Giacobini E
University Hospitals of Geneva, Department of Geriatrics, University of Geneva, Medical School, Thonex, Switzerland.
Neurochem Res. 2000 Oct;25(9-10):1185-90. doi: 10.1023/a:1007679709322.
During the last decade, a systematic effort to develop a pharmacological treatment for Alzheimer disease (AD) has resulted into three drugs being registered for the first time in USA and Europe for this specific indication. All three are cholinesterase inhibitors (ChEI). The major therapeutic effect of ChEI on AD patients is to maintain cognitive function at a constant level during a 6 months to one year period of treatment as compared to placebo. Additional drug effects might be slowing cognitive deterioration and improving behavioral and daily living conditions. Comparison of clinical effects of 6 ChEI demonstrates a rather similar magnitude of improvement in cognitive measures. For some drugs. this may represent an upper limit while for other it may still be possible to increase further the benefit. In order to maximize and prolong positive drug effects it is important to start early and adjust dosage during the treatment. Recent studies show that in many patients the stabilization effect produced by ChEI can be prolonged for as long as a 24 month period. In order to explain the stabilizing effect of ChEI, a mechanism other than AChE inhibition, based on beta-amyloid metabolism, is postulated.
在过去十年中，为开发治疗阿尔茨海默病（AD）的药物疗法而进行的系统努力，已促成三种药物首次在美国和欧洲获批用于这一特定适应症。这三种药物均为胆碱酯酶抑制剂（ChEI）。与安慰剂相比，ChEI对AD患者的主要治疗效果是在6个月至1年的治疗期内将认知功能维持在恒定水平。其他药物作用可能包括减缓认知衰退以及改善行为和日常生活状况。对6种ChEI临床效果的比较表明，认知指标的改善程度相当相似。对于某些药物而言，这可能代表了上限，而对于其他药物，可能仍有进一步提高疗效的空间。为了最大化并延长药物的积极作用，在治疗早期开始并调整剂量很重要。最近的研究表明，在许多患者中，ChEI产生的稳定作用可以延长至24个月。为了解释ChEI的稳定作用，人们假定了一种基于β-淀粉样蛋白代谢、不同于乙酰胆碱酯酶抑制作用的机制。
