Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages.
Overview
and 25 other authors
Tracy R Melzer10,11,22,23, Bratislav Misic1, Philip Mosley24, Conor Owens-Walton19, Laura M Parkes25,26, Clelia Pellicano27, Fabrizio Piras27, Kathleen L Poston28, Mario Rango29, Christian Rummel30, Petra Schwingenschuh31, Melanie Suette31, Paul M Thompson19, Duygu Tosun32, Chih-Chien Tsai33, Tim D van Balkom6,9,34, Odile A van den Heuvel6,9,34, Ysbrand D van der Werf6,9, Eva M van Heese6,9, Chris Vriend9,34,35, Jiun-Jie Wang36, Roland Wiest30, Clarissa L Yasuda8,37, Alain Dagher1, ENIGMA-Parkinson’s Study37 affiliations
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada
- Centre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montreal H4J 1C5, Canada
- Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4AT, UK
- Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
- Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- Amsterdam Neuroscience, Neurodegeneration, 1081 HV Amsterdam, The Netherlands
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK
- Department of Neurology, University of Campinas–UNICAMP, Campinas 13083-888, Brazil
- Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- Te Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing, University of Canterbury, 8041 Christchurch, New Zealand
- New Zealand Brain Research Institute, 8011 Christchurch, New Zealand
- Department of Neurology, Inselspital, University Hospital Bern, University of Bern, CH-3010 Bern, Switzerland
- Department of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GC Nijmegen, The Netherlands
- Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, The Netherlands
- Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA
- MoVeRe group, GIGA-CRC in vivo imaging, University of Liège, 4000 Liège, Belgium
- Department of Neurology, CHU Liège, 4000 Liège, Belgium
- Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson’s Disease Centre, Nuffield, University of Oxford, Oxford OX3 9DU, UK
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90033, USA
- Division 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
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
- Department of Medicine, University of Otago, 8011 Christchurch, New Zealand
- Pacific Radiology Canterbury, 8031 Christchurch, New Zealand
- QIMR Berghofer Medical Research Institute, Queensland 4006, Australia
- Division of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
- Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance & University of Manchester, Manchester M6 8HD, UK
- Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, 00179 Rome, Italy
- Department of Neurology & Neurological Sciences, Movement Disorders, Stanford University, Palo Alto, CA 94304, USA
- Excellence 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, 20122 Milan, Italy
- Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, CH-3010 Bern, Switzerland
- Department of Neurology, Medical University of Graz, 8036 Graz, Austria
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA
- Healthy Ageing Research Center, Chang Gung University, Taoyuan City 33302, Taiwan
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- Amsterdam Neuroscience, Brain Imaging, 1081 HV Amsterdam, The Netherlands
- Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City 33302, Taiwan
- Brazilian Institute of Neuroscience and Neurotechnology, Campinas 13083-888, Brazil
Abstract
Parkinson’s disease (PD) 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, only few studies assessed these biological frameworks in large patient samples across disease stages.
Analyzing the largest imaging cohort in PD to date (n = 3,096 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 PD to be associated with advancing disease stage, longer time since diagnosis, and poorer global cognition. Structural brain connectivity best explained cortical atrophy patterns in PD 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 PD.
In summary, this study demonstrates in a well-powered sample that structural brain abnormalities in PD across disease stages and within individual patients are influenced by both network spread and local vulnerability.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
The paper's code and data availability statement is in the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Datasets cited
- openneuro:ds000245, at OpenNeuro; found in “Data availability”
Data availability
Publicly available datasets used in this report include the Parkinson Progression Marker Initiative (PPMI; ppmi-info.org), OpenNeuro Japan including Udall cohort (openneuro.org/
Individual ENIGMA-PD sites retain ownership of their MRI data and only share anonymized derived data for analysis. Data are therefore not openly available but researchers are invited to join the ENIGMA-PD working group where they can formally request derived data via secondary proposals. Data requests are then considered by the individual site’s principal investigator(s). If you are interested in joining the ENIGMA-PD, please contact . For more information, please see the working group website: https://
Tools for mapping cortical parcellations to network and cytoarchitectonic partitions and for generating spatial null models are available as part of netneurotools available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → Oxford University Press
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 45 authors, 5 keywords, 13 MeSH terms, 23 funders, 99 references.
