Cholinergic system changes of falls and freezing of gait in Parkinson's disease
Cholinergic system changes of falls and freezing of gait in Parkinson's disease
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DOI：
10.1002/ana.25430
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发表时间：
2019-04-01
影响因子：
11.2
通讯作者：
Mueller, Martijn L. T. M.
中科院分区：
文献类型：
--
作者：
Bohnen, Nicolaas, I;Kanel, Prabesh;Mueller, Martijn L. T. M.
目的姿势不稳和步态困难(PIGDS)是帕金森病(PD)患者的衰弱障碍。过去的乙酰胆碱酯酶正电子发射断层扫描(PET)成像研究表明胆碱能改变是PIGD特征的重要因素。这些研究仅限于纹状体胆碱能突触完整性的量化。囊泡型乙酰胆碱转运体(Vacht)PET配体更适合于评估高结合区。我们研究了局部血管表达与冻结步态(雾)和跌倒之间的关系。方法对94例帕金森病患者进行临床评估和Vacht([F-18]FEOBV)PET检查。结果35例(37.2%)有跌倒史，15例(16%)有雾。单变量感兴趣体积分析显示，与非跌倒组相比，跌倒组丘脑VACHT表达显著降低(p=0.0016)。与非冷冻组相比，冷冻组纹状体(p=0.0012)和边缘皮质(p=0.004)的VACHT表达显著减少。基于全脑体素的FEOBV PET分析补充了这些发现，并显示与跌倒病史相关的更多颗粒状变化，包括右侧视觉丘脑(特别是右侧膝状核[LGN])、右侧尾状核和双侧前额叶区域。冷冻组大鼠双侧纹状体、颞叶和额叶近侧边缘区域的Vacht表达显著减少。解释我们的发现证实并扩展了先前的PET发现，即丘脑胆碱能缺陷与跌倒病史相关，现在强调右视丘脑复合体的变化，包括右LGN。雾化状态与纹状体胆碱能中间神经元和边缘皮质Vacht表达减少有关。这些观察表明，不同的胆碱能系统在帕金森病的跌倒和雾中发生变化。Ann Neurol 2019；85：538-549
Objective Postural instability and gait difficulties (PIGDs) represent debilitating disturbances in Parkinson's disease (PD). Past acetylcholinesterase positron emission tomography (PET) imaging studies implicate cholinergic changes as significant contributors to PIGD features. These studies were limited in quantification of striatal cholinergic synapse integrity. Vesicular acetylcholine transporter (VAChT) PET ligands are better suited for evaluation of high binding areas. We examined associations between regional VAChT expression and freezing of gait (FoG) and falls. Methods Ninety-four PD subjects underwent clinical assessment and VAChT ([F-18]FEOBV) PET. Results Thirty-five subjects (37.2%) reported a history of falls, and 15 (16%) had observed FoG. Univariate volume-of-interest analyses demonstrated significantly reduced thalamic (p = 0.0016) VAChT expression in fallers compared to nonfallers. VAChT expression was significantly reduced in the striatum (p = 0.0012) and limbic archicortex (p = 0.004) in freezers compared to nonfreezers. Whole-brain voxel-based analyses of FEOBV PET complemented these findings and showed more granular changes associated with falling history, including the right visual thalamus (especially the right lateral geniculate nucleus [LGN]), right caudate nucleus, and bilateral prefrontal regions. Freezers had prominent VAChT expression reductions in the bilateral striatum, temporal, and mesiofrontal limbic regions. Interpretation Our findings confirm and extend on previous PET findings of thalamic cholinergic deficits associated with falling history and now emphasize right visual thalamus complex changes, including the right LGN. FoG status is associated with reduced VAChT expression in striatal cholinergic interneurons and the limbic archicortex. These observations suggest different cholinergic systems changes underlying falls and FoG in PD. Ann Neurol 2019;85:538-549