Abstract
BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated.
OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging.
METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score.
RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax = -0.20, dmin = -0.09). The bilateral putamen (dleft = -0.14, dright = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures.
CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations.
| Original language | English |
|---|---|
| Pages (from-to) | 2583-2594 |
| Number of pages | 12 |
| Journal | Movement disorders : official journal of the Movement Disorder Society |
| Volume | 36 |
| Issue number | 11 |
| Early online date | 20 Jul 2021 |
| DOIs | |
| Publication status | Published - Nov 2021 |
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In: Movement disorders : official journal of the Movement Disorder Society, Vol. 36, No. 11, 11.2021, p. 2583-2594.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease
AU - ENIGMA-Parkinson's Study
AU - Laansma, Max A
AU - Bright, Joanna K
AU - Al-Bachari, Sarah
AU - Anderson, Tim J
AU - Ard, Tyler
AU - Assogna, Francesca
AU - Baquero, Katherine A
AU - Berendse, Henk W
AU - Blair, Jamie
AU - Cendes, Fernando
AU - Dalrymple-Alford, John C
AU - de Bie, Rob M A
AU - Debove, Ines
AU - Dirkx, Michiel F
AU - Druzgal, Jason
AU - Emsley, Hedley C A
AU - Garraux, Gäetan
AU - Guimarães, Rachel P
AU - Gutman, Boris A
AU - Helmich, Rick C
AU - Klein, Johannes C
AU - Mackay, Clare E
AU - McMillan, Corey T
AU - Melzer, Tracy R
AU - Parkes, Laura M
AU - Piras, Fabrizio
AU - Pitcher, Toni L
AU - Poston, Kathleen L
AU - Rango, Mario
AU - Ribeiro, Letícia F
AU - Rocha, Cristiane S
AU - Rummel, Christian
AU - Santos, Lucas S R
AU - Schmidt, Reinhold
AU - Schwingenschuh, Petra
AU - Spalletta, Gianfranco
AU - Squarcina, Letizia
AU - van den Heuvel, Odile A
AU - Vriend, Chris
AU - Wang, Jiun-Jie
AU - Weintraub, Daniel
AU - Wiest, Roland
AU - Yasuda, Clarissa L
AU - Jahanshad, Neda
AU - Thompson, Paul M
AU - van der Werf, Ysbrand D
N1 - Funding Information: Y.D.v.d.W.: none. M.A.L.: none. J.K.B.: none. S.A.: grant from the Dowager Countess Eleanor Peel Trust Medical Research Grant. T.J.A.: none. T.A.: grants from Alzheimer's Disease Neuroimaging Initiative (U01AG02490), Neurodegeneration in Aging Down Syndrome (U01AG051406). F.A.: none. K.A.B.: none. H.W.B.: grants from ZonMw, Michael J. Fox Foundation. J.B.: none. F.C.: Employment at National Council for Scientific and Technological Development (CNPq). J.C.D.: grants from New Zealand Neurological Foundation, Health Research Council of New Zealand, Brain Research New Zealand, School of Psychology, Speech and Hearing. R.M.A.d.B.: research support paid to the institution from Medtronic, Lysosomal Therapeutics, Neuroderm, ZonMw, Parkinson Vereniging, Stichting Parkinson Nederland. I.D.: grants from Boston Scientific, AbbVie, Medtronic, UCB, Bial. Reimbursement: Zambon, Boston Scientific. M.F.D.: none. J.D.: none. H.C.A.E.: grants from NIHR, EPSRC, MRC. G.G.: none. R.P.G.: Employment at National Council for Scientific and Technological Development (CNPq). B.A.G.: grant from Alzheimer's Association Grant 2018‐AARG‐592081. R.C.H.: grants from the Michael J. Fox Foundation (grants 16048 and 15581), Netherlands Organization for Scientific Research (VENI grant 91617077). J.C.K.: none. C.E.M.: none. C.T.M.: none. T.R.M.: none. L.M.P.: grants from Alzheimer's Society, EPSRC UK, EU. F.P.: grants from Italian Ministry of Health RC 19, RC 20. T.L.P.: grant from New Zealand Brain Research Institute; honorarium from Stata Australia Ltd. K.L.P.: grants from the Michael J. Fox Foundation for Parkinson's Research, NIH; honoraria from invited scientific presentations to universities and professional societies not exceeding $5000/year; reimbursement from Sanofi, AstraZeneca, Sangamo BioSciences; consultancies from Allergan, Curasen. M.R.: none. L.F.R.: employment at National Council for Scientific and Technological Development (CNPq). C.S.R.: employment at National Council for Scientific and Technological Development (CNPq). C.R.: grants from Swiss National Science Foundation (projects CRSK‐3_190817/1 and CRSII5_180365), Novartis AG (FreeNovation research grant). L.S.R.S.: employment at National Council for Scientific and Technological Development (CNPq). R.S.: none. P.S.: honoraria from AbbVie, GmbH. G.S.: none. L.S.: none. O.A.v.d.H.: