Objective Depressive symptoms and the apolipoprotein E (APOE) [Latin Small Letter Open E]4 allele are independent risk factors for cognitive decline. However, it is not clear whether the presence of both depressive symptoms and the APOE [Latin Small Letter Open E]4 allele increases cognitive decline.

Methods A prospective study of a population-based sample of 4150 (70% African American and 63% women) participants 65 years and older who were interviewed at 3-year intervals was conducted. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression scale, with each item coded as presence or absence of a symptom. The APOE genotype was ascertained by DNA samples collected during follow-up. Cognitive function was assessed at the initial and follow-up interviews (average follow-up of 9.2 years), using a standardized global cognitive score.

Results There were 1405 (34%) participants with one or more copies of the APOE [Latin Small Letter Open E]4 allele. In participants with no depressive symptoms, cognitive function decreased by 0.0412 unit per year among those with no copies and 0.0704 unit per year among those with one or more copies of the APOE [Latin Small Letter Open E]4 allele. For each additional symptom of depression, cognitive decline increased by 0.0021 unit per year among those with no copies and 0.0051 unit per year among those with one or more copies of the APOE [Latin Small Letter Open E]4 allele. The three-way interaction of depressive symptoms, APOE [Latin Small Letter Open E]4 allele, and time was significant (p = .021).

Conclusions The association of depressive symptoms on cognitive decline was increased among participants with one or more copies of the APOE [Latin Small Letter Open E]4 allele compared with those without the allele.