Partnered Rhythmic Rehabilitation for Enhanced Motor-Cognition in Prodromal Alzheimer's Disease-Enhancement-Refinement Supplement

合作韵律康复以增强阿尔茨海默氏病前驱期的运动认知-增强-细化补充剂

• 批准号: 10291663
• 负责人: Madeleine Eve Hackney
• 金额: $ 16.52万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291663
• 关键词: Affect; Alzheimer' s Disease; Amyloid beta-Protein; Attention; Biomechanics; Blood Vessels; Blood specimen; Brain; Cardiovascular system; Cognition; Cognitive; Communication; Complex; Dancing; Development; Elements; Equipment; Fostering; Future; Goals; Impairment; Inferior; Inflammatory; Intervention; Learning; Magnetic Resonance Imaging; Measures; Motion; Motor; Movement; Musculoskeletal Equilibrium; Neurons; Participant; Pathology; Patients; Pattern; Periodicity; Phase; Prognosis; Randomized Clinical Trials; Rehabilitation therapy; Safety; Sample Size; Short-Term Memory; Single-Blind Study; Social Interaction; Symptoms; System; Tactile; Thinking; Time; Training; Visuospatial; Walking; Work; cardiovascular fitness; cognitive function; comparative efficacy; fitness; functional decline; improved; phase III trial; prevent; prodromal Alzheimer' s disease; relating to nervous system; satisfaction; social; social engagement; systemic inflammatory response

Brief Summary This supplement request has key purposes for the PARTNER trial: 1) enhance the rigor of the trial by assessing participants for amyloid beta 40/42, which requires only a blood sample to determine prognosis for eventual development of Alzheimer’s disease (AD); 2) using state of the art equipment for motion analysis, enhance the biomechanical understanding of movement assessments and interventions implemented in the PARTNER trial. Interventions that affect multiple factors are more likely to be successful in AD. Functional decline in AD is severely impacted by impaired ability to integrate and modulate complex cognitive and motor abilities, ie, motor-cognitive integration. Many interventions have ignored motor-cognitive problems, which occur in the early stages of AD (i.e., prodromal AD, pAD) and may precede other symptoms. We will use partnered, rhythmic rehabilitation (PRR), an ideal intervention, to simultaneously target cardiovascular, social and motor-cognitive domains important to AD. PRR is moderate intensity, cognitively-engaging social dance that targets postural control systems, involves learning multiple rhythmic stepping patterns, while fostering tactile communication of motor goals between partners, enhancing social interaction’s effect on cognition. We are conducting a 1-year Phase II single-blind randomized clinical trial using PRR in 60 patients with pAD. Our hypothesis is that PRR is safe, tolerable and associated with improved motor-cognitive function, cardiovascular fitness and systemic inflammation and neuronal, vascular and inflammatory intermediaries. Prior work showed PRR impacts cognitive domains needed for motor-cognitive integration (visuospatial, executive and attention/working memory), and social domains via one-on-one tactile and rhythmic interactions. PRR training increases activity in the inferior frontal and inferior temporal gyri, regions implicated in motor-cognition and possible targets for AD-related pathologies. Participants with pAD will be assigned to three months of biweekly sessions, followed by nine months of weekly sessions of PRR or group walking (WALK) with 1:1 allocation. Group walking in WALK isolates our ability to detect the effect of the cognitively-engaging elements of PRR. Using an intent-to-treat approach, the PARTNER trial will 1. Determine acceptability, safety, tolerability and satisfaction with PRR in pAD. 2. Compare efficacy of PRR vs. WALK for improving motor-cognitive integration in pAD; 3. Identify the most sensitive endpoint for a Phase III trial from a set of motor-cognitive, volumetric MRI and cognitive measures; and 4. Explore neural, vascular, inflammatory and biomechanical mechanisms by which PRR affects pAD to derive effect sizes of intermediary measures and aid us in estimating the sample size for a future trial.

简要总结 本补充申请对PARTNER试验有以下主要目的：1）通过以下方式提高试验的严谨性 评估参与者的淀粉样蛋白β 40/42，这只需要血液样本来确定预后， 最终发展为阿尔茨海默病（AD）; 2）使用最先进的设备进行运动分析， 加强对运动评估和干预措施的生物力学理解， PARTNER试验。影响多种因素的干预措施更有可能在AD中取得成功。功能 AD的下降受到整合和调节复杂认知和运动能力受损的严重影响 运动认知整合（motor-cognitive integration）许多干预措施忽视了运动认知问题， 发生在AD的早期阶段（即，前驱AD，pAD），并可能先于其他症状。我们将使用 合作，节奏康复（PRR），一个理想的干预，同时针对心血管，社会， 和对AD重要的运动认知领域。PRR是一种中等强度的，认知参与的社交舞蹈 针对姿势控制系统，包括学习多种有节奏的步伐模式，同时培养 伙伴之间运动目标的触觉交流，增强社会互动对认知的影响。我们 正在60例pAD患者中进行为期1年的II期单盲随机临床试验，使用PRR。我们 假设PRR是安全的、可耐受的，并且与改善的运动认知功能、心血管 健身和全身炎症和神经元，血管和炎症介质。先前的工作表明， PRR影响运动认知整合所需的认知领域（视觉空间，执行和 注意力/工作记忆），以及通过一对一触觉和节奏互动的社交领域。PRR培训 增加额下回和颞下回的活动，这些区域与运动认知有关， AD相关病理的可能靶点。患有pAD的受试者将被分配到为期三个月的每两周一次的 会议，然后是9个月的每周会议的PRR或集体步行（步行）与1：1分配。 WALK中的集体行走隔离了我们检测PRR认知参与元素的影响的能力。 使用意向治疗方法，PARTNER试验将1。确定可接受性、安全性、耐受性和 对pAD中PRR的满意度。2.比较PRR与WALK改善运动-认知整合的疗效 在pAD中; 3.从一组运动认知、容积MRI中确定III期试验的最敏感终点 和认知测量;和4.探索神经，血管，炎症和生物力学机制， 哪个PRR影响pAD，以得出中介指标的效应量，并帮助我们估计样本 为将来的审判做准备。