Exploring the Link Between Menopause and Alzheimer’s


By Deborah Copaken

It started with an artichoke. Or rather, it started with my inability to recall the word artichoke, even though I was holding one in my hand. “What did you get for dinner?” my partner Will asked from the other room, and I said, “Salmon and… ” My brain went blank. Or rather it went from blank to asparagus, even though I knew that asparagus, while in the correct spiky vegetable ballpark, was wrong.

“Yes?” said Will.

I started to panic. Words are my stock-in-trade. They’re how I make my living. If I couldn’t come up with a simple word for the vegetable right there in my own hand, who was I? I carried the mystery object into the room where Will was working. “What is this?” I said. “I can’t remember how to say it.”

He looked alarmed. “You mean… an artichoke?” He smiled. Was this some sort of a joke?

My relief was palpable. “Oh my god, yes! Thank you!” And yet I was still disturbed. What just happened? I’d been having what I thought were all the normal issues with word recall, keys and glasses locating, and wait-why-did-I-just-go-into-this-room moments over the last few years after turning 50, but this felt different somehow, more disturbing. More urgent.

I immediately Googled “memory loss menopause,” and 13.8 million hits appeared on my screen. Was memory loss an inevitable by-product of menopause? And if so, why? I started digging. And that’s when I stumbled upon a recent op-ed in the New York Times by neuroscientist Lisa Mosconi, who is studying the link between menopause and Alzheimer’s. The question she asked herself, in her research, was a deceptively simple one: Why do twice as many women get Alzheimer’s as men? The statistics with regard to women’s longevity versus men’s cannot explain away this enormous discrepancy. Could menopause offer any answers?

So on a warm spring day, just after the artichoke incident, I biked from my home in Brooklyn to Dr. Mosconi’s office at Weill Cornell in New York City. (Exercise, we now know, is one of the key risk reducers for Alzheimer’s when done in conjunction with healthy eating, getting enough sleep, and stress reduction.) Herewith is a slightly condensed transcript of my conversation with Dr. Mosconi, which I’m keeping long not only because nearly everything she said was both fascinating and news to me, but also because I’m assuming if you are a menopausal woman reading this right now (or someone who loves us), you might have lots of questions and/or unnamable artichokes in your life too.

Dr. Mosconi in her office in New York Photo: Deborah Copaken

Deborah Copaken: So, let’s start at the beginning. How did you get interested in this specific topic? Alzheimer’s in general, but also women in Alzheimer’s specifically?

Lisa Mosconi: When I was in college, my grandmother started showing cognitive and behavioral changes, and within a couple of years she was just not herself anymore. She was diagnosed with dementia. It was a very slow and painful process. Everything went backward. She was up all night and asleep all day. My mom turned into the primary caregiver, and that was devastating for her, not just emotionally but also physically. And she was also trying to hold onto a job. And those were the years when my mom was going through menopause as well. So it really was shocking to witness what was happening to my grandmother and at the same time what was happening to my mom. My grandmother had three siblings; two girls, you know two sisters and one brother. The two sisters got the same exact thing years later. Her brother did not.

Oh my goodness.

So that was quite shocking, and I was like, “Oh dear, what if it runs in families?” I knew nothing about Alzheimer’s. I was 19. And so I started doing a lot of research on that. My parents are Nuclear Physicists. And their students were babysitting me when I was little, but we stayed in touch, and as soon as I mentioned wanting to look at the brain and Alzheimer’s, they said, “Volunteer with us. We’ll train you.”

You were 19, and you were researching in nuclear medicine already?

A year later, yes, I was 20.

Okay, so you were still in university, but studying nuclear medicine on the side. As one does. So how old is your mother right now?

74.

How’s she doing?

She’s fabulous. She goes to yoga three times a week, she can do headstands, she eats super healthily, she is incredibly intellectually active.

I’ve seen studies that show that instead of just doing brain games such as Sudoku or crossword puzzles, there’s evidence that just staying at your job in your sixties and seventies is good intellectual training if you want to try to avoid cognitive decline. What do you say to that?

There is an association between Alzheimer’s risk and education, and also occupational attainment: Having a job that you’re good at. So there’s an association between being good at your job — having a job that brings out the best in you in some ways, whether intellectually or in other forms — and lower risk of dementia down the line. There are some studies showing that postponing retirement has also been associated with a lower risk of dementia in later years. And I think it all comes down to cognitive reserve.

Cognitive reserve?

Yes, cognitive reserve. Your brain is built of neurons and connections between neurons. And these connections need to be strengthened because otherwise, they will die. There’s a process called pruning, where if you don’t use your dendrites, the connection between neurons, they will atrophy, and will actually withdraw. So it’s really kind of a “use it or lose it” situation in the brain.

Right. Which brings me to my next question, a personal one: I know that writing is good for my brain, but at 53 years old, having been a writer my entire life and now going through perimenopause, I find —

Would you want to get your brain scanned?

Yes, let’s do it, that would be fun!

That would be wonderful.

Because what I have noticed, as a writer who obviously needs words to create what I do, I sometimes cannot remember… the other day I could not remember the word… and here I am forgetting it again! It was, oh my God, see, here I go again. It’s not asparagus, but it’s the thing that looks like this, and it’s got the little pointy things —

Artichoke?

