Cardiometabolic risk, biological sex, and age do not share an interactive relationship with cognitive function: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

It is unclear whether cardiometabolic risk shares an interactive relationship with age-associated differences in cognition, and whether this relationship varies by biological sex. We conducted a cross-sectional analysis using baseline data from the Canadian Longitudinal Study on Aging (CLSA; 2010-2015) to examine whether 1) cardiometabolic risk has an interactive relationship with age-associated cognition; and 2) interactive effects are sex-dependent. We measured memory, executive function, and verbal fluency in the Comprehensive cohort ( N  = 25 830; 45-86 years). Each cognitive domain was modeled using restricted cubic splines for age and each cardiometabolic risk factor (HbA1c, HSCRP, TG, and LDL and HDL cholesterol). Sex was included as a predictor in all models. Wald χ ² statistics were used to determine the relative importance of age, cardiometabolic risk, sex, and their interactive effects on cognition. Age was the most important variable in each model (proportion χ ²  = 34%-48%). Biological sex was the second most important variable for memory (proportion χ ²  = 26%) but was unimportant for executive function and verbal fluency (proportion χ ²  = 3%-5%). Cardiometabolic risk factors were unimportant predictors in each model (proportion χ ²  = 1%-3%). Two- and 3-way interactions between cardiometabolic risk, age, and sex were also unimportant (proportion χ ²  = 0%-2%). Thus, cardiometabolic risk factors did not meaningfully account for age-associated differences in cognition, and these associations (or lack thereof) did not vary by sex. Novelty: Males have poorer age-associated cognitive performance than females. Females and males differ in cardiometabolic risk across middle and older adulthood. Cardiometabolic risk has a small association with age-associated cognition, and there are no sex differences in this relationship.