diagnosis of Alzheimer's. So what is it about metabolism, then, men versus women, that might explain these changes in the brain?

Yes, that's a really good question. And we can speculate, and this is a lot of my research really that's focused on hormones and the effects of these hormones, we call them sex hormones, in the brain. And I think everybody's aware that men and women have somewhat different hormones. Like women have more estrogens, like estradiol, estrogen per se, progesterone, and men have more androgens, like testosterone. Mm-hmm. The same thing happens inside our brains. So it's not just in the body, it's also in the brain. However, hormones in the brain are involved in a lot more functions than just reproduction. And in particular, both estrogen, especially estradiol, and testosterone are really crucial for energy production in the brain. So at the cellular level, these hormones literally push neurons to burn glucose to make energy. So if your estrogen is high as a woman and your testosterone is high as a man, your brain energy is high. But what the problem, if you will, is that these hormones have different lifespans. So testosterone doesn't quite run out abruptly until late in life, and even then it's not like a sudden loss of testosterone. It's kind of more of a gradual decline with age, whereas women lose their estrogens quite quickly in midlife during menopause. And that has consequences not just for the body, which are obvious, but also in the brain. And we have shown using brain scans that if you look at a woman's brain before menopause, you can see like these brain scans, they're really usually pretty energized, right? You can see a lot of activity. The scan is nice and bright. But then that same woman scanned again during perimenopause, which is right before menopause, and then after menopause, those brains literally show a decline in brain energy levels and in glucose metabolism or glucose utilization that can be as severe as 50%. Like, the average in our studies is about 30%. So there's quite a drop that serves as kind of the substrate for the Yeah. The symptoms that women talk about, like when women say, I'm having hot flashes, night sweats, insomnia, anxiety, depression. Brain fog is a big one that correlates with these changes in brain metabolism and even memory lapses. Those are really strongly related to the hormones not working as efficiently in specific parts of the brain and metabolic activity being suppressed as a result of that. And like you said, we know that metabolic reductions of a certain intensity, of a certain severity, have been strongly associated with a much higher risk of Alzheimer's disease later in life. So great news for women.

So what are your thoughts on hormone therapy moving forward after menopause?

I have a lot of thoughts, and I'm actually really excited that we're starting to look into that more specifically. The shortest possible answer is that hormonal therapy can be very helpful to alleviate some of the symptoms of menopause, like hot flashes, but also to minimize the risk of osteoporosis, for example, or it can help with reduced sex drive. In some women, but it's not currently recommended for dementia prevention. And that's for a number of reasons, including that for many, many years we were giving hormones to women who were too, just really many years past menopause. And then we learned that that actually might increase your risk of dementia if you start therapy after, I would say, more than 6 years past menopause. It's actually not helpful to your brain at all. And it can be harmful. And now we're actually looking if starting earlier could potentially have benefits because if you think about the physiology of how these hormones work inside your brain, the whole mechanism is that the estrogen needs to bind to a receptor and the receptor needs to be active to receive the estrogen. So if you haven't had any estrogens for a long time, the receptor just shuts down because that's what they do. And if you then try to reactivate these receptors by just giving hormones, that's just not going to work. So we need to catch women when their receptors are still working, and then we can give the estrogens to make sure that we get a response. And I'll just say, because I know you like this part, that one of the reasons we're having trouble timing the therapy and really calibrating the dose is that we do not yet have a tool that allows us to measure these hormones in women's brains. We can measure hormones in plasma, but there is no correlation between hormones in plasma and hormones inside your brain. So we need a tool that allows us to really understand how these hormones work inside our heads. And I'm really pleased to report that we developed this new technique, which is now with the FDA, for approval. So I'm hoping that very, very soon we're going to be able to, to provide this missing information that is really important for women's health and women's brain health.

