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

跑步机步行运动训练对多发性硬化症认知和脑功能的影响：一项系统开发的随机对照试验

• 批准号: 10477034
• 负责人: Brian M Sandroff
• 金额: $ 38.03万
• 依托单位: KESSLER FOUNDATION, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-08 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477034
• 关键词: Activities of Daily Living; American; Behavioral; Brain; Chronic; Clinical; Cognition; Cognitive; Community Participation; Data; Development; Disease; Educational Intervention; Exercise; Fostering; Functional Magnetic Resonance Imaging; General Population; Guidelines; Health; Home; Impaired cognition; Impairment; Intervention; Investigation; Knowledge; Literature; Mediating; Medical center; Methodology; Mission; Multiple Sclerosis; Nature; Outcome; Persons; Pharmacology; Placebo Control; Productivity; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Rehabilitation therapy; Research; Rest; Single-Blind Study; Site; Sports Medicine; Stimulus; Stretching; Supervision; Time; Walking; Work; active control; attentional control; base; brain health; cognitive rehabilitation; college; design; efficacy evaluation; evidence base; exercise intervention; exercise training; follow-up; functional outcomes; improved; innovation; member; multiple sclerosis patient; nervous system disorder; neural correlate; physically handicapped; processing speed; rehabilitation research; social contact; symptom management; treadmill

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.

多发性硬化症患者的认知障碍非常普遍，管理不善，并且致残 （MS）中定义。运动训练是管理MS认知功能障碍的一种有前途的方法;然而，结果 先前的随机对照试验（RCT）结果不明确。这与《好- 来自普通人群的文献一致记录了运动的有益效果 认知和大脑功能的训练。事实上，MS RCT存在显著的方法学缺陷 并且与运动训练研究对普通人群认知的严格性不一致。与 最后，我们最近完成了一系列研究，确定了渐进式（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; MS中最常见的受损认知领域）和丘脑皮质静息状态 功能性连接（RSFC），特别是在MS患者中。为此， 本建议的目的是使用活性药物进行充分的动力、单盲RCT。 控制条件，以改善认知受损的MS患者的CPS和脑功能， 研究现场。这项研究将检查3个月的监督，渐进式慢性跑步机的影响 步行锻炼（基于试点工作设计）与安慰剂对照条件（即，拉伸- 和调色活动）对CPS，功能磁共振成像（即，丘脑皮质RSFC）和功能结果，在88人， MS患者出现CPS减慢。我们将收集有关CPS、丘脑皮质RSFC和功能的数据， 基线和随访时的结果（即，在3个月干预期结束时）时间点。 我们假设跑步机步行运动训练将导致CPS的显着改善， 丘脑皮质RSFC和功能结果。我们进一步推测，丘脑皮质的改善 RSFC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 第一个I类证据证明跑步机步行运动训练作为康复方法的效果 改善CPS，其神经相关性，以及需要这种治疗MS患者的功能后果， 干预最多。这项研究将为运动训练的发展奠定基础 可由临床医生调整以供MS患者使用的指南，以专门改善认知， 大脑健康这样一个基于证据的康复方法，使用运动训练，是至关重要的 考虑到MS相关CPS损伤的普遍性、致残性和管理不善的性质。这是 与国家医疗康复研究中心的使命一致， 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。

项目成果

Cardiopulmonary Exercise Testing Using the Modified Balke Protocol in Fully Ambulatory People With Multiple Sclerosis.

• DOI: 10.1097/cpt.0000000000000141
• 发表时间: 2021-04
• 期刊: Cardiopulmonary physical therapy journal

Thalamic atrophy moderates associations among aerobic fitness, cognitive processing speed, and walking endurance in persons with multiple sclerosis.

• DOI: 10.1007/s00415-022-11205-9
• 发表时间: 2022-10
• 期刊: JOURNAL OF NEUROLOGY
• 影响因子: 6
• 作者: Sandroff, Brian M.;Motl, Robert W.;Roman, Cristina A. F.;Wylie, Glenn R.;DeLuca, John;Cutter, Gary R.;Benedict, Ralph H. B.;Dwyer, Michael G.;Zivadinov, Robert
• 通讯作者: Zivadinov, Robert

Aerobic reserve capacity in multiple sclerosis-Preliminary evidence.

• DOI: 10.1111/ane.13441
• 发表时间: 2021-09
• 期刊: ACTA NEUROLOGICA SCANDINAVICA
• 影响因子: 3.5
• 作者: Feasel, Corey D.;Sandroff, Brian M.;Motl, Robert W.
• 通讯作者: Motl, Robert W.