Alzheimer’s May Hit Women Harder

Article Content

Women account for nearly two-thirds of people living with Alzheimer’s disease, and research suggests they often experience a more aggressive course of the disease than men. Scientists at the University of California San Diego School of Medicine are working to understand why.

The Women: Inflammation and Tau Study (WITS), led by Sarah Banks, PhD, professor of neurosciences, and Erin Sundermann, PhD, associate professor of psychiatry, examines the biological and lifestyle factors that may make women more vulnerable to Alzheimer’s-related brain changes.

“Sex differences in Alzheimer’s disease are well documented, but the mechanisms driving those differences remain largely unknown,” said Banks. “That’s the gap WITS is designed to address.”

Launched in 2021 as a pilot project funded by the California Department of Public Health, WITS expanded in 2023 into a larger, federally funded study supported by the National Institute on Aging. The primary focus is understanding why women tend to show greater accumulation of tau, a protein that becomes abnormal in Alzheimer’s disease and forms knot-like clumps inside brain cells, known as tangles, that disrupt brain function. 

The amount of tau in the brain is strongly linked to memory decline. Previous research has shown that once women develop elevated tau levels, they often experience faster cognitive decline than men with equivalent levels of tau. WITS investigators are exploring several factors that may contribute to this pattern. A central area of focus is neuroinflammation, which plays a key role in Alzheimer’s disease and may affect women and men differently due to known sex differences in immune response.

Researchers are also examining sex hormones, including the effects of menopause and endocrine aging, as well as lifestyle factors such as physical activity, diet, sleep quality and obstructive sleep apnea. Each of these may influence inflammation and brain health.

“By looking at how biological and lifestyle factors interact, we hope to better understand why women may be more vulnerable to certain Alzheimer’s-related changes,” said Sundermann.

Early findings highlight the role of sleep

Now in its third year, WITS has enrolled 86 women and aims to reach 110 participants. As recruitment and data collection continue, early findings are beginning to emerge.

Their findings, recently published in Alzheimer’s and Dementia noted that sleep health stands out as a potentially powerful factor in women’s Alzheimer’s risk. Women who slept longer showed greater “resistance” and “resilience” to tau. More specifically, longer sleep duration was also associated with lower levels of tau in women with genetic risk for Alzheimer’s disease. Higher amounts of sleep also showed a weakened relationship between tau accumulation and memory decline.

“These findings suggest that sleep is not only important for overall health but may be a meaningful and modifiable factor that helps protect the brain in women as they age,” Banks said.

In another study currently under review, poor sleep was linked to worse memory and higher tau levels among women with a specific genetic risk factor for Alzheimer’s. The findings suggest that sleep problems could serve as an early warning sign of vulnerability in some women.

“Improving sleep could represent a promising target for risk reduction, particularly for those at higher genetic risk,” Banks added.

Rethinking risk assessment for women

Up to 45% of dementia cases may be associated with modifiable risk factors, including physical inactivity, high blood pressure, diabetes, hearing loss, smoking and social isolation. While age and genetics cannot be changed, lifestyle interventions may help lower risk or delay symptoms.

Sundermann said findings from WITS could ultimately help clinicians move beyond one-size-fits-all screening approaches.

“Women often show different patterns of memory performance than men, which may mask early signs of cognitive decline on standard tests,” she said. “By identifying sex-specific biological and lifestyle markers of risk, we hope to support earlier and more accurate detection, better risk stratification and more personalized prevention strategies.”

Closing a critical knowledge gap

Despite decades of research, there are still no widely available disease-modifying treatments for Alzheimer’s disease. Understanding why women bear a disproportionate burden is essential for developing more effective prevention and intervention strategies.

“Women carry the greatest burden of Alzheimer’s disease,” Sundermann said. “Closing the knowledge gap around sex differences is critical if we want to develop treatments and prevention approaches that truly work for everyone.”

More information about the WITS is available on the study website.