Artichoke! Yes. See, I knew it started with an “A,” and it looks like the top of the asparagus, so that came to mind, but I couldn’t think of the word for artichoke. And it was driving me crazy. I had it in my hands, even, and I couldn’t remember what it was called. And if you hadn’t just said it right now, I would have had to look up vegetables on my phone, I mean literally look up “green vegetables pointy leaves” and find it on Google. But this happens all the time to me now and I’m thinking that oh no —

Word finding.

Word finding. Exactly. And I don’t have any history of Alzheimer’s, but I have noticed that just in “brain abilities,” let’s call it, I’m losing it. And as a writer, that’s scary.

Well, for sure.

So when I read your op-ed, even though I work in this field, I did not know that women are twice as likely to get Alzheimer’s as men.

Yes.

At the same time, I also know that women’s health is poorly studied. I will give you an example from my own life. So when I had my uterus removed, a hysterectomy, I was asked, what do you want: a partial, full, or a supracervical? And I was like, I don’t know —

They’re asking you?

They’re asking me! And they said well, it’s believed that the cervix plays a role in sexual pleasure. And I was like, Seriously, are you kidding me? This was back in 2012. So they took out the uterus and kept the cervix. Five years later, the cervix becomes diseased, has to come out, and when I went to see the surgeon who was going to remove it, she said, “Why didn’t you get this out when you got the hysterectomy?” I said, “I was told that it plays a role in sexual pleasure.” She goes, “No, no, that was debunked last year.” I was like, “Why don’t we know these basic things about female health?” And she goes, “Welcome to my world.”

I agree. We know even less about women’s brains. I mean, if we can’t even get the cervix right —

We finally just got a 3D model of the clitoris two years ago! Two years ago! So now I know these things about my reproductive organs I should have known years ago. What I’m concerned about now is the brain, women’s brains in particular. So what does your research show? What have you found about menopause, perimenopause, and women’s brains?

Well for one we have known for a good 10 years that taking out the ovaries or the uterus, increases the risk of dementia in women.

Wait, what?

This is true.

This is news to me right now.

Is it?

Yeah.

[At this point, I have to turn off the tape recorder, catch my breath, and curse. Loudly.]

Let’s start again, shall we?

It’s true. There’s a strong association between early menopause and an increased risk of Alzheimer’s in women. And oophorectomy, which is the surgical removal of the ovaries, increases the risk up to 70%.

70%????!!!!??????

Yeah. If it’s done bilaterally, meaning you have both the ovaries taken out. But then there were other studies showing the risk is also increased when the uterus is removed, regardless of whether the ovaries are still in place.

What?

The reason being, when you remove the uterus, blood flow to the ovaries is also compromised, so you’re disrupting the system. In some ways, the ovaries may or may not be impacted by that. So there is an increased risk of Alzheimer’s also with a hysterectomy. And that’s why many people have been looking into estrogen, and the connection between estrogen and Alzheimer’s. There was that disastrous clinical trial called the Women’s Health Initiative. For many years, women were given estrogen as soon as they entered menopause, with the idea that lack of estrogen is what causes a lot of the problems during menopause, from increased bone frailty, increased risk of heart disease, increased risk of diabetes, and increased risk of dementia. The association was quite well established, so it makes sense to think, well, can I just give you the estrogen back? Right?

Right.

And so many providers did that. It was actually kind of the norm for women with the diagnosis of menopause, which is at least 12 consecutive months without your period, to be put on estrogen and left on estrogen for life. And that was done for so many years before the NIH started a clinical trial to test the efficacy of these formulations. So the Women’s Health Initiative started in 1993, and it was huge. There were like more than 50,000 women involved in the trials. The trials went on for many, many years and then all of a sudden there were halted because early findings showed an increased risk of pretty much everything: An increased risk of blood clots, an increased risk of stroke, an increased risk of cardiovascular disease… so it was basically a disaster.

Ugh. Let’s go back to women and Alzheimer’s and your family. So, you have your grandmother and your two great aunts, all of whom got Alzheimer’s. But your great uncle, their brother, didn’t. Why?

Yes. I wanted to know why this was happening. And everybody was like, it doesn’t matter if you’re a man or a woman, it’s exactly the same. I was like, no it’s not. You can see the patients! They walk in the door, and sometimes there are women who are clearly having a problem, but they do not “test” impaired. A doctor wouldn’t be able to give them a diagnosis of dementia or Mild Cognitive Impairment because their cognitive performance is still good even though they’re clearly dysfunctional in every other aspect of their lives. But they don’t score as impaired. This came out a few years ago, that the tests we were using to diagnose Alzheimer’s were not sensitive enough for women at the early stages because women score better than men on cognitive tests and always have. The cognitive score declines a bit with menopause, and then after menopause, but even women with a diagnosis of early Alzheimer’s may score better than men with the same diagnosis of Alzheimer’s.

So the doctor can see plaques on the brain, they know these women have Alzheimer’s, but they’re testing well on cognitive exams.

They’re testing fine! We couldn’t see the plaques in the brain until 10 years ago because we didn’t have the technology. So now that we have the technology to find the plaques, we actually understand that we probably misdiagnosed women forever. And that could be one of the reasons why some treatments don’t work that well in women. There’s also this whole thing, because we catch them too late, that the typical Alzheimer’s drugs work better in men than in women. And one possibility is that men and women with the same symptoms do not have the same brains. The men’s brains are still here, but the women’s brains are down here…

[She holds her right hand up high, representing men’s brains, her left hand down low, representing women’s brains.]

