The New Theory About What Causes Alzheimer’s in Women
Women are twice as likely as men to develop Alzheimer’s disease. New research provides a clue about why.
If you’re a living, breathing human being, chances are you know someone impacted by Alzheimer’s disease. It is the sixth leading cause of death in the United States, killing more people than breast cancer and prostate cancer combined. Currently, more than five million Americans have Alzheimer’s disease, and that number is projected to grow to nearly 14 million by the year 2050.
Women are twice as likely as men to develop Alzheimer’s, and the disease is more common in older Black and Hispanic adults than it is in white adults. The reason for this remains somewhat of a medical mystery. "We know Alzheimer’s and other dementias hit women harder than men, but we don’t know why,” says Keith Fargo, PhD, director of scientific programs & outreach at the Alzheimer's Association in Chicago. “Lifelong differences in women may affect their risk or protect them from dementia, and we need more research that helps us understand the full continuum of contributions to a person's risk.”
A new study in Neurology aims to better understand the reason for that gender imbalance. Researchers found a connection between menopausal hormone shifts and brain markers for Alzheimer’s. Lisa Mosconi, PhD, director of the Women's Brain Initiative and associate director of the Alzheimer's Prevention Clinic at Weill Cornell Medical College in New York City, explains why this is significant. “For a long time, the general mindset was that women lived longer than men, and Alzheimer's was a disease of old age, and that was why the prevalence was higher in women,” she says.
Now, there is reason to believe that menopause-related hormones may play a role in dementia risk and progression—and this could pave the way for better prevention options for women.
Menopause & Alzheimer’s Risk
While Alzheimer’s is typically thought of as a disease of the elderly, people begin showing changes in their brain long before symptoms appear. One study in The Journal of Neuroscience identified changes in brain functioning at least seven years prior to cognitive impairment. Other research suggests this can occur as much as two decades before an Alzheimer’s diagnosis. “Alzheimer's is not a disease of the old,” Mosconi says. “Rather, it starts with negative changes in the brain years, if not decades, before clinical symptoms emerge.”
Here’s how the study went down: Researchers looked at a small group of 85 women and 26 men between 40 and 65 years old, showing no signs of cognitive decline. They adjusted for external risk factors like sedentary lifestyle and family history, and then examined the brain scans of participants to look for Alzheimer’s biomarkers.
What they found was surprising. The women showed significantly higher biomarkers for dementia—they had less gray and white matter in their brains than men, more of a brain protein fragment called beta-amyloid (which is suspected to play a role in Alzheimer’s), and lower glucose metabolism. And here’s the especially interesting part: Second to female sex, menopausal status was the factor most strongly associated with these biomarkers.
“In this study, we show for the first time that women develop Alzheimer's related changes in their brains at a younger age than men,” Mosconi says. “So, it isn't just that women live longer—women also start showing the telltale signs of Alzheimer's earlier in life. Even more specifically, this seems to happen during the transition to menopause, which is in our forties and fifties.” In other words, hormonal shifts during menopause (such as the natural decline of estrogen) may play a role in a woman’s propensity to develop memory loss later in life.
Related Research is Also Telling
This isn’t the first time that women’s hormones have been studied in relation to Alzheimer’s disease. Fargo brings up research presented at the 2018 Alzheimer’s Association International Conference in Chicago, which examined a connection between reproductive history and Alzheimer’s risk. Women who had three or more children were found to be at lower dementia risk than women with one child, and miscarriages were also associated with higher dementia risk. In addition, researchers studied the total number of months women had spent pregnant, as well as the ages their periods started and began.
Fargo explains that this research is still new but promising. “The physical and hormonal changes that occur during pregnancy are considerable, and it’s important to understand what impact, if any, these changes may have on future brain health,” he says. “The potential link between reproduction history and brain health is intriguing, but still very much in its early stages. Much more study in this area is needed.”
Why This Matters
These studies provide a new way of thinking about Alzheimer’s risk for women, specifically how hormones may play a role in its development. “Studies like this help us paint a clearer picture of what may be contributing to the underlying biology of Alzheimer's disease, and this includes the role of hormones and hormonal changes,” Fargo explains.
