Exercise for Memory Rehabilitation in Epilepsy

项目概要/摘要 在美国，340万癫痫（PWE）患者中约有50%患有认知问题， 最常报告的记忆缺陷。记忆缺陷对个人和 PWE的专业成果，包括生活质量。虽然认知康复计划已经 用于帮助改善癫痫患者的记忆功能，其疗效仍不清楚。最近，记忆 正规运动训练的改善已经在健康人群中的随机对照试验中显示， 个人，并在我们的试点研究PWE谁参加了监督联合耐力和阻力 训练尽管有证据表明，体育锻炼对记忆和其他认知能力有好处，但临床试验表明， 运动作为PWE记忆改善的康复策略迄今尚未进行。 此外，我们缺乏对运动引起的大脑变化及其在改善大脑功能方面的作用的理解。 记忆功能以及运动对记忆和大脑变化的纵向影响。改善我们 了解和改善癫痫的负面影响，癫痫发作及其治疗是公认的 癫痫病，医学和科学界的一个重要研究重点。因此，运动训练是一种 有前途的康复策略，减轻癫痫经历的记忆缺陷。 本研究的主要目的是确定成人特发性全身性癫痫（IGE） 一个为期6周的监督和结构化的锻炼计划结合耐力和阻力的有效性 记忆康复训练，探讨运动相关记忆的作用机制 的好处，并确定是否记忆的好处和大脑的变化保留6周后完成 运动干预。根据我们在成年癫痫患者中的初步运动数据，我们假设运动会 与无干预对照组相比，运动组的言语记忆功能显著改善 组我们还假设，非文字记忆的改善是由休息时间的变化介导的。 海马体是一个大脑区域，在记忆功能中起着至关重要的作用。我们 提出了一个调解模型，其中运动引起的海马功能连接的变化是 介导运动对癫痫记忆功能的有益作用，我们将利用卡西尼步骤， 必须满足4个统计学显著性条件才能确定是否存在调解的方法。 使用随机延迟干预研究设计，我们将进行为期6周的监督临床试验， 在IGE成人中进行耐力和阻力训练相结合的运动计划，以测试我们的 假设完成拟议的研究将对该领域产生重大影响，因为它将为 用于癫痫记忆康复的锻炼，其中用于对抗记忆障碍的选择 是有限的。

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.