How Does Menopause Change Your Brain? (with neuroscientist Lisa Mosconi)

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0:58Here we go. Lisa Mosconi is a leading expert in women's brain health. She is an associate professor of neurology at Cornell, where she's also the director of its Women's Brain Initiative and the Alzheimer's Prevention Program. She is a New York Times bestselling author, and her latest book is called The Menopause Brain. Today, Lisa explains how hormonal shifts during perimenopause and menopause can impact cognitive health and how many of the symptoms, including hot flashes, brain fog, depression, and anxiety, start in the brain. We talked about how menopause is still overlooked and understudied and the societal stigma that marks menopause as the end of a woman's life.

1:43Instead, Lisa sees menopause as an opportunity, one that imbues a post-reductive woman with the value that she deserves. She shares some of the clinical trials and brain imaging work her lab is doing to better understand the stage of life and her key advice for what women should be aware of when it comes to keeping our brains healthy as we age. This book is great. Thank you. I have so many questions. Oh, good. I'm glad. There were so many things illuminated for me when I was reading, and then so many things that I wanted to double click on. I had never really fathomed that hormonal changes impacted the brain.

2:25So when I was looking at the brain scans that you've put in the book, anecdotally, you know, a lot about hormones and moods and all this, but I never realized that when you map the brain that you can see that there are biological changes happening in the brain. So does this start in puberty? And where does this, the impact of hormone shifts start to impact what the brain looks like? Like you said, they start the puberty. So there's a system that connects the brain to the ovaries that is called the neuroendocrine system. So neuro for brain, endocrine for hormonal system that we are born with. So all individuals who have two X chromosomes and they're born with ovaries are also born with this pathway that connects the brain to the reproductive organs that is silent, if you will, until puberty hits.

3:23And then the system is activated. And the way that the brain talks to the ovaries and the ovaries talk back to the brain is by shooting up and down hormones. These chemicals, they were called sex hormones, which is completely a mislabeling. So they were identified by scientists who were looking at reproductive function. And so as they were founded in 1930s, the scientists referred to them as sex hormones. But it wasn't until 1996 that other scientists discover that the same exact hormones that are important for having children and just having reproductive fertility are also just as important for the functioning of our minds and their brains.

4:06Those are neuroprotective hormones. They are growth hormones. They're energizing hormones. They do so many things inside your brain. They were just really starting to fully understand. But to your point, puberty is when the system is activated. And then what happens is like this connection between the brain and the ovaries is turned on and is consistently evolving every month as the ovaries cycle. The brain micro cycles, which is something that we never talk about. And then the system is over activated during pregnancy every time a woman gets pregnant. but then it needs to be turned down after menopause.

4:51And it's the turning down that triggers a rewiring in the brain that also prompts some of the symptoms of menopause, the vulnerability that we associate with menopause, but also at the same time changes your brain in such a way that enables women to outlive menopause and spend another 20, 30 years in a non-reproductive stage that can be just as productive. And it's really these changes that enable all this. And I think it's so important to talk about them because we don't. As a society, as women, even as academics, we just don't talk about the importance of this network for not just for reproductive function and reproductive health, but also for brain health.

5:41I want to know more about something you just said, which is that the changes enable us to live for another 30 years after menopause, plus or minus, which is super interesting. You know, you talk about in the book that we're really the only mammals that live a long time after menopause and that throughout nature, what's the most normal is that, you know, an ant, even chimpanzees, right? You say they're most closely related to us. They die a couple of years after menopause. So what did you find in your research about why human beings, like what is the evolutionary purpose of us being able to live 30 years after menopause when none of our cousins in the animal kingdom seem to mimic those patterns?

6:38That's right. Let's put it this way. The scientists are debating over this point. And there are two major schools of thought. There's scientists who believe that menopause is a mistake, that medical technology and hygiene and advancements have prolonged and extended women's lives beyond what nature intended. And then there are many more scientists, I would say myself included, who look at the evolutionary significance of menopause and the role that women serve for society and in the lives of the family. And then we land on the grandmother hypothesis, which is lovely and makes also a lot of sense.

