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

项目摘要 影响多种因素而不是单一因素的干预措施更有可能 成功预防和治疗阿尔茨海默病（AD）。AD的功能下降是 严重影响整合和调节复杂认知和运动的能力 能力，即，运动认知整合许多干预措施忽视了这一领域， 受损的运动-认知整合发生在AD的早期阶段（即，前驱AD，pAD） 并可能先于其他症状。结合运动和认知训练， 因此，我们建议使用伙伴，节奏康复（PRR）， 同时针对心血管、社交和运动认知领域的理想干预 对AD来说很重要。PRR是一种中等强度，认知参与的社交舞蹈， 姿势控制系统，包括学习多种多样的步伐和节奏模式， 促进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PI先前的研究表明，PRR类是安全的， 不会造成伤害性的福尔斯。最近，我们发现PRR可以改善运动认知整合， 老年人认知障碍。因此，我们建议进行为期一年的第二阶段单一- 在60例pAD患者中使用PRR的盲态随机临床试验。我们的首要假设是 PRR是安全的、可耐受的，并与运动认知功能的改善相关， 神经元、血管和炎症介质。我们的理由：PRR包括物理- 影响CV适应性和全身炎症的活性成分。我们之前的工作 还表明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（WM）），和社会领域通过一对一， 一种触觉和节奏的互动。我们发现PRR训练增加了 额下回和颞下回。这两个区域都与运动认知有关， AD相关病理的可能靶点。患有pAD的受试者将被分配到三个 两周一次的疗程持续9个月，然后是每周一次的PRR或对照疗程持续9个月 （组步行（WALK）），1：1分配。对照组的集体行走会隔离我们的 检测PRR的认知参与元素的效果的能力。使用意向治疗 这种创新的试点研究将1）确定可接受性，安全性，耐受性和 pAD患者对PRR的满意度; 2）比较PRR与WALK在改善运动功能方面的疗效， pAD中的认知整合; 3）确定III期试验的最敏感终点， 一组运动认知、体积MRI（海马体积）和认知测量;以及4） 探索PRR影响pAD的潜在神经、血管和炎症机制， 推导出这些中介指标的效应大小，从而帮助我们估计样本量 将来的审判。

Project Abstract Interventions that affect multiple factors rather than a single factor are more likely to be successful in preventing and treating Alzheimer’s disease (AD). Functional decline in AD is severely impacted by impaired ability to integrate and modulate complex cognitive and motor abilities, i.e., motor-cognitive integration. Many interventions have ignored this area, although impaired motor-cognitive integration occurs in the early stages of AD (i.e., prodromal AD, pAD) and may precede other symptoms. Combined motor and cognitive training has been recommended for pAD, thus we propose to 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, varied stepping and rhythmic patterns, and fosters tactile communication of motor goals between partners, enhancing social interaction’s effect on cognition. Previous research by the PI demonstrates that PRR classes are safe and result in no injurious falls. Recently, we discovered PRR improves motor–cognitive integration in older adults with cognitive impairment. As such, we propose to conduct a 1-year Phase II single- blind randomized clinical trial using PRR in 60 patients with pAD. Our overarching hypothesis is that PRR is safe, tolerable and associated with improved motor-cognitive function, and neuronal, vascular and inflammatory intermediaries. Our rationale: PRR includes a physical- activity component which impacts CV fitness and systemic inflammation. Our prior work has also shown that PRR impacts cognitive domains needed for motor-cognitive integration (visuospatial, executive and attention/working memory (WM)), and social domains via one-on- one tactile and rhythmic interactions. We discovered PRR training increases activity in the inferior frontal and inferior temporal gyri. Both regions are implicated in motor-cognition and are 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 control (group walking (WALK)) with 1:1 allocation. Group walking in the control group will isolate our ability to detect the effect of the cognitively-engaging elements of PRR. Using an intent-to-treat approach, this innovative pilot study 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 (hippocampal volume) and cognitive measures; and 4) Explore potential neural, vascular and inflammatory mechanisms by which PRR affects pAD to derive effect size of these intermediary measures and hence aid us in estimating sample size for a future trial.