Gene-behavior interaction of depressive symptoms and the apolipoprotein E {varepsilon}4 allele on cognitive decline

Abstract

Objective: Depressive symptoms and the apolipoprotein E (APOE) ε4 allele are independent risk factors for cognitive decline. However, it is not clear whether the presence of both depressive symptoms and the APOE ε4 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 ε4 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 ε4 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 ε4 allele. The three-way interaction of depressive symptoms, APOE ε4 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 ε4 allele compared with those without the allele.

Keywords: APOE gene; cognitive decline; depressive symptoms; gene-behavior interaction.

Figure 1. Cognitive decline in participants with no copies and one or more copies of the APOE ε4 allele

Cognitive decline in participants with no copies (A) and one or more copies (B) of the APOE ε4 allele for various levels of shortened Center for Epidemiologic Studies Depression scale are shown by each trend line. The lines are based on parameter estimates from a linear mixed model regression. The estimate of cognitive decline was 0.0412-unit per year (SE=0.0026) that increased by 0.0021-unit per year (SE=0.0008) for each additional symptom of depression among participants with no copies of the APOE ε4 allele (A). The estimate of cognitive decline was 0.0704-unit per year (SE=0.0046) that increased by 0.0051-unit per year (SE=0.0011) for each additional symptom of depression among participants with one or more copies of the APOE ε4 allele (B).