Cite
This paper
Vo, A., Tremblay, C., Rahayel, S., Al-Bachari, S., Berendse, H. W., Bright, J. K., Cendes, F., d’Angremont, E., Dalrymple-Alford, J. C., Debove, I., Dirkx, M. F., Druzgal, J., Garraux, G., Helmich, R. C., Hu, M. T., Jahanshad, N., Johansson, M. E., Klein, J. C., Laansma, M. A., . . . ENIGMA-Parkinson’s Study. (2026). Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages. Brain : a journal of neurology, 149(7), 2380-2394. https://
BibTeX
@article{vo2026global,
author = {Vo, Andrew and Tremblay, Christina and Rahayel, Shady and Al-Bachari, Sarah and Berendse, Henk W and Bright, Joanna K and Cendes, Fernando and d’Angremont, Emile and Dalrymple-Alford, John C and Debove, Ines and Dirkx, Michiel F and Druzgal, Jason and Garraux, Gaëtan and Helmich, Rick C and Hu, Michele T and Jahanshad, Neda and Johansson, Martin E and Klein, Johannes C and Laansma, Max A and McMillan, Corey T and Melzer, Tracy R and Misic, Bratislav and Mosley, Philip and Owens-Walton, Conor and Parkes, Laura M and Pellicano, Clelia and Piras, Fabrizio and Poston, Kathleen L and Rango, Mario and Rummel, Christian and Schwingenschuh, Petra and Suette, Melanie and Thompson, Paul M and Tosun, Duygu and Tsai, Chih-Chien and van Balkom, Tim D and van den Heuvel, Odile A and van der Werf, Ysbrand D and van Heese, Eva M and Vriend, Chris and Wang, Jiun-Jie and Wiest, Roland and Yasuda, Clarissa L and Dagher, Alain and {ENIGMA-Parkinson’s Study}},
title = {{Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages}},
journal = {Brain : a journal of neurology},
year = {2026},
month = jul,
volume = {149},
number = {7},
pages = {2380--2394},
publisher = {Oxford University Press},
issn = {0006-8950},
doi = {10.1093/
url = {https://
pmid = {41237265},
pmcid = {PMC13337226}
}
RIS
TY - JOUR
AU - Vo, Andrew
AU - Tremblay, Christina
AU - Rahayel, Shady
AU - Al-Bachari, Sarah
AU - Berendse, Henk W
AU - Bright, Joanna K
AU - Cendes, Fernando
AU - d’Angremont, Emile
AU - Dalrymple-Alford, John C
AU - Debove, Ines
AU - Dirkx, Michiel F
AU - Druzgal, Jason
AU - Garraux, Gaëtan
AU - Helmich, Rick C
AU - Hu, Michele T
AU - Jahanshad, Neda
AU - Johansson, Martin E
AU - Klein, Johannes C
AU - Laansma, Max A
AU - McMillan, Corey T
AU - Melzer, Tracy R
AU - Misic, Bratislav
AU - Mosley, Philip
AU - Owens-Walton, Conor
AU - Parkes, Laura M
AU - Pellicano, Clelia
AU - Piras, Fabrizio
AU - Poston, Kathleen L
AU - Rango, Mario
AU - Rummel, Christian
AU - Schwingenschuh, Petra
AU - Suette, Melanie
AU - Thompson, Paul M
AU - Tosun, Duygu
AU - Tsai, Chih-Chien
AU - van Balkom, Tim D
AU - van den Heuvel, Odile A
AU - van der Werf, Ysbrand D
AU - van Heese, Eva M
AU - Vriend, Chris
AU - Wang, Jiun-Jie
AU - Wiest, Roland
AU - Yasuda, Clarissa L
AU - Dagher, Alain
AU - ENIGMA-Parkinson’s Study
TI - Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages
T2 - Brain : a journal of neurology
J2 - Brain
PY - 2026
DA - 2026/
VL - 149
IS - 7
SP - 2380
EP - 2394
SN - 0006-8950
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1093/
"type": "article-journal",
"title": "Global network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages",
"container-title": "Brain : a journal of neurology",
"author": [
{
"family": "Vo",
"given": "Andrew"
},
{
"family": "Tremblay",
"given": "Christina"
},
{
"family": "Rahayel",
"given": "Shady"
},
{
"family": "Al-Bachari",
"given": "Sarah"
},
{
"family": "Berendse",
"given": "Henk W"
},
{
"family": "Bright",
"given": "Joanna K"
},
{
"family": "Cendes",
"given": "Fernando"
},
{
"family": "d’Angremont",
"given": "Emile"
},
{
"family": "Dalrymple-Alford",
"given": "John C"
},
{
"family": "Debove",
"given": "Ines"
},
{
"family": "Dirkx",
"given": "Michiel F"
},
{
"family": "Druzgal",
"given": "Jason"
},
{
"family": "Garraux",
"given": "Gaëtan"
},
{
"family": "Helmich",
"given": "Rick C"
},
{
