Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease
Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease
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DOI：
10.1176/appi.ajp.160.11.2003
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发表时间：
2003-11-01
影响因子：
17.7
通讯作者：
Rogers, S
中科院分区：
文献类型：
--
作者：
Krishnan, KRR;Charles, HC;Rogers, S
目的：作者研究了乙酰胆碱酯酶抑制剂多奈哌齐对阿尔茨海默病神经退行性变的磁共振标记物的影响。方法：在这项随机、双盲、安慰剂对照的试点研究中，67例轻度至中度阿尔茨海默病患者接受了24周的多奈哌齐（5毫克/天的第一个28天和10毫克/天之后）或安慰剂治疗。每隔6周对患者进行重新评估，以测量几个结果指标较基线的变化，包括用磁共振成像测量的右侧、左侧和总海马体积;用质子磁共振波谱测量的N-乙酰天冬氨酸脑浓度;和用阿尔茨海默病评估量表认知子量表评估的认知。在一些中期评估中，多奈哌齐治疗患者的N-乙酰天冬氨酸浓度的平均标准化测量值往往高于安慰剂治疗患者，但这些差异在终点时不显著。在终点，与安慰剂治疗的患者相比，多奈哌齐治疗的患者总海马体积和右侧海马体积的平均减少显著较小，左侧海马体积的平均减少较小，几乎显著。与安慰剂相比，多奈哌齐治疗后第6、12、18和24周阿尔茨海默病评估量表认知子量表评分均有所改善。结论：这些初步结果表明，多奈哌齐可能对阿尔茨海默病有潜在的保护作用。更大，更长期的药物效果的验证性研究是必要的。
Objective: The authors examined the effect of the acetylcholinesterase inhibitor donepezil on magnetic resonance markers of neurodegeneration in Alzheimer's disease.Method: In this randomized, double-blind, placebo-controlled pilot study, 67 patients with mild to moderate Alzheimer's disease received 24 weeks of treatment with donepezil (5 mg/day for the first 28 days and 10 mg/day thereafter) or placebo. Patients were reevaluated at 6-week intervals to measure change from baseline in several outcome measures, including right, left, and total hippocampal volumes, measured with magnetic resonance imaging; brain concentrations of N-acetylaspartate, measured with proton magnetic resonance spectroscopy; and cognition, assessed with the Alzheimer's Disease Assessment Scale cognitive subscale.Results: At some interim assessments, mean normalized measures of N-acetylaspartate concentration tended to be higher in the donepezil-treated patients than in the patients who received placebo, but these differences were not significant at endpoint. At endpoint, the donepezil-treated patients had significantly smaller mean decreases in total and right hippocampal volumes and a smaller, nearly significant mean decrease in left hippocampal volume, compared with the placebo-treated patients. Mean Alzheimer's Disease Assessment Scale cognitive subscale scores were improved after treatment with donepezil, relative to placebo, at weeks 6, 12, 18, and 24.Conclusions: These preliminary results suggest that donepezil may have a potentially protective effect in Alzheimer's disease. Larger, longer-term confirmatory studies of the medication's effects are warranted.