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-epsilon 4) 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-epsilon 4 status on memory and salivary cortisol in 91 nonclemented 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-epsilon 4-negative subjects obtained better scores than -4-positive subjects on immediate (p = < .01) and delayed (P < .01) recall of visual designs. Significant stress by APOE-epsilon 4 interaction effects on memory (p =.03) and cortisol (p < .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, epsilon 4-positive group. Conclusions: These findings are consistent with a model in which prolonged exposure of older, nonclemented individuals to stress in the presence of an e4 allele leads to memory decline. Further studies will assess whether stress and APOE-epsilon 4 interact to increase the risk of developing Alzheimer's disease.