"family": "Hu",
"given": "Michele T"
},
{
"family": "Jahanshad",
"given": "Neda"
},
{
"family": "Johansson",
"given": "Martin E"
},
{
"family": "Klein",
"given": "Johannes C"
},
{
"family": "Laansma",
"given": "Max A"
},
{
"family": "McMillan",
"given": "Corey T"
},
{
"family": "Melzer",
"given": "Tracy R"
},
{
"family": "Misic",
"given": "Bratislav"
},
{
"family": "Mosley",
"given": "Philip"
},
{
"family": "Owens-Walton",
"given": "Conor"
},
{
"family": "Parkes",
"given": "Laura M"
},
{
"family": "Pellicano",
"given": "Clelia"
},
{
"family": "Piras",
"given": "Fabrizio"
},
{
"family": "Poston",
"given": "Kathleen L"
},
{
"family": "Rango",
"given": "Mario"
},
{
"family": "Rummel",
"given": "Christian"
},
{
"family": "Schwingenschuh",
"given": "Petra"
},
{
"family": "Suette",
"given": "Melanie"
},
{
"family": "Thompson",
"given": "Paul M"
},
{
"family": "Tosun",
"given": "Duygu"
},
{
"family": "Tsai",
"given": "Chih-Chien"
},
{
"family": "van Balkom",
"given": "Tim D"
},
{
"family": "van den Heuvel",
"given": "Odile A"
},
{
"family": "van der Werf",
"given": "Ysbrand D"
},
{
"family": "van Heese",
"given": "Eva M"
},
{
"family": "Vriend",
"given": "Chris"
},
{
"family": "Wang",
"given": "Jiun-Jie"
},
{
"family": "Wiest",
"given": "Roland"
},
{
"family": "Yasuda",
"given": "Clarissa L"
},
{
"family": "Dagher",
"given": "Alain"
},
{
"literal": "ENIGMA-Parkinson’s Study"
}
],
"container-title-short":
"volume": "149",
"issue": "7",
"page": "2380-2394",
"DOI": "10.1093/
"PMID": "41237265",
"PMCID": "PMC13337226",
"ISSN": "0006-8950",
"publisher": "Oxford University Press",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
1
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1038/s41380-026-03547-x [code]
- Multiscale characterization of cortical signatures in positive and negative schizotypy: a worldwide ENIGMA study.Journal: Molecular psychiatryIn common: structural MRI / diffusion, 15 references, 2 authors
- [2] doi:10.1186/s12916-026-04903-y [code]
- Structural connectome architecture and biological vulnerability shape cortical atrophy in cocaine use disorder.Journal: BMC medicineIn common: structural MRI / diffusion, 15 references
- [3] doi:10.1038/s41531-026-01355-2
- Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study.Journal: NPJ Parkinson's diseaseIn common: Parkinson's, structural MRI / diffusion, genetics / omics, 11 references
- [4] doi:10.1093/schbul/sbaf078
- Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum.Journal: Schizophrenia bulletinIn common: structural MRI / diffusion, 8 references, author Bratislav Misic
- [5] doi:10.1186/s40035-026-00566-0
- Application of the Allen Human Brain Atlas in Alzheimer's disease and Parkinson's disease.Journal: Translational neurodegenerationIn common: Parkinson's, genetics / omics, 10 references
- [6] doi:10.1002/hbm.70605 [code]
- BrainEnrich: Revealing Biological Insights for Imaging-Derived Phenotypes Through Transcriptomic Enrichment.Journal: Human brain mappingIn common: genetics / omics, 11 references
- [7] doi:10.1038/s41467-026-75959-w [code]
- Charting higher-order models of brain function beyond pairwise interactions.Journal: Nature communicationsIn common: 11 references
- [8] doi:10.1093/brain/awaf443 [code]
- Cellular signatures underlying functional resilience in presymptomatic frontotemporal dementia.Journal: Brain : a journal of neurologyIn common: genetics / omics, 9 references
- [9] doi:10.1038/s41467-026-74466-2 [code]
- Neuromorphic hierarchical modular reservoirs.Journal: Nature communicationsIn common: 5 references, author Bratislav Misic
- [10] doi:10.1371/journal.pbio.3003856 [code]
- Aging and metabolism contribute separately to brain-body health.Journal: PLoS biologyIn common: structural MRI / diffusion, 4 references, author Bratislav Misic
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.