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@ARTICLE{Joza:279878,
author = {Joza, Stephen and Delva, Aline and Tremblay, Christina and
Vo, Andrew and Filiatrault, Marie and Tweedale, Max and
Gagnon, Jean-François and Postuma, Ronald B and Dagher,
Alain and Klein, Johannes and Hu, Michele and Dusek, Petr
and Marecek, Stanislav and Varga, Zsoka and Taylor,
John-Paul and O'Brien, John T and Firbank, Michael and
Thomas, Alan and Donaghy, Paul C and Lehéricy, Stéphane
and Vidailhet, Marie and Corvol, Jean-Christophe and Iceberg
Study Group and Camicioli, Richard and Chertkow, Howard and
Lewis, Simon and Matar, Elie and Ehgoetz Martens, Kaylena A
and Churchill, Lachlan and Sommerauer, Michael and Röttgen,
Sinah and Borghammer, Per and Knudsen, Karoline and Hansen,
Allan K and Arnaldi, Dario and Orso, Beatrice and Mattioli,
Pietro and Roccatagliata, Luca and Monchi, Oury and Rahayel,
Shady},
collaboration = {Arnulf, Isabelle},
othercontributors = {Arnulf, Isabelle and Bekadar, Samir and Benchetrit, Eve and
Brice, Alexis and Brochard, Vanessa and Chalançon, Alizé
and Colsch, Benoit and Cormier-Dequaire, Florence and
Corvol, Jean-Christophe and Czernecki, Virginie and Degos,
Bertrand and Delorme, Cécile and Dodet, Pauline and
Dongmo-Kenfack, Carole and Habert, Marie-Odile and Ichou,
Farid and Ihle, Jonas and Galléa, Cécile and Gaurav, Rahul
and Glachant, Marie-Alexandrine and Gomes, Manon and Grabli,
David and Hainque, Elodie and Jeancolas, Laetitia and
Laganot, Christelle and Lehéricy, Stéphane and Lesage,
Suzanne and Leu-Semenescu, Smaranda and Levy, Richard and
Maheo, Valentine and Mangone, Graziella and Mariani, Louise
Laure and Méneret, Aurelie and Menon, Poornima and Mochel,
Fanny and Perlbarg, Vincent and Petrovska, Dijana and
Pineau, Fanny and Pyatigorskaya, Nadya and Rivaud-Pechoux,
Sophie and Roze, Emmanuel and Sambin, Sara and Socha, Julie
and Tenenhaus, Arthur and Valabregue, Romain and Vidailhet,
Marie and Yahia-Cherif, Lydia},
title = {{D}istinct brain atrophy progression subtypes underlie
phenoconversion in isolated {REM} sleep behaviour disorder.},
journal = {EBioMedicine},
volume = {117},
issn = {2352-3964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2025-00845},
pages = {105753},
year = {2025},
abstract = {Synucleinopathies 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.},
keywords = {Humans / REM Sleep Behavior Disorder: pathology / REM Sleep
Behavior Disorder: etiology / REM Sleep Behavior Disorder:
diagnosis / REM Sleep Behavior Disorder: diagnostic imaging
/ Male / Female / Disease Progression / Aged / Magnetic
Resonance Imaging / Atrophy / Brain: pathology / Brain:
diagnostic imaging / Middle Aged / Lewy Body Disease:
pathology / Aged, 80 and over / Parkinson Disease: pathology
/ Dementia with Lewy bodies (Other) / MRI (Other) / Machine
learning (Other) / Parkinson's disease (Other) / REM sleep
behaviour disorder (Other) / Subtyping (Other)},
cin = {AG Petzold},
ddc = {610},
cid = {I:(DE-2719)1013020},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40447483},
pmc = {pmc:PMC12177146},
doi = {10.1016/j.ebiom.2025.105753},
url = {https://pub.dzne.de/record/279878},
}
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