Dr. Mosconi, I'd like to go back to just a moment to the energetics part. And certainly that relates to what we were just talking about with respect to estrogen. But you are really quite emphatic in the book in talking about carbohydrates And the specifics of carbohydrates that women should consider in the dietary recommendations. Why is that such an important player? And let me just say this in the context of something you just mentioned a moment ago. You said in the same sentence the words Alzheimer's and prevention, and who knew, right? But anyhow, let's go back to the whole carb question.

Yes, and I would like to also clarify that not all carbs are equal. There are some healthy carbs and some unhealthy carbohydrates. And the research in— the research focused on women's health and women's brains has shown that some carbohydrate-containing foods are actually really beneficial to women's brains. And these are the carbs that we don't usually think about as carbs, like especially fruits and veggies, right? So fruits and vegetables are in fact carbohydrates. Right, they're carbohydrate-rich foods. They're not necessarily pasta and bread, as much as I love those, being Italian. But yes, there is quite a bit of research showing that for women, especially having fiber in the diet is really important. There is a lot of research showing that fiber really has a positive effect on hormonal levels because it regulates the sex hormone binding globulin, which is that molecule that is responsible for kind of shuttling hormones around in the body and making them available for functionality. So having enough fiber in your diet is really something that turned out to be quite beneficial for women's health overall. Mm-hmm. For me personally, it doesn't matter where the fiber comes from. I'm more concerned about people who just do not consume enough fiber-rich foods. So I think it's really important to get You know, at least enough vegetables.

I mean, people just don't seem— they think fiber is this inert stuff that's contained in food. We never, until quite recently, made that connection between fiber, the microbiome, microbiome, and the

brain.

Right. And again, that's certainly where the science is now. And how wonderful, because it is really giving us a lot more, a lot more areas to explore, and a lot more tools in the toolbox.

Right, and also something that I think has been a little bit overlooked is the hormonal effect of foods. There are many foods that contain estrogens, for example, in the form of phytoestrogens, and there is quite a little bit of research showing that diets that contain enough of foods that contain phytoestrogens can really be supportive of women's health. And these foods are— soy is the food that contains the most phytoestrogens in the form of isoflavones, but there's a lot of doubts around soy and it is a common allergen, so I wouldn't recommend that. But there are many other foods that are actually safe and contain lignans, the other class of isoflavones that have been beneficial for a number of concerns that women have, like from hot flashes to depression to menstrual pain, fertility, infertility, depression. And these foods are really yummy. So I would go with sesame seeds, are a very good source, flaxseeds, dried apricots, some legumes. I don't know how you feel about legumes, probably don't eat much of those.

You know what, I really backed down off the lectin concern pretty much. And, you know, we have to, I think, have outreach that's a little bit more inclusive. I think when we become so exclusive, people are just going to abandon Most of what we're saying because there's nothing left to eat.

Yeah, this is not fun, right? If you just get food, it has to be something enjoyable that you just really— I don't know, I think there's also something to be said about frequency and quantity, right? If you have just a little bit of something once in a while, the effect is different than eating tons of the same thing every day in terms of exposure and

So

I

would like to share an experience that I had when I was going through menopause. I had a 4-centimeter fibroid, the largest one was 4 centimeters, and they were getting ready to schedule me for a hysterectomy. And I said, let us have just a little time, let me work with this. And I took all carbs out of my diet, I took dairy, alcohol, And caffeine. And within 2 months, I went to see my gynecologist and she looked at me and did an ultrasound. She said, you have the uterus of a 16-year-old. There's no way you have fibroids. And it was looking at all those different pieces of diet. And I also looked at medical qigong, but the diet was instrumental.

And that's wonderful. And it really makes me feel that We could benefit from research on this because I would love to know if it's the same for all women. You know, what kind of factors—

That kind of takes us to your comments in the book about gene polymorphisms and being able to be, you know, being able to take advantage of what you call precision medicine. So how far along are we on that continuum, do you think?

