Rationale and Design of the PARTNER Trial: Partnered Rhythmic Rehabilitation for Enhanced Motor-Cognition in Prodromal Alzheimer’s Disease

Abstract

Background: Functional decline in Alzheimer’s disease (AD) is impacted by impaired ability to integrate and modulate complex cognitive and motor abilities, commonly known as motor-cognitive integration. Impaired motor-cognitive integration occurs in the early stages of AD, prodromal AD (pAD), and may precede other symptoms. Combined motor and cognitive training have been recommended for people with pAD and need to be better researched. Our data suggest that partnered rhythmic rehabilitation (PRR) improves motor-cognitive integration in older adults with cognitive impairment. PRR is an ideal intervention to simultaneously target cardiovascular, social, and motor-cognitive domains important to AD. Objective/Methods: We propose to conduct a 1-year Phase II, single-blind randomized controlled trial using PRR in 66 patients with pAD. Participants 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 the control group will allow us to compare physical exercise alone versus the added benefit of the cognitively engaging elements of PRR. Results/Conclusion: Using an intent-to-treat approach, this innovative pilot study will 1) Determine acceptability, safety, tolerability, and satisfaction with PRR; 2) Compare efficacy of PRR versus WALK for improving motor-cognitive integration and identify the most sensitive endpoint for a Phase III trial from a set of motor-cognitive, volumetric MRI, and cognitive measures. The study will additionally explore potential neural, vascular, and inflammatory mechanisms by which PRR affects pAD to derive effect size of these intermediary measures and aid us in estimating sample size for a future trial.