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

点击翻译按钮获取中文摘要

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.