Introduction: The relationships between Alzheimer disease (AD), cognitive performance, and depression are poorly understood. It is unclear whether depressive features are a prodrome of AD. In addition, some studies of aging exclude depressed individuals, which may inappropriately limit generalizability. The aim of the present study was to determine whether depressive symptoms affect cognitive function in the context of preclinical AD. Methods: Cross-sectional multivariate analysis of participants in a longitudinal study of aging (n=356) that evaluates the influence of depressive symptoms on cognitive function in cognitively normal adults. Results: There is no relationship between the presence of depressive symptoms and cognitive function in those with either no evidence of preclinical AD or biomarker evidence of early-stage preclinical AD. However, in later stages of preclinical AD, the presence of depressive symptoms demonstrated interactive effects, including in episodic memory (0.96; 95% confidence interval, 0.31-1.62) and global cognitive function (0.46; 95% confidence interval, 0.028-0.89). Conclusions: The presence of depressive symptoms may be a late prodrome of AD. In addition, studies investigating cognitive function in older adults may not need to exclude participants with depressive symptomology, but may still consider depressive symptoms as a potential confounder in the context of more extensive neuronal injury. © 2018 Wolters Kluwer Health, Inc. All rights reserved.