I think, well, I think we've done— there's been quite a little bit of progress in many fields. In the brain field, I think we're not quite there yet. There are some genotypes that we're very familiar with and have been quite thoroughly explored, especially in Alzheimer's disease. Everyone is kind of obsessed with this APOE gene. It's an apolipoprotein E, which is encoded on chromosome 19, and it's It comes in with 3 different variants. There's the APOE2, APOE3, and APOE4 variant. And for some reasons, the APOE2 variant is very protective against Alzheimer's disease. APOE3 is kind of neutral, and APOE4 has been linked to an increased risk of Alzheimer's disease. So it's not a genetic mutation, it doesn't make you sick, but it does seem to increase the risk, especially if you have 2 copies. of the gene. And we're now understanding that that gene is involved in cholesterol metabolism. It's like a chaperone for cholesterol, and the APOE4 variant is less efficient than the other 2 variants at moving cholesterol around. So I think that works in combination with other factors, like are you an overproducer of cholesterol? Are you an overabsorber of cholesterol? And what is your APOE4 genotype? And all this information together can really help guide the recommendations that are being given.

So let's say we have a patient who is either heterozygous or homozygous for APOE4. Do the recommendations that you make, do they change based upon that genotype?

Sometimes. So I am the associate director of the Alzheimer's Prevention Clinic at Weill Cornell, which is really led by Dr. Richard Isaacson, whom I'm sure you know very well. And he has this incredible way of diagnosing a person's APOE genotype by looking at your legs. I have no idea how he does it, but it's like 100% accuracy. For a scientist, it's just so upsetting, right? It's like, how is that happening? But he has a whole procedure that does incorporate APOE genotyping into the evaluations. And we— We look at so many different parameters and that really includes brain scans. For me personally, the brain scan is really the way to go along with everything else. So I really, I find that looking at people's brains is an incredible way to really diagnose and treat.

Yeah, that's really sort of the endgame there, isn't it?

I think so. I personally, I can't wait to see my brain. And schedule to scan my brain. I was too young before, now I'm old enough that I can fit in my own protocols and I'm excited about it.

Actually, we both have a pretty sophisticated brain-based genotyping program going on right now. We haven't gotten our results back, but we're looking at that. I want to just go back to the idea of differences in What might the manifestations be of carrying the APOE4 allele or not? And one of the studies that I find is really kind of compelling for audiences is comparing the risk of having a brain scan with high levels of beta amyloid, in looking at either, do you have insulin resistance? Do you carry the APOE4 allele? Do you have both, or do you have none? Right. And it turns out that insulin resistance is a much higher predictor of having a positive amyloid brain scan than is APOE4 allele, which is to say that pretty much a lifestyle choice is far more influential in determining that you do or don't have a lot of amyloid in your brain in comparison to something that you really can't change, in other words, a genetic issue that you've inherited. So, you know, I think that what you're talking about throughout your book is that, yeah, we have our genes, but that lifestyle is so hugely important here. That said, one of the questions I always get is, how did you— how did you get so involved in Alzheimer's? And I know your story, and you recapitulated it this time in your book as well, Mm-hmm. with your grandmother and her I think her sisters, was it? Or—

Yes, yes, I am.

Tell us what that was like and how that might have motivated you.

