Cognitive impairment in PD often does not respond to dopaminergic therapy suggesting involvement of other neurotransmitter systems or brain regions beyond the nigrostriatal pathway. Most neuroimaging studies of PD have focused on striatal dopaminergic circuitry; this approach may not fully explain cognitive impairment. The cerebellum has reciprocal anatomic connections to motor and association cortex including extrastriate occipital cortex. The cerebellar vermis harbors a rich population of cholinergic neurons; its malfunction could also contribute to cognitive impairments.

The purpose of this study was to investigate the contributions of altered cerebellar resting-state functional connectivity to motor and cognitive impairments in Parkinson disease (PD).

To investigate the role of the cerebellum, we conducted volumetric and resting-state functional connectivity MRI analyses in 81 PD and 43 age-matched healthy controls using rigorous quality assurances measures. Comprehensive measures of cognition were assessed. To calculate group differences based on cognitive status, we contrasted PD participants with normal cognition (Clinical Dementia Rating scale, CDR = 0; n = 47) versus participants with cognitive impairment (CDR ≥ 0.5; n = 34).

No significant differences in cerebellar lobular volumes were observed. The PD group had significantly greater functional connectivity between the vermis and visual association cortex that inversely correlated with visuospatial functions and global cognition. The cognitively impaired PD group had significantly lower functional connectivity between the vermis and dorsolateral prefrontal cortex. This effect correlated with deficits in attention, executive functions and global cognition. There were no behavioral correlates of greater cerebellar-sensorimotor cortex or lower intracerebellar functional connectivity in the PD cohort.

These results demonstrate a contribution of the cerebellar vermis to cognitive impairment in PD. The findings in PD participants with relatively mild degrees of cognitive impairment suggest that vermal functional connectivity may be an early imaging biomarker of subsequent cognitive decline.