@article{ea48843c2f394047bc90cc092fbd8b22,
title = "Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study",
abstract = "Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. Objective: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. Methods: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. Results: Overall, people with PD had a regionally smaller posterior lobe (dmax = −0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = −0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = −0.17). Conclusions: We provide evidence of a dissociation between anterior “motor” lobe and posterior “non-motor” lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions.",
keywords = "cerebellum, disease staging, MRI, Parkinson's disease",
author = "Rebecca Kerestes and Laansma, {Max A.} and Conor Owens-Walton and Andrew Perry and {van Heese}, {Eva M.} and Sarah Al-Bachari and Anderson, {Tim J.} and Francesca Assogna and Aventurato, {{\'I}talo K.} and {van Balkom}, {Tim D.} and Berendse, {Henk W.} and {van den Berg}, {Kevin R.E.} and Rebecca Betts and Ricardo Brioschi and Jonathan Carr and Fernando Cendes and Clark, {Lyles R.} and Dalrymple-Alford, {John C.} and Dirkx, {Michiel F.} and Jason Druzgal and Helena Durrant and Emsley, {Hedley C.A.} and Ga{\"e}tan Garraux and Haroon, {Hamied A.} and Helmich, {Rick C.} and {van den Heuvel}, {Odile A.} and Jo{\~a}o, {Rafael B.} and Johansson, {Martin E.} and Khachatryan, {Samson G.} and Christine Lochner and McMillan, {Corey T.} and Melzer, {Tracy R.} and Mosley, {Philip E.} and Benjamin Newman and Peter Opriessnig and Parkes, {Laura M.} and Clelia Pellicano and Fabrizio Piras and Pitcher, {Toni L.} and Poston, {Kathleen L.} and Mario Rango and Annerine Roos and Christian Rummel and Reinhold Schmidt and Petra Schwingenschuh and Silva, {Lucas S.} and Viktorija Smith and Letizia Squarcina and Stein, {Dan J.} and Zaruhi Tavadyan and Tsai, {Chih Chien} and Daniela Vecchio and Chris Vriend and Wang, {Jiun Jie} and Roland Wiest and Yasuda, {Clarissa L.} and Young, {Christina B.} and Neda Jahanshad and Thompson, {Paul M.} and {van der Werf}, {Ysbrand D.} and Harding, {Ian H.} and {the ENIGMA-Parkinson{\textquoteright}s Study}",
note = "Funding Information: T.J.A. is funded by Health Research Council New Zealand grants (20/538, 21/165). H.W.B. is funded by the Netherlands Organisation for Health Research and Development (ZonMw) and The Michael J. Fox Foundation. F.C. is funded by S{\~a}o Paulo Research Foundation (FAPESP) grant 2013/07559‐3. M.D. is funded by a grant from ParkinsonNL (P2023‐14). H.C.A.E. is supported by Lancashire Teaching Hospitals NHS Foundation Trust. J.D. is supported by an ENIGMA‐PD R01 grant (R01NS107513). J.D.A. is funded the Health Research Council of New Zealand (20/538), Marsden Fund New Zealand (UOC2105), Neurological Foundation of New Zealand (2232 PRG), and the Research and Education Trust Pacific Radiology (MRIJDA). G.G. is funded by a National Fund for Scientific Research grant (Belgian fund for Scientific Research; University of Liege Grant (Fonds Rahier). R.C.H. is funded by The Michael J. Fox Foundation and the Netherlands Organization for Scientific Research. I.H.H. is funded by grants from the National Health and Medical Research Council, Friedreich Ataxia Research Alliance, and National Ataxia Foundation and Telethon Fondazione. N.J. is funded by grants R01AG059874, R01MH117601, R01NS107513, and P41EB015922. P.E.M. receives salary from a job as neuropsychiatrist at St. Andrew's War Memorial Hospital, Brisbane, and salary as research scientist at Commonwealth Scientific and Industrial Research Organization. C.M. is funded by the National Institutes of Health (NIH) R01 grants NIH R01AG066152, NIH P01AG066597, NIH U54NS092091, NIH U01NS107027, NIH R01NS109260, NIH U19AG062418, Pennsylvania Department of Health 2019NF4100087335, NIH R01 AG070885, NIH P30AG072979, NIH R01NS107513, NIH R01 AG076832, and NIH R01AG080734. T.R.M. is funded by a Health Research Council grant (20/538). K.L.P. is funded by The Michael J. Fox Foundation for Parkinson's Research, the Lewy Body Dementia Association, the Alzheimer's Drug Discovery Foundation, and the NIH grant (6440). F.P. is funded by the Italian Ministry of Health, grant number RF‐2019‐12370182. C.R. is funded by SNF grants 204593 and 180365. D.J.S. is funded by the South African Medical Research Council. C.Y. is funded by the NIH, Alzheimer's Association, and New Vision Research. L.M.P. is funded by the University of Manchester and UK Research and Innovation. T.P. is funded by a Health Research Council grant (21/165). O.A.v.d.H. is funded by the Netherlands Organisation for Health Research and Development (ZonMw), Hersenstichting, and the National Institute of Mental Health. C.V. is funded by The Michael J. Fox Foundation (grants 6440). D.V. is funded by the Italian Ministry of Health, Ricerca Corrente 2023. J.W. is funded by the National Science and Technology Council, Taiwan. R.W. is funded by Swiss National Science Foundation (SNF) grant 180365. C.Y. is funded by S{\~a}o Paulo Research Foundation FAPESP‐BRAINN grant 2013‐07559‐3 and National Council for Scientific and Technological Development (CNPQ) (315953/2021‐7) National Council for Scientific and Technological Development. C.L. is funded by the South African Medical Research Council. Publisher Copyright: {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",
year = "2023",
month = dec,
doi = "10.1002/mds.29611",
language = "English",
volume = "38",
pages = "2269--2281",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley & Sons",
number = "12",
}