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阿尔茨海默病的治疗策略,重点关注早期药物干预。

Treatment strategies in Alzheimer's disease with a focus on early pharmacological interventions.

作者信息

Marksteiner Josef, Schmidt Reinhold

机构信息

Department of Psychiatry, Medical University Innsbruck, Innsbruck, Austria.

出版信息

Drugs Aging. 2004;21(7):415-26. doi: 10.2165/00002512-200421070-00001.

Abstract

Complex interactive effects of genetic predisposition, neurochemical changes and disease comorbidity have been elucidated in the genesis of dementia syndromes. Alzheimer's disease is the most prevalent type of dementia in developed Western countries. In Alzheimer's disease, pharmacological treatment aims at symptomatic relief, disease modification or disease prevention. Cholinesterase inhibitors are established for the treatment of mild-to-moderate Alzheimer's disease. In Europe and the US, memantine is approved for the treatment of moderate-to-severe Alzheimer's disease. To date, there are no drugs with a disease modifying action that have proven efficacy in randomised, double-blind, placebo-controlled clinical trials. In patients not fulfilling the diagnostic criteria for early Alzheimer's disease, e.g. mild cognitive impairment, the efficacy of several drugs, mainly cholinesterase inhibitors, is currently tested in prospective studies by determining the conversion rate to Alzheimer's disease. However, prevention and disease-modifying strategies raise ethical questions because interventions are focused on non-diseased elderly at risk, which means that emphasis should be not only on efficacy but also on long-term safety. No disease-modifying strategy can presently be offered to patients; however, given the pace of recent research there is optimism that slowing progression of Alzheimer's disease will soon be possible.

摘要

遗传易感性、神经化学变化和疾病共病的复杂交互作用已在痴呆综合征的发病机制中得到阐明。阿尔茨海默病是西方发达国家最常见的痴呆类型。在阿尔茨海默病中,药物治疗旨在缓解症状、改变疾病进程或预防疾病。胆碱酯酶抑制剂已被确立用于治疗轻至中度阿尔茨海默病。在欧洲和美国,美金刚被批准用于治疗中至重度阿尔茨海默病。迄今为止,尚无在随机、双盲、安慰剂对照临床试验中被证明有效的具有疾病修饰作用的药物。在未达到早期阿尔茨海默病诊断标准的患者中,如轻度认知障碍患者,目前正在前瞻性研究中通过测定向阿尔茨海默病的转化率来测试几种药物(主要是胆碱酯酶抑制剂)的疗效。然而,预防和疾病修饰策略引发了伦理问题,因为干预措施针对的是有风险的未患病老年人,这意味着不仅应关注疗效,还应关注长期安全性。目前无法为患者提供疾病修饰策略;然而,鉴于近期研究的速度,人们乐观地认为不久将有可能减缓阿尔茨海默病的进展。

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