Why Alzheimer’s Disease Is More Common in Women

Experts now see a more layered picture that includes biology, genetics, brain changes during menopause, immune differences, and social factors that influence health across the lifespan. These discoveries are important for several reasons, perhaps most importantly because if some of the root causes and risk factors of Alzheimer’s disease are different in women, more targeted treatments and prevention efforts could improve outcomes for both sexes.

Women and Alzheimer’s Risk

Women represent about 70 percent of people with the diagnosis, says Jessica Z.K. Caldwell, PhD, associate professor of neurology and codirector of the Wisconsin Registry for Alzheimer’s Prevention at the University of Wisconsin at Madison School of Medicine and Public Health in Madison.

“In the past, this was thought to be an artifact of women — on average — just living longer than men. While age is definitely part of why more women are diagnosed with Alzheimer’s, we understand that there are also a lot of other different factors that go into women’s risks — for example, genetics and lifestyle,” says Dr. Caldwell.

Even among women, there isn’t a “one-size-fits-all” rule, she says. Women in different countries, cultures, and socioeconomic groups may experience different patterns of risk, depending on factors like education, cardiovascular health, or access to medical care.

“So women who live in developing countries, versus women who live in the United States, for example, may have slightly different sets of risk factors or importance of risk,” says Caldwell.

Biological and Brain Differences May Increase Women’s Vulnerability

Research suggests that men and women experience Alzheimer’s disease differently at a biological level.

Some genes have been identified that increase the risk of developing Alzheimer’s disease (having an APOE-e4 allele) in both men and women, says Karen Martinez, PhD, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Nevada.

“However, women with this specific allele have greater risk and may develop Alzheimer’s earlier than men who have this same allele,” says Dr. Martinez.

In terms of the disease, both men and women will get amyloid plaques in their brain and tau tangles in their brain, says Caldwell.

“But what studies have shown more recently is that women may have a different relationship between those two pathologies or proteins that build up in the brain. Specifically, when a woman gets amyloid, it appears that she more quickly gets tau, compared to a man,” she says.

Hormones and Menopause May Play in Role in Alzheimer’s Disease Development

One of the most significant differences between men and women is the sudden decline in estrogen during menopause. Researchers increasingly believe that this shift may increase susceptibility to Alzheimer’s for some women.

“People tend to think about the estrogen that women have in relation to having a [menstrual] cycle, but estrogen is a master regulator that’s found throughout the entire body. It’s found in the brain, and specifically in our memory system and in our hippocampus,” says Caldwell.

She explains that when women lose estrogen at menopause, that could create a vulnerability for some women, in terms of estrogen no longer supporting the memory system.

When the protective benefits of estrogen are no longer present, you can see faster development and greater accumulation of beta-amyloid and tau, the proteins associated with Alzheimer’s disease, says Martinez,

“Additionally, because estrogen is a regulator, losing it may also change the way our immune system responds, or the way our stress system responds,” says Caldwell.

Those are the more direct methods by which the loss of estrogen might be impacting memory and risk, says Caldwell. But there may also be more indirect ways that are linked to menopause symptoms.

Women’s Response to Inflammation May Put Them at Higher Risk

Immune differences may contribute to why women are more likely to have Alzheimer’s disease. At a high level, the immune system has a response, and then it has a recovery, says Caldwell.

“In the case of someone being sick, someone exercising, or having an injury, the recovery from the response is really important. While women tend to mount stronger immune responses to stressors, they tend to not recover as well as men,” she says.

Caldwell gives exercise as an example. “When you exercise, and right after you have a lot of inflammation in your body, it’s related to your immune system responding, and that’s not something you should sustain. If you sustain that much inflammation in your body, it can be really negative and can create all sorts of issues,” she says.

How does that relate to Alzheimer’s? The brain has an inflammatory response — called neuroinflammation — to Alzheimer’s abnormal proteins in the brain. That inflammation is the immune system’s response, as it’s attacking and trying to get that pathology out, says Caldwell.

“Unfortunately, that doesn’t work with Alzheimer’s pathology at a level that would remove Alzheimer’s disease. And so what happens is that the inflammation response goes on and on. When that response lasts a long time, it actually promotes Alzheimer’s disease, and so it becomes a vicious cycle with those amyloid and tau proteins. And we think that may happen more in women compared to men,” she says.

Modifiable Risk Factors May Be Greater in Women

While many of these risk factors appear to impact women and men equally, there are a few that are more common in women, says Caldwell.

Depression “The No. 1 here is depression. Depression is a risk factor for dementia, and it is just more common in women, so if you’re a woman, you’re more likely to experience that risk factor,” she says.

Low Education In this case, this is defined as not finishing high school, and that factor is also more common in women who are currently aging into the risk range for Alzheimer’s, says Caldwell. “This will be different for later generations, but right now, it’s still a risk factor that impacts more women than men, at least in the United States,” she says.

Physical Inactivity On average, women just exercise less than men, says Caldwell.

Degree of Impact Another way modifiable risks can impact women differentially is by being worse (in terms of brain health and Alzheimer’s disease) for women when they do appear, she says.

“One example of that is diabetes. While diabetes is a risk factor for men and women when it comes to dementia, it’s worse for women. When we have it, it creates more brain impact than it does for a man,” says Caldwell.

There are also other modifiable risk factors that aren’t included in the list yet, she says.

“On a more positive note (for women), there are some large, long-running studies that show better impact in women in terms of protecting the brain when you work to change your cognitive activity, your nutrition, and your exercise,” says Caldwell.

Gender Expectations May Contribute to Risk

“Women oftentimes face risks that relate not just to our biological sex but to gender expectations that are more common for women,” says Caldwell.

Many women are caregiving for kids and for aging parents — part of the “sandwich generation.”

“That can take a lot of time and energy and be a source of stress for some people. And then maybe that stress leads to poor sleep — and that’s a risk factor — and lack of sleep might put you at risk for another risk factor like depression, and so on,” she says.

Providers need to understand that while women may know they need to exercise more and manage their stress, they may have fewer mental resources and less time to do it compared to men, says Caldwell.

Those societal expectations are another kind of “gray area” that can put women at a disadvantage when it comes to Alzheimer’s prevention, she says.

What Women Can Do to Protect Their Brain Health

While there are some risk factors related to being a woman that can’t be changed, many can be, says Caldwell.

“No one is destined to get dementia. If you have a parent with dementia, that isn’t a guarantee that you’ll have it someday. There are things that are under your control — and if you can prioritize yourself and make some changes, you can really have an impact on your aging,” she says.

As noted above, it may be particularly important for women to maintain cerebrovascular health, stay physically active, and manage stress and sleep earlier in life, to help account for the changes that occur post-menopause with the loss of estrogen,” says Martinez.

Taking care of your overall health and seeking treatment for menopause symptoms as well conditions such as depression, diabetes, and sleep apnea may have protective benefits for your brain.

The Takeaway

• Women face a higher risk of Alzheimer’s disease, but not just because they live longer. Biological factors, menopause-related changes, genetics, and lifestyle also play a role.
• The decrease in estrogen at menopause, stronger and less regulated immune responses, and sex-specific patterns of amyloid and tau buildup may increase women’s vulnerability to Alzheimer’s disease.
• Modifiable risk factors such as depression, inactivity, diabetes, and poor sleep are more common or more harmful in women.
• Taking steps to improve cardiovascular health, getting regular exercise, sleeping well, managing stress, and getting treated for conditions like depression and sleep apnea may help women reduce their risk over time.