Cardiovascular Risk Associated with Poorer Memory in Middle-Aged Adults from the Healthy Brain Project

Background: Midlife cardiovascular risk factors (CVRF) are associated with reduced cognition and an increased risk of dementia. Objective: To further investigate this association using remote unsupervised online assessment of cognition and cardiovascular risk in middle-aged adults; and to explore the extent to which the association is altered by carriage of the APOE ϵ4 allele. Methods: The Healthy Brain Project is an online cohort of middle-aged cognitively unimpaired adults (40-70 years) who have undergone cognitive assessment and provided self-reports of demographic and health history. Cardiovascular risk was determined by ascertaining history of hypertension, hypercholesterolemia, diabetes mellitus, overweight (body mass index≥25), and current cigarette smoking. Participants (n = 2,480) were then grouped based on the number of reported CVRF into no CVRF, 1, 2, and≥3 CVRF. Associations between the number of CVRF as a continuous variable, CVRF group, and each individual CVRF with composite measures of attention, memory and subjective cognitive function were investigated. Results: Higher number of CVRF was associated with poorer attention (β= -0.042, p = 0.039) and memory (β= -0.080, p < 0.001), but not with subjective cognitive function. When considered individually, current smoking (β= -0.400, p = 0.015), diabetes (β= -0.251, p = 0.023), and hypercholesterolemia (β= -0.109, p = 0.044) were independently associated with poorer memory performance. APOE ϵ4 carriers with≥1 CVRF performed worse on memory than ϵ4 carriers with no CVRFs (β(SE) = 0.259(0.077), p = 0.004). This was not observed in ϵ4 non-carriers. Conclusion: In cognitively normal middle-aged adults, CVRF were associated with poorer cognition, particularly in the memory domain. These results support feasibility of online assessment of cardiovascular risk for cognitive impairment.