The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults

Background Chronic elevations in cortisol associated with prolonged stress have been associated with memory loss, as has the apolipoprotein E gene (APOE-ε4) 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-ε4 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-ε4-negative subjects obtained better scores than ε4-positive subjects on immediate (p= < .01) and delayed (p< .01) recall of visual designs. Significant stress by APOE-ε4 interaction effects on memory (p = .03) and cortisol (p< .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, ε4-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 ε4 allele leads to memory decline. Further studies will assess whether stress and APOE-ε4 interact to increase the risk of developing Alzheimer’s disease.