Prediction of Phenoconversion into Alpha-Synucleinopathy in Patients with isolated REM Sleep Behavior Disorder Using Event-Related Potentials During Visuospatial Attention Tasks

Abstract Study Objectives Isolated REM 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 task 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 (HCs; 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 as 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.