7:28So the pushback that we're getting in this respect is that the theory of evolution states that the only purpose of life is to pass on your genes to the next generations. So menopause, in that respect, is a pure contradiction of Darwin and whatever he's thinking about. Menopause goes directly against this year of evolution because when women stop being further in midlife and they live past it, then that is very bizarre from an evolutionary perspective. But if you think about it, it makes a lot more sense for women to stop having children at some point in time and to remain available to their daughters and sons and help them raise their kids, basically.

8:20So our prehistoric grandmothers at some point most likely had an evolutionary advantage by becoming grandmothers, not longer being reproductive, but being able to stay there and raise the grandchildren and make sure that their own daughters could have more children and still be safe and fed and taken care of. And I think this is a much more flattering view of women of all ages. And anyone who's ever had a grandmother could probably attest to the fact that grandmothers are extremely productive and extremely valuable and extremely important for families. And some even say that these grandmothers who were able to survive multiple childbirths and also live past menopause, but not just any grandmothers.

9:09Those were the fittest women in the tribe. Therefore, most likely they also had some kind of super genes that made them particularly strong and resilient against aging and a number of issues. And therefore, we are now blessed with their genetics that enable us to live very long lives that can be very healthy and fulfilling, just not reproductive for a certain amount of time and the thing is it makes a lot more sense to me it's a very beautiful theory as well and a theory that imbues an older post-reproductive woman with the value that she deserves you know it's like a societal place that that she's fought for and won and and deserved and gives a lot of respect yes for sure i think it's this whole narrative of women only being helpful for as long as we are reproductive is completely outdated and the sad part is that it's really the backbone of modern medicine and it's one of the reasons that we know so little about women's health just for context the fact that estrogen is not just a sex hormone but also a brain hormone was discovered in 1996.

10:29Men landed on the moon 30 years prior. We know more about space than about women's brains. I find this so bizarre. And I think it's time for scientists to start looking into women's health in a more integrative way, not just breasts and ovaries, but we need to look at women as organisms, not just some parts and bits and pieces that magically come together and make a person. Do you think we're starting to have a more female-centric understanding in medicine? Is there a shift towards wanting to understand and provide care? I would say yes. There was this really important study that was published almost 15 years ago now, showing the heart disease manifests differently in women than in men, right?

11:24And now everybody is aware of that. I mean, I don't know if everybody, but many people are aware of that. And that was really shocking. I feel like it was quite groundbreaking for not just for cardiology, but in general for scientists to be able to push back a little bit more. For me, my background is in neuroscience. I'm a neuroscientist and I study Alzheimer's disease, especially prevention of Alzheimer's disease. Because your mother had Alzheimer's, right? My grandmother. Your grandmother. Yes. So my grandmother was one of four siblings, three sisters and one brother. And all three sisters developed Alzheimer's disease and died of it, whereas the brother did not.

12:08And that was very scary for us. And I'm from Italy, like we were talking about before. And there's no senior homes in Italy. There's no assisted living. So my grandmother was living with us. And that was shocking in so many ways and heartbreaking in so many ways. But also as a PhD student, my question immediately was like, is it just me? Is it just my family or are women overall at higher risk for dementia? Now we know better. We know that almost two thirds of all Alzheimer's patients are women. And there's a strong interest to understand why. whereas for a long time people would just say oh it's just longevity like for me it was consistent everybody would say to me oh you know sweetheart it's just that women live longer than men and Alzheimer's disease is a disease of old age therefore more women than men end up with dementia and I was like but we don't live that much longer than men and so my PhD thesis actually was about showing that Alzheimer's is not a disease of old age, but it's a disease of midlife with symptoms that start in old age.

13:25And that changed the whole question because then the question was, okay, if Alzheimer's starts in midlife, then what happens to women and not to men in midlife, it could potentially explain the higher risk of dementia later in life. and we tried all these different things we did so many different studies and then we realized that menopause was really what was tipping the scales wow and that's how i started to study menopause but it was really going against what we were told there's just longevity there's nothing about women it's not important and as soon as we started talking about hormones everybody thought I lost my mind.

