Cholinergic Deficit and Response to Donepezil Therapy in Parkinson's Disease with Dementia
Cholinergic Deficit and Response to Donepezil Therapy in Parkinson's Disease with Dementia
复制标题
DOI：
10.1159/000338774
复制
发表时间：
2012-01-01
影响因子：
2.4
通讯作者：
Mori, Etsuro
中科院分区：
文献类型：
--
作者：
Hiraoka, Kotaro;Okamura, Nobuyuki;Mori, Etsuro
背景：尽管乙酰胆碱酯酶抑制剂多奈哌齐已被证明能有效改善帕金森病合并痴呆(PDD)患者的认知功能障碍，但患者对多奈哌齐治疗的反应各不相同。[5-C-11-甲氧基]多奈哌齐是多奈哌齐的放射性标记形式，是正电子发射断层扫描(PET)的配基，可用于定量分析多奈哌齐与乙酰胆碱酯酶的结合以及胆碱能成像。目的：探讨PDD患者脑胆碱能系统的改变及其与多奈哌齐治疗反应的关系。方法：对12例PDD患者和13例正常对照组进行[5-C-11-甲氧基]多奈哌齐-PET显像。对于PDD患者，在[5-C-11-甲氧基]多奈哌齐-PET显像后开始每日给药，持续3个月。结果：PDD组大脑皮层平均总分布体积较正常对照组减少22.7%。PDD患者的平均总分布体积与多奈哌齐治疗3个月后视功能的改善显著相关。结论：多奈哌齐治疗对乙酰胆碱酯酶下降较少的患者更有效，至少在特定认知领域是有效的。版权所有(C)2012 S.Karger AG，巴塞尔
Background: Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-C-11-methoxy] donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging. Objectives: To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy. Methods: Twelve patients with PDD and 13 normal control subjects underwent [5-C-11-methoxy] donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-C-11-methoxy] donepezil-PET imaging and continued for 3 months. Results: In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy. Conclusion: The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain. Copyright (C) 2012 S. Karger AG, Basel