We examined whether hypertension moderated the effects of apolipoprotein ε4 (APOE ε4) on individual differences in level and change in cognitive functions over a 21-year period using data from the Seattle Longitudinal Study (SLS). A total of 563 nondemented adults ages 32 to 74 years in 1984 (M = 51.06, SD = 12.03) were included in the study. Cognitive performance was assessed spanning 7 domains-verbal comprehension, numeric facility, episodic memory, spatial orientation, inductive reasoning, perceptual speed, and cognitive flexibility-over 4 occasions of measurement at 7-year intervals. Multilevel modeling was used to test the cross-sectional and longitudinal effects of hypertension, APOE, and their interaction, after adjusting for age, gender, and education. APOE and hypertension had additive and interactive effects on select cognitive functions. APOE ε4 carriers had a performance advantage at baseline on reasoning ability, relative to non-ε4 carriers. The additive effect of hypertension on level of cognitive flexibility (i.e., lower performance for hypertensives) was qualified by a significant APOE × Hypertension interaction on the slope. Hypertension moderated the effects of APOE ε4 on the rate of change for cognitive flexibility, such that the presence of the APOE ε4 allele and hypertension was associated with steeper cognitive decline over a 21-year period. A double dose of genetic vascular risk factors accounted for variation in the slope in normal cognitive aging, suggesting that clinical interventions aimed at lowering vascular risk may benefit cognitive health.
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