Evidence map›Paper›PMID 40492073›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Convergent large-scale network and local vulnerabilities underlie brain atrophy across Parkinson's disease stages: a worldwide ENIGMA study.

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 35 more

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Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

Andrew VoDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Christina TremblayDepartment of Medicine, Centre for Advanced Research in Sleep Medicine, University of Montreal, Montreal, Canada.
Shady RahayelDepartment of Medicine, Centre for Advanced Research in Sleep Medicine, University of Montreal, Montreal, Canada.
Sarah Al-BachariFaculty of Health and Medicine, Lancaster University, Lancaster, UK.
Henk W BerendseDepartment of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Joanna K BrightSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Fernando CendesDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.ORCID 0000-0001-9336-9568
Emile d'AngremontDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
John C Dalrymple-AlfordTe Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand.
Ines DeboveDepartment of Neurology, Inselspital, University of Bern, Bern, 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, The Netherlands.
Jason DruzgalDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
Gaëtan GarrauxMoVeRe group, GIGA-CRC in vivo imaging, University of Liège, Liège, 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, The Netherlands.ORCID 0000-0003-4035-6573
Michele HuDivision of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, UK.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, 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, The Netherlands.
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, UK.ORCID 0000-0002-8553-2801
Max A LaansmaDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Corey T McMillanDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-7581-6405
Tracy R MelzerTe Kura Mahi ā-Hirikapo | School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand.
Bratislav MisicDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Philip MosleyQIMR Berghofer Medical Research Institute, Queensland, 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, USA.ORCID 0000-0003-0589-638X
Laura M ParkesDivision of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.ORCID 0000-0001-6488-507X
Clelia PellicanoLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Fabrizio PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Kathleen L PostonDepartment of Neurology & Neurological Sciences, Movement Disorders, Stanford University, Palo Alto, CA, USA.ORCID 0000-0003-3424-7143
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, Italy.
Christian RummelSupport Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland.
Petra SchwingenschuhDepartment of Neurology, Medical University of Graz, Graz, Austria.
Melanie SuetteDepartment of Neurology, Medical University of Graz, Graz, 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, USA.ORCID 0000-0002-4720-8867
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Chih-Chien TsaiHealthy Ageing Research Center, Chang Gung University, Taoyuan City.
Tim D van BalkomDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-6643-2776
Odile A van den HeuvelDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ysbrand D van der WerfDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Eva M van HeeseDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-1954-5014
Chris VriendDepartment of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-3111-1304
Jiun-Jie WangDepartment of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City, Taiwan.
Roland WiestSupport Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland.
Clarissa YasudaDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Alain DagherDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
ENIGMA-Parkinson’s Study

Funding

Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI MONTINE, THOMAS J · 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
Worldwide Tractometry Initiative to Investigate Brain Microstructure, Cognitive Impairment & Dementia in Parkinsons DiseaseRF1NS136995 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA, THOMPSON, PAUL M · 2024 to 2024
$2.2M
Basal Ganglia Modulation of Cognitive Systems in Parkinson's diseaseK23NS075097 · NINDS · STANFORD UNIVERSITY · PI POSTON, KATHLEEN LOMBARD · 2011 to 2015
$936k
NIA NIH HHS P50 AG047366NINDS NIH HHS K23 NS075097NINDS NIH HHS R01 NS115114NINDS NIH HHS RF1 NS136995Wellcome Trust
6 · The paper itself

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.

Indexed as

connectivityimaging transcriptomicsneurodegenerationParkinson’s diseasestructural MRI

Identifiers

PMID40492073
PMCPMC12148252

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.