Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study

Background: Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from four prospective cohorts(n=15,001, ages 18-95). Methods: We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, mid-life, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Exam (3MS)) and processing speed (Digit Symbol Substitution Test (DSST)), adjusting for demographics, education, and cohort.Results: Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late-life ( Conclusions: We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late-life may not be as helpful for these outcomes.