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000279878 1001_ $$aJoza, Stephen$$b0
000279878 245__ $$aDistinct brain atrophy progression subtypes underlie phenoconversion in isolated REM sleep behaviour disorder.
000279878 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000279878 520__ $$aSynucleinopathies include a spectrum of disorders varying in features and severity, including idiopathic/isolated REM sleep behaviour disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Distinct brain atrophy patterns may already be seen in iRBD; however, how brain atrophy begins and progresses remains unclear.A multicentric cohort of 1276 participants (451 polysomnography-confirmed iRBD, 142 PD with probable RBD, 87 DLB, and 596 controls) underwent T1-weighted MRI and longitudinal clinical assessments. Brain atrophy was quantified using vertex-based cortical surface reconstruction and volumetric segmentation. The unsupervised machine learning algorithm, Subtype and Stage Inference (SuStaIn), was used to reconstruct spatiotemporal patterns of brain atrophy progression.SuStaIn identified two distinct subtypes of brain atrophy progression: 1) a 'cortical-first' subtype, with atrophy beginning in the frontal lobes and involving the subcortical structures at later stages; and 2) a 'subcortical-first' subtype, with atrophy beginning in the limbic areas and involving cortical structures at later stages. Both cortical- and subcortical-first subtypes were associated with a higher rate of increase in MDS-UPDRS-III scores over time, but cognitive decline was subtype-specific, being associated with advancing stages in patients classified as cortical-first but not subcortical-first. Classified patients were more likely to phenoconvert over time compared to stage 0/non-classified patients. Among the 88 patients with iRBD who phenoconverted during follow-up, those classified within the cortical-first subtype had a significantly increased likelihood of developing DLB compared to PD, unlike those classified within the subcortical-first subtype.There are two distinct atrophy progression subtypes in iRBD, with the cortical-first subtype linked to an increased likelihood of developing DLB, while both subtypes were associated with worsening parkinsonian motor features. This underscores the potential utility of subtype identification and staging for monitoring disease progression and patient selection for trials.This study was supported by grants to S.R. from Alzheimer Society Canada (0000000082) and by Parkinson Canada (PPG-2023-0000000122). The work performed in Montreal was supported by the Canadian Institutes of Health Research (CIHR), the Fonds de recherche du Québec - Santé (FRQS), and the W. Garfield Weston Foundation. The work performed in Oxford was funded by Parkinson's UK (J-2101) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The work performed in Prague was funded by the Czech Health Research Council (grant NU21-04-00535) and by The National Institute for Neurological Research (project number LX22NPO5107), financed by the European Union - Next Generation EU. The work performed in Newcastle was funded by the NIHR Newcastle BRC based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The work performed in Paris was funded by grants from the Programme d'investissements d'avenir (ANR-10-IAIHU-06), the Paris Institute of Neurosciences - IHU (IAIHU-06), the Agence Nationale de la Recherche (ANR-11-INBS-0006), Électricité de France (Fondation d'Entreprise EDF), the EU Joint Programme-Neurodegenerative Disease Research (JPND) for the Control-PD Project (Cognitive Propagation in Prodromal Parkinson's disease), the Fondation Thérèse et René Planiol, the Fonds Saint-Michel; by unrestricted support for research on Parkinson's disease from Energipole (M. Mallart) and the Société Française de Médecine Esthétique (M. Legrand); and by a grant from the Institut de France to Isabelle Arnulf (for the ALICE Study). The work performed in Sydney was supported by a Dementia Team Grant from the National Health and Medical Research Council (#1095127). The work performed in Cologne was funded by the Else Kröner-Fresenius-Stiftung (grant number 2019_EKES.02), the Köln Fortune Program, Faculty of Medicine, University of Cologne, and the 'Netzwerke 2021 Program (Ministry of Culture and Science of Northrhine Westphalia State). The work performed in Aarhus was supported by funding from the Lundbeck Foundation, Parkinsonforeningen (The Danish Parkinson Association), and the Jascha Foundation.