14:07So what conclusions or what lines were you able to draw between loss of estrogen and the propensity to develop Alzheimer's? I would say that estrogen is a very brain protective hormone and so is progesterone. So as women go through menopause, the brain needs to adjust to the loss of a very strong protective element. Therefore, for a certain number of years, the brain becomes more vulnerable in some ways. And that is potentially why we see that women have an increased risk of depressive symptoms during menopause or of anxiety, or women who have a predisposition to Alzheimer's disease, like women with a family history or the APOE4 genotype, we tend to see the signs of Alzheimer's disease in their brains during the transition of menopause.

15:06So in a way, menopause doesn't make you sick. It doesn't cause any diseases, but you as a woman may be more vulnerable to developing certain medical risks or conditions as you transition to menopause. It's a little bit like an activator it's not something that makes makes a sick and it's certainly not a disease or a medical condition but it is it feels like it sometimes i heard that i hear that often but there's a difference between a disease and a risk factor so i would say that menopause is a risk factor for certain medical disorders or certain medical conditions, but it's certainly not illness.

15:55What are some common misconceptions about menopause and aging that you aren't aligned with? Oh, there are quite a few. I would say the most immediate one is that most people think that menopause happens when you're old. And I think it's important to realize that that is not the case. The average age of onset in the United States at 51, 52, but globally is 49. At Goop, we believe the spaces we spend time in shape how we feel and how we connect. That's why we're drawn to Convene, a global hospitality brand reimagining work in meeting spaces centered around design and care. Convene's sophisticated, purpose-built locations are designed to inspire connection, whether it's a board meeting for 10, a team off-site, or a workplace membership that gives you and your team a home base.

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17:31Even earlier than that. For some women, it's even earlier. So the average age perimenopause is 47, but the range is between 32 and 55. I think just a couple of women can make it to 55. Yes. So it can span easily a decade. The average duration is seven years, between four and seven years, depending on ethnicity. But it can last a decade. And a lot of women are just not aware that that's something that can happen to them in their 30s or 40s. I have a friend of mine who's 38 and she was having a really hard time and she went to so many doctors and the doctors just could not place it, could not understand what was happening.

18:16And it just - That's insane. It's like the most simple blood test to do. Or even just ask, I asked her, is your period consistent? Are you skipping periods? And she's like, yeah, I just missed my period a couple of times. I was a little worried. I said, well, you know, it could be perimenopause. And she's like, I'm 38. I said, yeah, it could be like, exactly, you're 38. You need to go see a doctor. You need to have it tested. And so she went and sure enough, she's in perimenopause. And it's very early, but we know that the age of onset, so women who are like African-American women, Hispanic women tend to start the process even earlier.

18:59And do you attribute that to what? I mean, is it tied to a socioeconomic thing as well, like environmental toxins or? Potentially, surely there's some genetic background and then there's stress, perhaps stress. And yeah, there's a trauma seems to be associated with that too. The thing about menopause is that it is shockingly understudied. This is something I do not understand. Every woman who lives long enough, but just pretty much all women go through menopause in the course of their lives. And we know so little about this process. We know more about puberty by a long shot. We know more about pregnancy, even though not all women get pregnant.

19:49And we should know about pregnancy. We should really know a lot about pregnancy. But then menopause arrives and nobody knows what it is. We don't talk about it in the family. My mom never talked to me about menopause until I asked her because I wanted to know, okay, what am I, you know, what's it going to be like? Because it's linked in part, it's genetically linked. So your mother is actually your best predictor of what your menopause is going to be like, at least in terms of when, what age, what kind of symptoms. My mother can't remember. I'm like, what's the deal? Like, what am I up against here?

20:26And she's like, I can't remember what happened. That's a good sign. Maybe it wasn't that bad. And then she just does it. Oh, it was bad. Believe me. I think she just doesn't remember when it happened, when it was all over with. So if someone like to this end, if somebody is experiencing symptoms earlier, as opposed to later, how is that that in and of itself affecting cognitive function and overall brain health? I think it depends on why you were experiencing menopause earlier. There are women who unfortunately go through menopause for medical procedures like oophorectomies and hysterectomies, and the age of onset tends to be much earlier in life.