Yes, so I have a family history of Alzheimer's disease that really hits hard the women in my family. My grandmother was one of 4 siblings. There were 3 sisters and 1 brother, and all 3 sisters developed Alzheimer's and died of it, whereas the brother did not, even though They all lived to the same age. And I was in it. I'm from Italy. I'm from Florence in Italy. And in Italy, there was no assisted living. There were no senior homes. So my grandmother was with us until the day that she passed away. And my mom was the primary caregiver. And that was incredibly shocking for us as a family. It was incredibly hard to witness that kind of— Just decline and all the different symptoms and the implications of those. So I was 19 when I said, I'm going to look at Alzheimer's disease, and especially Alzheimer's disease in women. And back then, number one, we didn't know at that point that Alzheimer's affects more women than men. We didn't even have the statistics. And once the statistics became available, people would just completely dismiss that. Because there were 2 erroneous assumptions being made on this topic. And really what people said would be that, well, Alzheimer's disease is a disease of old age and women live longer than men, so of course they get Alzheimer's more. So it was basically a question not worth looking into. But I was like, well, I want to look into that because there's something in my family that suggests otherwise. And so my entire career has really been dedicated to better understanding women's brains, and especially in terms of risk of Alzheimer's disease. And I think we were very helpful in really changing the question to, well, number one, women don't live that much longer than men. Just even just that, right? So in the United States, women live on average 4.5 years longer than men, not 20. Yeah. And in England, for example, the gap is like 3 years. But Alzheimer's disease is the number one cause of death only for women and not for men. So that can't be the only explanation. And in fact, it turns out that Alzheimer's disease is not actually a disease of old age. We associate Alzheimer's with the elderly because that's really when the symptoms become manifest. But in reality, the disease starts With negative changes in the brain years, if not decades, prior to cognitive symptoms and clinical symptoms. And once we understood that, then the question changed to, well, then what happens only to women and not to men in midlife when Alzheimer's begins inside your brain that could potentially impact your Alzheimer's risk later on in life? And that's really how we came across menopause, which was very surprising to me as a neuroscientist. Who would have thought?

So I have one other question, and that is you talked about exercise in the book and that as you get older, maybe it is better to do exercise but not nearly as aggressively. Can you address that?

It's interesting. We just talked about that with Maria. on the Today Show how important it is to remain physically active besides mentally active at any age and how that is specifically important for women. Because if you think about it, women tend to exercise less than men to start with. These are official statistics in part for a number of reasons like you have kids, you have to raise the kids, and then you have to care for older parents and you're holding a full-time job. And then there's the hormonal changes leading up to menopause and after menopause that can make a woman feel tired or fatigued. So everything is more appealing than going to the gym. Like, the couch is definitely the place to be. But it's really important to challenge ourselves more, especially during midlife, which is really any age from 35 to 60, let's say 40 to 65 and beyond, because I encourage everyone to think of their brains as a muscle. There are things that you can do to strengthen it. So if you feed it properly and you exercise it properly and you take care of your brain properly, then it's going to just perform so much better for you. And exercise is a really big preventative against aging and Alzheimer's disease, especially in women. New studies have shown that women who are physically active in midlife and afterwards have a low— have a 30% lower chance of developing Alzheimer's and dementia. Whereas women who are sedentary, literally 1 in 3 have been found to develop Alzheimer's and dementia as they get older. So my point was—

I don't want that to get lost because that's really quite something, that women who are active have a 30% reduction for the— for a disease that has no treatment.

Yes, 30%.

Yes. 30% reduction in a disease that has no treatment. which we have no treatment whatsoever. Who wouldn't take that information and staple it to the wall? I mean,

that's huge.

Yes,

I agree with you.

I

always say, you know, if I had a pill that reduced risk of Alzheimer's by 30%, I would be rich and everybody would buy it. Instead, I'm just a scientist and the prescription is just try and exercise as much as you can consistently.

Yeah, but you're putting out information. And that the people who hopefully need it are going to buy. The problem is people have a lot of information. It's really acting on the information, doing what Dr. Mosconi is saying, and that is cut down on your refined carbohydrates, get some exercise. By the way, recognize that sleep is pretty important, and you might consider taking some supplements. You do have a relatively short list of supplements that you recommend, including—

Yes.

B vitamins and ginkgo. Can we go through those real quickly?

Sure, yes. The reason that the list is short is that I really went for supplements that were validated in clinical trials that focused on women. So that narrows the options quite a bit. But there is literature and there are studies that show an advantage if you take supplements in some specific conditions. I would not recommend like a blanket use of supplements as much as a targeted and again, the precision medicine approach that we mentioned before. I'm also, I should say that I'm part of the Global Council on Brain Health at the AARP, and we just recently had this big meeting about supplements for brain health. We were 36 scientists who do look at diet and nutrition and lifestyle and Alzheimer's disease, and the overall conclusion was that supplements are not Quite, but the supplements cannot replace a healthy diet for starters. But if you haven't—

That's why they're called supplements, of course.

