Why Are Women at a Greater Risk of Alzheimer’s Disease?

Breast cancer awareness is front and center in the U.S. However, a woman in her 60s is actually more at risk of Alzheimer’s disease. In fact, women in their 60s are twice as likely to develop Alzheimer’s disease than breast cancer during their lifetime.

Nearly two-thirds of Americans with Alzheimer’s are women. The exact cause is unknown, but there are several contributing factors, some of which affect women more than men.

“We can identify certain risk factors that are stronger in women,” said Sarah Banks, PhD, director of neuropsychology at the UC San Diego Health Memory Disorders Clinic. “Some things may be tied in with gender as a psychosocial construct, as opposed to sex as a biological construct. For example, having an executive job where you’re juggling complicated ideas is correlated with less risk, but women tend not to go into higher managerial roles for psychosocial reasons and, potentially, sexism.”

Let’s take a look at some of the risk factors for Alzheimer’s:

Genetic Mutations—The Role of the APOE4 Gene

There isn’t a single gene linked to Alzheimer’s, but the APOE4 gene variant increases risk. “One copy of APOE4 raises your risk by about 50%, and with two copies, your risk is about five times higher,” said Paul Newhouse, MD, professor of psychiatry, director of the Center for Cognitive Medicine and clinical core leader of the Vanderbilt University Alzheimer’s Disease Research Center in Nashville, Tennessee.

The APOE4 gene may increase Alzheimer’s risk in some women, although more research is needed. “While we know APOE4 is a risk factor, and more so in women, the research to date has mostly been in non-Hispanic white women,” Dr. Banks said. “The few studies in other races indicate that the risk may not be the same in all groups.”

Menopause, Estrogen and Brain Health

Men’s hormone levels decrease gradually as they age, but women experience a sudden drop in hormone levels during menopause. Some hypothesize that this dramatic change may contribute to the risk of Alzheimer’s disease in women.

“We know that estrogen is protective in the brain, and with menopause, a woman’s estrogen level falls off a cliff,” Dr. Banks said. “Menopause is often accompanied by complaints of word-finding difficulties, memory loss and brain fog, which is probably associated, in part, with that lack of estrogen.”

In the ongoing Cognitive Health After MenoPause (CHAMP) study, Dr. Newhouse and colleagues have observed the impact of hormone changes on the brain’s cholinergic system, which is an important system that uses the neurotransmitter acetylcholine to transmit signals throughout the body. Acetylcholine plays an important role in learning and memory, and some research has shown that people with Alzheimer’s disease have lower levels of this chemical in the brain.

“If the cholinergic system is under stress due to genetics or other factors, the loss of estrogen at menopause combined with other biological risk factors could accelerate the development of Alzheimer’s disease,” Dr. Newhouse said.

Racism, Sexism and Structural Risk Factors

Dementia, including Alzheimer’s disease, affects about twice as many older Black Americans as older white Americans. Certain factors may put Black women at increased risk, according to research from neuropsychologist Tanisha Hill-Jarrett, PhD, assistant professor of neurology at the UCSF Memory and Aging Center.

“We know people age in their lived environment, and what research has shown is that Black women are more likely to live in economically deprived environments regardless of their upward mobility or socioeconomic status, due to the joint influence of structural racism and sexism,” Dr. Hill-Jarrett said. “There’s an interaction between neighborhood environment, largely influenced by structural factors, and a person’s individual-level factors. If they don’t have green space, parks, if it’s not a walkable area, that naturally impacts risk factors like [body mass index, or BMI], the number of minutes you exercise and access to healthy foods.”

Dr. Hill-Jarrett’s work has looked at the area deprivation index, which is a neighborhood-level composite of psychosocial stressors based on where Black women live, in relation to subjective cognitive decline.

“We found an association initially, but once we started accounting for factors like the person’s education and other clinical risk factors, etc., that association no longer existed,” she said. “That suggests to me that neighborhood context is important, but there are other factors related to one’s lived experience that are important too, like a person’s education.”

Sleep Quality

Sleep apnea, which diminishes sleep quality, may increase Alzheimer’s disease risk. During the baseline evaluation for her Women Inflammation and Tau Study, Dr. Banks found that more than 70% of study participants age 65 and older had sleep apnea.

“What was interesting was the correlation with tau pathology, one of the key Alzheimer’s pathologies in the brain,” Dr. Banks said. “The more severe the sleep apnea, the more severe the tau pathology.”

After menopause, sleep apnea becomes more prevalent among women, but it isn’t commonly diagnosed because women’s symptoms differ from men’s.

“We’re less likely to snore loudly, gasp and have dramatic symptoms that get us to the doctor,” Dr. Banks said. “Women tend to have headaches, grogginess, feeling that they didn’t sleep well. The symptoms are non-specific, very easy to dismiss.”

Cognitive Reserve

Some people who develop Alzheimer’s pathology don’t experience symptoms because of their cognitive reserve, a cognitive buffer based on life experiences that counteracts the manifestation of clinical symptoms. Factors such as higher education, complex jobs and being bilingual can contribute to cognitive reserve.

Older women may have less of an opportunity to build robust cognitive reserves, compared to men. “There are historical differential experiences across men and women in terms of access to education and occupation,” Dr. Hill-Jarrett said. “Oftentimes, older women may not have had a formal or complex occupation to create a cognitive buffer.”

How Neuropsychologists Assess Alzheimer’s Symptoms

If you’re concerned about Alzheimer’s disease, your primary care provider may refer you to a neuropsychologist for an assessment.

“We do an evaluation of all areas of cognition, including memory, attention, word-finding, problem-solving, visual-spatial skills and functional abilities like medication management, bill-paying and driving,” explained neuropsychologist Kami Marchese, PsyD, director of the Main Line HealthCare Bryn Mawr Rehab practice in Pennsylvania. “We compare test results to the peer group, to see if they’re where we’d expect them to be for their age. And we recommend things they might do to prevent further decline.”

Steps Women Can Take to Lower Alzheimer’s Risk

Taking care of your overall health may help reduce your Alzheimer’s risk. “What’s good for the heart is usually good for the brain,” Dr. Newhouse said. “Maintaining rigorous control of blood pressure, exercising, following the MIND diet (a modified Mediterranean diet) and prioritizing social engagement are critical factors in maintaining brain health.”

Here are other ways to potentially decrease your risk:

• Stay physically active. Engage in exercise regularly. “There’s quite good evidence that increasing physical exercise is more beneficial to women, in terms of Alzheimer’s risk, than it is to men,” Dr. Banks said.
• Improve sleep quality. If you’re always tired, ask for a sleep study. “We don’t know enough from a research standpoint whether treating sleep apnea will reduce dementia risk, but CPAP use is associated with less risk of dementia,” Dr. Banks said.
• Consider hormone therapy. It may help during perimenopause or early menopause. “There’s reasonably good evidence that early menopausal hormone treatment can provide benefits to the brain,” Dr. Newhouse said. “Prolonging the overall exposure of the brain to sex hormones probably pays dividends years later.”
• Maintain your cognitive reserve. Mentally stimulating experiences may protect against cognitive impairment. “When people retire, they’ll notice more significant cognitive decline,” Dr. Marchese said. “If they’re thinking about retirement, they should find activities they enjoy to keep themselves cognitively stimulated.”
• Investigate cognitive changes. Seek help to rule out dementia or receive an early diagnosis. “What we see in research is that Black individuals oftentimes are diagnosed later, when the disease is more advanced,” Dr. Hill-Jarrett said. “There are medications that can slow the rate of progression, especially early one, so recognizing signs and asking your primary care provider for cognitive screeners is important.”