Elevated blood pressure and the Apolipoprotein e4 allele (APOE e4) are independent risk factors for Alzheimer’s disease. We sought to determine whether the combined presence of the APOE e4 allele and elevated blood pressure is associated with lower cognitive performance in cognitively healthy middle-aged adults. Methods: A total of 975 participants aged 30–54 (mean age = 44.47) were genotyped for APOE. Cardiometabolic risk factors including blood pressure, lipids, and glucose were assessed and cognitive function was measured using the Trail Making Test and the Visual Reproduction and Logical Memory subtests from the Wechsler Memory Scale. Results: Multivariable regression analysis showed that the association between APOE e4 and episodic memory performance varied as a function of systolic blood pressure (SBP), such that elevated SBP was predictive of poorer episodic memory performance only in APOE e4 carriers (ß = -.092; t = -2.614; p = .009). Notably, this association was apparent at prehypertensive levels (=130 mmHg), even after adjusting for physical activity, depression, smoking, and other cardiometabolic risk factors. Conclusions: The joint presence of APOE e4 and elevated SBP, even at prehypertensive levels, is associated with lower cognitive performance in healthy, middle-aged adults. Results of this study suggest that the combination of APOE e4 and elevated SBP may synergistically compromise memory function well before the appearance of clinically significant impairments. Interventions targeting blood pressure control in APOE e4 carriers during midlife should be studied as a possible means to reduce the risk of cognitive decline in genetically susceptible samples.
