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; Kwang Su Cha; Tae-Gon Noh; Seolah Lee; Yong Woo Shin; Jung-Ick Byun; Jin-Sun Jun; Jung Hwan Shin; Han-Joon Kim; Ki-Young Jung

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

Sleep. 2024 Dec 28:zsae308. doi: 10.1093/sleep/zsae308. Online ahead of print.

Authors

Kang-Min Choi¹, Kwang Su Cha¹, Tae-Gon Noh¹, Seolah Lee¹, Yong Woo Shin², Jung-Ick Byun³, Jin-Sun Jun⁴, Jung Hwan Shin¹, Han-Joon Kim¹, Ki-Young Jung^{1

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Affiliations

¹ Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
² Department of Neurology, Inha University Hospital, Incheon, Republic of Korea.
³ Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
⁴ Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea.
⁵ Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, South Korea.
⁶ Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

PMID: 39731299
DOI: 10.1093/sleep/zsae308

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.

Keywords: Attention; Dementia with Lewy bodies; EEG; Multiple system atrophy; Parkinson’s disease; REM sleep behavior disorder.

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