21:16And that also correlates with more severe symptoms of menopause because the change in hormonal concentration is more sudden, and it's more abrupt, you basically go through menopause almost overnight. Then there's other procedures like for patients who have breast cancer, right? There's chemotherapy and endocrine therapy that can trigger menopause either temporarily or permanently as well. And the symptoms tend to be more acute and potentially more severe. So this is also something, you know, This is something that is so upsetting to me that the medical framework for menopause completely ignores the range of symptoms.

21:58To think about it, for pregnancy, we finally acknowledge and formalize the fact that different women have different experiences where some women just breathe through pregnancy and postpartum, which is wonderful, but many women have the baby blues. Some women experience postpartum depression and some women have postpartum psychosis. So there is an understanding that the experience can really range in severity and intensity and duration. And that is extremely important because now you go to the pediatrician and they screen you for depression as a mother. And there are medications that are being developed specifically for postpartum depression and postpartum psychosis.

22:40There's no such thing for menopause. for as long as you have a menstrual period even if it's just once every 11 months the answer is pretty much just oh you have your period still so just kind of green and better and once you have the symptoms it's like it's like a one-size-fits-all experience do you have half flashes well let's talk about how many how long how severe what kind how do you respond to them Do you feel dizzy? Do you have palpitations? Let's check that your vascular system is intact. There's none of that. There's no acknowledgement that there are some women, 10%, who breathe through menopause again, who are perfectly fine, have no brain symptoms, at least, on menopause.

23:26And there are women who are suicidal. And there's no acknowledgement to that. And that really, in a way, invalidates women's experience and makes you less able to advocate for yourself when you go to your doctor. And it also limits your physician's ability to help you. yeah what are the things that we should ask for when we go to the doctor whether we're 38 and experiencing you know some thing we don't even know it's hormonal changes like up through full on symptomatic perimenopause like what are the things when we go in what do we need to be asking our doctors we need to be asking for a thought of medical evaluation that also includes information from our family, family history.

24:15In my opinion, it's very helpful to know if your mother went through menopause early, late, somewhere in between, maybe you have a sister, an older sister, your aunts, because it does run in families to some extent. And then it's important to discuss things that one may have done to impact their own menopause, like smoking. We don't talk about it that much but tobacco smoke is the number one ovarian toxin and if if you've smoked at least 100 cigarettes in your entire life they may lower your age of menopause oh boy so only 100 cigarettes god i think i burned through that that number and by 1997 i think that may lower your age a menopause and i i think in that case it's really important to focus on antioxidants to help balance out whatever damage the cigarettes may have done i take vitamin c supplements daily for the same reason because i grew up in italy everybody was smoking and so i did too and 100 cigarettes not that many at the end of today seriously i feel like i had certain bad weeks where I smoked a hundred cigarettes in a week.

25:31But then other things that we need to ask is for a complete medical checkup. And what does that involve? Like, tell us exactly. So you said, you mentioned the thing about our vascular systems. How do we check that? What do we ask for? Yes. In terms of blood work, like give us the list. So it depends on which specialist we're going to, right? So right now, menopause is OBGYN territory. And that is wonderful because the ovaries are really important. However, there's more to menopause than just the menstrual cycle. So what we do, I run the Alzheimer's Prevention Program at Wild Cornell Medicine in New York City, where we have an Alzheimer's Prevention Clinic as part of the program.

26:20And we work very closely with our colleagues in OBGYN, but also in cardiology, in preventative cardiology, and we work with endocrinology, and we work with metabolic health, so that our patients really receive integrative care that covers many different aspects of menopause. So for my part, a lot of our patients come to us with brain fog. Yeah. Over 60 % of women going through perimenopause and menopause, postmenopause. They're coming to be evaluated in the Alzheimer's prevention clinic? Yes, they're terrified. Right. They're so scared that they might be developing dementia, early onset dementia.

