Vitamin E and donepezil for the treatment of mild cognitive impairment
Vitamin E and donepezil for the treatment of mild cognitive impairment
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DOI：
10.1056/nejmoa050151
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发表时间：
2005-06-09
影响因子：
158.5
通讯作者：
Thal, LJ
中科院分区：
文献类型：
--
作者：
Petersen, RC;Thomas, RG;Thal, LJ
背景：轻度认知功能障碍是介于正常衰老和早期阿尔茨海默病之间的一种过渡状态。方法：在一项双盲研究中，我们评估了轻度认知功能障碍的遗忘亚型。受试者被随机分配每天接受2000 IU维生素E，每天10 mg多奈哌齐或安慰剂，为期三年。主要结果是临床上可能或可能的阿尔茨海默氏病;次要结果是认知和function.Results：共769名受试者参加，可能或可能的阿尔茨海默氏病在212。从轻度认知障碍到阿尔茨海默病的总体进展率为每年16%。与安慰剂组相比，维生素E组进展为阿尔茨海默病的概率没有显著差异（风险比，1.02; 95%置信区间，0.74至1.41; P=0.91）或多奈哌齐组（风险比，0.80; 95%置信区间，0.57至1.13; P=0.42）。在6个月的间隔治疗效果的预先规定的分析表明，与安慰剂组相比，多奈哌齐组在研究的前12个月内进展为阿尔茨海默病的可能性降低（P=0.04），这一发现得到了次要结局指标的支持。在携带一个或多个载脂蛋白E（ε）4等位基因的患者中，多奈哌齐的益处在整个三年随访中是明显的。维生素E组和安慰剂组在任何时间点进展为阿尔茨海默病的速率均无显著差异，无论是在所有患者中还是在载脂蛋白E（APOE）4 carriers.CONCLUSIONS：维生素E对轻度认知功能障碍患者无任何益处。虽然多奈哌齐治疗与治疗前12个月内阿尔茨海默病进展率较低相关，但多奈哌齐治疗患者3年后阿尔茨海默病进展率并不比安慰剂治疗患者低。
BACKGROUND:Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease.METHODS:In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function.RESULTS:A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E (epsilon)4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E (epsilon)4 carriers.CONCLUSIONS:Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.