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

项目摘要 影响多个因素而不是单一因素的干预措施更有可能是 成功预防和治疗阿尔茨海默病(AD)。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，尽管 运动-认知整合受损发生在AD的早期阶段(即前驱AD，PAD) 并可能先于其他症状。运动和认知相结合的训练已经 建议用于PAD，因此我们建议使用配对、节律康复(PRR)、 同时针对心血管、社会和运动认知领域的理想干预 对AD来说很重要。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，包括学习多种不同的步法和节奏模式，以及 促进伴侣之间对运动目标的触觉交流，增强社交互动 对认知的影响。PI之前的研究表明，PRR类是安全的 不会导致有伤害的跌倒。最近，我们发现PRR改善了运动-认知整合。 有认知障碍的老年人。因此，我们建议进行为期一年的第二阶段单一项目- PRR在60例PAD患者中的随机盲法临床试验。我们最重要的假设是 PRR是安全、可耐受的，并与改善运动认知功能有关，以及 神经元、血管和炎症的中介。我们的理由是：PRR包括体检- 影响CV适合性和全身炎症的活动成分。我们之前的工作是 研究还表明，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(WM))和社交领域 一种触觉和节奏的互动。我们发现PRR训练增加了小鼠的活动 额叶下回和颞叶下回。这两个区域都与运动认知有关，并且 AD相关病理的可能靶点。有PAD的参与者将被分配到三个 两个月的双周会议，然后九个月的每周PRR或对照会议 (团体步行(步行))，1：1分配。对照组中的集体散步将隔离我们的 能够检测PRR的认知参与要素的影响。使用意向治疗 方法，这项创新的试点研究将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与步行对改善运动功能的效果。 PAD中的认知整合；3)从以下方面确定III期试验的最敏感终点 一套运动认知、体积MRI(海马体体积)和认知测量；以及4) 探讨PRR影响PAD的潜在神经、血管和炎症机制 得出这些中介措施的影响大小，从而帮助我们估计样本量 为将来的审判做准备。

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.