Evidence map›Paper›PMID 41237265›Full record

ArticleBrain : a journal of neurology2026

Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages.

Andrew Vo, Christina Tremblay, Shady Rahayel, Sarah Al-Bachari, Henk W Berendse, Joanna K Bright, Fernando Cendes, Emile d'Angremont, John C Dalrymple-Alford, Ines Debove and 34 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Structure-function coupling in the human brainstem.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

44 authors.

Andrew VoDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.
Christina TremblayCentre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada H4J 1C5.
Shady RahayelCentre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada H4J 1C5.ORCID 0000-0001-5786-3278
Sarah Al-BachariFaculty of Health and Medicine, Lancaster University, Lancaster LA1 4AT, UK.
Henk W BerendseDepartment of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands.
Joanna K BrightSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Fernando CendesDepartment of Neurology, University of Campinas-UNICAMP, Campinas 13083-888, Brazil.
Emile d'AngremontNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.
John C Dalrymple-AlfordTe Kura Mahi ā-Hirikapo, School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand.
Ines DeboveDepartment of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern CH-3010, Switzerland.
Michiel F DirkxDepartment of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GC, The Netherlands.ORCID 0000-0001-8763-8071
Jason DruzgalDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA.
Gaëtan GarrauxMoVeRe Group, GIGA-CRC In Vivo Imaging, University of Liège, Liège 4000, Belgium.
Rick C HelmichDepartment of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GC, The Netherlands.ORCID 0000-0003-4035-6573
Michele T HuDivision of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford OX3 9DU, UK.ORCID 0000-0001-6382-5841
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90033, USA.
Martin E JohanssonDepartment of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6525 GC, The Netherlands.ORCID 0000-0002-9778-6278
Johannes C KleinDivision of Clinical Neurology, Department of Clinical Neurosciences, Oxford Centre for Integrative Neuroimaging, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford OX3 9DU, UK.ORCID 0000-0002-8553-2801
Max A LaansmaNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.ORCID 0000-0002-8216-6690
Corey T McMillanDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tracy R MelzerTe Kura Mahi ā-Hirikapo, School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand.
Bratislav MisicDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.ORCID 0000-0003-0307-2862
Philip MosleyQIMR Berghofer Medical Research Institute, Queensland 4006, Australia.
Conor Owens-WaltonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90033, USA.
Laura M ParkesDivision of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.ORCID 0000-0001-6488-507X
Clelia PellicanoLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome 00179, Italy.
Fabrizio PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome 00179, Italy.
Kathleen L PostonDepartment of Neurology & Neurological Sciences, Movement Disorders, Stanford University, Palo Alto, CA 94304, USA.
Mario RangoExcellence Interdepartmental Center for Advanced MR Techniques and Department of Neurosciences, Neurology Unit, Parkinson's Disease Center, Fondazione Cà Granda, IRCCS, Ospedale Policlinico, University of Milan, Milan 20122, Italy.
Christian RummelSupport Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern CH-3010, Switzerland.
Petra SchwingenschuhDepartment of Neurology, Medical University of Graz, Graz 8036, Austria.
Melanie SuetteDepartment of Neurology, Medical University of Graz, Graz 8036, Austria.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90033, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California SanFrancisco, San Francisco, CA 94143, USA.ORCID 0000-0001-8644-7724
Chih-Chien TsaiHealthy Ageing Research Center, Chang Gung University, Taoyuan City 33302, Taiwan.
Tim D van BalkomNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.
Odile A van den HeuvelNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.
Ysbrand D van der WerfNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.
Eva M van HeeseNeurodegeneration, Amsterdam Neuroscience, Amsterdam 1081 HV, The Netherlands.
Chris VriendDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands.
Jiun-Jie WangDepartment of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City 33302, Taiwan.ORCID 0000-0002-2422-9059
Roland WiestSupport Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern CH-3010, Switzerland.
Clarissa L YasudaDepartment of Neurology, University of Campinas-UNICAMP, Campinas 13083-888, Brazil.
Alain DagherDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.ORCID 0000-0002-0945-5779

Funding

Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Kelvin C Luk · 2024 to 2026
$15.2M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI HENDERSON, VICTOR · 2015 to 2019
$7.9M
The impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's diseaseR01NS115114 · NINDS · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I., POSTON, KATHLEEN LOMBARD · 2019 to 2023
$4.2M
High Capacity, High Performance Storage System for NeuroscienceS10OD032285 · OD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2022 to 2022
$1.7M
Basal Ganglia Modulation of Cognitive Systems in Parkinson's diseaseK23NS075097 · NINDS · STANFORD UNIVERSITY · PI POSTON, KATHLEEN LOMBARD · 2011 to 2015
$936k
CPTENIGMA PD R01European Platform for Neurodegenerative Disorders H2020Fonds de recherche du QuebecGE HealthcareHealth Research Council of New Zealand 20/538Lab10XMarsden Fund New Zealand UOC2105Michael J. Fox Foundation for Parkinson's ResearchNational Institute for Health and Care ResearchNeurological Foundation of New Zealand 2232 PRGNIA NIH HHS P01 AG084497NIA NIH HHS P50 AG047366NIH HHS S10OD032285NIHR BRCNIHR Oxford Biomedical Research CentreNINDS NIH HHS K23 NS075097NINDS NIH HHS R01 NS115114Parkinson's UKPSP Association RF1NS136995Research and Education Trust Pacific RadiologySão Paulo Research Foundation 2013/07559-3University of OxfordWellcome Trust 203139/A/16/ZWellcome Trust 203139/Z/16/Z
6 · The paper itself

Abstract

Parkinson's disease is associated with extensive structural brain changes. Recent work has proposed that the spatial pattern of disease pathology is shaped by both network spread and local vulnerability. However, few studies have assessed these biological frameworks in large patient samples across disease stages. Analysing the largest imaging cohort in Parkinson's disease to date (n = 3096 patients), we investigated the roles of network architecture and local brain features by relating regional abnormality maps to normative profiles of connectivity, intrinsic networks, cytoarchitectonics, neurotransmitter receptor densities and gene expression. We found widespread cortical and subcortical atrophy in Parkinson's disease to be associated with advancing disease stage, longer time since diagnosis and poorer global cognition. Structural brain connectivity best explained cortical atrophy patterns in Parkinson's disease and across disease stages. These patterns were robust among individual patients. The precuneus, lateral temporal cortex and amygdala were identified as likely network-based epicentres, with high convergence across disease stages. Individual epicentres varied significantly among patients, yet they consistently localized to the default mode and limbic networks. Furthermore, we showed that regional overexpression of genes implicated in synaptic structure and signalling conferred increased susceptibility to brain atrophy in Parkinson's disease. In summary, this study demonstrates in a well-powered sample that structural brain abnormalities in Parkinson's disease across disease stages and within individual patients are influenced by both network spread and local vulnerability.

Indexed as

BrainNerve NetParkinson DiseaseAgedAtrophyCohort StudiesDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeural Pathwaysconnectivityimaging transcriptomicsneurodegenerationParkinson’s diseasestructural MRI

Identifiers

PMID41237265
PMCPMC13337226

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.