Differences across males and females in cognitive aging and mortality risk: a trajectory-based approach

This study examined hypothesized differences across males and females in the relationship between cognitive trajectories and mortality in older adults. Data were drawn from the ZARADEMP study on dementia and depression in adults aged 55 and older in Zaragoza, Spain. A total of 2403 cognitively healthy individuals who completed at least three of four waves over a 12-year follow-up were included. Cognitive trajectories were derived from Mini-Mental State Examination (MMSE) scores. Using growth mixture modeling (GMM), four trajectories in men and three in women were previously identified. Mortality data, obtained from official records, covered up to 6 years after the final wave. Cox proportional hazards models assessed mortality risk across trajectories, adjusting for sociodemographic, medical, and lifestyle factors. Mortality was higher among participants with steeper cognitive decline in both sexes. In men, those in the declining-low and stable-medium trajectories had 133% and 36% higher mortality risk, respectively, compared to the stable-high group. In women, declining-low and stable-medium classes had 133% and 30% increased risk, respectively. The association in women followed a clear gradient; in men, this pattern was absent. Differences in mortality predictors were identified: medical conditions (e.g., hypertension, diabetes, alcohol use) were significant only in men, whereas psychosocial and functional variables (e.g., anxiety, ADL dependency, marital status) were significant only in women. This is the first report showing differences across males and females in the association between cognitive decline trajectories and mortality. Sex-specific strategies may be needed to mitigate mortality associated with trajectories of cognitive decline.