Objective: To examine the relationship between depression and cognitive ability, genetic risk, and hippocampal differences in an older sample of adults with a history of traumatic brain injury (TBI). Method: 121 participants with a history of moderate to severe or complicated mild TBI were included. All participants underwent buccal swabs for genetic testing, a comprehensive neuropsychological battery, surveys, and 46 participants underwent an MRI scan. Results: APOE e4 carrier status significantly predicted clinically significant depressive symptomatology on the Geriatric Depression Scale (GDS) with an odds ratio of 3.63, and carriers presented with a higher mean GDS score. GDS was not predictive of scores on measures of executive function, list learning delayed recall, or retention. Although GDS score was initially associated with poorer semantic memory scores and poorer story memory delayed recall, this variance was accounted for by age and cognitive reserve. Higher GDS scores were also associated with decreased hippocampal volume. Conclusions: APOE carrier status was predictive of depression in a sample of older individuals with a history of TBI a mean of 10 years post-injury. Depressive symptoms were also associated with decreased hippocampal volume but did not predict cognitive deficits in the examined domains above and beyond the effects of age and cognitive reserve. These results indicate that despite the relationship between depression and biological risks for decline, depressive symptoms in older adults with msTBI may not lead to exacerbated cognitive decline, which is better predicted by other factors (e.g., cognitive reserve).

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