Context: The social environment may influence cognitive function in aging. However, to our knowledge, no studies have investigated whether specific genes modify this association.
Objective: To examine whether the apolipoprotein E (APOE) ε4 allele modifies the association of neighborhood psychosocial hazards and cognitive function.
Design: A cross-sectional analysis.
Setting: The Baltimore Memory Study, a population-based sample of older urban residents. The 65 study neighborhoods in Baltimore, Maryland, were characterized using the Neighborhood Psychosocial Hazards Scale, designed to assess social disorganization, physical disorder, public safety, and economic deprivation.
Participants: One thousand one hundred forty urban residents aged 50 to 70 years at baseline.
Main outcome measures: Cognitive performance on 20 standard tests was measured and combined to form 7 summary domain scores (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction).
Results: In analyses fully adjusted for individual covariates, we found that high (ie, worse) neighborhood psychosocial hazards were not consistently associated with worse cognitive performance. However, the interaction of high neighborhood psychosocial hazards and APOE ε4 genotype was found to be associated with worse cognitive domain scores, with evidence of associations in the domains of processing speed (P = .02) and executive functioning (P < .001). Suggestive evidence was also found for eye-hand coordination (P = .05).
Conclusion: Living in a psychosocially hazardous neighborhood was associated with worse cognitive function in persons with the APOE ε4 allele, evidence of a novel gene × environment interaction.