… and that’s why the drug just can’t bring them back up. So there’s an entire field that’s been severely gender-biased, and the bias is just now being revealed. It literally has been only two years now that everybody is talking about it, finally.

That’s great?

Yes, it is, but it took me 20 years to get grants to actually look into this discrepancy.

It took you 20 years to get grants to look into this?

It took many years to convince the medical community that Alzheimer’s differs by gender.

I’m reading a book right now, I forget the name because I probably have Alzheimer’s too, but I’m reading a book right now about women and data bias. [Note: Invisible Women: Data Bias in a World Designed for Men by Caroline Criado Perez.] The author has this part where she talks about how they studied Viagra —

Yes! Female Viagra, which was tested in 23 men!! And only two women.

Yeah, but they studied Viagra, and they found that with women, it completely eliminated period cramps for four hours at a time with no side effects. And the doctor that discovered this went back to the NIH, twice, and said, “We need further studies on this. This is the holy grail for women,” and they said, “Well, dysmenorrhea is not a real issue.” So we now know everything we need to know about penises and how they get hard, and how Viagra can make them harder, but nothing about how Viagra could be helping the other 50% of the population, enormously.

Yes, there are so many things that were just completely disregarded.

Even this desk. This desk is not built for me, and it’s not built for you either. I was at the New York Public Library before I came here, and I was sitting there going, this table, this is made for a 6-foot man. I can’t type here. It’s too high. I was with my boyfriend, who is 6 feet tall, and I was like, you are comfortable at this table, I am not: Discuss.

Yes, absolutely, we need pillows! And then the solution for a woman is to sit on a pile of pillows and make it work. We get this all the time, you know, just make it work. And the same is true in medicine. What we found, when we finally got an opportunity to look into that, is that women’s brains age differently than men’s brains.

That seems really important and unknown. What? Women’s brains age differently than men’s brains? How so?

For example… wait, I also want to underline that it’s not that we age worse, but differently. That’s important because —

Because there’s a judgment associated with better and worse, got it —

There’s a judgment, yes. We just age differently, that’s all. And basically what we found — and this is a lot of my own research — is that Alzheimer’s is not a disease of old age. We tend to associate it with the elderly because that’s when the clinical symptoms become manifest, but in reality, Alzheimer’s begins with negative changes in the brain at least a decade prior. Most often than not, in middle age. Middle age is considered to be 40 to 60 years old.

So then the question that we asked was okay, we know that Alzheimer’s affects more women than men, and we know that Alzheimer’s starts in midlife. What happens to women and not to men, in midlife, that could potentially trigger an Alzheimer’s predisposition, and that could potentially initiate Alzheimer’s? And I was thinking, thinking, thinking, and I said, menopause? It’s the one defining event in a woman’s life that happens to every single woman and does not happen to men. Could that impact the brain? And my background is in nuclear medicine, which is a branch of radiology, then I work in neurology. Nobody talks about hormones. Nobody talks about menopause as something that could potentially impact your brain, because nobody has done the studies. So we were like, hmm, we have the population, which is quite unique, because usually people who do brain scans, like I do, look at patients who are 60 and older, whereas I wanted to look at risk factors for Alzheimer’s, so I’ve always been working with people who are younger, like 40-60. Because before 40 you shouldn’t have hormonal changes unless you have a hysterectomy. But we looked at women that hadn’t had a hysterectomy or OVX who were 40-60 years old and divided them into pre-menopause/regular cycle, perimenopause—when you start skipping your cycle and you start having hot flashes, night sweats…

Yup. That’s where I am. Fun!

… insomnia, some depression, some word-finding issues, and cognitive slippage. And then we have men, exactly the same age. And we did brain scans in all of them, and then we looked at the data. And what we found is that if you are a man, 40 to 60 years old, your brain is broadly fine. You have high brain activity, you have no Alzheimer’s plaques, and if you do it’s just a few, and your brain is not shrinking. On average, you’re fine. But if you’re a woman, it makes a huge difference whether you’re pre-, peri-, or postmenopausal. If you’re a premenopausal woman, your brain is broadly the same as a man’s the same age. If you’re perimenopausal, we find a dip in brain energy levels, which is really brain glucose metabolism, the way the brain burns glucose to make energy. In some cases, it’s up to 20% worse for women, and that gets even worse once they transition to menopause. The scan literally goes from bright red and yellow to green.

What does that mean? What does the red and the yellow mean?

That your brain activity is nice and bright, and then it drops. In some women by as much as 50%.

And green is bad?

Well, darker is worse, yes. You want your brain scans… I’ll show you.

Yes, I’d love to see.

[She opens a file on her computer.]

Dr. Mosconi shows the difference between pre-menopausal and menopausal brains. Photo: Deborah Copaken

At the same time, we found that the women who show these energy drops, they start accumulating Alzheimer’s plaques. We have at this point hundreds of patients, and we also follow them over time, and we really show the change as women go from premenopause to perimenopause to postmenopause. Not all of them. There are some women who are fine, and some women whose brains are much worse. Because, when women tell you, “I’m having hot flashes, I’m having night sweats, I can’t sleep at night, I can’t think straight, I have brain fog, I get confused, I can’t multitask” — so many women tell me they used to be so good at multitasking, and now just can’t quite do it as well — those symptoms don’t start in your ovaries. They start in your brain! And it’s something that’s been completely overlooked. These are neurological symptoms of hormonal changes.

