Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
Department of Psychiatry, University of Cambridge, Herschel Smith Building for Brain & Mind Sciences, Cambridge, United Kingdom.
Mov Disord. 2021 Aug;36(8):1879-1888. doi: 10.1002/mds.28564. Epub 2021 May 11.
Parkinson's disease (PD) is associated with cholinergic dysfunction, although the role of M1 and M4 receptors remains unclear.
To investigate spatial covariance patterns of cholinergic muscarinic M /M receptors in PD and their relationship with cognition and motor symptoms.
Some 19 PD and 24 older adult controls underwent I-iodo-quinuclidinyl-benzilate (QNB) (M /M receptor) and Tc-exametazime (perfusion) single-photon emission computed tomography (SPECT) scanning. We implemented voxel principal components analysis, producing a series of images representing patterns of intercorrelated voxels across individuals. Linear regression analyses derived specific M /M spatial covariance patterns associated with PD.
A cholinergic M /M pattern that converged onto key hubs of the default, auditory-visual, salience, and sensorimotor networks fully discriminated PD patients from controls (F = 135.4, P < 0.001). In PD, we derived M /M patterns that correlated with global cognition (r = -0.62, P = 0.008) and motor severity (r = 0.53, P = 0.02). Both patterns emerged with a shared topography implicating the basal forebrain as well as visual, frontal executive, and salience circuits. Further, we found a M /M pattern that predicted global cognitive decline (r = 0.46, P = 0.04) comprising relative decreased binding within default and frontal executive networks.
Cholinergic muscarinic M /M modulation within key brain networks were apparent in PD. Cognition and motor severity were associated with a similar topography, inferring both phenotypes possibly rely on related cholinergic mechanisms. Relative decreased M /M binding within default and frontal executive networks could be an indicator of future cognitive decline. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
帕金森病（PD）与胆碱能功能障碍有关，尽管 M1 和 M4 受体的作用仍不清楚。
研究 PD 中胆碱能毒蕈碱 M/M 受体的空间协变模式及其与认知和运动症状的关系。
19 例 PD 患者和 24 例老年对照者接受 I-碘-喹诺环定（QNB）（M/M 受体）和 Tc-外马托唑胺（灌注）单光子发射计算机断层扫描（SPECT）扫描。我们实施了体素主成分分析，产生了一系列代表个体间相关体素模式的图像。线性回归分析得出了与 PD 相关的特定 M/M 空间协变模式。
一种胆碱能 M/M 模式，汇聚到默认、视听、突显和感觉运动网络的关键枢纽，可完全区分 PD 患者和对照组（F=135.4，P<0.001）。在 PD 中，我们得出了与整体认知（r=-0.62，P=0.008）和运动严重程度（r=0.53，P=0.02）相关的 M/M 模式。这两种模式都具有共同的拓扑结构，涉及基底前脑以及视觉、额叶执行和突显回路。此外，我们发现了一种可以预测整体认知下降的 M/M 模式（r=0.46，P=0.04），包括默认和额叶执行网络内相对减少的结合。
在 PD 中，胆碱能毒蕈碱 M/M 调节在关键脑网络中是明显的。认知和运动严重程度与类似的拓扑结构相关，推断这两种表型可能依赖于相关的胆碱能机制。默认和额叶执行网络内相对减少的 M/M 结合可能是未来认知下降的一个指标。
