Memantine in moderate-to-severe Alzheimer's disease
Memantine in moderate-to-severe Alzheimer's disease
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DOI：
10.1056/nejmoa013128
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发表时间：
2003-04-03
影响因子：
158.5
通讯作者：
Mobius, HJ
中科院分区：
文献类型：
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作者：
Reisberg, B;Doody, R;Mobius, HJ
背景：谷氨酸对N-甲基-D-天冬氨酸（NMDA）受体的过度刺激与神经退行性疾病有关。因此，我们研究了美金刚，NMDA拮抗剂，用于治疗阿尔茨海默病。方法：中度至重度阿尔茨海默病患者被随机分配到接受安慰剂或20毫克的美金刚，每天28周。主要疗效变量为基于临床医生访谈的变化印象加护理人员输入（CIBIC-Plus）和针对重度痴呆修改的阿尔茨海默病合作研究日常生活活动量表（ADCS-ADLsev）。次要疗效终点包括严重损害成套测验和其他认知、功能和行为指标。评估基线和终点之间的治疗差异。通过使用最近的既往观察值（末次观察值结转）插补缺失观察值。结果也进行了分析，只有观察值包括在内，没有取代缺失值（重复病例分析）。结果：252例患者（67%的女性，平均年龄76岁）从32个美国中心入组。其中，181人（72%）完成了研究，并在第28周进行了评估。71名患者提前停止治疗（42名服用安慰剂，29名服用美金刚）。根据CIBIC-Plus（P=0.06，末次观察值结转，观察病例P=0.03）、ADCS-ADL sev（P= 0.02，末次观察值结转，观察病例P=0.003）和严重损害成套测验（P
BACKGROUND:Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease.METHODS:Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis).RESULTS:Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P