And we’re associating hormones only with what’s going on in the uterus, right?

Yes. We’re just thinking it’s about not having kids anymore. But that’s not the point. The point is that my brain, in middle age, is changing, and how do I make it better?

Yes. How do you make it better?

Well, it depends. So there are two separate components, and this is really what I’m trying to clarify. All women experience hormonal changes. For some women, they’re not a big deal. For some women, they range in severity, from mild to severe, and need to be addressed. For some women, they are so severe, that they can actually trigger Alzheimer’s.

Wow.

Yeah. If you have a predisposition for Alzheimer’s disease.

Genetic predisposition to it, right? Or just any sort of predisposition?

Any sort, because we have patients here who do not have any known genetic predisposition for Alzheimer’s, but they start accumulating Alzheimer’s plaques, and we know that Alzheimer’s is genetic in 1% of the population. Then about 30% has some genetic risk factor that doesn’t cause Alzheimer’s, but they increase your risk, like having a family history or having some specific genes. But the rest of the population has none of this, and they still get Alzheimer’s. So the question is why? One day we’ll find out what causes Alzheimer’s in people. Right now we don’t know, but we do have markers of risk. So, if I know that if you’re at risk, then I’d want you to take action. And then it depends, are you having the symptoms of menopause but not the increase of Alzheimer’s risks? Then we address menopause only. But if you also have a risk for Alzheimer’s then we really need to address that now. Because that’s when your brain is triggering these changes. Estrogen is a really strong neuroprotective hormone. It’s strongly associated with the immune system, it’s a neuroplastic hormone, so if you lose it, your brain starts aging faster.

And is that the same as testosterone in men?

No.

So what do they have in their bodies that’s equivalent to estrogen that’s keeping their brains plastic?

Men’s brains are more testosterone-driven, but the thing is that they also have a little bit of estrogen. The thing is that testosterone can be converted into estrogen at any time.

I did not know that.

Yes, and the other thing is that in men, they go through andropause, which is the male equivalent of menopause, but it’s a slow gradual process that takes a long time. There are men who become first-time fathers when they are 75.

Saul Bellow. He became a father at 84.

Then there’s Mick Jagger.

Right, exactly. I’d probably have Mick Jagger’s baby if I still had a uterus.

[She laughs.] There are plenty of examples. They’re given a chance, they can still have babies, whereas women can’t.

Dr. Mosconi has an easy laugh. Photo: Deborah Copaken

So unfair!

So for them, their brains are not as nearly affected by that. It’s almost the same as aging. What I think happens is that for men, chronological aging and hormonal aging kinda go hand in hand, slow and steady. Whereas for women, chronological aging is the same as men, but endocrine aging is just: Boom!

Endocrine aging?

Yes, endocrine aging, so hormonal aging —

Endocrine aging, meaning you fall off the cliff, basically.

Yes. And we know that in the rest of the body when you lose your sex hormones — your estrogen and progesterone, FSH, all these hormones — the rest of your body starts aging faster. Your arteries harden faster, your bones become more fragile faster, pretty much anything that can age, ages a bit faster than before. All women know intuitively that when you’re past 45 if you go on a diet, it will take forever to lose the weight because your metabolism changes too.

Yes! I’ve eaten the same as I’ve always had, and I’ve put on like a pound a year since my mid-forties. It’s all sitting here, right in my midsection, and I don’t do anything different. And I used to be thin and now I’m —

No, you are still thin, but your body changes.

And the shape of it changes, where the fat goes, everything. And I see the number on the scale climb, and I’m like what, why? I’m being nice to you, body! I feed you good food, I exercise…

Yeah, it’s the same for every woman, and it is a consequence of estrogen depletion. Every woman knows that as you reach menopause, your hair goes dry, your skin goes dry, that’s aging. Nobody ever thought that the same thing would happen in the brain. Now, why are we not thinking that? Because, in neurology, we are trained to think that the brain is completely separated from the rest of the body. The brain is in charge of the rest of the body, but pretty much everybody assumes that the rest of the body doesn’t have much of an impact on the brain. And that turns out not to be true, in every possible discipline. I think people who discovered the microbiome really helped change this view of the brain.

You mean bacteria in the gut?

The bacteria in the gut, yes. They have shown that the microbiome has a huge impact on the health of the brain. So if your bad bacteria outnumber your good bacteria, that has an impact on the brain. And everyone said that’s impossible, but it’s not. There are products of these bacteria that can travel up the vagus nerve and affect the permeability of the brain, they can get inside your brain, they can change your production of GABA, which is a soothing, calming neurotransmitter. So if GABA is not being produced, you get stressed out and anxious, which is what the bad bacteria do to you. They kinda hijack your brain and then you get all stressed out and you keep doing all the negative things that will put even more bad bacteria into your body. So they’ve shown very clearly that your gut health has a strong effect on the health of your brain, but we know that. We know your heart, if your heart is not healthy, your brain is not healthy, because the oxygen can’t get in, the nutrients can’t get in, your iron can’t get in, you get anemia, you feel crappy. And the same for your ovaries; there’s a feedback loop between the ovaries and the brain, it’s called the HPG axis: A highway that we have inside the body, it connects the brain to the pituitary gland to the ovaries and the thyroid. So hormones can travel back and forth. And that’s how your ovaries are communicating with your brain. And that changes your brain in a big way.

