Association Between Elevated Depressive Symptoms and Cognitive Function Moderated by APOE4 Status: Framingham Offspring Study.

Background Depression and Apolipoprotein E4 (APOE4) are associated with decreased cognitive function and differences in brain structure. Objective This study investigated whether APOE4 status moderates the association between elevated depressive symptoms, cognitive function, and brain structure. Methods Stroke- and dementia-free participants (n = 1,968) underwent neuropsychological evaluation, brain MRI, and depression screening. Linear and logistic regression was used to examine all associations. Secondary analyses were performed using interaction terms to assess effect modification by APOE4 status. Results Elevated depressive symptoms were associated with lower cognitive performance in several domains. In stratified analyses, elevated depressive symptoms were associated with poorer visual short- and long-term memory performance for APOE4 + participants. Elevated depressive symptoms were not associated with any brain structure in this study sample. Conclusion Elevated depressive symptoms impact cognitive function in non-demented individuals. Having the APOE4 allele may exacerbate the deleterious effects of elevated depressive symptoms on visual memory performance. Screening for elevated depressive symptoms in both research studies and clinical practice may be warranted to avoid false positive identification of neurodegeneration, particularly among those who are APOE4 + .