Distinct brain atrophy progression subtypes underlie phenoconversion in isolated REM sleep behaviour disorder
Stephen Joza1, Aline Delva2, Christina Tremblay3
1The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, H3A 2B4, Canada; Division of Neurology, Department of Medicine, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
Ebiomedicine
|May 30, 2025
Summary
Two brain atrophy progression subtypes exist in synucleinopathies like idiopathic REM sleep behavior disorder (iRBD). The cortical-first subtype increases dementia with Lewy bodies (DLB) risk, while both worsen motor symptoms.
Area of Science:
- Neuroscience
- Neurology
- Medical Imaging
Background:
- Synucleinopathies, including idiopathic REM sleep behavior disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB), present with diverse clinical features.
- Brain atrophy patterns are observable in iRBD, but the initiation and progression of atrophy remain incompletely understood.
Purpose of the Study:
- To investigate and characterize the spatiotemporal patterns of brain atrophy progression in synucleinopathies.
- To identify distinct subtypes of atrophy progression and their clinical implications.
Main Methods:
- Utilized a multicentric cohort of 1276 participants (iRBD, PD with RBD, DLB, controls) with T1-weighted MRI and longitudinal assessments.
- Employed vertex-based cortical surface reconstruction and volumetric segmentation for atrophy quantification.
- Applied the Subtype and Stage Inference (SuStaIn) algorithm to model atrophy progression patterns.
Main Results:
- Identified two distinct atrophy progression subtypes: 'cortical-first' (frontal lobe onset) and 'subcortical-first' (limbic onset).
- Both subtypes showed increased motor symptom progression (MDS-UPDRS-III); cognitive decline was linked to advancing stages in the cortical-first subtype.
- Patients classified into subtypes were more likely to phenoconvert; iRBD patients in the cortical-first subtype had a higher likelihood of developing DLB compared to PD.
Conclusions:
- Two distinct brain atrophy progression subtypes exist in iRBD.
- The cortical-first subtype is associated with an increased risk of developing dementia with Lewy bodies (DLB).
- Both identified subtypes correlate with worsening parkinsonian motor features, suggesting utility in disease monitoring and clinical trial stratification.
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