So are you just studying women right now, or are you treating women as well?

We’re doing both. We have a research-only component, and we have the Alzheimer’s prevention clinic, in which we treat patients. And everybody has an option to go either route. So we have some patients who are just research patients because they don’t necessarily want to be treated. Also, we charge insurance with the clinic, which I think is fantastic because usually when you go to other Alzheimer’s prevention clinics —

You’re paying out of pocket.

You’re paying out of pocket, and it’s an enormous amount of money, whereas we take insurance.

And where are you finding your subjects?

They come to us.

Because they’re feeling foggy?

Yes. They’re concerned, perhaps, that they might be at risk for Alzheimer’s. They have a family history of Alzheimer’s, or they do a test that now is giving a lot of us headaches because it’s being marketed in some ways as an Alzheimer’s gene, like a mutation or something causative of disease and it’s not. It’s called APOE. But it does increase risk, so it makes sense to look into it. For the research study, I’m trying to do more community outreach, because I really want a diverse population.

Right, you need to get into the Black community and to the Indian community and the —

Yes, I want to have a research study that resembles the population we live in. Minorities are so important and unfortunately so underrepresented in research.

But also, one of the reasons that we know so little about women’s brains and risk of cognitive decline and Alzheimer’s is that every time somebody mentions it — even now, when I go give a talk, and I say, two-thirds of all Alzheimer’s patients are women all over the world — every time the answer I get is that it’s because women live longer. Every single time. And it makes sense, and for so many years, people were like, well, yeah, that must be true. And then nobody would look into that. And if you think about that, how much longer do women live?

Not much?

Four and a half years. In England, two years. Can that explain the fact that women have twice as much Alzheimer’s as men?

No.

No. So people started looking into that. They showed that when you have this complicated survival rate and all these models where you account for everything, you can account for current age, age of death, differences in lifespan, differences in mortality rates, differences in cause of death. So if you do your best, statistically, to account for all these parameters, still women outnumber men 2-to-1 in the population. Even in England, where the difference is only two years, it’s the same exact ratio. So we know there’s more to it than that. And what we’re showing is that it’s not just aging. Our study shows that possibly, women start the disease earlier.

Meaning what age?

Menopause.

So women start getting Alzheimer’s basically the moment that menopause hits if they’re going to get it?

Yeah, if they’re going to get Alzheimer’s, it looks like the disease starts when your brain is the most discombobulated it’s ever been past puberty. Whereas puberty was an explosion of joy and hormonal health, menopause is the opposite. There’s a crisis. Your brain is going through a crisis, and that’s when Alzheimer’s probably kicks in. Which means that women start the disease when they’re in their late forties/early fifties. In some cases before that if they get surgical menopause. And so you live with these changes in your brain and then, let’s say it takes 10 years to develop the symptoms, then if you go through menopause at 50, you might get symptoms earlier at 60. Whereas if you’re a man, and these changes happen to your brain just because you’re aging chronologically, then you might get it at 70 or 80. So, that might be part of the problem: That women have more years to experience the disease. Not because they live longer, but because they start earlier.

So interesting.

And so upsetting!

So here’s something that may be completely unrelated, but I think it’s worth mentioning. As a young child, I had severe headaches, and I was going to all these headache clinics, and they couldn’t figure it out. We never figured it out. And then I went through puberty, and they went away. So now here I am in perimenopause and getting severe headaches again.

They’re coming back. They might be hormonal headaches.

Exactly.

I never had this issue [headaches] either until I got pregnant, and after my daughter, Lily was born. Now, two days before my cycle, I get this migraine that’s just blinding. It’s right here where you said, in the back and then it creeps up so I can’t see from this eye.

How old are you if you don’t mind my asking?

I’m 41.

Are you going through menopause or perimenopause right now?

No.

Are you going to study yourself when you do?

Yes. Well, I’m going to study myself now. So I’m scheduled to do my brain scans in the summer.

Because you’re interested enough with that history of it to want to know.

I want to know.

What about your mother, did she do brain scans as well?

No. She lives in Italy, and they don’t do it there.

They don’t do brain scans there?

No, not preventative, no. It’s very unique what we’re doing.

Dr. Mosconi with brain scans of her subjects. Photo: Deborah Copaken

Did your mother, at age 74, become nervous about getting Alzheimer’s, or has she kinda pushed those thoughts away?

No, she’s great. She has an incredible personality, and she tends to worry a lot about me, but not that much about herself. Then, of course, she has concerns, like when she can’t come up with words, or she forgets things, but I think she’s just a happy person.

What would you tell a 50-year-old woman to do right now in terms of estrogen replacement?

So that’s a great question. I think it depends, and I just finished writing a new book about this. [The XX Brain, Avery/Penguin Random House, March 2020.] I describe this thoroughly in the book, but to give you a general sense:

First of all, I would like to know if there’s a risk of Alzheimer’s in the family. I would start with Alzheimer’s because we do Alzheimer’s prevention. If there isn’t, then I would go one route and if there is I would go more aggressive in a different direction. So generally, what came out is that the approach to menopause, especially where the brain is concerned, needs to be highly individualized. So I do need to know your breast cancer risk, and have you ever had cancer of any sort? And what is your risk of getting it in the future? There is a way to calculate a risk score that gives you a sense of not only occurrence but also recurrence.

