Striatal and Cortical β-Amyloidopathy and Cognition in Parkinson's Disease.
Striatal and Cortical β-Amyloidopathy and Cognition in Parkinson's Disease.
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DOI：
10.1002/mds.26369
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Bohnen NI
中科院分区：
文献类型：
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作者：
Shah N;Frey KA;Müller ML;Petrou M;Kotagal V;Koeppe RA;Scott PJ;Albin RL;Bohnen NI
虽然大多数关于帕金森病（PD）中β-淀粉样斑块沉积的认知研究集中在皮层斑块沉积，但最近的尸检研究指出纹状体β-淀粉样斑块沉积的重要作用。探讨纹状体和皮层β-淀粉样变性对帕金森病患者认知功能障碍的影响。PD患者62例，年龄68.9±6.4岁，Hoehn和Yahr分期2.7±0.5分，蒙特利尔认知评估评分25.2±3.0分，行[11C]匹兹堡化合物B β-淀粉样蛋白成像，[11C]二氢四苯那嗪单胺能成像，[11C]甲基-4-哌啶酰丙酸乙酰胆碱酯酶脑正电子发射断层成像及神经心理评估。[11C]匹兹堡化合物B β-淀粉样蛋白数据来自年轻至中年健康受试者，用于确定患者中升高的[11C]匹兹堡化合物B结合。在这组以非痴呆为主的PD患者中，皮层和纹状体β-淀粉样蛋白沉积升高的比例分别为38%和16%。在皮层β-淀粉样蛋白沉积增加的所有受试者中，有一半出现纹状体β-淀粉样蛋白沉积增加。相反，纹状体β-淀粉样蛋白沉积增加并不发生在皮质β-淀粉样蛋白沉积增加的情况下。采用整体复合认知z评分作为结局参数的协方差分析显示，在调整了皮质胆碱能活性（F=5.67， P=0.02）、尾状核单胺能结合、病程和年龄（总模型：F=3.55， P=0.0048）的协变量效应后，纹状体和皮质β-淀粉样变性合并存在显著的回归效应（F=4.18， P=0.02）。事后分析显示，纹状体和皮层β-淀粉样变性合并组的认知z评分明显低于单纯皮层β-淀粉样变性和非β-淀粉样变性亚组。纹状体和皮层β-淀粉样变性的联合存在比单独的皮层β-淀粉样变性与更大的认知障碍相关。
Although most prior cognitive studies of β-amyloidopathy in Parkinson disease (PD) focused on cortical plaque deposition, recent post-mortem studies point to an important role of striatal β-amyloid plaque deposition. To investigate the relative contributions of striatal and cortical β-amyloidopathy to cognitive impairment in PD. Patients with PD (n=62; age 68.9±6.4 years, Hoehn and Yahr stage 2.7±0.5, Montreal Cognitive Assessment score 25.2±3.0) underwent [11C]Pittsburgh compound B β-amyloid, [11C]dihydrotetrabenazine monoaminergic and [11C]methyl-4-piperidinyl propionate acetylcholinesterase brain positron emission tomography imaging and neuropsychological assessment. [11C]Pittsburgh compound B β-amyloid data from young to middle-aged healthy subjects were used to define elevated [11C]Pittsburgh compound B binding in the patients. Elevated cortical and striatal β-amyloid deposition were present in 38% and 16%, respectively, of this predominantly non-demented cohort of patients with PD. Increased striatal β-amyloid deposition occurred in half of all subjects with increased cortical β-amyloid deposition. In contrast, increased striatal β-amyloid deposition did not occur in the absence of increased cortical β-amyloid deposition. Analysis of covariance using global composite cognitive z-scores as the outcome parameter showed significant regressor effects for combined striatal and cortical β-amyloidopathy (F=4.18, P=0.02) after adjusting for covariate effects of cortical cholinergic activity (F=5.67, P=0.02), caudate nucleus monoaminergic binding, duration of disease and age (total model: F=3.55, P=0.0048). Post-hoc analysis showed significantly lower cognitive z-score for combined striatal and cortical β-amyloidopathy compared to cortical-only β-amyloidopathy and non-β-amyloidopathy subgroups. The combined presence of striatal and cortical β-amyloidopathy is associated with greater cognitive impairment than cortical β-amyloidopathy alone in PD.