Locomotion adaptation deficits in older adults with mild cognitive impairment and Alzheimers disease

患有轻度认知障碍和阿尔茨海默病的老年人的运动适应缺陷

• 批准号: 10754072
• 负责人: Trisha Kesar
• 金额: $ 42.31万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10754072
• 关键词: Activities of Daily Living; Adverse event; Aerobic; Affect; Age; Alzheimer' s Disease; Biological Markers; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Communities; Complex; Disease Progression; Elderly; Equilibrium; Evaluation; Exercise; Fall prevention; Feasibility Studies; Future; Gait; Gait abnormality; Gait speed; Goals; Human; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Length; Literature; Locomotion; Locomotor adaptation; Measures; Motor; Movement; Outcome; Participant; Patients; Pattern; Performance; Persons; Physical Function; Process; Publishing; Quality of life; Research; Resources; Science; Standardization; Stimulus; Telephone; Testing; Time; Training; Walking; burden of illness; cognitive function; cognitive task; cohort; comparison group; environmental change; exercise intervention; falls; flexibility; gait rehabilitation; improved; improved mobility; innovation; mild cognitive impairment; motor impairment; multimodal data; neural; neuropathology; post stroke; sensory feedback; therapeutic target; walking intervention

PROJECT ABSTRACT Community walking function requires complex motor coordination, sensory feedback, dynamic balance, adaptation to changing environmental stimuli, while also attending to tasks such as crossing a street or talking over the phone. Unfortunately, cognitive dysfunction, the hallmark of mild cognitive impairments (MCI) and Alzheimer’s Disease (AD), directly impacts the cognitive-motor neural resources available to carry out such activities of daily living. The rigor of previous research shows that compared to healthy older adults (HOA), people with MCI and AD walk slower, fall more, and have deficits in gait performance. Notably, gait disturbances and changes in gait variability often precede cognitive decline. Thus, our overall goal is to understand the effects of MCI and AD on gait function and locomotor flexibility, and the inter-relationships with cognitive impairments. Locomotor adaptation is a fundamentally important process that enables humans to flexibility respond to environmental demands, enabling normal community walking function. Split-belt walking is a standardized, robust, well studied paradigm for quantifying capacity for locomotor adaptation, with potential implications for walking function and fall prevention. Despite a large body of literature on split-belt adaptation in individuals of multiple ages and neuro-pathologies, surprisingly, split-belt adaptation has not been assessed in MCI and AD. A previous study showed reduction in the rate of split-belt adaptation when able-bodied participants were distracted by a cognitive task, suggesting that adaptation processes interact with cognitive functions. Another study showed multiple sessions of split-belt walking improved mobility outcomes post- stroke, suggesting its potential as an exercise intervention. However, there is a knowledge gap regarding if and how split-belt adaptation relates to cognitive deficits and walking function in individuals with MCI and AD. The current R21 will build upon MPI Kesar and Nocera’s new published study that provides the first preliminary evidence that split-belt adaptation is significantly impaired in people with MCI and AD compared to HOA. Our premise is that in people with MCI and AD, reduced capacity for locomotor adaptation is a fundamental but poorly understood mechanism that can be a sensitive biomarker of cognitive-motor impairments, and an important therapeutic target for exercise-based interventions. Here, we propose the first comparison of split- belt adaptation, in conjunction with comprehensive assessments of gait and cognitive function, in MCI, AD, and HOA. We propose a unique combination of cross-sectional between-group comparisons (Aim 1) and repeated- measures longitudinal time-point comparisons of disease progression (Aim 2). Aim 3 is a preliminary feasibility study to guide future clinical trials on split-belt aerobic walking exercise interventions in MCI and AD. Further, in parallel with locomotor adaptation (not previously studied), we will also evaluate walking function (gait speed, gait endurance, mobility outcomes), gait performance (step length, gait variability, stride time), and cognition in the same participant cohort, generating an innovative, rich, multi-modal dataset.

项目摘要 社区步行功能需要复杂的运动协调、感觉反馈、动态平衡、 适应不断变化的环境刺激，同时还要处理过马路或说话等任务 在电话里。不幸的是，认知功能障碍，轻度认知障碍(MCI)和 阿尔茨海默病(AD)，直接影响可用于执行此任务的认知运动神经资源 日常生活活动。先前研究的严谨性表明，与健康的老年人(HOA)相比， 患有MCI和AD的人走路更慢，摔倒更多，步态表现也有缺陷。值得注意的是，步态 步态变异性的干扰和变化往往先于认知能力下降。因此，我们的总体目标是 了解MCI和AD对步态功能和运动灵活性的影响，以及两者之间的相互关系 认知障碍。运动适应是一个基本的重要过程，它使人类能够 灵活性响应环境需求，实现正常的社区步行功能。劈带行走是 一个标准化的、健壮的、经过充分研究的范例，用于量化运动适应能力，具有潜力 对行走功能和预防跌倒的影响。尽管有大量关于分裂带适应的文献 令人惊讶的是，不同年龄和神经病理的个体，分裂带适应还没有在 MCI和AD。先前的一项研究表明，身体健全时，分裂腰带的适应率会降低 参与者被一项认知任务分散了注意力，这表明适应过程与认知 功能。另一项研究显示，多个时段的分裂腰带步行改善了术后的活动效果 中风，表明它作为一种运动干预的潜力。然而，关于如果和 分裂腰带适应与MCI和AD患者的认知缺陷和行走功能的关系。这个 目前的R21将建立在MPI Kesar和Nocera的新发表的研究基础上，该研究提供了第一个初步的 有证据表明，与HOA相比，MCI和AD患者的分裂带适应能力显著受损。我们的 前提是在患有MCI和AD的人中，运动适应能力降低是基本的，但 知之甚少的机制可能是认知运动障碍的敏感生物标记物，而 以运动为基础的干预的重要治疗目标。在这里，我们提出了第一个拆分的比较- 腰带适应，结合步态和认知功能的综合评估，在MCI、AD和 哇。我们提出了横断面组间比较(目标1)和重复比较的独特组合。 测量疾病进展的纵向时间点比较(目标2)。目标3是初步的可行性 本研究旨在指导未来裂带式有氧步行运动干预MCI和AD的临床试验。此外， 除了运动适应(以前没有研究过)，我们还将评估行走功能(步态 速度、步态耐力、活动效果)、步态表现(步长、步态可变性、步态时间)，以及 同一参与者队列中的认知，生成创新的、丰富的、多模式的数据集。