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 ( 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.