Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA‐PD Study

Author:

Kerestes Rebecca1ORCID,Laansma Max A.23ORCID,Owens‐Walton Conor4,Perry Andrew5,van Heese Eva M.23,Al‐Bachari Sarah6,Anderson Tim J.78,Assogna Francesca9,Aventurato Ítalo K.1011,van Balkom Tim D.2312ORCID,Berendse Henk W.13,van den Berg Kevin R.E.1415,Betts Rebecca16,Brioschi Ricardo10,Carr Jonathan17,Cendes Fernando1011ORCID,Clark Lyles R.18,Dalrymple‐Alford John C.71920,Dirkx Michiel F.21,Druzgal Jason22,Durrant Helena16,Emsley Hedley C.A.2324,Garraux Gaëtan2526,Haroon Hamied A.27,Helmich Rick C.1415ORCID,van den Heuvel Odile A.2312,João Rafael B.1011,Johansson Martin E.21,Khachatryan Samson G.2829,Lochner Christine30,McMillan Corey T.18,Melzer Tracy R.71920ORCID,Mosley Philip E.3132,Newman Benjamin22,Opriessnig Peter33,Parkes Laura M.3435ORCID,Pellicano Clelia9,Piras Fabrizio9,Pitcher Toni L.719ORCID,Poston Kathleen L.36ORCID,Rango Mario3738,Roos Annerine39,Rummel Christian40,Schmidt Reinhold41,Schwingenschuh Petra41,Silva Lucas S.1011,Smith Viktorija36,Squarcina Letizia42,Stein Dan J.39,Tavadyan Zaruhi2829,Tsai Chih‐Chien43,Vecchio Daniela9,Vriend Chris21244,Wang Jiun‐Jie43454647ORCID,Wiest Roland40,Yasuda Clarissa L.1011,Young Christina B.36,Jahanshad Neda4,Thompson Paul M.4,van der Werf Ysbrand D.23,Harding Ian H.148ORCID,

Affiliation:

1. Department of Neuroscience, Central Clinical School Monash University Melbourne Victoria Australia

2. Department Anatomy and Neurosciences, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

3. Amsterdam Neuroscience Neurodegeneration Amsterdam The Netherlands

4. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine University of Southern California Marina del Rey California USA

5. Monash Bioinformatics Platform Monash University Melbourne Victoria Australia

6. Faculty of Health and Medicine The University of Lancaster Lancaster United Kingdom

7. New Zealand Brain Research Institute Christchurch New Zealand

8. Neurology Department Te Whatu Ora ‐ Health New Zealand Waitaha Canterbury Christchurch New Zealand

9. Laboratory of Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy

10. Department of Neurology University of Campinas – UNICAMP Campinas Brazil

11. Brazilian Institute of Neuroscience and Neurotechnology Campinas Brazil

12. Department Psychiatry, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

13. Department Neurology, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

14. Department of Neurology and Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Centre Nijmegen The Netherlands

15. Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour Radboud University Nijmegen Nijmegen The Netherlands

16. School of Physics and Astronomy, Faculty of Science and Engineering The University of Manchester Manchester United Kingdom

17. Division of Neurology Tygerberg Hospital and Stellenbosch University Cape Town South Africa

18. Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

19. Department of Medicine University of Otago Christchurch New Zealand

20. School of Psychology, Speech and Hearing University of Canterbury Christchurch New Zealand

21. Department of Neurology and Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour Radboud University Nijmegen Medical Centre Nijmegen The Netherlands

22. Department of Radiology and Medical Imaging University of Virginia Charlottesville Virginia USA

23. Lancaster Medical School Lancaster University Lancaster United Kingdom

24. Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health The University of Manchester, Manchester Academic Health Science Centre Manchester United Kingdom

25. GIGA‐CRC in vivo imaging University of Liège Liège Belgium

26. MoVeRe group Department of Neurology, CHU de Liège Belgium

27. Division of Psychology, Communication and Human Neuroscience, Faculty of Biology, Medicine and Health, The University of Manchester Manchester Academic Health Science Centre Manchester United Kingdom

28. Department of Neurology and Neurosurgery National Institute of Health Yerevan Armenia

29. Centers for Sleep and Movement Disorders Somnus Neurology Clinic Yerevan Armenia

30. Department of Psychiatry, SA MRC Unit on Risk and Resilience in Mental Disorders Stellenbosch University Cape Town South Africa

31. Clinical Brain Networks Group QIMR Berghofer Medical Research Institute Brisbane Queensland Australia

32. The Australian eHealth Research Centre CSIRO Health and Biosecurity Brisbane Queensland Australia

33. Department of Neurology, Clinical Division of Neurogeriatrics Medical University Graz Graz Austria

34. Division of Psychology, Communication and Human Neuroscience, School of Health Sciences, Faculty of Biology, Medicine and Health The University of Manchester Manchester United Kingdom

35. Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre Northern Care Alliance and University of Manchester Manchester United Kingdom

36. Department of Neurology and Neurological Sciences Stanford University Palo Alto California USA

37. Excellence Center for Advanced MR Techniques and Parkinson's Disease Center, Neurology unit, Fondazione IRCCS Cà Granda Maggiore Policlinico Hospital University of Milan Milan Italy

38. Department of Neurosciences, Neurology Unit, Fondazione Ca' Granda, IRCCS, Ospedale Policlinico University of Milan Milano Italy

39. Department of Psychiatry and Neuroscience Institute, SA MRC Unit on Risk and Resilience in Mental Disorders University of Cape Town Cape Town South Africa

40. Support Center for Advanced Neuroimaging, (SCAN) University Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern University Hospital, University of Bern Bern Switzerland

41. Department of Neurology Medical University of Graz Graz Austria

42. Department of Pathophysiology and Transplantation University of Milan Milan Italy

43. Healthy Aging Research Center Chang Gung University Taoyuan City Taiwan

44. Amsterdam Neuroscience Brain Imaging Amsterdam The Netherlands

45. Department of Medical Imaging and Radiological Sciences Chang Gung University Taoyuan City Taiwan

46. Department of Diagnostic Radiology Chang Gung Memorial Hospital Keelung Branch, Keelung City Keelung Taiwan

47. Department of Chemical Engineering Ming‐Chi University of Technology New Taipei City Taiwan

48. Monash Biomedical Imaging Monash University Melbourne Victoria Australia

Abstract

AbstractBackgroundIncreasing 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.ObjectiveTo quantify cross‐sectional regional cerebellar lobule volumes using three dimensional T1‐weighted anatomical brain magnetic resonance imaging from the global ENIGMA‐PD working group.MethodsCerebellar 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.ResultsOverall, 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).ConclusionsWe 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. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Funder

Canterbury Medical Research Foundation

Centros de Pesquisa, Inovação e Difusão, Fundação Amazônia Paraense de Amparo à Pesquisa

Parkinson Vereniging

Health Research Council of New Zealand

Lancaster University

Ministero della Salute

National Institutes of Health

National Institute of Neurological Disorders and Stroke

Sir John Fisher Foundation

U.S. Department of Defense

Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii

University of Virginia

Neurological Foundation of New Zealand

National Health and Medical Research Council

Michael J. Fox Foundation for Parkinson's Research

Lewy Body Dementia Association

Alzheimer's Drug Discovery Foundation

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

South African Medical Research Council

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Hersenstichting

National Institute of Mental Health

National Science and Technology Council

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Healthy Aging Research Center

Chang Gung Memorial Hospital

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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