a-synucleinopathies represent the second most common neurodegenerative disorders. Adding to motor deterioration, cognitive decline is a key element of their non-motor symptom complex. Early detection and intervention to halt accelerated brain-ageing are critical yet unmet needs in these disorders. Optimizing lifestyle factors in individuals with isolated REM sleep behaviour disorder (iRBD) holds great potential as iRBD signals an early stage of an a-synucleinopathy, representing an ideal therapeutic window for prevention strategies.

Specifically, increasing physical activity has shown beneficial effects on various outcomes including preservation of cognitive function in the context of neurodegenerative processes. We will apply a novel strategy to increase physical activity by a remotely applied motivational, gamification-based smartphone app, which has already been established in pilot trials and proven to be both feasible and effective.

 Taking advantage of easy application for long-term uses and the large existing cohorts within our consortium, we will conduct a multicentre, randomized, double-blind, active-controlled trial on more than 250 individuals with iRBD evaluating the efficacy of this motivational app to ameliorate cognitive decline over a one-year period. Adding to classic neuropsychological cognitive testing as our primary outcome, we will assess MRI and blood-based markers of brain-ageing. For evaluation of a broader application, we will also test our gamification smartphone app in healthy elderly without known risk-factors for accelerated brain-ageing.

Our study may tremendously change the perspective on early disease detection as a disease-modification intervention will become available, being easy to apply and at low risk for side effects. In addition, we will leverage the mechanistic aspects on how increased physical activity influences brain health and gain insights into the generalizability of our approach for a broader application.