Sex Differences in Modifiable Risk Factors of Dementia and Their Associations with Cognition

Women not only face higher rates of Alzheimer’s disease and other forms of dementia, but new research suggests they may also be more strongly affected by several common risk factors linked to cognitive decline. A comprehensive analysis conducted by scientists at the University of California San Diego School of Medicine has revealed that certain modifiable dementia risk factors appear to exert a disproportionately larger impact on women’s cognitive function compared to men’s. This groundbreaking research, published on May 19, 2026, in the esteemed journal Biology of Sex Differences, has significant implications for how we understand, prevent, and treat dementia.

Unveiling the Disproportionate Impact on Women’s Cognition

The study, which meticulously analyzed data from over 17,000 middle-aged and older adults, aimed to move beyond simply identifying which risk factors are most prevalent. Instead, the researchers sought to understand the differential impact of these factors on cognitive health across sexes. "Looking beyond which risk factors are most common, we found that some have a disproportionately larger impact on women’s cognition," stated Megan Fitzhugh, PhD, assistant professor of neurosciences at UC San Diego School of Medicine and the study’s first author. "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."

These findings offer a crucial piece of the puzzle in explaining why women constitute nearly two-thirds of Alzheimer’s cases in the United States. The Alzheimer’s Association reported in 2023 that approximately 6.7 million Americans are living with Alzheimer’s disease, with women comprising an estimated 4.5 million of those individuals. While it is a known fact that women generally live longer than men, this lifespan difference alone does not fully account for the stark disparity in Alzheimer’s prevalence. The new research underscores the necessity of a sex-specific approach to understanding and combating this debilitating disease.

A Deeper Dive into the Data and Methodology

Fitzhugh and senior author Judy Pa, PhD, professor of neurosciences at UC San Diego School of Medicine, delved into a wealth of information from the Health and Retirement Study. This nationally representative longitudinal survey of U.S. adults aged 50 and older provided the robust dataset required for their in-depth analysis. The researchers focused on 13 established dementia risk factors, a comprehensive list that included a range of biological, social, and lifestyle-related elements known to influence cognitive health.

The modifiable risk factors examined were:

• Education Level: Lower educational attainment has been consistently linked to an increased risk of cognitive decline later in life.
• Hearing Loss: Emerging evidence suggests a strong correlation between untreated hearing loss and dementia.
• Smoking: A well-established contributor to vascular and overall health problems, including those affecting the brain.
• Alcohol Consumption: Excessive alcohol intake can have detrimental effects on brain structure and function.
• Obesity: High body mass index (BMI) is associated with a greater risk of cardiovascular disease and diabetes, both of which are linked to dementia.
• Depression: Chronic or severe depression can impact cognitive processes and may be an early indicator or contributing factor to dementia.
• Physical Inactivity: Lack of regular exercise is detrimental to cardiovascular health and brain function.
• Hypertension (High Blood Pressure): Uncontrolled high blood pressure damages blood vessels, including those in the brain, increasing the risk of stroke and vascular dementia.
• Diabetes: Both Type 1 and Type 2 diabetes are associated with an elevated risk of cognitive impairment and dementia.
• Other Cardiometabolic Conditions: This broad category encompasses conditions like high cholesterol and metabolic syndrome, which share common pathways with cardiovascular disease and diabetes.

By examining these factors in relation to cognitive performance in a large, diverse cohort, the study aimed to identify not just correlations, but the differential strength of these associations between men and women.

Key Dementia Risks: A Divergent Landscape for Men and Women

The analysis revealed significant differences in the prevalence of certain risk factors between men and women in the study cohort. These differences, even before considering their impact on cognition, paint a picture of varied risk profiles.

Women in the study were more likely to report:

• Higher rates of depression: This finding aligns with existing epidemiological data suggesting that women experience higher rates of mood disorders. Depression, as noted, is a significant factor that can influence cognitive function and is considered a risk factor for dementia.
• Lower levels of physical activity: This sedentary behavior pattern in women contributes to poorer cardiovascular health and may impede the protective mechanisms that exercise offers to the brain.
• Higher instances of hearing loss: While sometimes attributed to occupational exposures in men, the higher prevalence in women in this study warrants further investigation into potential biological or social determinants.

Furthermore, women in the study exhibited slightly lower average educational attainment. Lower education is a recognized marker for cognitive reserve, meaning individuals with less formal education may have fewer neural pathways to compensate for brain changes associated with dementia, making them more susceptible to noticeable cognitive decline.

In contrast, men showed higher rates of:

• Smoking: Despite declining smoking rates overall, men in this cohort were more likely to be current or former smokers, a habit with well-documented negative impacts on vascular and brain health.
• Higher alcohol consumption: While not specifying the nature of the consumption, higher reported intake in men suggests a potential area for targeted intervention.
• Hypertension: High blood pressure was a prevalent issue across both sexes.

