张金枝 刘真真 王丽娟 张潇 李晓佳

摘 要 目的：探讨多奈哌齐单用及与美金刚联用治疗中、重度阿尔茨海默病（AD）的临床疗效和安全性。方法：选取2018年3月至2020年3月于四川省医学科学院·四川省人民医院（东院）就诊的100例中、重度AD患者作为研究对象，采用随机数字表法将其分为对照组和治疗组，各50例。对照组给予多奈哌齐单药治疗（初始剂量为5 mg/d，睡前服用;4周后剂量改为10 mg/d，睡前服用，服药时间共为6个月）。治疗组患者在对照组治疗基础上联用美金刚治疗（初始剂量为5 mg/d，如无不良反应者每周剂量增加5 mg，直至增加至20 mg/d，服药时间共为6个月）。比较两组患者治疗前后蒙特利尔认知评估量表（MoCA）评分、简易智力状态检查量表（MMSE）评分、日常生活能力量表（ADL）评分及治疗有效率和不良反应发生情况。结果：与同组治疗前比较，两组患者治疗后的MoCA、MMSE和ADL评分均显著升高（P<0.05）。治疗后，与对照组比较，治疗组患者MoCA、MMSE、ADL评分和总有效率均显著升高（P<0.05），而不良反应发生率显著降低（P<0.05）。结论：多奈哌齐联合美金刚相较于多奈哌齐单药治疗中、重度AD具有更好的临床疗效，更有助于改善AD患者的神经功能，且安全性较好。

关键词 阿尔茨海默病;多奈哌齐;美金刚;临床疗效;安全性

ABSTRACT   OBJECTIVE： To investigate the clinical efficacy and safety of donepezil monotherapy versus donepezil combined with memoriam in the treatment of Alzheimers disease （AD）. METHODS： Totally 100 patients with moderate and severe AD who received medical care in Sichuan Academy of Medical Sciences & Sichuan Provincial Peoples Hospital （East Hospital） from March 2018 to March 2020 were enrolled as study subjects， and then were divided into control group and treatment group randomly. Control group was given donepezil monotherapy treatment （initial dose of 5 mg/d， before bedtime; after 4 weeks， the dose was changed to 10 mg/d before bedtime; the total medication time was 6 months）. Treatment group was treated with memantine （initial dose was 5 mg/d， the dose of those without adverse reactions was increased by 5 mg until 20 mg/d， for 6 months） on the basis of the control group， with 50 patients in each group. Montreal cognitive assessment scale （MoCA） score， MMSE score， ADL score， treatment response rate and the occurrence of ADR were compared between 2 groups before and after treatment. RESULTS： Compared with same group before treatment， MoCA score， MMSE score and ADL score of the two groups were significantly improved after treatment （P<0.05）. After treatment， compared with control group， MoCA score， MMSE score， ADL score and total response rate in the treatment group were significantly increased （P<0.05）， while the incidence of ADR was decreased significantly （P<0.05）. CONCLUSIONS： Donepezil combined with memantine has better clinical efficacy than donepezil monotherapy in the treatment of moderate and severe AD， and is helpful to improve the neurological function of AD patients， with good safety.

KEYWORDS   Alzheimers disease; Donepezil; Memantine; Clinical efficacy; Safety

阿爾茨海默病（AD）是最常见的神经认知障碍性疾病，据2014年的数据统计，全球约有5 000多万人患有AD[1]。AD患者的护理给社会带来了巨大的负担。据报道，仅2018年全球AD患者的护理费用就达到了1万亿美元[2]。因此，寻找有效的治疗方法是当前临床亟需解决的主要问题之一。在AD的早期阶段，通常使用胆碱酯酶抑制剂（ChEIs），例如多奈哌齐、加兰他敏、艾斯能和利斯明等进行治疗。其中，多奈哌齐是临床上常用的ChEIs，因其具有活性强、选择性高、低剂量起效、毒性小的优势，被广泛应用于中、重度AD的治疗[3]。……