ArticleNPJ Parkinson's disease2024
A worldwide study of white matter microstructural alterations in people living with 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 16 papers, 1 of them a synthesis that pooled it.
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16citing papers in PubMed, 1 pooled it
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Human leukocyte antigen (HLA) class I and II genetic relationships with brain imaging measures: A systematic review and meta-analysis.Brain, behavior, and immunity · 2025Pooled it
- Integrating retinal and brain imaging biomarkers for diagnosis of parkinson's disease: findings from a time-lagged cross-sectional persian cohort study.Scientific reports · 2026Article
- What's in a name? reframing advanced Parkinson's disease as a multidimensional state.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Local and global microstructural and functional thalamomotor connectivity alterations in Parkinson's disease following motor learning.NPJ Parkinson's disease · 2026Article
- The degenerome-a novel streamline-wise approach for white matter integrity in neurodegeneration.NPJ Parkinson's disease · 2026Article
- Fronto-caudate and callosal microstructural alterations: unveiling multimodal MRI biomarkers in early Parkinson's disease.The British journal of radiology · 2026Article
- In-vivo histology of Parkinson's disease using quantitative multiparametric mapping.NPJ Parkinson's disease · 2026Article
- Preserved white matter integrity is a promising indicator of cognitive resilience in Parkinson's disease.Scientific reports · 2025Article
- Synthetic MRI study of brain volume and subcortical myelin in various Parkinson's disease motor subtypes.NPJ Parkinson's disease · 2025Article
- Altered white matter architecture in patients with isolated congenital anosmia.Brain structure & function · 2025Article
- Early Alterations in De Novo Parkinson's Disease Revealed by Diffusion Tensor Imaging: Preliminary Study.Diagnostics (Basel, Switzerland) · 2025Article
- Synthetic Diffusion Tensor Imaging Maps Generated by 2D and 3D Probabilistic Diffusion Models: Evaluation and Applications.bioRxiv : the preprint server for biology · 2025Article
- Genetic analyses identify circulating genes related to brain structures associated with Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Microstructural Mapping of Neural Pathways in Alzheimer's Disease using Macrostructure-Informed Normative Tractometry.bioRxiv : the preprint server for biology · 2024Article
- Diffusion microstructure alterations in subcortical gray matter are associated with cognitive and motor performance in Parkinson's disease: a pilot study.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
58 authors.
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. Conor.Owens-Walton@loni.usc.edu.ORCID http://orcid.org/0000-0003-0589-638X
Talia M NirImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Sarah Al-BachariLancaster Medical School, Lancaster University, Lancaster, UK.
Sonia AmbrogiLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Tim J AndersonDepartment of Medicine, University of Otago, Christchurch, Christchurch, New Zealand.ORCID http://orcid.org/0000-0002-1116-3839
Ítalo Karmann AventuratoDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.ORCID http://orcid.org/0000-0001-9314-1109
Fernando CendesDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Yao-Liang ChenDepartment of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC.
Valentina CiulloLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Phil CookUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
John C Dalrymple-AlfordNew Zealand Brain Research Institute, Christchurch, New Zealand.
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.
Rachel GuimarãesDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Hamied A HaroonDivision of Psychology, Communication & Human Neuroscience, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.ORCID http://orcid.org/0000-0002-3506-8430
Rick C HelmichDepartment 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.
Michele T HuOxford Parkinson's Disease Centre, Nuffield, Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford, UK.
Martin E JohanssonDepartment 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.
Ho Bin KimDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Johannes C KleinOxford Parkinson's Disease Centre, Nuffield, Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8553-2801
Max LaansmaAmsterdam UMC, Dept. Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-8216-6690
Katherine E LawrenceImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Christine LochnerSA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Clare MackayOxford Parkinson's Disease Centre, Nuffield, Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford, UK.
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
Leila NabulsiImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Ben NewmanDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-0668-2853
Peter OpriessnigDepartment of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
Laura M ParkesDivision of Psychology, Communication & Human Neuroscience, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, 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.
Federica PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Lukas PirpamerDepartment of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
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
Annerine RoosSA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Lucas Scárdua SilvaDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.
Reinhold SchmidtDepartment of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
Petra SchwingenschuhDepartment of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.ORCID http://orcid.org/0000-0002-3294-6824
Marian Shahid-BesantiDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Gianfranco SpallettaLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.ORCID http://orcid.org/0000-0002-7432-4249
Dan J SteinSA MRC Unit on Risk and 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
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8644-7724
Chih-Chien TsaiHealthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan, ROC.
Odile A van den HeuvelDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Eva van HeeseDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-1954-5014
Daniela VecchioLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Julio E Villalón-ReinaImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Chris VriendDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-3111-1304
Jiun-Jie WangDepartment of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC.
Yih-Ru WuDepartment of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan, ROC.ORCID http://orcid.org/0000-0003-1191-2542
Clarissa Lin YasudaDepartment of Neurology, University of Campinas-UNICAMP, Campinas, Brazil.ORCID http://orcid.org/0000-0001-9084-7173
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.
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.
Ysbrand van der WerfDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-2370-9584
Funding
Project IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2019 to 2023
$18.1MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1MENIGMA World Aging CenterR01AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2021 to 2025
$3.3MENIGMA Parkinson’s Initiative: A Global Initiative for Parkinson’s DiseaseR01NS107513 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI POSTON, KATHLEEN LOMBARD, THOMPSON, PAUL M · 2021 to 2025
$3.2MHigh resolution mapping of the genetic risk for disease in the aging brainR01AG059874 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA · 2018 to 2022
$3.1MGlobal studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-ConsortiumR01MH134004 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Neda Jahanshad · 2023 to 2026
$2.6MWorldwide 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
$2.2MA global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA ConsortiumR01MH117601 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA, SCHMAAL, LIANNE · 2018 to 2021
$1.5MNeural Mechanisms and Developmental Trajectories of ASD and ADHDF32MH122057 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LAWRENCE, KATHERINE E · 2020 to 2022
$183kNIA NIH HHS R01 AG058854NIA NIH HHS R01 AG059874NIA NIH HHS U19 AG062418NIBIB NIH HHS P41 EB015922NIMH NIH HHS F32 MH122057NIMH NIH HHS R01 MH117601NIMH NIH HHS R01 MH134004NINDS NIH HHS R01 NS107513NINDS NIH HHS RF1 NS136995U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS107513
Abstract
The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.
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