0799 Resting-State EEG Subtype and Stage Inference Identifies Distinct Prodromal Biotypes and Staging in iRBD

Abstract Introduction Idiopathic REM Sleep Behavior Disorder (iRBD) provides a critical preclinical window into α-synucleinopathy. Given the substantial heterogeneity in clinical trajectories, developing a biologically grounded framework for staging this prodromal phase is essential. We applied SuStaIn (Subtype and Stage Inference) modeling to resting-state electroencephalography (EEG) to identify distinct prodromal biotypes and evaluate their relevance using long-term phenoconversion outcomes. Methods A total of 285 participants (51 healthy controls, 234 iRBD) were drawn from a prospective cohort with standardized assessments and baseline/biannual EEG. Among iRBD participants, 39 converted (iRBD-CV) and 195 remained non-converted (iRBD-NC). Twenty-four EEG spectral-power features across eight cortical regions, standardized to healthy controls, were entered into the SuStaIn model to infer latent subtypes and stage trajectories. Longitudinal EEG was used to validate subtype stability, track stage progression, and examine associations with cognitive and clinical outcomes. Results SuStaIn modeling revealed two distinct EEG-based prodromal biotypes. Subtype 1 exhibited a focal reduction in posterior beta power that remained stable across stages. During follow-up, the majority of this group (89.5%) transitioned toward “Subtype 0,” indicating reversal of the posterior beta abnormality, and all individuals remained non-converted. Subtype 1 also showed higher educational attainment and a greater proportion of males. In contrast, Subtype 2 demonstrated a progressive trajectory beginning with early frontal theta elevations and extending to delta abnormalities. Within Subtype 2, higher stages were significantly associated with lower MoCA scores. Longitudinal EEG demonstrated significant stage advancement (p = 0.00013), with the most pronounced progression occurring in Subtype 2 and among converters. Conclusion SuStaIn modeling of resting-state EEG delineated biologically prodromal biotypes in iRBD, revealing two mechanistically distinct progression pathways: an adaptive–compensatory subtype (Subtype 1) and a progressive–degenerative subtype (Subtype 2). Subtype 1, marked by isolated posterior beta reduction without abnormalities in other regions and subsequent reversal over time, appears to reflect a compensatory mechanism underlying clinical stability. In contrast, Subtype 2, characterized by early and widespread theta–delta increases, represents an actively degenerating trajectory associated with cognitive decline. These findings demonstrate that early EEG-monitoring–based SuStaIn staging can stratify stable versus progressing iRBD, underscoring the prodromal period as a key window for disease-modifying interventions. Support (if any)