27:03That comes up a lot. Like, I can't think straight. My brain is not functioning. I can't turn my brain on. My brain just is not responding to me. And I'm so scared. This happens a lot to our patients who come to us because they can't remember things. They're fumbling with words. They lose their train of thoughts. They walk in a room and can't remember why they're there. This happens to me all the time, by the way. Is this scary or are you more like whatever? You know, I think at first I was scared by it because I used to have a very strong facility with language and word recall. And I consider myself to be relatively articulate.

27:44articulate, but when, but now what will happen is I will literally not, I'll know sort of the abstraction, the shape of the word in my head, but I can't translate it into something that will come out of my mouth. So at first I was really scared when it started happening. It was also dovetailing with long COVID. So I had brain fog anyway, but this was really cognitively, I was like, Oh my God. But then I started to have, there was some pattern recognition that around right before my cycle, it got really bad. And then afterwards, the words would sort of slowly start to come back, but really through my menstrual cycle, I had really low cognitive function.

28:29I mean, for, for me. And so now I'm not as scared by it. And, but I'm like, you know, and I've had a brain scan just to make sure. Well, I strongly recommend it. This is what we do with our patients. When they come to us for brain fog, obviously we need to do a lot of exclusion analysis to make sure that this is not like a vitamin deficiency or it's not thyroid disease or you don't have a brain tumor. So we do a lot of tests, including cognitive testing and brain imaging because my background is in nuclear medicine. I do brain scans for a living and I think it's so helpful and so important to check that your brain is okay, because otherwise, how would you know?

29:12So when we do cognitive testing, what we've learned about brain fog in particular is that if you start up here, right, there's a high chance that most women experience a dip during perimenopause. And then there's either a stabilization or a rebound, or some women keep declining. And it's really important to understand the trajectory of changes over time, because for those who rebound, great. That's a sign of pain. Have you identified the factors that help them rebound? We are studying this. The whole field is trying to understand that better. There are a few things for sure. Overall medical health is a big factor.

30:02How you go through menopause is another big factor. Women who go through menopause spontaneously as part of the aging process tend to have a more gentle transition as compared to women who are... What is spontaneously? Like it just stops one day? Yeah, spontaneously is for most women when there's no surgeries involved. There's no medical procedures. There's no POI. Most women go through menopause. Clinicians say natural menopause. Menopause, I find that it's not a very thoughtful word in some instances, because you are suggesting that a woman who goes through menopause because of a medical procedure is doing something unnatural, unnatural.

30:43So I prefer spontaneous. So I say spontaneous. Other people do too. But so most women go through menopause just as part of the aging process. Usually the transition is more gentle, but then for some women, the cognitive decline is persistent and it doesn't resolve a few years after menopause. That's when we start talking about Alzheimer's prevention and we're a little bit more aggressive, if you will, in terms of what to do and what not to do. But overall, medical health is a big factor. History of smoking and toxin exposure is another factor. Certainly your exercise levels, overall inflammation in your body is another factor.

31:27And for some women, hormone therapy is helpful or other interventions that reduce and alleviate the symptoms of menopause. Because the more symptoms you have, the more half-flashes you have, the more night sweats you have, the less sleep you get, the more stress you have, that all impacts your cognitive performance in the end. And it's kind of hard to disentangle what's driving what. So we're just mostly trying to go after solutions. And I'm just excited that today we have a new study that was published just this morning that is the largest meta-analysis, the largest integration of all data available that looks at hormone therapy and the impact on cognitive function in women going through menopause.

32:15Because every time we try saying that hormone therapy might be helpful for brain fog, then the pushback immediately is that where are the clinical trials? And so we put them all together, our clinical trials, so we put them all together. And the analysis shows that hormone therapy may help support cognition, at least for some women. So it's something that is worth looking into. And so it's diet and exercise, but you need to, you know, one step at a time. Yeah. Can we spend a little bit of time on hormone replacement therapy? Because this is something that I've read a lot about and I still am a little bit confused.