Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults

Background-Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-epsilon 4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-epsilon 4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results-Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73 +/- 7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and epsilon 4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-epsilon 4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac outputxAPOE-epsilon 4 status interaction and again stratified by FA carrier status. Cardiac outputxAPOE-epsilon 4 status related to naming (beta=0.91, P=0.0009), category fluency (beta=1.2, P=0.01), information processing speed (beta=-5.4, P=0.001), visuospatial skill (beta=0.85, P=0.003), and executive function performances (beta=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-epsilon 4 carriers. Conclusions-APOE-epsilon 4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the epsilon 4 allele. These findings add to increasing evidence that APOE-epsilon 4 carrier status has important implications for associations between vascular and brain health in aging adults.