Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease?
Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease?
复制标题
DOI：
10.1176/appi.ajp.162.4.676
复制
发表时间：
2005-04-01
影响因子：
17.7
通讯作者：
Mori, E
中科院分区：
文献类型：
--
作者：
Hashimoto, M;Kazui, H;Mori, E
目标：在日本，唯一批准的用于阿尔茨海默病对症治疗的药理学方法是使用胆碱酯酶抑制剂盐酸多奈哌齐。最近的体内和体外研究提出了胆碱酯酶抑制剂可以减缓阿尔茨海默病进展的可能性。本研究的目的是通过使用海马萎缩率作为疾病进展的替代标志物来确定多奈哌齐是否对阿尔茨海默病具有神经保护作用。在一项前瞻性队列研究中，54名接受多奈哌齐治疗的阿尔茨海默病患者和93名从未接受过抗阿尔茨海默病药物的阿尔茨海默病对照患者进行了磁共振成像（MRI）每隔一年两次。通过使用基于MRI的体积技术确定每个受试者海马萎缩的年发生率。治疗组和对照组的背景特征、年龄、性别、病程、教育程度、MRI间隔、载脂蛋白E（APOE）基因型和基线阿尔茨海默病评估量表评分具有可比性。治疗患者海马体积丢失的平均年速率（平均值= 3.82%，SD = 2.84%）显著小于对照组（平均值= 5.04%，SD = 2.54%）。在协方差分析中，这些混杂变量将年龄、性别、病程、教育程度、MRI间隔、APOE基因型和基线阿尔茨海默病评估量表评分作为协变量输入模型，多奈哌齐治疗对海马萎缩的影响仍然显著。多奈哌齐治疗减缓海马萎缩的进展，表明多奈哌齐在阿尔茨海默病中具有神经保护作用。
Objective: The only approved pharmacological approach for the symptomatic treatment of Alzheimer's disease in Japan is the use of a cholinesterase inhibitor, donepezil hydrochloride. Recent in vivo and in vitro studies raise the possibility that cholinesterase inhibitors can slow the progression of Alzheimer's disease. The purpose of the present study was to determine whether donepezil has a neuroprotective effect in Alzheimer's disease by using the rate of hippocampal atrophy as a surrogate marker of disease progression.Method: In a prospective cohort study, 54 patients with Alzheimer's disease who received donepezil treatment and 93 control patients with Alzheimer's disease who never received anti-Alzheimer drugs underwent magnetic resonance imaging (MRI) twice at a 1-year interval. The annual rate of hippocampal atrophy of each subject was determined by using an MRI-based volumetric technique. Background characteristics, age, sex, disease duration, education, MRI interval, apolipoprotein E ( APOE) genotype, and baseline Alzheimer's Disease Assessment Scale score were comparable between the treated and control groups.Results: The mean annual rate of hippocampal volume loss among the treated patients ( mean = 3.82%, SD = 2.84%) was significantly smaller than that among the control patients ( mean = 5.04%, SD = 2.54%). Upon analysis of covariance, where those confounding variables ( age, sex, disease duration, education, MRI interval, APOE genotype, and baseline Alzheimer's Disease Assessment Scale score) were entered into the model as covariates, the effect of donepezil treatment on hippocampal atrophy remained significant.Conclusions: Donepezil treatment slows the progression of hippocampal atrophy, suggesting a neuroprotective effect of donepezil in Alzheimer's disease.