Anatomical Abnormalities Suggest a Compensatory Role of the Cerebellum in Early Parkinson’s Disease

Abstract Brain atrophy is detected in early Parkinson’s disease (PD) and accelerates over the first few years post-diagnosis. This was captured by multiple cross-sectional studies and a few longitudinal studies in early PD. Yet only a longitudinal study with a control group can capture accelerated atrophy in early PD and differentiate it from healthy ageing. Accordingly, we performed a multicohort longitudinal analysis between PD and healthy ageing, examining subcortical regions implicated in PD pathology, including the basal ganglia, thalamus, corpus callosum (CC), and cerebellum. Longitudinal volumetric analysis was performed on 56 early PD patients and 53 matched controls, with scans collected 2-3 years apart. At baseline, the PD group showed a greater volume in the pallidum, thalamus, and cerebellar white matter (WM), suggesting potential compensatory mechanisms in prodromal and early PD. After 2-3 years, accelerated atrophy in PD was observed in the putamen and cerebellar WM. Interestingly, healthy controls – but not PD patients – demonstrated a significant decline in Total Intracranial Volume (TIV), and atrophy in the thalamus and mid-CC. Between-group analysis revealed more severe atrophy in the right striatum and cerebellar WM in PD, and in the mid-posterior CC in controls. Using CEREbellum Segmentation (CERES) for lobule segmentation on the longitudinal PD cohort, we found a significant decline in the WM of non-motor regions in the cerebellum, specifically Crus I and lobule IX. Our results highlight an initial increase in cerebellar WM volume during prodromal PD, followed by significant degeneration over the first few years post-diagnosis. Competing Interest Statement The authors have declared no competing interest.