However, he also cautions against making personal decisions about hormone replacement therapy based on these findings. “Women with questions about hormone therapy should talk to their physician about potential risks and benefits,” he suggests. Much more research needs to be done in this area before experts fully understand which hormones matter here.
But Mosconi notes that the Neurology study represents a new way of thinking about Alzheimer’s prevention. “Usually, when we discuss Alzheimer's prevention, we talk about managing things like high cholesterol and high blood pressure,” she says. “We don't talk about managing menopause, or female hormones. Our findings indicate that hormonal factors need to become a strong focus of Alzheimer's prevention strategies in women.”
Protect Your Brain
This naturally leads to the question… what can I do to protect my brain? After all, menopause is inevitable for all menstruating women, so it’s not like you can just opt out of that. As this line of research continues, there are things you can do right now to protect your brain health and lower your Alzheimer’s risk. Here are just a few:
Stay active. Research has shown that exercising regularly can help increase blood flow to the brain. Even a brisk walk around the block can get your body moving.
Eat whole foods. According to the Alzheimer’s Association, there is no one “best diet” out there for everyone. But eating a diet rich in heart-healthy foods like fruits, vegetables, and whole grains can keep you healthy throughout your life—and yes, lower your risk of dementia.
Sleep. Sleep deprivation has been associated with elevated beta-amyloid levels (that protein that plays a role in Alzheimer’s development). Try for at least seven hours per night.
Manage your pre-existing conditions. If you already deal with high blood pressure, insulin resistance, or obesity, Mosconi suggests that your best bet is to keep those managed under the care of a doctor. There is evidence that chronic high blood pressure could increase your likelihood of Alzheimer’s.
Train your brain. Research has shown that cognitive training may help improve brain function in patients with Alzheimer’s disease. Even before a diagnosis, it’s worth keeping your brain in tip-top shape by doing daily activities that stimulate challenging thought: reading books, playing brain-teaser games, or doing crafts.
Ask questions. Mosconi urges women to ask questions about their brain health–to their doctors, local health advocacy groups, and anyone else who will listen. “Still today, women's brain health is one of the most under-researched, under-diagnosed and under-treated fields of medicine,” she says. The more women demand answers about how to protect their brains, the more momentum there will be to keep this research going.
Participate in research! If you’re interested in getting involved in the search for an Alzheimer’s cure, contact your local or national advocacy group to find out about ongoing studies. “I encourage everyone to participate in research because when you participate in research, you are informing research too,” Mosconi says. “It's the best way to make sure your own risks and concerns are addressed.”
The bottom line is simple, Mosconi explains: “The best time to start taking care of your brain is now.”
New Study: Neurology. (2020.) “Sex-driven modifiers of Alzheimer risk: A multimodality brain imaging study.” n.neurology.org/content/early/2020/06/24/WNL.0000000000009781
Alzheimer’s Statistics: Alzheimer’s Association. (n.d.) “Facts and Figures.” alz.org/alzheimers-dementia/facts-figures#
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Beta-Amyloid Protein: Alzheimer’s Association. (2017.) “Beta-amyloid and the amyloid hypothesis.” alz.org/national/documents/topicsheet_betaamyloid.pdf
Reproductive History Research: Alzheimer’s Association. (2018.) “Pregnancy and Reproductive History May Impact Dementia Risk Plus, the Move to Re-Think the Impact of Hormone Therapy on Cognition.” alz.org/aaic/releases_2018/AAIC18-Mon-women-dementia-risk.asp
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Sleep: National Institutes of Health. (2018.) “Sleep deprivation increases Alzheimer’s protein.” nih.gov/news-events/nih-research-matters/sleep-deprivation-increases-alzheimers-protein
Cognitive Training: Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews. (2006.) “Cognitive training in Alzheimer's disease: a meta-analysis of the literature.” ncbi.nlm.nih.gov/books/NBK73309/