VIDI grant from The Netherlands Organization for Health Research (ZonMw; project number: 91717306); consultancy from Lundbeck. C.V.: none. J.W.: grants MOST 109‐2314‐B‐182‐021‐MY3, MOST 109‐2221‐E‐182‐009‐MY3, MOST 106‐2314‐B‐182‐018‐MY3. D.W.: grants from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), the International Parkinson and Movement Disorder Society (IPMDS), the National Institute on Aging (NIA); honoraria from Acadia, Aptinyx, CHDI Foundation, Clintrex LLC (Alkahest, Aptinyx, Avanir, Otsuka), Eisai, Enterin, Great Lake Neurotechnologies, Janssen, Sage, Scion, Signant Health, Sunovion, and Vanda. license fee payments from the University of Pennsylvania for the QUIP and QUIP‐RS. R.W.: grants from the Swiss National Science Foundation (projects CRSII5_180365, 320030L_170060), Swiss Personalized Health Network (driver project 2018DRI10), Swiss Innovation Council (project 43087.1 IP‐LS) University of Bern (sitem‐insel Support Funds 2019), Biogen (research project CHE‐TYS‐18‐11,316). C.L.Y.: employment at National Council for Scientific and Technological Development (CNPq). N.J.: grants from Biogen Inc. P.M.T.: NIH grants U01AG024904, R01MH111671. Funding Information: K.L.P. reports honoraria from invited scientific presentations to universities and professional societies not exceeding $5000/year, is reimbursed by Sanofi, AstraZeneca, and Sangamo BioSciences for the conduct of clinical trials, has received consulting fees from Allergan and Curasen, and is funded by grants from the Michael J. Fox Foundation for Parkinson's Research and the NIH. R.M.A.d.B. received unrestricted research grants from Medtronic, GEHealth, Lysosomal Therapeutics, all paid to the Institution. R.H. serves on the Clinical Advisory Board of Cadent Therapeutics. O.A.v.d.H. received funding for a honorarium lecture from Benecke. C.T.M. receives research funding from Biogen, Inc., and provides consulting services for Invicro and Axon Advisors on behalf of Translational Bioinformatics, LLC. He also receives an honorarium as Associate Editor of NeuroImage: Clinical. N.J. and P.M.T. received partial grant support from Biogen, Inc., for research unrelated to the topic of this article. None of the other authors declares any competing financial interests. Relevant conflicts of interest/financial disclosures: Funding Information: Y.D.v.d.W.: none. M.A.L.: none. J.K.B.: none. S.A.: grant from the Dowager Countess Eleanor Peel Trust Medical Research Grant. T.J.A.: none. T.A.: grants from Alzheimer's Disease Neuroimaging Initiative (U01AG02490), Neurodegeneration in Aging Down Syndrome (U01AG051406). F.A.: none. K.A.B.: none. H.W.B.: grants from ZonMw, Michael J. Fox Foundation. J.B.: none. F.C.: Employment at National Council for Scientific and Technological Development (CNPq). J.C.D.: grants from New Zealand Neurological Foundation, Health Research Council of New Zealand, Brain Research New Zealand, School of Psychology, Speech and Hearing. R.M.A.d.B.: research support paid to the institution from Medtronic, Lysosomal Therapeutics, Neuroderm, ZonMw, Parkinson Vereniging, Stichting Parkinson Nederland. I.D.: grants from Boston Scientific, AbbVie, Medtronic, UCB, Bial. Funding Information: ENIGMA Core — This work was supported in part by NIH grants R56AG058854, R01AG059874, R01MH116147, R01MH117601, and U54EB020403, the Michael J. Fox Foundation grant 14848, and the Kavli Foundation Neurodata Without Borders. PPMI cohort — Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up‐to‐date information on the study, visit www.ppmi-info.org . PPMI, a public‐private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol‐Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Janssen Neuroscience, Eli Lilly and Company, Lundbeck, Merck, Meso Scale Discovery (MSD), Pfizer, Piramal Enterprises, Ltd, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily and Voyager Therapeutics. OpenNeuro Japan cohort — These data were obtained from the OpenfMRI database. Its accession number is ds000245. This research was supported in part by the following: a Grant‐in‐Aid from the Research Committee of Central Nervous System Degenerative Diseases by the Ministry of Health, Labour, and Welfare, Integrated Research on Neuropsychiatric Disorders project, carried out by SRBPS; a Grant‐in‐Aid for Scientific Research on Innovative Areas (Brain Protein Aging and Dementia Control 26117002) from