We found that HRF was significantly associated with cognitive performance (higher HRF, worse cognitive performance) independent of a combination of widely acknowledged risk factors of cognitive impairment including demographic (age, sex), socioeconomic (level of education, gross family income), genomic (APOE-ε4 allele), behavioral (smoking, alcohol consumption, degree of physical activity), mental health (depression) variables, and CV risk factors (hypertension, hyperlipidemia, diabetes and CAC). The gene discussed is APOE; the disease is major depressive disorder.