Thank you. Yes. But a lot of people kind of, you know, they're like, well, I have that big pizza and then maybe take some vitamins and maybe an ice cream, but I have my vitamins. I think that's something important to mention, that supplements just cannot replace a diet. They need to be taken on top of that. And I find them to be very helpful in case of deficiencies. Or even just if you're on the low range of what an optimal nutritional profile is based on testing. So at the Women's Brain Initiative, which I lead, and also the Alzheimer's Prevention Clinic, we do quite thorough testing and we look at levels of omega-3 fatty acids, for example. The omega-3, omega-6 index is a really important predictor of brain health and brain aging. We look at antioxidants, which I'm personally obsessed with because a lot of my research has shown really strong correlations between a high intake of antioxidant vitamins, especially vitamin C and vitamin E, and higher brain energy in women. And we know that brain energy is a problem for aging women because it drops during menopause, doesn't quite get back up until much later on. And so these vitamins could potentially be very, very helpful, as well as the B vitamins you mentioned, especially vitamin B12, B6, and B9, or folic acid, for women.

When you talk about vitamin C and E, are we looking at extrapolation from food frequency questionnaire, blood levels?

No, blood levels.

Or are we looking at actual intervention with a given amount? And if so, how much?

Well, so it depends. I think what we do is that we really test it in plasma. So for every patient we know, there's a range that is considered healthy, and if you are below range or even just borderline close to too low, I think it's helpful to recommend supplementation. And that's usually, it depends on the person, body weight and a number of factors, but in general, studies have shown that, I think it's about 300 milligrams of vitamin E per day, then in combination with— actually, I can tell you the exact numbers. 400 to 800 IUs a day of vitamin E and about 500 mg of vitamin C.

And do you make any specific recommendation on the type of vitamin D? Is it D-alpha-tocopherol, mixed tocopherols, gamma?

I'm sorry, I meant vitamin E and vitamin C.

Right.

For vitamin E, usually we recommend a mix of alpha, beta, gamma, and delta tocopherol. Vitamin C, I think, is just one isoform, right?

Right. And then with respect to omega-3 supplementation, are you delineating between— in terms of the ratios of EPA and DHA, or how does that work?

We try to maximize the DHA in the diet and we measure both, of course. We measure ALA, EPA, DHA. What the brain really needs is DHA. So I think the concern is for people who don't eat any fish, which is one of the best sources, natural sources of DHA. Mm-hmm. My concern would be for people who are strictly vegan or very strict vegetarians or just people who really hate fish or are allergic to fish for some reasons because the omega-3s that you can get from plants is mostly ALA and it needs to be converted to DHA in the brain and about 75% is lost in the conversion. So you need to have, you know, you need to eat 3 times more to reach the same level. If we're thinking about omega-3s from the diet, then research has shown that you want to have at least 4 grams of omega-3s per day in your diet to really support the health of your brain. And if you're able to reach 6 grams, it's even better.

So, you know, there is obviously an algae-derived DHA that's available for those who choose Purely vegetable, plant-based diet. And then as it relates to B6 and B12, you do talk in the book a bit about homocysteine. Maybe for our viewers, we could just walk through that a little bit?

Yes. So high homocysteine is a risk factor for vascular damage, stroke, and also vascular dementia. And it's not uncommon. It's found in quite a few people, especially after age 50. And the interesting thing about homocysteine is that it works in balance with specific B vitamins, especially vitamin B6, B12, and B9, or folate. So when we test it, all our patients get tested for high homocysteine levels, and in some cases, B vitamin supplementation has been shown to be very helpful in normalizing the homocysteine because they work in balance. And the concern about homocysteine is that it's been associated with brain shrinkage already in midlife. And the good news is that clinical trials using brain scans have shown that in patients with mild cognitive impairment, especially those with high homocysteine levels, high-dose supplementation with B vitamins was really able to bring down the homocysteine, and that correlated with much better brain scan outcomes. over time. So the rate of atrophy was much lower in those who were treated with the B vitamins as compared to those who were not. And I think that's an incredible demonstration that diet really has an impact.

