Objective: To evaluate the effects of increased physical activity on cognitive decline in patients with isolated REM sleep behavior disorder (iRBD).

Background: Physical activity has been shown to improve cognitive function in healthy adults as well as in individuals with various neurodegenerative diseases. It is also associated with a reduced risk of developing Parkinson’s disease (PD). IRBD is considered an early alpha synucleinopathy. It represents the clinical prodromal phase of PD with or without dementia, providing a crucial window for early intervention. Therefore, it can be hypothesized that increasing physical activity may help slow cognitive decline in patients with iRBD. In addition, healthy controls will also be included as a reference group to investigate whether exercise may be associated with improved cognitive performance in individuals without iRBD.

Method: ALPHA-FIT is a program of linked randomized controlled trials (RCTs) that are carried out in Bonn, Innsbruck and Nijmegen. Participants increase their physical activity levels by either 100% or 10% for the duration of 12 months. Physical activity will be recorded via FitBit and supported through a motivational smartphone app. Altogether 270 iRBD patients (50-80 years) and 100 healthy age- and sex-matched controls will be included. Cognitive performance is the primary endpoint, which is operationalized as change in a global composite z-score derived from a Level II neuropsychological battery covering executive, visuospatial, attentional, memory, and language domains. Secondary outcomes include motor assessments (MDS-UPDRS III, digital motor testing), body composition, sleep metrics, blood-based biomarkers, and multimodal MRI markers of brain structure and function. Effects will be measured using in-group comparison between baseline and follow-ups as well as between-group comparisons.

Results: Recruitment is ongoing. At time of submission 10 participants in Bonn have been included. Recruitment status and baseline data as of Q3 2026 will be presented.

Conclusion: This study will provide data on whether an increase in physical activity can modify the trajectory in early stages of alpha-synucleinopathies. Findings may inform scalable, non-pharmacological intervention strategies for early disease phases. In the future, data will be compared to other coordinated trials in the USA and UK.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-fit-slowing-cognitive-decline-in-alpha-synucleinopathies-by-enhancing-physical-activity/