Treadmill Walking Exercise Training Effects on Cognition and Brain Function in Multiple Sclerosis: A Systematically-Developed Randomized Controlled Trial

认知障碍在多发性硬化症患者中非常普遍，管理不善，并致残 (毫秒)。运动训练是治疗多发性硬化症认知功能障碍的一种有前景的方法；然而，结果 来自以前的随机对照试验(RCT)一直是模棱两可的。这与油井不一致- 来自普通人群的可靠文献，始终如一地证明锻炼的有益效果 认知和脑功能方面的训练。事实上，MS RCT在方法学上存在重大缺陷 与运动训练研究对普通人群认知的严谨性不同。到那时候 最后，我们最近完成了一系列研究，确定了渐进性(即强度和持续时间) 跑步机步行运动作为改善认知加工的最佳运动训练干预 速度(CPS；多发性硬化症最常受损的认知域)和丘脑皮质静息状态 功能连接(RSFC)，特别是在患有多发性硬化症的完全活动的人之间，为此， 本提议的目的是使用有源随机对照试验，进行动力充足的单盲随机对照试验 认知受损多发性硬化症患者一次性改善CPS和脑功能的控制条件 研究网站。这项研究将检验为期3个月的有监督的渐进性慢性跑步机的效果 步行锻炼(基于试点工作设计)与安慰剂控制条件(即，伸展- CPS、功能磁共振成像(即丘脑皮质RSFC)和功能结局方面的研究 出现CPS减慢的MS。我们将收集有关CPS、丘脑皮质RSFC和功能的数据 基线和后续(即3个月干预期结束时)时间点的结果。 我们假设跑步机步行运动训练将导致CPS的显著改善， 丘脑皮质RSFC和功能结果。我们进一步推测，丘脑皮质功能的改善 RSFC可能可以解释CPS中与运动相关的改善。如果成功，拟议的研究将提供 作为康复方法的跑步机步行运动训练效果的第一个I类证据 改善多发性硬化症患者的CPS、其神经相关性和功能后果 最多的是干预。这一研究方向将为运动训练的发展奠定基础 可由临床医生改编的指南，供多发性硬化症患者使用，以特别改善认知和 大脑健康。这种以证据为基础的康复方法，使用运动训练，是至关重要的。 考虑到多发性硬化症相关CPS损害的普遍、禁用和管理不善的性质。这是 与国家医疗康复研究中心的使命一致，促进 提高人们的健康、生产力、独立性和生活质量所需的科学知识 身体残疾的人。

Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with multiple sclerosis (MS). Exercise training is a promising approach for managing cognitive dysfunction in MS; however, results from previous randomized controlled trials (RCTs) have been equivocal. This is inconsistent with the well- established literature from the general population that consistently documents beneficial effects of exercise training on cognition and brain function. Indeed, the MS RCTs suffer from significant methodological flaws and are not on par with the rigor of exercise training studies on cognition in the general population. To that end, we recently completed a line of research that identified progressive (i.e., both intensity and duration) treadmill walking exercise as an optimal exercise training intervention for improving cognitive processing speed (CPS; the most commonly impaired cognitive domain in MS) and thalamocortical resting-state functional connectivity (RSFC), in particular, among fully-ambulatory persons with MS. To that end, the purpose of the present proposal is to conduct an adequately-powered, single-blind, RCT, using an active control condition for improving CPS and brain function in cognitively-impaired persons with MS at a single research site. This study will examine the effects of 3-months of supervised, progressive chronic treadmill walking exercise (designed based on pilot work) compared with a placebo control condition (i.e., stretching- and-toning activities) on CPS, fMRI (i.e., thalamocortical RSFC), and functional outcomes in 88 persons with MS who present with slowed CPS. We will collect data on CPS, thalamocortical RSFC, and functional outcomes at baseline and follow-up (i.e., at the conclusion of the 3-month intervention period) time points. We hypothesize that treadmill walking exercise training will result in significant improvements in CPS, thalamocortical RSFC, and functional outcomes. We further speculate that improvements in thalamocortical RSFC might explain exercise-related improvements in CPS. If successful, the proposed study will provide the first Class I evidence for the effects of treadmill walking exercise training as a rehabilitative approach to improve CPS, its neural correlate, and functional consequences in persons with MS who need such an intervention the most. This line of research will lay the groundwork for the development of exercise training guidelines that can be adapted by clinicians for use by MS patients for specifically improving cognition and brain health. Such an evidence-based approach for rehabilitation, using exercise training, is paramount considering the prevalent, disabling, and poorly-managed nature of MS-related CPS impairment. This is consistent with the National Center for Medical Rehabilitation Research’s mission to foster development of scientific knowledge needed to enhance the health, productivity, independence, and quality of life of persons with physical disabilities.