It is noteworthy that high blood pressure was remarkably widespread, affecting approximately six out of every ten participants. Similarly, the average body mass index for both sexes fell within the overweight to obese range, indicating a broad societal challenge with metabolic health that impacts both men and women significantly.

The Differential Cognitive Impact: Where Sex Truly Matters

The most compelling findings emerged when the researchers analyzed how these risk factors translated into actual cognitive performance. The study uncovered that several risk factors were linked to poorer cognitive outcomes more strongly in women than in men, even when controlling for the prevalence of the risk factor itself.

• Cardiovascular and Metabolic Health: Conditions related to heart and metabolic health, including hypertension and elevated body mass index (obesity), demonstrated steeper negative associations with cognitive function among women. This suggests that the damage wrought by high blood pressure and excess weight on the brain’s blood supply and cellular function may be more pronounced in the female brain.
• Hearing Loss and Diabetes: Intriguingly, even factors that were more common in men, such as hearing loss and diabetes, were also tied to lower cognitive scores in women. This points to a potential vulnerability in women’s cognitive resilience when faced with these conditions.

These discoveries challenge the long-held assumption that dementia risk factors operate with uniform effect across the population. A health issue that might cause a moderate decline in cognitive function for a man could potentially exert a far more significant and detrimental influence on a woman’s brain health.

"These differences highlight the importance of considering sex as a key variable in dementia research," emphasized Pa. "Sex differences are profoundly overlooked among many leading causes of death like Alzheimer’s, heart disease, and cancer." This statement underscores a critical gap in medical research, where findings from predominantly male populations have historically been generalized to women, often with insufficient consideration for biological and physiological differences.

Towards Precision Dementia Prevention: Tailoring Interventions for Women

The study’s implications strongly support the growing movement towards precision medicine, an approach that aims to customize prevention and treatment strategies based on individual characteristics, including sex. The researchers advocate for a paradigm shift in dementia prevention, moving away from a one-size-fits-all model.

Instead of solely concentrating on the most common dementia risk factors across the entire population, the findings suggest a more effective strategy would be to prioritize those risk factors that demonstrate the greatest cognitive impact within specific groups, particularly women. This targeted approach could lead to more efficient and impactful interventions.

The researchers underscored the modifiable nature of many of the identified risk factors. This inherent controllability offers significant opportunities to reduce dementia risk through precisely targeted interventions. For women, the findings suggest that specific areas warrant heightened attention:

• Managing Depression: Given its higher prevalence and strong link to cognitive decline in women, enhanced mental health support and treatment for depression could be a critical component of dementia prevention strategies.
• Increasing Physical Activity: Encouraging and facilitating regular physical activity could help mitigate the negative impact of sedentary lifestyles on women’s cardiovascular and brain health.
• Improving Cardiovascular Health: Proactive management of hypertension, especially untreated high blood pressure, is paramount. This includes regular monitoring, lifestyle modifications, and adherence to prescribed medications. Early and effective treatment of hypertension in women may offer substantial protection against cognitive decline.

The Road Ahead: Understanding the ‘Why’ and Implementing Change

While this study provides crucial insights into the differential impact of risk factors, the underlying biological and social mechanisms driving these sex differences remain an active area of inquiry. The researchers acknowledge the need for further investigation to fully unravel these complexities.

Potential explanations for why dementia risk factors may affect women differently include:

• Hormonal Influences: Fluctuations in estrogen levels throughout a woman’s life, particularly during menopause, are known to influence brain health and cognitive function.
• Genetic Differences: Sex-linked genetic variations could play a role in how the brain responds to risk factors.
• Unequal Access to Healthcare: Social determinants of health, such as disparities in access to quality healthcare, may contribute to women experiencing worse outcomes from unmanaged risk factors.
• Lifestyle and Social Factors: Differences in social roles, caregiving responsibilities, and exposure to stress can also influence health behaviors and outcomes.

"Ultimately, a more nuanced understanding of these differences could help us design smarter, more targeted interventions," Fitzhugh concluded. "That’s an essential step toward reducing the burden of dementia for everyone, but especially for women, who are disproportionately affected."

The study, titled "Sex differences in modifiable risk factors of dementia and their associations with cognition," was made possible through funding from the National Institute on Aging (grant numbers RF1AG088811, PI: Pa) and the Alzheimer’s Association (grant number SAGA23-1141238, PI: Pa). The authors reported no conflicts of interest, ensuring the objectivity and integrity of their findings. This research marks a significant stride in our understanding of dementia and paves the way for more equitable and effective strategies to protect brain health for all.