the MEXT of Japan; Integrated Research on Neuropsychiatric Disorders carried out under the Strategic Research Program for Brain Sciences, Scientific Research on Innovative Areas (Comprehensive Brain Science Network); and Integrated Research on Depression, Dementia, and Development Disorders by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development (AMED). NEUROCON cohort — This work was partially supported by the NEUROCON project (84/2012), financed by UEFISCDI. Stanford cohort — This work was supported by the NIH/NINDS (K23 NS075097) and the Michael J. Fox Foundation for Parkinson's Research. Oxford DISCOVERY cohort — This work was funded by Parkinson's UK, NIHR Oxford Health Biomedical Research Centre. Amsterdam I cohort — Grant support (not for this study) from the Netherlands Organisation for Health Research and Development, the Michael J. Fox Foundation, and the Hersenstichting. Amsterdam II (Cogtips) cohort — Cogtips is supported by the Dutch Parkinson's Disease Association (“Parkinson Vereniging” 19‐2015) and Brain Foundation of the Netherlands (“Hersenstichting” HA‐2017‐00227). Liege I & II cohorts — This work was funded by PDR Grant T0.165.14, National Fund for Scientific Research (FNRS), Belgium. Donders cohort — This work was funded by a grant of the Dutch Brain Foundation (grant F2013(10‐15 to R.H.), from the Netherlands Organization for Scientific Research (VENI grant 91617077), and from the Michael J. Fox Foundation. Rome SLF cohort — This work was funded by the Italian Ministry of Health, Italian Ministry of Health RC12‐13‐14‐15‐16‐17‐18‐19/A. UNICAMP cohort — This work was funded by the São Paulo Research Foundation FAPESP‐BRAINN (2013–07559‐3). Christchurch cohort — This work was supported by the Health Research Council of New Zealand, Canterbury Medical Research Foundation, Neurological Foundation of New Zealand, University of Otago Research Grant, Brain Research New Zealand. Charlottesville I–III cohorts — This work was supported by grants from Department of Defense, Commonwealth of Virginia's Alzheimer's and Related Diseases Research Award Fund, and University of Virginia. NW‐England I and II cohorts — This work was funded by the Sydney Driscoll Neuroscience Foundation, Lancaster University and the Sir John Fisher Foundation, University of Manchester Biomedical Imaging Institute, Medical Research Council UK Doctoral Training Programme, Engineering and Physical Science Research Council UK (EP/M005909/1). BE I and II cohorts — Coauthor for the Bern cohort receives a grant from Boston Scientific. Pennsylvania cohort — This work was funded by the NINDS, NIH AG062418 (U19) and NS053488 (P50). We acknowledge the support of Alice Chen Plotkin for MRI and clinical data collection. Chang Gung cohort — This work was supported by MOST 106‐2314‐B‐182‐018‐MY3, EMRPD1K0451, EMRPD1K0481. Schol‐AR: Support for this work was provided by the National Institutes of Health (grants P41EB015922 and U54EB020406) and by the Michael J. Fox Foundation's Parkinson's Progression Markers Initiative (PPMI, award 8283.03). Funding agencies: Publisher Copyright: © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
PY - 2021/11
Y1 - 2021/11
N2 - BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated.OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging.METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score.RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax = -0.20, dmin = -0.09). The bilateral putamen (dleft = -0.14, dright = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures.CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations.
AB - BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated.OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging.METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score.RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax = -0.20, dmin = -0.09). The bilateral putamen (dleft = -0.14, dright = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures.CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations.
UR - http://www.scopus.com/inward/record.url?scp=85110849327&partnerID=8YFLogxK
U2 - 10.1002/mds.28706
DO - 10.1002/mds.28706
M3 - Article
C2 - 34288137
SN - 0885-3185
VL - 36
SP - 2583
EP - 2594
JO - Movement disorders : official journal of the Movement Disorder Society
JF - Movement disorders : official journal of the Movement Disorder Society
IS - 11
ER -