Researchers from the University of California San Diego School of Medicine have found that women not only experience a higher burden of certain modifiable dementia risk factors, but also appear more vulnerable to their effects on cognitive function. The study, which analyzed data from more than 17,000 middle-aged and older adults, is published in Biology of Sex Differences.
“Looking beyond which risk factors are most common, we found that some have a disproportionately larger impact on women’s cognition,” said Megan Fitzhugh, Ph.D., assistant professor of neurosciences at UC San Diego School of Medicine and first author of the study. “This suggests that prevention efforts may be more effective if they are tailored not just to risk factor prevalence, but to how strongly each factor affects cognition in women versus men.”
Dementia, including Alzheimer’s disease, affects women at higher rates than men, a disparity that has drawn increasing scientific attention. In fact, of the seven million adults living with Alzheimer’s disease, nearly two-thirds are women. While women tend to live longer, longevity alone does not fully explain the difference in Alzheimer’s outcomes. Researchers are now examining how combinations of biological, social, and lifestyle factors contribute to this imbalance—particularly those that can be modified over time.
Study design and risk factors examined
In the new study, Fitzhugh and Judy Pa, Ph.D., professor of neurosciences at UC San Diego School of Medicine and corresponding author of the study, evaluated 13 established, modifiable dementia risk factors using data from the Health and Retirement Study, a nationally representative cohort of U.S. mid- to late-life adults. These factors included education level, hearing loss, smoking, alcohol use, obesity, depression, physical inactivity, and cardiometabolic conditions such as hypertension and diabetes.
The analysis revealed clear sex-based differences in the prevalence of these risk factors. Women were more likely than men to report:
- Depression (nearly twice as common in women as men—17% vs. 9%)
- Physical inactivity (48% vs. 42%)
- Sleep problems (45% vs. 40%)
Women also had slightly lower average educational attainment—a known risk factor for later-life cognitive decline.
How risk profiles differ by sex
Men, on the other hand, had:
- Higher rates of hearing loss (64% vs. 50%)
- Diabetes (24% vs. 21%)
- Heavy alcohol use (22% vs. 12%)
Hypertension was common in both groups, affecting about six in 10 participants, while average body mass index in both sexes fell in the overweight-to-obese range.
Beyond prevalence, the study found that several risk factors were more strongly associated with poorer cognitive performance in women. For example, cardiovascular and metabolic conditions such as hypertension and increased BMI showed steeper negative associations with cognition in women compared to men. However, hearing loss and diabetes—both more common among men—were linked to poorer cognitive scores in women.
These findings suggest that the same risk factor may not carry equal meaning across sexes. A condition that is moderately associated with cognitive decline in men may have a substantially stronger effect in women, amplifying its overall contribution to dementia risk.
Implications for research and prevention
“These differences highlight the importance of considering sex as a key variable in dementia research,” said Pa. “Sex differences are profoundly overlooked among many leading causes of death like Alzheimer’s, heart disease, and cancer.”
The study’s results align with a broader push toward precision medicine—developing prevention and treatment strategies tailored to individual characteristics, including sex. Rather than focusing solely on the most common risk factors in the population, the findings suggest it may be more effective to prioritize those with the strongest cognitive impact within each group.
The researchers emphasize that these risk factors are modifiable, offering actionable opportunities for intervention. For example, this could mean placing greater emphasis on managing depression, increasing physical activity, and improving cardiovascular health—such as untreated hypertension—among women, as these factors are strongly associated with cognitive health.
Next steps in understanding sex differences
Looking ahead, Fitzhugh and Pa call for further research to better understand the biological and social mechanisms driving sex-based differences in Alzheimer’s risk factors. Hormonal influences, genetic susceptibility, and disparities in health care access may all play a role, but more work is needed to clarify how they interact over time.
“Ultimately, a more nuanced understanding of these differences could help us design smarter, more targeted interventions,” Fitzhugh said. “That’s an essential step toward reducing the burden of dementia for everyone, but especially for women, who are disproportionately affected.”