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

Rebecca Kerestes; Max A Laansma; Conor Owens-Walton; Andrew Perry; Eva M van Heese; Sarah Al-Bachari; Tim J Anderson; Francesca Assogna; Ítalo K Aventurato; Tim D van Balkom; Henk W Berendse; Kevin R E van den Berg; Rebecca Betts; Ricardo Brioschi; Jonathan Carr; Fernando Cendes; Lyles R Clark; John C Dalrymple-Alford; Michiel F Dirkx; Jason Druzgal; Helena Durrant; Hedley C A Emsley; Gaëtan Garraux; Hamied A Haroon; Rick C Helmich; Odile A van den Heuvel; Rafael B João; Martin E Johansson; Samson G Khachatryan; Christine Lochner; Corey T McMillan; Tracy R Melzer; Philip E Mosley; Benjamin Newman; Peter Opriessnig; Laura M Parkes; Clelia Pellicano; Fabrizio Piras; Toni L Pitcher; Kathleen L Poston; Mario Rango; Annerine Roos; Christian Rummel; Reinhold Schmidt; Petra Schwingenschuh; Lucas S Silva; Viktorija Smith; Letizia Squarcina; Dan J Stein; Zaruhi Tavadyan; Chih-Chien Tsai; Daniela Vecchio; Chris Vriend; Jiun-Jie Wang; Roland Wiest; Clarissa L Yasuda; Christina B Young; Neda Jahanshad; Paul M Thompson; Ysbrand D van der Werf; Ian H Harding; ENIGMA-Parkinson's Study

doi:10.1002/mds.29611

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

Mov Disord. 2023 Dec;38(12):2269-2281. doi: 10.1002/mds.29611. Epub 2023 Nov 14.

Authors

Rebecca Kerestes¹, Max A Laansma^{2

3}, Conor Owens-Walton⁴, Andrew Perry⁵, Eva M van Heese^{2

3}, Sarah Al-Bachari⁶, Tim J Anderson^{7

8}, Francesca Assogna⁹, Ítalo K Aventurato^{10

11}, Tim D van Balkom^{2

3

12}, Henk W Berendse¹³, Kevin R E van den Berg^{14

15}, Rebecca Betts¹⁶, Ricardo Brioschi¹⁰, Jonathan Carr¹⁷, Fernando Cendes^{10

11}, Lyles R Clark¹⁸, John C Dalrymple-Alford^{7

19

20}, Michiel F Dirkx²¹, Jason Druzgal²², Helena Durrant¹⁶, Hedley C A Emsley^{23

24}, Gaëtan Garraux^{25

26}, Hamied A Haroon²⁷, Rick C Helmich^{14

15}, Odile A van den Heuvel^{2

3

12}, Rafael B João^{10

11}, Martin E Johansson²¹, Samson G Khachatryan^{28

29}, Christine Lochner³⁰, Corey T McMillan¹⁸, Tracy R Melzer^{7

19

20}, Philip E Mosley^{31

32}, Benjamin Newman²², Peter Opriessnig³³, Laura M Parkes^{34

35}, Clelia Pellicano⁹, Fabrizio Piras⁹, Toni L Pitcher^{7

19}, Kathleen L Poston³⁶, Mario Rango^{37

38}, Annerine Roos³⁹, Christian Rummel⁴⁰, Reinhold Schmidt⁴¹, Petra Schwingenschuh⁴¹, Lucas S Silva^{10

11}, Viktorija Smith³⁶, Letizia Squarcina⁴², Dan J Stein³⁹, Zaruhi Tavadyan^{28

29}, Chih-Chien Tsai⁴³, Daniela Vecchio⁹, Chris Vriend^{2

12

44}, Jiun-Jie Wang^{43

45

46

47}, Roland Wiest⁴⁰, Clarissa L Yasuda^{10

11}, Christina B Young³⁶, Neda Jahanshad⁴, Paul M Thompson⁴, Ysbrand D van der Werf^{2

3}, Ian H Harding^{1

48}; ENIGMA-Parkinson's Study

Affiliations

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

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 (d_max = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (d_max = 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 (d_max = -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. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: MRI; Parkinson's disease; cerebellum; disease staging.

MeSH terms

Brain
Cerebellum
Cross-Sectional Studies
Humans
Magnetic Resonance Imaging
Parkinson Disease* / complications

Abstract

MeSH terms

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