Regional cerebral cholinergic nerve terminal integrity and cardinal motor features in Parkinson's disease.
Regional cerebral cholinergic nerve terminal integrity and cardinal motor features in Parkinson's disease.
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DOI：
10.1093/braincomms/fcab109
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发表时间：
2021
影响因子：
4.8
通讯作者：
Müller MLTM
中科院分区：
文献类型：
--
作者：
Bohnen NI;Kanel P;Koeppe RA;Sanchez-Catasus CA;Frey KA;Scott P;Constantine GM;Albin RL;Müller MLTM
抗胆碱能药物的临床作用涉及帕金森病中某些主要运动障碍的病理生理学中胆碱能系统的改变。受影响的胆碱能系统缺陷和运动域特异性的地形知之甚少。帕金森病患者（n = 108）进行了临床和运动评估和囊泡乙酰胆碱转运蛋白[18 F]-氟乙氧基苯并维索霉素PET成像。基于感兴趣体积的分析包括详细的丘脑和小脑包裹。在88例患者中，大多数小尺寸包裹的PET采样成功。一个数据驱动的方法，逐步回归使用正向选择方法，被用来确定胆碱能脑区与基数域特定的运动评级。对模型选择的区域进行运动域评分回归，然后对发病年龄、运动疾病持续时间和左旋多巴等效剂量的影响进行混杂因素分析。在与姿势不稳定和步态困难领域评分相关的7个模型衍生区域中，3个在混杂变量分析中保持显著性：内侧膝状体核（标准化β = −0.34，t = −3.78，P = 0.0003），外侧膝状体核（β =-0.32，t =-3.4，P = 0.001）和内嗅皮质（β =-0.23，t =-2.6，P = 0.011）。对非发作性姿势不稳定和步态困难评分的子分析表明，内侧膝状体核、内嗅皮质和苍白球内侧部具有显著影响。在6个震颤域模型选择区域中，两个区域在混杂变量分析中保持显著性：小脑蚓部VIIIb小叶（β = −0.22，t = −2.4，P = 0.021）和壳核（β = −0.23，t = −2.3，P = 0.024）。刚性域的三个模型选择变量均未通过混杂因素分析。远端肢体运动迟缓领域的4个模型选择区域中有2个区域在混杂因素分析中存活：苍白球外侧部（β = 0.36，t = 3.9，P = 0.0097）和中央旁小叶（β = 0.26，t = 2.5，P = 0.013）。强调帕金森病主要运动特征的病理生理学的系统网络概念的效用，我们的结果与基底前脑皮质脑、脚桥-背侧被盖复合体和内侧前庭核胆碱能通路的特定缺陷一致，而黑质纹状体多巴胺能缺陷的背景下，显著促进姿势不稳定、步态困难、震颤和远端肢体运动迟缓是帕金森病的主要运动特征。我们的研究结果表明，显着和不同的后果退化的胆碱能peduncupontine-laterodorphous被盖复合传入苍白球的两个部分。非特异性区域胆碱能神经末梢与硬度评分的相关性可能反映了更复杂的多因素信号传导机制，其中胆碱能通路的贡献较小。Bohnen等人使用互补分析方法研究了帕金森病中主要运动症状的胆碱能PET相关性。轴向运动和震颤评分与不同的和全系统的胆碱能通路显著相关，但远端肢体运动迟缓评分的证据有限。没有发现特异性胆碱能转运蛋白与僵硬评分相关。
Clinical effects of anti-cholinergic drugs implicate cholinergic systems alterations in the pathophysiology of some cardinal motor impairments in Parkinson’s disease. The topography of affected cholinergic systems deficits and motor domain specificity are poorly understood. Parkinson's disease patients (n = 108) underwent clinical and motor assessment and vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol PET imaging. Volumes-of-interest-based analyses included detailed thalamic and cerebellar parcellations. Successful PET sampling for most of the small-sized parcellations was available in 88 patients. A data-driven approach, stepwise regression using the forward selection method, was used to identify cholinergic brain regions associating with cardinal domain-specific motor ratings. Regressions with motor domain scores for model-selected regions followed by confounder analysis for effects of age of onset, duration of motor disease and levodopa equivalent dose were performed. Among 7 model-derived regions associating with postural instability and gait difficulties domain scores three retained significance in confounder variable analysis: medial geniculate nucleus (standardized β = −0.34, t = −3.78, P = 0.0003), lateral geniculate nucleus (β = −0.32, t = −3.4, P = 0.001) and entorhinal cortex (β = −0.23, t = −2.6, P = 0.011). A sub-analysis of non-episodic postural instability and gait difficulties scores demonstrated significant effects of the medial geniculate nucleus, entorhinal cortex and globus pallidus pars interna. Among 6 tremor domain model-selected regions two regions retained significance in confounder variable analysis: cerebellar vermis section of lobule VIIIb (β = −0.22, t = −2.4, P = 0.021) and the putamen (β = −0.23, t = −2.3, P = 0.024). None of the three model-selected variables for the rigidity domain survived confounder analysis. Two out of the four model-selected regions for the distal limb bradykinesia domain survived confounder analysis: globus pallidus pars externa (β = 0.36, t = 3.9, P = 0.0097) and the paracentral lobule (β = 0.26, t = 2.5, P = 0.013). Emphasizing the utility of a systems-network conception of the pathophysiology of Parkinson's disease cardinal motor features, our results are consistent with specific deficits in basal forebrain corticopetal, peduncupontine-laterodorsal tegmental complex, and medial vestibular nucleus cholinergic pathways, against the background of nigrostriatal dopaminergic deficits, contributing significantly to postural instability, gait difficulties, tremor and distal limb bradykinesia cardinal motor features of Parkinson’s disease. Our results suggest significant and distinct consequences of degeneration of cholinergic peduncupontine-laterodorsal tegmental complex afferents to both segments of the globus pallidus. Non-specific regional cholinergic nerve terminal associations with rigidity scores likely reflect more complex multifactorial signalling mechanisms with smaller contributions from cholinergic pathways. Bohnen et al. investigated cholinergic PET correlates of cardinal motor symptoms in Parkinson's disease using complementary analysis approaches. Axial motor and tremor scores significantly associated with different and system-wide cholinergic pathways but evidence for distal limb bradykinesia scores was limited. No specific cholinergic transporter associations were found for rigidity scores.
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DOI：
10.1038/npjparkd.2016.25
发表时间：
2016
期刊：
NPJ Parkinson's disease
影响因子：
--
作者：
Caligiore D;Helmich RC;Hallett M;Moustafa AA;Timmermann L;Toni I;Baldassarre G
通讯作者：
Baldassarre G
帕金森病抗胆碱能负担与不良健康结果之间的关联。
影响因子：
3.7
作者：
Crispo JA;Willis AW;Thibault DP;Fortin Y;Hays HD;McNair DS;Bjerre LM;Kohen DE;Perez-Lloret S;Mattison DR;Krewski D
通讯作者：
Krewski D
影响因子：
3.1
作者：
Best, Christoph;Lange, Elena;Dieterich, Marianne
通讯作者：
Dieterich, Marianne
影响因子：
11.2
作者：
Bohnen, Nicolaas, I;Kanel, Prabesh;Mueller, Martijn L. T. M.
通讯作者：
Mueller, Martijn L. T. M.
影响因子：
9.2
作者：
Aristieta, Asier;Barresi, Massimo;Mallet, Nicolas P.
通讯作者：
Mallet, Nicolas P.