To test the hypothesis that the cerebellum (CbL) is an important site to support compensation and reserve mechanisms across Parkinson’s disease (PD) stages.
Altered CbL–basal ganglia connectivity has been implicated in normal aging and speculated to be associated with dopaminergic decline. However, how CbL–basal ganglia and CbL–cortical functional connectivity are altered in PD, and how these patterns are related to age, disease duration, and cognitive status remains unclear.
Resting-state fMRI data from the Parkinson’s Progression Markers Initiative were analyzed in PD subjects (n =172) and stratified by cognitive status (cognitively normal, mild cognitive impairment, dementia). ROI-to-ROI and seed-to-voxel analyses were conducted to examine CbL-BG and CbL-cortical functional connectivity, respectively. Effects of age, disease duration, and cognitive status were examined.
Across all PD participants, higher connectivity was observed between the pallidum and both Right CbL Lobule VI and Vermis VI, in addition to strengthened intra/within-CbL connectivity, suggesting compensatory recruitment. Disease duration was positively correlated with Lobule V – medial temporal gyrus/inferior temporal gyrus connectivity and negatively with inferior occipital lobe, while Crus I connectivity with Left precuneus cortex was lower with longer disease duration. Of note, cognitively normal PD participants (n = 105) demonstrated stronger Crus I – Left precentral gyrus connectivity than PD-mild cognitive impairment/dementia (n = 67) when controlling for disease duration; however, no age-related effects emerged within cognitively normal PD, suggesting disease progression, rather than chronological aging, primarily drives connectivity alterations.
Our findings identify cerebellar connectivity shifts as potential neuroimaging biomarkers of disease progression and cognitive reserve in PD. Enhanced CbL-pallidal and CbL-premotor connectivity in earlier cognitive stages may reflect compensatory recruitment, whereas longer disease duration is linked to declining cortical association connectivity. These alterations, independent of chronological aging, highlight their specificity to PD and suggest cerebellar connectivity markers could aid in tracking progression and guiding interventions.