Altered Cerebellar Resting-State Functional Connectivity in Early-Stage Parkinson's Disease Patients With Cognitive Impairment.

Xiaojuan Dan,Jinghong Ma,Julien Doyon,Junyan Sun,Linlin Gao,Yongtao Zhou,Tao Wu,Piu Chan,Yang Hu

doi:10.3389/fneur.2021.678013

Abstract

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear.Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed.Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the “motor” cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups.Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD.

Highlights

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized clinically by classical motor features including bradykinesia, rigidity, tremor, and postural instability
These findings indicate that as assessed through activity at rest, the cerebellar functional connectivity (FC) may be involved in coping with both motor and cognitive demands, shedding additional light on our understanding of the pathophysiology of cognitive deficits in early-stage PD patients
After stratifying patients based on their cognitive status, we found that the “motor” and “cognitive” cerebellar FC changed in PD patients with cognitive impairment, but not in early PD patients with normal cognition

Summary

Introduction

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized clinically by classical motor features including bradykinesia, rigidity, tremor, and postural instability. Using structural and resting-state functional magnetic resonance imaging (rs-fMRI), O’Callaghan et al [20] revealed gray matter loss across the “motor” and “cognitive” cerebellar territories and altered cerebellar functional connectivity (FC) with the cortex in patients with PD compared to normal controls. Whether such alterations in resting-state cerebellar FC are due to the motor deficits or cognitive deficits in PD patients remains unclear, especially in the early-stage of the disease. Whether these changes are due to the cognitive deficits in PD remain unclear

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Results

Conclusion