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. 2025 Mar 11;48(3):zsae308.
doi: 10.1093/sleep/zsae308.

Prediction of phenoconversion into alpha-synucleinopathy in patients with isolated REM sleep behavior disorder using event-related potentials during visuospatial attention tasks

Kang-Min Choi  1 , Kwang Su Cha  1 , Tae-Gon Noh  2 , Seolah Lee  1 , Yong Woo Shin  3 , Jung-Ick Byun  4 , Jin-Sun Jun  5 , Jung Hwan Shin  1 , Han-Joon Kim  1 , Ki-Young Jung  1   6   7
Affiliations

Prediction of phenoconversion into alpha-synucleinopathy in patients with isolated REM sleep behavior disorder using event-related potentials during visuospatial attention tasks

Kang-Min Choi et al. Sleep. .

Abstract

Study objectives: Isolated rapid eye movement sleep behavior disorder (iRBD) is recognized as a prodromal stage of alpha-synucleinopathies. Predicting phenoconversion in iRBD patients remains a key challenge. We aimed to investigate whether event-related potentials (ERPs) recorded during visuospatial attention tasks can serve as predictors of phenoconversion in iRBD patients.

Methods: We conducted a longitudinal study with 126 iRBD patients (aged 67.1 ± 6.4, 77 males) and 41 healthy controls (aged 66.1 ± 6.9, 29 males). Among the patients, those who further developed synucleinopathies during the follow-up period (average 6.3 years) were classified as converters (iRBD-CV), while the others were non-converters (iRBD-NC). Posner's visuospatial cueing task was performed at baseline. The N2 and P3 components were acquired for both the cue and target (valid and invalid) stimuli. Based on group comparisons, Kaplan-Meier survival analysis was performed.

Results: Twenty-nine patients converted to alpha-synucleinopathies (aged 69.4 ± 7.1, 14 males). iRBD patients exhibited overall reductions in N2 components for cue, valid, and invalid stimuli compared to HC (p = 0.012, 0.047, and 0.001, respectively). iRBD-CV patients displayed a significant increase in cue-elicited P3 (p < 0.001) and a decreasing trend in cue-elicited N2 (p = 0.079) compared to iRBD-NC. These ERP alterations were strongly associated with faster rate of phenoconversion (p < 0.001 for both components).

Conclusion: Our findings suggest that altered cue-elicited ERPs could serve as early biomarkers for predicting phenoconversion in iRBD patients, likely reflecting attention-related neurodegeneration pathways. These biomarkers potentially enable the detection of preclinical phenotypes in alpha-synucleinopathies, facilitating timely intervention.

Keywords: EEG; Parkinson’s disease; REM sleep behavior disorder; attention; dementia with Lewy bodies; multiple-system atrophy.

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