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000279878 650_7 $$2Other$$aDementia with Lewy bodies
000279878 650_7 $$2Other$$aMRI
000279878 650_7 $$2Other$$aMachine learning
000279878 650_7 $$2Other$$aParkinson's disease
000279878 650_7 $$2Other$$aREM sleep behaviour disorder
000279878 650_7 $$2Other$$aSubtyping
000279878 650_2 $$2MeSH$$aHumans
000279878 650_2 $$2MeSH$$aREM Sleep Behavior Disorder: pathology
000279878 650_2 $$2MeSH$$aREM Sleep Behavior Disorder: etiology
000279878 650_2 $$2MeSH$$aREM Sleep Behavior Disorder: diagnosis
000279878 650_2 $$2MeSH$$aREM Sleep Behavior Disorder: diagnostic imaging
000279878 650_2 $$2MeSH$$aMale
000279878 650_2 $$2MeSH$$aFemale
000279878 650_2 $$2MeSH$$aDisease Progression
000279878 650_2 $$2MeSH$$aAged
000279878 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000279878 650_2 $$2MeSH$$aAtrophy
000279878 650_2 $$2MeSH$$aBrain: pathology
000279878 650_2 $$2MeSH$$aBrain: diagnostic imaging
000279878 650_2 $$2MeSH$$aMiddle Aged
000279878 650_2 $$2MeSH$$aLewy Body Disease: pathology
000279878 650_2 $$2MeSH$$aAged, 80 and over
000279878 650_2 $$2MeSH$$aParkinson Disease: pathology
000279878 7001_ $$aDelva, Aline$$b1
000279878 7001_ $$aTremblay, Christina$$b2
000279878 7001_ $$aVo, Andrew$$b3
000279878 7001_ $$aFiliatrault, Marie$$b4
000279878 7001_ $$aTweedale, Max$$b5
000279878 7001_ $$aGagnon, Jean-François$$b6
000279878 7001_ $$aPostuma, Ronald B$$b7
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000279878 7001_ $$aKlein, Johannes$$b9
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000279878 7001_ $$aO'Brien, John T$$b15
000279878 7001_ $$aFirbank, Michael$$b16
000279878 7001_ $$aThomas, Alan$$b17
000279878 7001_ $$aDonaghy, Paul C$$b18
000279878 7001_ $$aLehéricy, Stéphane$$b19
000279878 7001_ $$aArnulf, Isabelle$$b20$$eCollaboration Author
000279878 7001_ $$aVidailhet, Marie$$b21
000279878 7001_ $$aCorvol, Jean-Christophe$$b22
000279878 7001_ $$aIceberg Study Group$$b23
000279878 7001_ $$aCamicioli, Richard$$b24
000279878 7001_ $$aChertkow, Howard$$b25
000279878 7001_ $$aLewis, Simon$$b26
000279878 7001_ $$aMatar, Elie$$b27
000279878 7001_ $$aEhgoetz Martens, Kaylena A$$b28
000279878 7001_ $$aChurchill, Lachlan$$b29
000279878 7001_ $$0P:(DE-2719)9003277$$aSommerauer, Michael$$b30$$udzne
000279878 7001_ $$aRöttgen, Sinah$$b31
000279878 7001_ $$aBorghammer, Per$$b32
000279878 7001_ $$aKnudsen, Karoline$$b33
000279878 7001_ $$aHansen, Allan K$$b34
000279878 7001_ $$aArnaldi, Dario$$b35
000279878 7001_ $$aOrso, Beatrice$$b36
000279878 7001_ $$aMattioli, Pietro$$b37
000279878 7001_ $$aRoccatagliata, Luca$$b38
000279878 7001_ $$aMonchi, Oury$$b39
000279878 7001_ $$aRahayel, Shady$$b40
000279878 7001_ $$aArnulf, Isabelle$$b41$$eContributor
000279878 7001_ $$aBekadar, Samir$$b42$$eContributor
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000279878 7001_ $$aColsch, Benoit$$b47$$eContributor
000279878 7001_ $$aCormier-Dequaire, Florence$$b48$$eContributor
000279878 7001_ $$aCorvol, Jean-Christophe$$b49$$eContributor
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