Then I need to know your cardiovascular disease risk score, also to know if you’re a high risk for cardiovascular disease, then we need to go this way. And if you are low risk, then we can go this other way. I actually have diagrams in the book that one can follow. Are you having hot flashes? Yes/no. Do you have a history of breast cancer? Yes/no. And then there’s one solution for every branch of the diagram because they’re so different. And some are pharmaceutical, in some cases, drugs can be very helpful. In many cases, they’re not needed, and I always tell everybody before you take any medication that could potentially impact your brain or increase your risk of breast cancer, to always do the behavioral changes first.

If you’re a smoker, you should quit instantly, and so many women don’t appreciate how bad smoking is for you. And in fact, men’s brains and women’s brains are wired slightly different, in a way that the effect of smoking on dopamine activates different parts of the brain. In men, it makes you crave the effect of nicotine, but in women, it stimulates the brain centers that are involved in addiction. So women tend to develop a habit that becomes more psychological. It’s a habit. And that’s why the rates of successfully quitting smoking are higher in men than women. Because you can give men a patch and then you have the nicotine, and the brain is happy. But for women, this patch doesn’t help you with the ritual of smoking a cigarette. So it’s harder to break a woman’s addiction than a man’s addiction.

What about diet?

I think diet is very important. There is a lot of evidence that the right foods and nutrients can really help support the brain whereas the wrong foods and nutrients can increase risk of cognitive decline, increase risk of Alzheimer’s, and also make the brain symptoms of menopause worse. My first book, Brain Food, clarifies which foods and nutrients are crucial for long-term brain health for both men and women. In the new book, The XX Brain, I look into which foods and nutrients are specifically brain protective for women.

Okay, so what are the good foods for a woman going through menopause and what are the bad foods?

I would think about nutrients first, especially omega-3-fatty acids and antioxidants and probably phytoestrogen. I would go with these three. Omega-3 fatty acids mostly in fish, especially cold water fatty fish like salmon, trout, herring, anchovies, and sardines.

What about swordfish and tuna?

Swordfish, not so much. Also, it is high in mercury and could be contaminated. Tuna is not a particularly fatty fish unless you choose mahi-mahi which is the fancy variety. Any fish that contains omega-3 fatty acids is really important for the brain and has also been shown to reduce the risk of hormonal depression, especially during menopause. And antioxidants are really important for women’s brains.

So berries.

Yes, berries are great. So usually we think blueberries, but blackberries have a higher antioxidant potential.

Really?

Yes. Goji berries are also such a great source of Vitamin C. They are the most concentrated source of Vitamin C.

Where do you even find a goji berry these days?

Health food stores. Amazon. Actually, I buy them on Amazon often. You can also find the dark chocolate covered goji berries, and those are very good because the dark chocolate that is really, really dark, is good quality dark chocolate. So dark chocolate is actually an antioxidant. It contains theobromine, and theobromine is a substance that has a similar effect to caffeine in the body, but doesn’t give you the jitters, and stimulates blood flow to the brain, and is an anti-aging nutrient. It slows down cellular aging.

Dark chocolate slows down cellular aging? I am going to go buy a bar right now.

And it is good for your heart. It is very rich in flavanols.

Okay, so dark chocolate and berries, what else?

Fruit are generally good, and rich in antioxidants, like oranges, lemons, grapefruit, citrus fruits, they are very good. Apples are perfectly fine. Very legitimate.

What about bananas?

No, no. They are not a good source of antioxidants. Cherries. Fruits that are very bright that have bright, strong deep colors.

Kiwi?

Yes. Kiwi is very good. It is very rich in Vitamin C. Also olive oil, flax seed, flax oil. And almonds. Many nuts and seeds are actually good, too.

I was just in Istanbul yesterday. That is their diet. You’re just describing the diet of Turkey.

So the Mediterranean diet has been shown over and over again to be incredibly protective for women’s brains and for women’s health in general. There is a ton of evidence that it lowers the risk of cardiovascular disease, diabetes, obesity, breast cancer, and dementia in women.

What about dried apricots? Those are good too, right?

So, that is the third nutrient that I wanted to say, phytoestrogens. You get phytoestrogens from plants. So the fascinating thing about estrogen is that it is the most ancient of hormones, and so it goes across species. It’s found in plants.

It goes… across species?

Yes. You know all the formulations for HRT [hormonal replacement therapy.] The first ones were made from the urine of pregnant horses. It was called Premarin: Pregnant mare urine.

Oh my God. [Laughs.] I never knew that’s what it stood for.

I know. Such a lack of imagination, right? So there are specific foods that contain very high doses of phytoestrogens, like vegetables and other plant-based foods. All plants. Like from the berries of the plants, the grains of the plants, the fruit of the plant, and dried apricots are some of those with the highest concentration of phytoestrogens. Strawberries, also good. Melon, watermelon. Cherries. Chickpeas, flax seeds, and then soy. Soy is the one plant that has levels of phytoestrogens that are off the charts.

Wow. Okay, I am going to change our diet in our house. More Turkish apricots and nuts.

You know which nuts are really good? Brazilian nuts. They contain a good amount of selenium. Selenium is a very strong antioxidant mineral that is really hard to find in food, and Brazilian nuts are very rich in it.

Brazilian nuts are the big ones, right?

Yes, but they don’t taste that good.

I know, but you can mash them up into a smoothie. What else do I need to do, diet-wise, to keep my perimenopausal brain healthy?

