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

简要总结 该补充申请对PARTNER试验有一个关键目的：提高受试者的安全性， 通过采购重要的个人信息，减轻因COVID-19疫情而产生的负担 保护设备，聘请经验丰富的物理治疗师提供建议和进行评估，以及 获得血管成像设备，以便在获准继续为患者看病的方便地点使用。 影响多种因素的干预措施更有可能在AD中取得成功。AD的功能下降是 严重影响整合和调节复杂认知和运动能力的能力受损，即， 运动认知整合许多干预措施忽视了运动认知问题，这发生在 AD的早期阶段（即，前驱AD，pAD），并可能先于其他症状。我们将使用合作伙伴， 节律性康复（PRR）是一种理想的干预措施，同时针对心血管、社会和运动， 认知领域对AD很重要。PRR是一种中等强度，认知参与的社交舞蹈， 姿势控制系统，包括学习多种有节奏的步伐模式，同时培养触觉 合作伙伴之间的运动目标的沟通，加强社会互动对认知的影响。我们 在60例pAD患者中使用PRR进行为期1年的II期单盲随机临床试验。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。

Brief Summary This supplement request has a key purpose for the PARTNER trial: increase the safety of participants and relieve burden that has been incurred because of the COVID-19 pandemic through procuring crucial personal protective equipment, hiring an experienced physical therapist to advise and conduct assessments, and obtaining vascular imaging equipment to use at a convenient location approved to continue seeing patients. 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.