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Why More Women Than Men Get Alzheimer's

Author of best-selling 'The XX Brain' says hormones play a huge role

spinner image The XX Brain and author Lisa Mosconi, PhD
Avery/Allison Hooban Photograpy

Neuroscientist Lisa Mosconi, whose new book The XX Brain instantly topped best seller lists, became interested in women's brain health because of her own family history. Born and raised in Italy, her grandmother and her grandmother's two sisters died of Alzheimer's disease, while their brother, who lived to the same age, did not develop the disease.

Today, as the director of the Weill Cornell Women's Brain Initiative in New York, Mosconi and her team investigate sex differences in Alzheimer's disease by using brain imaging. In this Q&A, she talks about the book, how hormones affect brain health and the steps women can take to benefit their brains in midlife and beyond.

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Your book addresses the fact that two out of every three Alzheimer's patients are women. Historically, what have scientists thought accounted for this, and what does your research show?

When I started out, the general mindset was that women live longer than men and that Alzheimer's disease is a disease of old age. So of course, women have Alzheimer's more so than men. It took many years for the conversation to change.

My question has always been: How are women's brains different from men's brains? Is there anything in women's brains that could potentially explain why women have Alzheimer's more than men?

What really made a big difference for me was the understanding that women don't live that much longer than men. In the United States, women tend to live four and a half years longer than men. In other countries, like the U.K., the difference is more or less two or three years, not 20. Still, in the U.K., Alzheimer's disease and dementia is the number one cause of death for women and not for men, even though the difference in longevity is literally a couple of years.

If not longevity, what helps explain the difference?

Alzheimer's does not actually start in old age. Rather, Alzheimer's starts with negative changes in the brain years, if not decades, prior to clinical symptoms. This brings us away from age 70, when the clinical symptoms of Alzheimer's tend to become manifest, and closer to midlife.

My question became: If Alzheimer's disease starts in midlife, then what happens only to women and not men in midlife that could potentially explain the increased prevalence of Alzheimer's disease in women?

Surprisingly, the answer was menopause.

My research has shown that menopause changes the female brain in a big way. For some women, it's hot flashes and mood swings and disturbed sleep. For other women, it's actually a higher risk of Alzheimer's. Our studies have shown that it's not just that women live a little bit longer than men, but rather that women develop these Alzheimer's changes in their brains earlier than men, specifically due to menopause.

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How is brain health affected by menopause, specifically in terms of hormones like estrogen, which you call the “master regulator” of the female brain?

We think about sex hormones — like estrogen for women and testosterone for men — as chiefly for reproduction. However, these hormones serve a number of functions in the brain that have nothing to do with reproduction, but that have everything to do with brain energy. Both estrogen and testosterone literally push your neurons to burn glucose to make energy.

For women, our estrogen drops in midlife during menopause. That has consequences in the brain because estrogen supports energy metabolism in the brain and is also involved in growth, plasticity, and immunity. Basically, it keeps your brain younger and healthier. So if you lose your estrogen, a lot of things happen inside your brain.

When women experience menopause symptoms like hot flashes, what's going on in the brain?

There are specific brain regions that are very connected to our estrogen levels. The number one brain region is called the hypothalamus, which is in charge of regulating body temperature. So if estrogen doesn't activate the hypothalamus correctly, then the brain cannot regulate body temperature. And that's why we get hot flashes.

Then there's another part of the brain called the brain stem that is in charge of sleep and wake and also stress. If estrogen doesn't activate the brain stem correctly, we can get mood swings, for example, or we have trouble sleeping at night.

Then there's the hippocampus, which is the memory center of the brain. It's also really heavily estrogen-dependent. If estrogen is all over the place in the hippocampus, we may have trouble remembering information. So there's a whole network in the brain that is in trouble as women go through menopause and that creates all these symptoms.

Menopause isn't something women can avoid, but you write how lifestyle choices like diet and exercise, along with hormone replacement therapy, can help. For someone who's reading this and thinking, I'm going through menopause and now I'm worried, what sort of guidance would you give them?

The fact is, science validates these concerns: 20 percent of women going through menopause have no problems whatsoever, but 80 percent of women do. So, number one, it's really important to acknowledge that.

Number two, menopause is something you can't avoid. But the way you experience menopause has something to do with the choices you make in your life on a daily basis. For example, smoking is the number one cause of early menopause in women. A bad diet is also something that's been linked to early menopause in women, especially consumption of refined sugar, refined grains and processed foods.

Exercise is really important as well and has been shown to be incredibly good for your brain. It's linked to a lower risk of Alzheimer's disease and dementia later in life, and much better fertility and ovarian health — which means better outcomes during menopause, like a later age of onset of menopause and also less severe symptoms.

Another big thing is stress reduction. Studies have shown that chronic stress, especially with high cortisol levels, accelerates brain shrinkage in midlife and correlates with poor memory, and much more so for women than for men.

Speaking of stress, women are also more likely to be caregivers than men. Is there a relationship between caregiving and brain health?

Women account for, at the very least, 60 percent of all caregivers, and about two-thirds of all caregivers for Alzheimer's patients specifically. We know that there's a condition called caregiver burden that really severely taxes a caregiver's health. There's some evidence showing that if you're really stressed as a caregiver, you even have a higher chance of Alzheimer's yourself, which is really unfair in so many ways.

I think it's really important as a caregiver to take all the help you can get without feeling bad about it. It's a lesson for women, not just as caregivers but in general. Midlife is such a big turning point in a woman's life. It's a time when we should be taking extra care of ourselves, rather than less.

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