A DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TACRINE FOR ALZHEIMERS-DISEASE
A DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TACRINE FOR ALZHEIMERS-DISEASE
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DOI：
10.1056/nejm199210293271801
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发表时间：
1992-10-29
影响因子：
158.5
通讯作者：
DOODY, RS
中科院分区：
文献类型：
--
作者：
DAVIS, KL;THAL, LJ;DOODY, RS
背景在阿尔茨海默病中，大脑中胆碱能神经元的功能显著下降。然而，用胆碱酯酶抑制剂治疗的研究产生了相互矛盾的结果。我们进行了一项多中心试验，以评估胆碱酯酶抑制剂他克林（1，2，3，4-四氢-9-吖啶胺单盐酸盐一水合物）是否可以改善阿尔茨海默病患者的认知能力。方法。在632名符合条件的可能患有阿尔茨海默病的患者中，215名在初步交叉阶段接受他克林以确定反应性和最佳剂量时有所改善。在为期6周的双盲试验中，215名患者被随机分配接受安慰剂或最佳剂量的他克林（10或20 mg，每天4次）。疗效的主要指标为阿尔茨海默病评估量表的认知子量表和临床总体印象变化量表;次要指标包括简易精神状态检查和日常生活活动能力评估。在为期六周的试验结束时，接受他克林治疗的患者的平均调整认知子量表得分为30.3（阿尔茨海默病评估量表），而接受安慰剂治疗的患者为32.7。这表明他克林组的认知能力下降较小（2.4分）（P
Background. In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease.Methods. Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living.Results. At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P