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

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.