In my day, we didn't have— all we had were correlative studies that demonstrated higher homocysteine correlated with increased risk and certainly correlated with increased risk of cerebrovascular disease as well. And we took the leap and said, therefore, We need B6, B12, and folic acid. We didn't know about people with MTHFR polymorphisms and why some people were not responding. But interestingly, back in the day— I'm really sounding old— is we would use methylated B12 injections and finally that would turn the trick. And now we understand that probably, you know, we might have had some of the MTHFR individuals who were not responding.

Yes, and it's so much more common than we thought. The specific genotype and the different variants.

That's me. I'm all

of

those.

Oh,

really? Oh my goodness.

We didn't know there was something similar. Before we go, can we, as I look over here at Matthew Walker's book, can we talk about the value of sleep in terms of protecting the brain?

Yes, gladly. I actually really loved his TED Talk. It was a big inspiration for my talk, which actually comes out next Tuesday. I'm really excited, my TED Talk.

Oh, I can't wait. Comes out next Tuesday. I'll promote it for you.

Thank you, thank you. Yes, so sleep is very important for brain health, and according to the National Sleep Foundation, women have a harder time sleeping than men, which is not, you know, every woman can tell you that within the new statistics. But it looks like women have a harder time not just falling asleep but also staying asleep. sleep. And that is a problem for a number of reasons. I mean, poor sleep or disturbed sleep has been associated with every possible risk factor or risk under the sun, from impaired memory, which is, you know, my daughter didn't sleep for 2 and a half years after she was born and I could barely think straight. But also with an increased risk of anxiety and depression. And also now recent studies have shown that Especially if your slow-wave sleep is disturbed, that really impairs the brain's ability to get rid of toxins and waste products, including Alzheimer's plaques. So sleep is not just something that makes you feel better, it's also something that your brain really needs from a physiological level just to be able to stay healthy. And it's hard to get a good night's sleep. Yeah. But there are things that people can do to really at least prioritize sleep. I think we live in a society where sleep is seen a little bit like a commodity. And I come from a society where sleep is really celebrated. Like, my grandfather used to take naps every day after lunch. And there's a whole culture around sleep as something that really benefits your body and your soul and your mind. And I think we could really all learn to really look at sleep more respectfully and just really try to optimize

it. Well, this is an amazing book,

and thank you, and thank you so much for your quote. If you notice, it's the very first one on the, on the back.

An empowering guide giving women the ability to direct their brain's destiny. I mean, that's pretty empowering, but you, uh, the book absolutely lives up to that, and it's, it's super And I think it's so timely that we recognize the differences. And, you know, you make it very clear at the beginning of the book, the shortcomings as it relates to research, medical research in general, as it relates to women throughout, you know, decades, centuries, particularly as it relates to the brain. And it's, it's great that you're moving the needle in terms of setting things right. That's terrific.

Thank you. I'm really hoping that we can make, we can make a difference because Still today, women's brain health is one of the most underdiagnosed, under-researched, and undertreated fields of medicine. And honestly, women are half of the population. So we really— I think it's wonderful that everybody's coming together to really support women's health and women's brains and trying to change the conversation for the best.

Well, it's, it's great to spend time with you, and I'm sure Your book is going to do incredibly well. So I hope we get to see each other soon.

Thank you. Oh good. Thank you so much. And you're most welcome to go to come and get a brain scan if you like.

We will.

Together. That way

we'll make a day of it after a good night's sleep. So thanks again and we'll talk soon.

Thank you so much. Really appreciate it.

Okay. Bye for now.

It was lovely to meet you. Bye.

Bye. Well, we learned a lot today, didn't we? Dr. Mosconi, as usual, is just a wealth of really important information, really at the end of the day letting us know, in this case letting women know, that their lifestyle choices are hugely important as it relates to determining their brain's destiny. Thank you for joining us. I'm Dr. David Perlmutter. Bye for now. Bye for now.