Laake K, Oeksengaard A R
Department of Geriatric Medicine, Ullevaal Hospital, Kirkevn. 166, Oslo, Norway.
Cochrane Database Syst Rev. 2002;2002(2):CD003153. doi: 10.1002/14651858.CD003153.
Evidence supports a role for the NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses.
To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer*.
Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.
Two larger and two smaller randomized controlled trials were identified. The clinical global impression scale was used in all studies and was a primary outcome measure.
It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months.
REVIEWER'S CONCLUSIONS: The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
有证据支持N-甲基-D-天冬氨酸（NMDA）受体在学习和记忆中发挥作用。抗生素D-环丝氨酸可以对其进行调节，从而增强兴奋性递质谷氨酸的作用。一项针对用东莨菪碱预处理以模拟阿尔茨海默病的健康受试者的研究显示，低剂量的D-环丝氨酸有积极效果。
评估D-环丝氨酸对阿尔茨海默病患者的疗效和安全性。
通过2001年6月14日检索Cochrane痴呆与认知改善小组专业注册库，使用检索词：环丝氨酸、D-环丝氨酸、阿尔茨海默*，来确定试验。
比较D-环丝氨酸与对照治疗的随机、双盲且无混杂因素的试验。
确定了两项较大规模和两项较小规模的随机对照试验。所有研究均使用临床总体印象量表，这是主要结局指标。
无法提取两项交叉研究第一阶段的结果，因此荟萃分析基于两项为期6个月的平行组研究。对于任何剂量，通过临床总体印象评估，在6个月时显示改善的人数方面，没有迹象表明D-环丝氨酸有积极效果。在6个月治疗结束前，与D-环丝氨酸相比，30毫克/天（比值比2.94，95%可信区间1.52，5.70）和100毫克/天（比值比3.23，95%可信区间1.67，6.25）剂量水平下，因任何原因退出的人数明显有利于安慰剂组（退出人数更少）。在6个月时，治疗组（2、10、30、100或200毫克/天）和安慰剂组因不良事件导致的退出人数没有显著差异。
在有足够统计学效力以检测出有临床意义效果的对照临床试验中，D-环丝氨酸对认知结局缺乏积极效果，这意味着D-环丝氨酸在阿尔茨海默病患者的治疗中没有立足之地。
