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

小结 此补充请求对合作伙伴试用有一个主要目的：提高参与者的安全性和 通过采购关键的个人资源来缓解因新冠肺炎疫情而产生的负担 保护设备，聘请有经验的理疗师提供建议和进行评估，以及 获得血管成像设备，以便在经批准的方便地点继续接诊患者。 影响多种因素的干预措施更有可能在AD中取得成功。阿尔茨海默病的功能衰退是 严重影响整合和调节复杂认知和运动能力的能力，即， 运动-认知整合。许多干预措施忽视了运动认知问题，这些问题发生在 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Partnered， 节律康复(PRR)是一种理想的干预措施，可同时针对心血管、社会和运动- 认知领域对阿尔茨海默病很重要。PRR是中等强度的、认知上吸引人的社交舞蹈，目标是 姿势控制系统，包括学习多种有节奏的踏步模式，同时培养触觉 在伴侣之间交流运动目标，增强社会互动对认知的影响。我们是 使用PRR对60名PAD患者进行为期一年的II期单盲随机临床试验。我们的 假设PRR是安全的、可耐受的，并与改善运动认知功能、心血管 健身和全身炎症以及神经元、血管和炎症的中介。先前的工作表明 PRR影响运动-认知整合所需的认知域(视觉空间、执行和 注意力/工作记忆)，以及通过一对一的触觉和节奏互动的社交领域。PRR培训 增加额叶下部和颞叶下部回的活动，这两个区域与运动认知和 AD相关病理的可能靶点。患有PAD的参与者将被分配为期三个月的双周 9个月的每周PRR或1：1分配的集体散步(散步)。 步行中的集体行走隔离了我们检测认知参与的PRR元素的影响的能力。 使用意向治疗方法，合作伙伴试验将1.确定可接受性、安全性、耐受性和 对PAD中的PRR的满意度。2.比较PRR和WAKE在改善运动-认知整合方面的效果 在PAD中；3.从一组运动认知容量MRI中确定III期试验最敏感的终点 探索神经、血管、炎症和生物力学机制 哪个PRR影响PAD以得出中介措施的有效大小，并帮助我们估计样本 未来试验所需的大小。

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.