This supplement request has key purposes for the PARTNER trial: 1) enhance the rigor of the trial by assessing participants for amyloid beta 40/42, which requires only a blood sample to determine prognosis for eventual development of Alzheimer?s disease (AD); 2) using state of the art equipment for motion analysis, enhance the biomechanical understanding of movement assessments and interventions implemented in the PARTNER trial. 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.
Study Description In early AD, people have trouble physically doing things while thinking, which might be helped by doing activities that challenge the brain while moving around at the same time. We have developed an intervention, partnered, rhythmic rehabilitation (PRR), which targets fitness, cognition, mobility and social engagement. PRR may prevent future functional problems in AD. This supplement would increase the surety of patient prognosis, and allow us to know much more about movement quality while thinking and doing in the PARTNER trial.
