Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder

Abstract Idiopathic REM sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies including Parkinson’s disease (PD), yet its clinical heterogeneity remains underexplored. This study aimed to identify novel brain-clinical biotypes in iRBD by integrating structural MRI and clinical a...

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Main Authors: Shi Tang, Bei Huang, Yanlin Wang, Yaping Liu, Jing Wang, Li Zhou, Siyi Gong, Yuhua Yang, Joey WY Chan, Steven WH Chau, Winnie CW Chu, Jill Abrigo, Jean-François Gagnon, Yun Kwok Wing
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01012-0
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author Shi Tang
Bei Huang
Yanlin Wang
Yaping Liu
Jing Wang
Li Zhou
Siyi Gong
Yuhua Yang
Joey WY Chan
Steven WH Chau
Winnie CW Chu
Jill Abrigo
Jean-François Gagnon
Yun Kwok Wing
author_facet Shi Tang
Bei Huang
Yanlin Wang
Yaping Liu
Jing Wang
Li Zhou
Siyi Gong
Yuhua Yang
Joey WY Chan
Steven WH Chau
Winnie CW Chu
Jill Abrigo
Jean-François Gagnon
Yun Kwok Wing
author_sort Shi Tang
collection DOAJ
description Abstract Idiopathic REM sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies including Parkinson’s disease (PD), yet its clinical heterogeneity remains underexplored. This study aimed to identify novel brain-clinical biotypes in iRBD by integrating structural MRI and clinical assessments. We included 172 patients with video-polysomnography-confirmed iRBD and 126 controls who underwent multimodal MRI and clinical evaluation. Similarity Network Fusion was used to integrate cortical thickness, surface area, subcortical volume, and clinical data, followed by spectral clustering to identify iRBD biotypes. Two distinct biotypes were identified: Biotype 1 showed widespread cortical-subcortical-cerebellar atrophy, functional hypoconnectivity, more motor and cognitive deficits with higher prodromal PD risk; Biotype 2 demonstrated increased surface area in limbic and parietal regions, cortical-cerebellar hyperconnectivity, and preserved neurocognitive function. These findings underscore the presence of distinct neurobiological subtypes in iRBD, highlighting the need for longitudinal monitoring to clarify their trajectories and implications for disease progression.
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spelling doaj-art-0f23ca114d9643b0b1e4eeb1374e2f122025-08-20T02:31:03ZengNature Portfolionpj Parkinson's Disease2373-80572025-06-0111111010.1038/s41531-025-01012-0Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorderShi Tang0Bei Huang1Yanlin Wang2Yaping Liu3Jing Wang4Li Zhou5Siyi Gong6Yuhua Yang7Joey WY Chan8Steven WH Chau9Winnie CW Chu10Jill Abrigo11Jean-François Gagnon12Yun Kwok Wing13Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongBrain and Mind Institute, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong KongCenter for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de MontréalDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongAbstract Idiopathic REM sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies including Parkinson’s disease (PD), yet its clinical heterogeneity remains underexplored. This study aimed to identify novel brain-clinical biotypes in iRBD by integrating structural MRI and clinical assessments. We included 172 patients with video-polysomnography-confirmed iRBD and 126 controls who underwent multimodal MRI and clinical evaluation. Similarity Network Fusion was used to integrate cortical thickness, surface area, subcortical volume, and clinical data, followed by spectral clustering to identify iRBD biotypes. Two distinct biotypes were identified: Biotype 1 showed widespread cortical-subcortical-cerebellar atrophy, functional hypoconnectivity, more motor and cognitive deficits with higher prodromal PD risk; Biotype 2 demonstrated increased surface area in limbic and parietal regions, cortical-cerebellar hyperconnectivity, and preserved neurocognitive function. These findings underscore the presence of distinct neurobiological subtypes in iRBD, highlighting the need for longitudinal monitoring to clarify their trajectories and implications for disease progression.https://doi.org/10.1038/s41531-025-01012-0
spellingShingle Shi Tang
Bei Huang
Yanlin Wang
Yaping Liu
Jing Wang
Li Zhou
Siyi Gong
Yuhua Yang
Joey WY Chan
Steven WH Chau
Winnie CW Chu
Jill Abrigo
Jean-François Gagnon
Yun Kwok Wing
Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
npj Parkinson's Disease
title Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
title_full Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
title_fullStr Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
title_full_unstemmed Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
title_short Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder
title_sort brain clinical biotyping in patients with idiopathic rem sleep behavior disorder
url https://doi.org/10.1038/s41531-025-01012-0
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