Exercise for Memory Rehabilitation in Epilepsy

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Project Summary/Abstract Approximately 50% of the 3.4 million persons with epilepsy (PWE) in the U.S. have cognitive problems with memory deficits reported most commonly. Memory deficits negatively contribute to the personal and professional outcomes of PWE including quality of life. While cognitive rehabilitation programs have been utilized to help improve memory function in epilepsy, their efficacy remains unclear. Recently, memory improvements with formal exercise training have been shown in randomized controlled trials in healthy individuals, and in our pilot study in PWE who participated in supervised combined endurance and resistance training. Despite evidence of memory and other cognitive benefits derived from physical exercise, clinical trials of exercise as a rehabilitative strategy for memory improvement in PWE have not been conducted to date. Further, we lack understanding of the brain changes that occur with exercise and their role in improving memory function as well as the longitudinal effects of exercise on memory and brain changes. Improving our understanding and ameliorating the negative impact of epilepsy, seizures, and its treatment are recognized by the epilepsy, medical and scientific community as an important focus of research. Thus, exercise training is a promising rehabilitative strategy for mitigating the memory deficits experienced in epilepsy. The primary objectives of this study are to determine in adults with idiopathic generalized epilepsy (IGE) the efficacy of a 6-week supervised and structured exercise program combining endurance and resistance training for memory rehabilitation, investigate a putative mechanisms of action for exercise-related memory benefits, and determine if the memory benefits and brain changes are retained 6 weeks after completing the exercise intervention. Based on our pilot exercise data in adults with epilepsy, we hypothesize that exercise will significantly improve verbal memory function in the exercise group compared to the no-intervention control group. We also hypothesize that the verbal memory improvements are mediated by the changes in resting state functional connectivity of the hippocampus, a brain region that plays a vital role in memory function. We propose a mediation model in which exercise-induced changes in the hippocampus functional connectivity is mediating the beneficial effect of exercise on memory function in epilepsy, and we will utilize the causal-steps approach in which 4 conditions of statistical significance must be met to determine if mediation is present. Using a randomized delayed intervention study design, we will conduct a clinical trial of the 6-week supervised exercise program combining endurance and resistance training in adults with IGE in order to test our hypotheses. Completion of the proposed study will significantly impact the field in that it will lay the groundwork for the use of exercise for memory rehabilitation in epilepsy, in which option for combatting memory impairment are limited.