Depressive Symptoms Moderate the Influence of the ApolipoproteinE ε4 Allele on Cognitive Decline in a Sample of Community Dwelling Older Adults

Objectives: The apolipoproteinE epsilon 4 (APOE epsilon 4) allele and a history of depression are each separate risk factors for cognitive decline (CD). However, little research has investigated whether a history of depression influences the relationship between APOE epsilon 4 and CD. The present study examined whether depressive symptoms had greater influence on subsequent CD among participants with APOE epsilon 4 than those without the allele. Design: Prospective 6-year longitudinal study. Setting: Community in-home interviews. Participants: A biracial sample of community dwelling older adults (N = 1,992) from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Measurements: Data were drawn from Waves 1 to 3 of the EPESE, which were conducted 6 years apart. Cognitive functioning and depressive symptoms were assessed at both waves, and APOE genotyping was completed during the Wave 3 assessment. Results: Regression analyses revealed that depressive symptoms and the APOE epsilon 4 allele independently predicted CD. Importantly, the influence of depressive symptoms on CD was greater for individuals with the APOE epsilon 4 allele compared with those without the allele. Conclusion: Depressive symptoms and the APOE epsilon 4 allele are independent contributors to CD. Moreover, the influence of depressive symptoms on CD is greater among individuals with the APOE epsilon 4 allele. Depression and the APOE epsilon 4 allele may act together in disrupting neurological functioning, which may in turn lower an individual's cognitive reserve capacity. Given the efficacious treatments currently available for depression, future research should investigate the extent to which interventions for depression may reduce the risk for subsequent CD. (Am J Geriatr Psychiatry 2009; 17: 155-165)