Protocol for the DREAMER study: Design and methodological framework of a multicenter trial-ready cohort of individuals with isolated REM sleep without atonia

Abstract

Isolated rapid eye movement sleep behavior disorder is a strong clinical marker of future alpha-synucleinopathy, but earlier stages of this risk pathway remain insufficiently characterized. Rapid eye movement sleep without atonia is the polysomnographic substrate of this disorder and may also be detected in individuals without clinical dream-enactment behavior. Whether isolated rapid eye movement sleep without atonia is a benign finding or an early risk state for future rapid eye movement sleep behavior disorder and neurodegeneration remains unknown. DREAMER is a multicenter, prospective, observational cohort protocol designed to identify adults without clinical rapid eye movement sleep behavior disorder who show isolated rapid eye movement sleep without atonia during full-night laboratory video-polysomnography. Four Italian sleep centers will use harmonized eligibility criteria, standardized clinical and sleep assessment, quantitative REM Atonia Index scoring, secure web-based data capture, and planned longitudinal follow-up. Adults aged 40 years or older undergoing video-polysomnography will be screened. Participants with prior rapid eye movement sleep behavior disorder or technically inadequate REM sleep/chin electromyographic data will be excluded. Isolated rapid eye movement sleep without atonia will be defined in participants without clinical rapid eye movement sleep behavior disorder using a REM Atonia Index threshold of <0.85. The target recruitment is more than 500 participants over 18 months, with an expected enriched subgroup of approximately 85 individuals with isolated rapid eye movement sleep without atonia. Ancillary neurophysiological assessments and blood sampling for future biomarker studies will be obtained when feasible. DREAMER is intended to create a harmonized, trial-ready cohort for evaluating isolated rapid eye movement sleep without atonia as a potential early risk marker for incident rapid eye movement sleep behavior disorder and subsequent neurodegenerative outcomes. The study is registered at ClinicalTrials.gov as DREAMER, ClinicalTrials.gov Identifier NCT06140511.