Exercise, memory, and the hippocampus: Uncovering modifiable lifestyle reserve factors in refractory epilepsy

Physical exercise is an emerging target for improving cognition in aging and neurological disease. Due to the beneficial impact of exercise on hippocampal health and the vulnerability of the hippocampus in medication-resistant temporal lobe epilepsy (TLE), exercise could present a promising intervention in TLE. We investigated whether exercise engagement is associated with verbal memory function and hippocampal integrity in 29 young to middle-aged adults with refractory TLE and 21 demographically matched controls. Participants completed a self-reported questionnaire of weekly exercise, three tests of verbal memory, and a subset (n = 44) underwent structural MRI. Individuals with TLE self-reported lower exercise scores than controls across all levels of exercise intensity (p < 0.001). In TLE, greater exercise engagement was associated with better verbal memory (word-list recall and associative learning; rho = 0.46-0.47; ps _FDR < 0.05), and with larger contralateral hippocampal volumes (rho = 0.61; p < 0.01). These effects remained significant when controlling for epilepsy-related and demographic factors. Within the limitations of a cross-sectional observational study, these findings suggest that exercise may be a cognitive reserve factor in TLE, potentially mitigating memory decline by enhancing contralateral hippocampal integrity. With future replication and longitudinal studies to clarify the causal pathways of these relationships, exercise holds promise as a low-cost, accessible, and modifiable lifestyle target for improving cognitive health in individuals with refractory TLE.