Eat healthy. Do not eat processed foods. Processed foods are actually specifically bad news for women and women’s brains. They have been associated with an increased risk of many diseases in women and also with early onset of menopause.

Early onset of menopause from eating Cheez-Its?

Any altered processed food.

A Twinkie?

100%. Candy, too. All commercial products to some extent are processed foods. Some are clearly more processed. The Twinkie thing looks like plastic. So the closer it looks to plastic.

Or the closer it tastes to plastic. [Laughs.]

Exactly. The more processed it is. Fast food is highly-processed food because they use trans-saturated fats and many other products. They have partially hydrogenated oils, fully hydrogenated oils. Anything that is not natural is to some extent processed food. So we need to be careful with that. Soda! No soda. We need to drink water instead of refined sugar, which also affects hormonal balance in the body.

Alright, so refined sugar we know is bad.

It’s gotta go.

But let’s say you’re at a dinner and there is an amazing dessert. Do you eat the dessert or not?

Of course.

Okay, good. [Laughs.]

Of course. The thing is, I am not going to eat it every day. It has to be an indulgence. It has to be an award, a special thing. And another thing I was surprised to learn is so bad for women is commercially grown, non-organic foods, whether they are vegetables and fruits or animal products, which then act like bad estrogens, so they really mess up your hormonal balance to the point that they are putting xenoestrogens — foreign estrogens — into your body. They have such an estrogen disrupting effect in the body that the American Endocrine Society clearly labeled them as a health hazard.

Wow.

Yes. So even some doctors now are like, you have to eat organic or that could really become a problem because everything from pesticides to plastics is in non-organic food, which can increase the risk of breast cancer, precocious puberty in women, man boobs in men. But most of these are particularly bad for children, especially girls, and pregnant women because it can cross the placenta. And also for women in general because they disrupt hormonal activity. So, my recommendation is to go organic whenever possible. If you have fruits and veggies that you peel, going organic is not as necessary because all of the chemicals are on the peel. Like bananas.

Avocados?

Avocados. But other fruits are highly contaminated. Like strawberries. Strawberries are the most contaminated non-organic fruit, and there are many other fruits and veggies that are best bought organic.

My mother and I, every summer, we have this stupid argument about organic fruit versus non-organic fruit, ever since I was diagnosed with atypia of the breast, which one doctor called atypia, the other called DCIS [ductal carcinoma in situ, cells within the ducts of the breast that have become cancer, but have not spread to surrounding tissue], but whatever. I say, “Please, when you go to the store, please bring back organic fruit. I’m not supposed to eat non-organic fruit.” What happens to the female body when you eat non-organic fruit? I know it’s bad, but I can never remember, in the heat of our argument, why.

I think we need more evidence to really know for sure what happens, but what many endocrinologists say is that it can really disrupt your hormonal balance. They compete with your own hormones. The way hormones work is that you make the hormones, and the hormones are in the bloodstream, and they find the receptor. They attach themselves to the receptor, and then the receptor does a number of wonderful things. It makes your brain more plastic, it makes your bones stronger, it makes your heart healthier. Xenoestrogens — like the kind found in non-organic strawberries — compete for uptake so they block the receptors. Your own estrogens cannot bind. They bind for you. And that, depending on you and your genetic predisposition and everything else that is going on in your life can trigger a number of issues. So, number one, they block the receptor, but they don’t trigger the same reaction. They kind of send the receptors a message saying, “Woooooo, what is happening?” At the same time, if you have a predisposition for breast cancer, it can actually have the opposite effect, making bad estrogens, overstimulating your receptors, increasing risk.

So where else are we getting these, what are they called, xeno…?

Xenoestrogens. They are everywhere, even in makeup. They’re in household products.

But specifically on non-organic fruit, where are we getting the xenoestrogens from? From the spray on top of the fruit?

Yes, from the spray on top of the fruit. Pesticides. All the substances that we use to make them grow faster and stronger.

They’re disrupting the hormones in our own body?

Yes, if you eat them. And the same in animal products. All these chemicals they are giving to animals to make them grow fast and strong and taste a certain way. Arsenic has been given to chickens as an antibiotic. And then the same chemicals are being passed on to the eggs, or to the milk in the cows. So for me, when I eat animal products, which is not super often except fish, I go organic.

So I am a 53-year-old woman who grew up in the United States which means I grew up on Ho Hos, Twinkies, fast food, and Coca-Cola. I am not unusual for my generation. I was born in the mid-’60s. A lot of people reading our blog are going to be in that same generation and have eaten the same crap that I grew up eating. So here’s my question: Are we doomed?

I think it is case by case. What happens, I find, especially to women, is that if you have a health risk, there is a strong chance of the risk becoming a natural medical problem as you go through menopause. So this is the time when — it’s my opinion but I think also common sense really — it is really when women need to pay extra attention to their health. Because this is a vulnerable time, definitely the time to start really paying attention to your food and to everything that you put into your body. Right? It is just so important to do that. So it is important to talk to your doctor if you have a family history of Alzheimer’s, and it’s good to maybe consider prevention as well. We know that women are more likely than men to end up with Alzheimer’s, even those without the genetic predisposition or an obvious predisposition, and hormonal health is something we need to address. So many of us don’t take care of ourselves because of stress.

Right. Stress reduction. Big issue.

