Cognitive correlates of cerebellar resting-state functional connectivity in Parkinson disease

Abstract

ObjectiveTo investigate in a cross-sectional study the contributions of altered cerebellar resting-state functional connectivity (FC) to cognitive impairment in Parkinson disease (PD).MethodsWe conducted morphometric and resting-state FC-MRI analyses contrasting 81 participants with PD and 43 age-matched healthy controls using rigorous quality assurance measures. To investigate the relationship of cerebellar FC to cognitive status, we compared participants with PD without cognitive impairment (Clinical Dementia Rating [CDR] scale score 0, n = 47) to participants with PD with impaired cognition (CDR score ≥0.5, n = 34). Comprehensive measures of cognition across the 5 cognitive domains were assessed for behavioral correlations.ResultsThe participants with PD had significantly weaker FC between the vermis and peristriate visual association cortex compared to controls, and the strength of this FC correlated with visuospatial function and global cognition. In contrast, weaker FC between the vermis and dorsolateral prefrontal cortex was found in the cognitively impaired PD group compared to participants with PD without cognitive impairment. This effect correlated with deficits in attention, executive functions, and global cognition. No group differences in cerebellar lobular volumes or regional cortical thickness of the significant cortical clusters were observed.ConclusionThese results demonstrate a correlation between cerebellar vermal FC and cognitive impairment in PD. The absence of significant atrophy in cerebellum or relevant cortical areas suggests that this could be related to local pathophysiology such as neurotransmitter dysfunction.

Visual Dysfunction Predicts Cognitive Impairment and White Matter Degeneration in Parkinson's Disease

“…A composite cognitive Z score (averaged across the 5 individual cognitive domains) was also computed. 41 Prior to processing, all volumes of raw data sets were visually inspected, and each volume evaluated for the presence of artifact; only scans with <15 volumes containing artifacts 42 were included. DWI images that passed quality control underwent denoising, 43 removal of ringing artifacts, 44 eddy-current and motion correction 45 and bias-field correction.…”

“…76,77 In patients with Parkinson's disease, functional connectivity between the vermis and visual association and prefrontal cortex is weaker than in controls and correlates with cognitive performance, even in the absence of cerebellar volume loss or changes in cortical thickness. 41 Although traditionally regarded as unaffected by α-synuclein pathology, recent evidence suggests that cerebellar nuclei and surrounding white matter do accumulate α-synuclein aggregates. 78 Our findings provide further support for structural white matter changes within the cerebellum in patients with PD and cognitive impairment.…”

Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

“…The cortico-ponto-cerebellar pathway, which connects cortical regions to the cerebellum via the contralateral middle cerebellar peduncle, may play a key role in cognition 42,43 . In patients with Parkinson's disease, functional connectivity between the vermis and visual association and pre-frontal cortex is weaker than controls and correlates with cognitive performance, even in the absence of cerebellar volume loss or changes in cortical thickness 21 . Although traditionally regarded as unaffected by alpha-synuclein pathology and excluded from the Braak Lewy body pathological staging, recent evidence suggests that cerebellar nuclei and surrounding white matter do accumulate alpha-synuclein aggregates 44 .…”

“…All other PD participants were classified as PD with normal cognition (PD-NC, n=50). A composite cognitive z score (averaged across the 5 individual cognitive domains) was also computed 21 .…”

Editorial: The Cerebellum: From Vascular Disease to Neurodegeneration

“…The classical theories focused on the role of the cerebellum in fine-tuning of muscle control have been widely reconsidered, and new hypotheses have been advanced ( 2 ). These include its role as a sensory acquisition device, beyond motor control and learning, as well as a pivotal role in cognition, with a recognized cerebellar participation in a variety of cognitive functions (ranging from mood control to language, memory, attention, and spatial data management) ( 3 – 5 ), and pathological conditions ( 6 – 13 ).…”