A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease

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.

Authors

Institutions

Publication Details

Journal
npj Parkinson s Disease
Published
2024-08-11
DOI
https://doi.org/10.1038/s41531-024-00758-3
Citations
21
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
7.75

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease

Tracy R. Melzer, Peter Opriessnig, Rachel Guimarães, Conor Owens‐Walton et al.
21 citations
npj Parkinson s Disease
Parkinson's Disease Mechanisms and Treatments
7.75
article

A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease

Tracy R. Melzer, Peter Opriessnig, Rachel Guimarães, Conor Owens‐Walton, Duygu Tosun, Federica Piras, Max A. Laansma, Gianfranco Spalletta, Ysbrand D. van der Werf, Chris Vriend, Sophia I. Thomopoulos, Clare E. Mackay, Neda Jahanshad, Ho Bin Kim, Petra Schwingenschuh, Yao-Liang Chen, Jiun‐Jie Wang, Rick C. G. Helmich, Phil Cook, Hedley Emsley, Johannes Klein, Lukas Pirpamer, Benjamin T. Newman, Sarah Al–Bachari, Valentina Ciullo, Corey T. McMillan, Annerine Roos, Tim Anderson, Lucas Scárdua Silva, Fernando Cendes, Kathleen L. Poston, John C. Dalrymple‐Alford, Daniela Vecchio, Michiel F. Dirkx, Ítalo Karmann Aventurato, Yih‐Ru Wu, Laura M. Parkes, Leila Nabulsi, Clelia Pellicano, Toni L. Pitcher, Eva M. van Heese, Julio E. Villalón‐Reina, Odile A. van den Heuvel, Dan Joseph Stein, Martin E. Johansson, Talia M. Nir, Katherine E. Lawrence, Marian Shahid, Clarissa Lin Yasuda, Jason Druzgal, Sonia Ambrogi, Christine Löchner, Hamied Haroon, Paul M. Thompson, Chih‐Chien Tsai, Reinhold Schmidt, Fabrizio Piras
article en
21 citations

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.

npj Parkinson s DiseaseVol. 10(1)
South African Medical Research Council (ZA), University of Southern California (US), Ming Chi University of Technology (TW), Lancashire Teaching Hospitals NHS Foundation Trust (GB), Radboud University Nijmegen (NL), University of Cape Town (ZA), Chang Gung University (TW), University of California, San Francisco (US), Universidade Estadual de Campinas (UNICAMP) (BR), University of Canterbury (NZ), Medical University of Graz (AT), Stellenbosch University (ZA), Manchester Academic Health Science Centre (GB), Radboud University Medical Center (NL), University of California System (US), University of Manchester (GB), Chang Gung Memorial Hospital (TW), University of Oxford (GB), Canterbury Health Laboratories (NZ), New Zealand Brain Research Institute (NZ), Amsterdam Neuroscience (NL), Brazilian Institute of Neuroscience and Neurotechnology (BR), Fondazione Santa Lucia (IT), Amsterdam University Medical Centers (NL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University of Virginia (US), Lancaster University (GB), University of Pennsylvania (US), University of Otago (NZ), Vrije Universiteit Amsterdam (NL), Stanford University (US)
Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Sanofi, Biogen, Teva Pharmaceutical Industries, Celgene, Boston Scientific Corporation, Jazz Pharmaceuticals, Neurocrine Biosciences, Verily Life Sciences, Voyager Therapeutics, National Institute for Health and Care Research, Parkinson's UK, Neurological Foundation of New Zealand, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministero della Salute, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Servier, H. Lundbeck A/S, Sun Pharma, National Science and Technology Council, National Institutes of Health, Genentech, Allergan, Avid Radiopharmaceuticals, Medical Research Council, Engineering and Physical Sciences Research Council, Health Research Council of New Zealand, Marsden Fund, National Institute on Aging
Openalex Percentile: Top 2%
Parkinson's Disease Mechanisms and Treatments
7.75
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.