Giacobini E
University Hospitals of Geneva, Department of Geriatrics, University of Geneva Medical School, Thonex, Switzerland.
CNS Drugs. 2001;15(2):85-91. doi: 10.2165/00023210-200115020-00001.
During the last decade, a systematic effort to develop a pharmacological treatment for Alzheimer disease (AD) has resulted in drugs being registered for the first time in the US and Europe for this specific indication. The 3 agents registered are cholinesterase inhibitors (ChEIs). The major therapeutic effect of ChEIs in patients with AD is the maintenance of cognitive function, as compared with placebo, during a 6-month to 1-year period of treatment. Additional drug effects that may occur are the slowing of cognitive deterioration and improvement of behaviour and daily living activities. Comparison of clinical effects of 6 ChEIs demonstrates a rather similar magnitude of improvement in cognitive outcome measures. For some drugs, this level may represent an upper limit, while for others it may be possible to increase the benefit further. In order to maximise and prolong positive drug effects it is important to start treatment early and adjust the dosage during treatment. Recent studies that used this administration strategy have shown that in many patients, the stabilisation effect produced by ChEIs can be prolonged for as long as 36 months. This long-lasting effect suggests mechanisms of action other than symptomatic ones. In this article, the effects of ChEIs on beta-amyloid metabolism are postulated to explain the stabilising (i.e. disease-modifying) effects of the drugs. Evidence for such a mechanism is available at the experimental but not yet at the clinical level.
在过去十年中，为开发阿尔茨海默病（AD）的药物治疗方法而进行的系统性努力，已促使药物首次在美国和欧洲获批用于这一特定适应症。获批的3种药物为胆碱酯酶抑制剂（ChEIs）。与安慰剂相比，ChEIs对AD患者的主要治疗效果是在6个月至1年的治疗期间维持认知功能。可能出现的其他药物作用包括减缓认知衰退以及改善行为和日常生活活动。对6种ChEIs临床效果的比较表明，认知结果测量指标的改善程度相当相似。对于某些药物，这一水平可能代表上限，而对于其他药物，可能有可能进一步提高疗效。为了最大化并延长药物的积极作用，尽早开始治疗并在治疗期间调整剂量很重要。最近采用这种给药策略的研究表明，在许多患者中，ChEIs产生的稳定作用可持续长达36个月。这种持久作用提示了除对症作用之外的作用机制。在本文中，假定ChEIs对β-淀粉样蛋白代谢的作用可解释这些药物的稳定（即疾病修饰）作用。这种机制的证据在实验层面有，但在临床层面尚无。
