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<p>Isolated REM sleep behavior disorder is a high-risk prodromal syndrome for Lewy body diseases but highly heterogeneous. Neurophysiologic markers resolving this heterogeneity and predicting phenoconversion remain limited. We applied Subtype and Stage Inference (SuStaIn) modeling to longitudinal resting-state EEG from a prospective cohort of 285 participants. SuStaIn identified a progressive degenerative subtype (Subtype 2), characterized by delta/theta increases and lower MoCA scores, and a posterior beta-low subtype (Subtype 1), which was longitudinally unstable and of uncertain independent prognostic significance. Longitudinal validation demonstrated substantial subtype shifting in Subtype 1 and stage advancement predominantly in Subtype 2. In Kaplan–Meier analysis, subtype shifting and accelerated annual stage advancement (ΔStage≥2) identified individuals at exceptionally high phenoconversion risk with survival approaching 0–15% by 7.5 years. These findings extend SuStaIn beyond cross-sectional inference by incorporating longitudinal subtype-shifting and stage-advancement features to stratify prodromal heterogeneity and predict neurodegenerative progression.</p>

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Longitudinal resting-state EEG–based modeling predicts phenoconversion and delineates heterogeneity in isolated REM sleep behavior disorder

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Soonhyun Yook,
  • Jung-Won Shin,
  • Tae-Gon Noh,
  • Gilsoon Park,
  • Sumin Bae,
  • Kang-Min Choi,
  • Jung-Hwan Shin,
  • Han-Joon Kim,
  • Arthur W. Toga,
  • Ki-Young Jung,
  • Hosung Kim

摘要

Isolated REM sleep behavior disorder is a high-risk prodromal syndrome for Lewy body diseases but highly heterogeneous. Neurophysiologic markers resolving this heterogeneity and predicting phenoconversion remain limited. We applied Subtype and Stage Inference (SuStaIn) modeling to longitudinal resting-state EEG from a prospective cohort of 285 participants. SuStaIn identified a progressive degenerative subtype (Subtype 2), characterized by delta/theta increases and lower MoCA scores, and a posterior beta-low subtype (Subtype 1), which was longitudinally unstable and of uncertain independent prognostic significance. Longitudinal validation demonstrated substantial subtype shifting in Subtype 1 and stage advancement predominantly in Subtype 2. In Kaplan–Meier analysis, subtype shifting and accelerated annual stage advancement (ΔStage≥2) identified individuals at exceptionally high phenoconversion risk with survival approaching 0–15% by 7.5 years. These findings extend SuStaIn beyond cross-sectional inference by incorporating longitudinal subtype-shifting and stage-advancement features to stratify prodromal heterogeneity and predict neurodegenerative progression.