Exactly. We didn’t talk about stress. So something else that really strongly impacts women’s brains more than men’s is stress. So if stress gets to you, and you feel like frazzled or really suffering from stress, your brain is suffering with you. High cortisol levels (the stress hormone) have been associated with memory changes, memory decline, and brain shrinkage in women. Not so much in men.

Wow.

At this age in particular, during menopause and postmenopause. So stress reduction is also something that is really important to consider as a strategy.

This is why I got divorced. [Laughs.]

That is also a solution. I was thinking more yoga.

Yoga, divorce, a little meditation…

Yes, exactly. And exercise.

I try to exercise every day. Even if it just means going on a half hour walk with the dogs.

Yes. So many people don’t. So many people just don’t have time or don’t have the energy at the end of the day. So it is important to get creative and find ways to incorporate all these things that we are talking about into our daily lives, and everybody says “yes” in principle, and then you do it for two weeks and then you stop.

Like when you go to the grocery store and park in the farthest parking spot. When you have a chance to go either up an elevator, or an escalator, or stairs, take the stairs. I mean, there are shortcuts to exercise that happen every day. Or, for example, I was in LA for two months working on a TV show. So, I decided what I was going to do was not have a car, and get an Airbnb two miles from the office, so then I’d be forced to walk my two miles every day and back and forth.

Yes. Exactly. Also, planking is great. I tell everybody. I managed to get up to 10 minutes straight. There is no way I can do more than 10. You’re sweating, you’re cursing. But it is wonderful. It works your entire body and most people have a hard time losing fat around the waist. So that really works your abs.

Ruth Bader Ginsburg who is a Supreme Court Justice right now, there is a documentary about her, and they show this 80-something-year-old woman doing planks every day, and her brain is still sharp as a tack. Okay, so planking good, stress and smoking bad. Anything else?

Yes, I hate to say it but caffeine.

No. Please don’t say that. Caffeine is not good?

It depends. For some women, it is a trigger for night sweats.

What about wine? I read one study that said that wine, in moderation, is good for the brain.

Yes, but you know, just drink pomegranate juice instead. It has the same antioxidant capacity. I don’t drink alcohol, which is weird for an Italian, I know, but I don’t like it. I think I’m allergic to tannins. So I have been drinking pomegranate juice. Also dark cherry extract. You dilute it with water, and it is great. It tastes wonderful, is very refreshing, and is so good for your brain.

So, you’re now 41 years old. You have a lifetime ahead of you in terms of research, in terms of what you could get done. When you get to the end of your life, what do you hope you will have done with these next 40 years?

Oh, I want to find a cure for Alzheimer’s.

Yeah, simple. Just a cure for Alzheimer’s, no biggie.

It’s what I have been trying to do since college. So, it’s not like I changed my goals much. And, especially, I find myself to be really passionate about women’s health. So, I am really hoping to make a difference for women. All over the world still today, women are treated very poorly. Women’s rights are constantly being reevaluated. Equality is constantly being reassessed. Women can’t even drive in some countries, and in other countries, they’re even being sold off when they’re very young as wives. Maybe at least we can change the bias that we have in health care and the fact that all the research that has been done so far, in all the medical textbooks is based on the research of men. It’s either male cells, male mice, male animals, or men, and that leads to underdiagnosing women, misdiagnosing women, giving us the wrong drugs, and it’s just a disaster! So I hope that I can help in that regard.

That’s a great goal, but one of the things that you said earlier sort of struck me which is that if we can figure out what this hormonal change in women does to the brain in terms of Alzheimer’s that could have wide-ranging results for Alzheimer’s in general.

Yes.

So, maybe the fact that we’re finally looking at women and at these hormones could be at the root why this disease takes hold?

Yes, there seems to be an important effect of hormones and the way that the brain ages so that’s associated with Alzheimer’s in some ways in women. We just don’t know how.

So, we also know that men have different levels of estrogen in them, correct?

They have very little estrogen.

They have very little estrogen. Are there ways to study transgender people?

That’s a good point, yes.

To see what happens to women who transition to men or vice versa?

Actually, I wrote about it in the book.

In a new book?

Yes, in the new book, The XX Brain, because it’s a logical question and we have no data. But all the hormones they are taking must have an impact on the brain and we just don’t know about this.

Well, you also probably don’t have the same number of subjects you would need to study the issue because it’s so new that transgender men and women are transitioning hormonally, so this is something you can be studying now, as we’re seeing this new population emerge.

Yes, yes, for sure. Cancer patients, too. All the cancer patients who are taking estrogen-blocking medications. What happens to their brains? Do they get more Alzheimer’s?

Right. Of course.

Who really knows? It’s really rethinking women’s brains. Women’s brain health. It’s a complete revamping of what we know because until now, women’s health has been basically —

Boobs and —

Breasts, tubes, yeah, that’s women’s health. What I’m trying to do, in my own small way, is to say women’s health really should include the brain because there are so many diseases that affect women more than men in terms of brain health, and Alzheimer’s is perhaps the most spectacular because of the numbers. We are going to have 15 million Alzheimer’s patients in 20 years, just here in the U.S., and 130 million in the world. And two-thirds of these cases are most likely going to be women. At the same time, 850 million women are about to enter menopause, over the next three years.

Hot flashes all over the city right now. [Laughs.]

Yeah, for many that’s when Alzheimer’s starts though, and nobody knows why, so raising awareness is really important right now.

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