This project examined whether frequency of moderate-intensity exercise was associated with episodic memory and depressive symptoms in middle-aged adults at risk for Alzheimer’s disease (AD), and whether hippocampal volume mediated these relationships. Data were drawn from adults aged 45–60 in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and included MRI, depressive symptoms, and verbal and visual memory scores. Mediation analyses tested both direct and indirect effects of exercise frequency on the outcomes, accounting for hippocampal volume. It was hypothesized that greater hippocampal volume would be associated with more frequent exercise, fewer depressive symptoms, and better memory, and that hippocampal volume would mediate these associations. Results partially supported hypotheses: more frequent exercise was associated with fewer depressive symptoms but was not linked to memory performance. Hippocampal volume did not mediate any relationships. However, right hippocampal volume predicted visual memory, suggesting a lateralized effect. Additional research is needed to explore alternative neurobiological mechanisms.