Background: Chronic elevations in cortisol associated with prolonged stress have been associated with memory loss, as has the apolipoprotein E gene (APOE-epsilon4) genotype. Combined effects of stress and APOE status on memory and cortisol in humans have not been studied.
Methods: A semistructured interview with standardized scoring was used to measure stress level and univariate analysis of variance to assess effects of stress and APOE-epsilon4 status on memory and salivary cortisol in 91 nondemented subjects (mean age 78.8 years).
Results: Low-stress subjects performed better than high-stress subjects on delayed recall of stories (p = .04), word lists (p = .02), and visual designs (p = .04). APOE-epsilon4-negative subjects obtained better scores than epsilon4-positive subjects on immediate (p = < .01) and delayed (p < .01) recall of visual designs. Significant stress by APOE-epsilon4 interaction effects on memory (p = .03) and cortisol (p < .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, epsilon4-positive group.
Conclusions: These findings are consistent with a model in which prolonged exposure of older, nondemented individuals to stress in the presence of an epsilon4 allele leads to memory decline. Further studies will assess whether stress and APOE-epsilon4 interact to increase the risk of developing Alzheimer's disease.