Distinct brain atrophy progression subtypes underlie phenoconversion in isolated REM sleep behaviour disorder

被引：0

作者：

Joza, Stephen ^{[1
,2
,3
]}

Delva, Aline ^{[1
]}

Tremblay, Christina ^{[1
,4
]}

Vo, Andrew ^{[1
]}

Filiatrault, Marie

Tweedale, Max ^{[1
]}

Gagnon, Jean-Francois ^{[4
,5
,6
]}

Postuma, Ronald B. ^{[1
,4
,7
]}

Dagher, Alain ^{[1
]}

Klein, Johannes ^{[8
,9
]}

Hu, Michele ^{[8
,9
]}

Dusek, Petr ^{[10
,11
,12
]}

Marecek, Stanislav ^{[10
,11
,12
]}

Varga, Zsoka ^{[10
,11
,12
]}

Taylor, John-Paul

O'Brien, John T. ^{[13
,14
]}

Firbank, Michael ^{[13
]}

Thomas, Alan ^{[13
]}

Donaghy, Paul C. ^{[13
]}

Lehericy, Stephane ^{[15
]}

Arnulf, Isabelle ^{[15
]}

Vidailhet, Marie ^{[15
]}

Corvel, Jean-Christophe ^{[15
]}

Camicioli, Richard ^{[2
,3
]}

Chertkow, Howard ^{[16
,17
]}

Lewis, Simon ^{[18
,19
]}

Matar, Elie ^{[18
]}

Martens, Kaylena A. Ehgoetz ^{[18
,20
]}

Churchill, Lachlan ^{[18
]}

Sommerauer, Michael ^{[21
,22
,23
,24
]}

Roettgen, Sinah ^{[23
,24
]}

Borghammer, Per ^{[4
,25
]}

Knudsen, Karoline ^{[25
]}

Hansen, Allan K.

Arnaldi, Dario ^{[26
,27
]}

Orso, Beatrice ^{[26
]}

Mattioli, Pietro ^{[26
,27
]}

Roccatagliata, Luca ^{[26
,27
]}

Monchi, Oury ^{[6
,28
]}

Rahayel, Shady ^{[4
,29
]}

机构：

[1] McGill Univ, Neuro Montreal Neurol Inst Hosp, Montreal, PQ H3A 2B4, Canada

[2] Univ Alberta, Div Neurol, Dept Med, Edmonton, AB, Canada

[3] Univ Alberta, Neurosci & Mental Hlth Inst, Edmonton, AB, Canada

[4] CIUSSS NIM Hop Sacre Coeur Montreal, Ctr Adv Res Sleep Med, Montreal, PQ H4J 1C5, Canada

[5] Univ Quebec Montreal, Dept Psychol, Montreal, PQ H2X 3P2, Canada

[6] Inst Univ Geriat Montreal, Res Ctr, Montreal, PQ H3W 1W5, Canada

[7] Montreal Gen Hosp, Dept Neurol, Montreal, PQ H3G 1A4, Canada

[8] Univ Oxford, Oxford Parkinson Dis Ctr, Oxford, England

[9] Univ Oxford, Nuffield Dept Clin Neurosci, Div Neurol, Oxford, England

[10] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic

[11] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague, Czech Republic

[12] Gen Univ Hosp, Prague, Czech Republic

[13] Newcastle Univ, Translat & Clin Res Inst, Newcastle, England

[14] Univ Cambridge, Sch Clin Med, Dept Psychiat, Cambridge, England

[15] Sorbonne Univ, Paris Brain Inst ICM, Inst Cerveau, Clin Invest Ctr CIC,INSERM,UMR 1127,CNRS 7225, F-75013 Paris, France

[16] Univ Toronto, Dept Med Neurol, Toronto, ON, Canada

[17] Baycrest Hlth Serv, Rotman Res Inst, Toronto, ON, Canada

[18] Macquarie Univ, Macquarie Med Sch, Parkinson Dis Res Clin, Sydney, Australia

[19] Univ Sydney, Brain & Mind Ctr, Parkinsons Dis Res Clin, Camperdown, NSW 2050, Australia

[20] Univ Waterloo, Dept Kinesiol & Hlth Sci, Waterloo, ON N2L 3G1, Canada

[21] Univ Hosp Bonn, Ctr Neurol, Dept Parkinson Sleep & Movement Disorders, Bonn, Germany

[22] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[23] Univ Cologne, Univ Hosp Cologne, Fac Med, Dept Neurol, Cologne, Germany

[24] Forschungszentrum Julich, Inst Neurosci & Med INM 3, Cognit Neurosci, Julich, Germany

[25] Aarhus Univ Hosp, Dept Nucl Med, DK-8200 Aarhus, Denmark

[26] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Clin Neurol, I-16132 Genoa, Italy

[27] IRCCS Osped Policlin San Martino, I-16132 Genoa, Italy

[28] Univ Montreal, Dept Radiol Radiooncol & Nucl Med, Montreal, PQ H3T 1A4, Canada

[29] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada

来源：

EBIOMEDICINE | 2025年 / 117卷

基金：

加拿大健康研究院; 英国医学研究理事会;

关键词：

REM sleep behaviour disorder; Parkinson's disease; Dementia with Lewy bodies; MRI; Subtyping; Machine learning; DEMENTIA; RATES;

D O I：

10.1016/j.ebiom.2025.105753

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background 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. Methods 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. Findings 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. Interpretation 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. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页数：18

共 59 条

[1] Predicting longitudinal brain atrophy in Parkinson's disease using a Susceptible-Infected-Removed agent-based model [J].