帕金森病认知衰退中大脑全局活动与脑脊液流动的解耦。

Decoupling of Global Brain Activity and Cerebrospinal Fluid Flow in Parkinson's Disease Cognitive Decline.

机构信息

Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.

Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, USA.

出版信息

Mov Disord. 2021 Sep;36(9):2066-2076. doi: 10.1002/mds.28643. Epub 2021 May 17.

DOI:10.1002/mds.28643

PMID:33998068

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8453044/

Abstract

BACKGROUND

Deposition and spreading of misfolded proteins (α-synuclein and tau) have been linked to Parkinson's disease cognitive dysfunction. The glymphatic system may play an important role in the clearance of these toxic proteins via cerebrospinal fluid (CSF) flow through perivascular and interstitial spaces. Recent studies discovered that sleep-dependent global brain activity is coupled to CSF flow, which may reflect glymphatic function.

OBJECTIVE

The objective of this current study was to determine if the decoupling of brain activity-CSF flow is linked to Parkinson's disease cognitive dysfunction.

METHODS

Functional and structural MRI data, clinical motor (Unified Parkinson's Disease Rating Scale), and cognitive (Montreal Cognitive Assessment [MoCA]) scores were collected from 60 Parkinson's disease and 58 control subjects. Parkinson's disease patients were subgrouped into those with mild cognitive impairment (MoCA < 26), n = 31, and those without mild cognitive impairment (MoCA ≥ 26), n = 29. The coupling strength between the resting-state global blood-oxygen-level-dependent signal and associated CSF flow was quantified, compared among groups, and associated with clinical and structural measurements.

RESULTS

Global blood-oxygen-level-dependent signal-CSF coupling decreased significantly (P < 0.006) in Parkinson's disease patients showing mild cognitive impairment, compared with those without mild cognitive impairment and controls. Reduced global blood-oxygen-level-dependent signal-CSF coupling was associated with decreased MoCA scores present in Parkinson's disease patients (P = 0.005) but not in controls (P = 0.65). Weaker global blood-oxygen-level-dependent signal-CSF coupling in Parkinson's disease patients also was associated with a thinner right entorhinal cortex (Spearman's correlation, -0.36; P = 0.012), an early structural change often seen in Alzheimer's disease.

CONCLUSIONS

摘要

背景

错误折叠的蛋白质（α-突触核蛋白和 tau）的沉积和扩散与帕金森病认知功能障碍有关。通过脑脊髓液（CSF）流经血管周围和细胞间隙，神经胶细系统可能在清除这些毒性蛋白方面发挥重要作用。最近的研究发现，睡眠依赖的全脑活动与 CSF 流动相关，这可能反映了神经胶细系统的功能。

目的

本研究旨在确定大脑活动与 CSF 流动的解耦是否与帕金森病认知功能障碍有关。

方法

从 60 名帕金森病患者和 58 名对照组中收集功能和结构 MRI 数据、临床运动（统一帕金森病评定量表）和认知（蒙特利尔认知评估 [MoCA]）评分。将帕金森病患者分为有轻度认知障碍（MoCA<26）的患者（n=31）和没有轻度认知障碍的患者（MoCA≥26）（n=29）。量化了静息状态全局血氧水平依赖信号与相关 CSF 流动之间的耦合强度，比较了各组之间的耦合强度，并与临床和结构测量相关。

结果

与无轻度认知障碍和对照组的患者相比，有轻度认知障碍的帕金森病患者的全局血氧水平依赖信号-CSF 耦合明显降低（P<0.006）。在帕金森病患者中，较弱的全局血氧水平依赖信号-CSF 耦合与 MoCA 评分降低有关（P=0.005），但在对照组中无相关性（P=0.65）。帕金森病患者的全局血氧水平依赖信号-CSF 耦合减弱也与右侧内嗅皮层变薄相关（Spearman 相关性，-0.36；P=0.012），这是阿尔茨海默病中常见的早期结构变化。