ArticleNPJ Parkinson's disease2024
A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.
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Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
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Who cites it
8 citing papers in PubMed.
- A 3D Brain Geometry Toolkit for Multisite Neuroimaging Analysis.bioRxiv : the preprint server for biology · 2026Article
- Local and global microstructural and functional thalamomotor connectivity alterations in Parkinson's disease following motor learning.NPJ Parkinson's disease · 2026Article
- A NOVEL BAYESIAN FRAMEWORK UNCOVERING BRAIN CONNECTIVITY-TO-SHAPE RELATIONSHIP IN PRECLINICAL ALZHEIMER'S DISEASE.The annals of applied statistics · 2026Article
- Selective amygdala subregional atrophy in Parkinson's disease: from subjective cognitive decline to mild cognitive impairment.Frontiers in aging neuroscience · 2026Article
- The relationship between neuropsychiatric dimensions and markers of Parkinson's disease risk in the UK Biobank.NPJ Parkinson's disease · 2025Article
- Synthetic MRI study of brain volume and subcortical myelin in various Parkinson's disease motor subtypes.NPJ Parkinson's disease · 2025Article
- Current Clinical Applications of Structural MRI in Neurological Disorders.Journal of clinical neurology (Seoul, Korea) · 2025Review
- Cortical, subcortical, and cerebellar atrophy and cognition deficits in Metropolitan Mexico City teens and young adults exposed to fine particulate matter (PMFrontiers in neurologyArticle
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Authors and funding
53 authors.
Max A Laansma *Amsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. m.laansma@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-8216-6690
Yuji Zhao *Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
Eva M van Heese *Amsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1954-5014
Joanna K BrightSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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 http://orcid.org/0000-0003-0589-638X
Sarah Al-BachariFaculty of Health and Medicine, The University of Lancaster, Lancaster, UK.
Tim J AndersonDepartment of Medicine, University of Otago, Christchurch, Christchurch, New Zealand.ORCID http://orcid.org/0000-0002-1116-3839
Francesca AssognaLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Tim D van BalkomAmsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Henk W BerendseAmsterdam UMC, Department Neurology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Fernando CendesDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
John C Dalrymple-AlfordNew Zealand Brain Research Institute, Christchurch, New Zealand.ORCID http://orcid.org/0000-0002-6672-033X
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 Nijmegen Medical Centre, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0001-8763-8071
Jason DruzgalDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
Hedley C A EmsleyLancaster Medical School, Lancaster University, Lancaster, UK.
Jean-Paul FoucheDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Gaëtan GarrauxGIGA-CRC in vivo imaging, University of Liège, Liège, Belgium.ORCID http://orcid.org/0000-0001-7829-2806
Rachel P GuimarãesDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Rick C HelmichDepartment of Neurology and Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
Michele HuDivision of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, UK.
Odile A van den HeuvelAmsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Dmitry IsaevDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Ho-Bin KimDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Johannes C KleinDivision of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8553-2801
Christine LochnerSA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Corey T McMillanUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Tracy R MelzerDepartment of Medicine, University of Otago, Christchurch, Christchurch, New Zealand.ORCID http://orcid.org/0000-0003-0621-212X
Benjamin NewmanDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-0668-2853
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 http://orcid.org/0000-0001-6488-507X
Clelia PellicanoLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Fabrizio PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Toni L PitcherDepartment of Medicine, University of Otago, Christchurch, Christchurch, New Zealand.
Kathleen L PostonDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-3424-7143
Mario RangoExcellence Center for Advanced MR Techniques and Parkinson's Disease Center, Neurology unit, Fondazione IRCCS Cà Granda Maggiore Policlinico Hospital, University of Milan, Milan, Italy.
Leticia F RibeiroDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Cristiane S RochaDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Christian RummelSupport Center for Advanced Neuroimaging, (SCAN) University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Lucas S R SantosDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Reinhold SchmidtDepartment of Neurology, Medical University of Graz, Graz, Austria.
Petra SchwingenschuhDepartment of Neurology, Medical University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0002-3294-6824
Letizia SquarcinaDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Dan J SteinSA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0001-7218-7810
Daniela VecchioLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Chris VriendAmsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3111-1304
Jiunjie WangDepartment of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan City, Taiwan.
Daniel WeintraubUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Roland WiestSupport Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland.
Clarissa L YasudaDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.ORCID http://orcid.org/0000-0001-9084-7173
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.
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.
Ysbrand D van der WerfAmsterdam UMC, Department of Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-2370-9584
Boris A GutmanDepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
Funding
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Corey T McMillan · 2021 to 2026
$24.8MProject IV: "Alpha-Synuclein Strains & Diverse Synucleinopathies"P50NS053488 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2007 to 2017
$20.9MUncovering new genes and disease modifiers for ALS and related disordersU54NS092091 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Michael Benatar · 2014 to 2026
$19.8MUnderstanding Environmental Contributions to Heterogeneity in bvFTD.P01AG066597 · NIA · UNIVERSITY OF PENNSYLVANIA · PI David John Irwin, Corey T McMillan · 2020 to 2026
$18.8MUdall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3MProject IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 2019 to 2023
$18.1MProject IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · NIA · UNIVERSITY OF PENNSYLVANIA · PI ALICE S CHEN-PLOTKIN · 2024 to 2026
$15.2MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1MTraining U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MIBIC: Integrated Brain Imaging Center for the University of WashingtonRC4NS073008 · NINDS · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 2010 to 2010
$4.8MNEUROBEHAVIOR, NEUROENDOCRINOLOGY, AND GENETICS OF ADT32AG000258 · NIA · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 1999 to 2013
$4.7MThe 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
$4.2MFoundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01AG058854-01A1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01AG059874Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01MH116147Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01MH117601Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01NS107513Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R56AG058854Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U54EB020403Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 021683Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 14848NIA NIH HHS P01 AG066597NIA NIH HHS P01 AG084497NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG058854NIA NIH HHS R01 AG059874NIA NIH HHS R01 AG066152NIA NIH HHS R01 AG070885NIA NIH HHS R01 AG076832NIA NIH HHS R01 AG080734NIA NIH HHS R56 AG058854NIA NIH HHS T32 AG000258NIA NIH HHS U19 AG062418NIBIB NIH HHS P41 EB015922NIBIB NIH HHS U54 EB020403NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH117601NINDS NIH HHS K23 NS075097NINDS NIH HHS P50 NS053488NINDS NIH HHS P50 NS062684NINDS NIH HHS R01 NS107513NINDS NIH HHS R01 NS109260NINDS NIH HHS R01 NS115114NINDS NIH HHS RC4 NS073008NINDS NIH HHS U01 NS107027NINDS NIH HHS U54 NS092091U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1RO1NS107513-01A1
Abstract
Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4-5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.
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