Gallarda Th, Lôo H
Hôpital Sainte-Anne, 7, rue Cabanis, 75674 Paris cedex 14.
Encephale. 2004 Jan-Feb;30(1):69-79. doi: 10.1016/s0013-7006(04)95418-8.
Alzheimer's disease has definitively emerged from its ghetto and has been identified as a (priority) public health concern in view of the increasing age of the population. Considerable advances have been made in this disease over the last 15 Years, with progress in the following fields: knowledge of the underlying aetiopathogenetic, genetic and biochemical mechanisms; semiological, clinical and paraclinical approaches; creation of early diagnostic centres and multidisciplinary care networks; therapy available to patients or currently under development. The four existing acetylcholinesterase inhibitors having confirmed symptomatic action in patients with mild to moderate Alzheimer's disease have now been joined by memantine (Ebixa), a non-competitive agonist of N-methyl-D-aspartate (NMDA) receptors. One pathogenic mechanism of Alzheimer's disease appears to be hyperactivity of the glutaminergic neurons. Various preclinical studies have shown that memantine (Ebixa) inhibits glutaminergic hyperactivity in Alzheimer's disease through modulation of NMDA receptors. Since the early 1990s, several controlled clinical trials in patients with moderate to severe Alzheimer's disease (3<MMSE< or =14) have demonstrated the efficacy of memantine on cognitive criteria (cognitive evaluation of severe dementia) (Severe Impairment Battery--SIB), functional criteria (Functional Assessment Stage--FAST) and global clinical criteria (Clinician's Interview-Based Impression of Change--CIBIC-Plus). The data from these studies together with clinical experience of memantine in Germany since 1982 confirm the safety of use and good tolerability profile of this medication at the recommended dosages (10 to 30 mg/day). Treatment with memantine reduces the global costs of the disease by lightening the burden on helpers and delaying institutionalisation of patients. These different studies have resulted in approval of memantine in this particular indication by the European Medicines Agency. The efficacy of memantine in mild to moderate Alzheimer's disease is currently being assessed. The preliminary results also appear to militate in favour of the efficacy of the drug in certain forms of vascular dementia. Finally, the good safety profile of combined use of this drug with antiacetylcholinesterases opens up a realistic perspective of bitherapy in Alzheimer's disease.
鉴于人口老龄化加剧，阿尔茨海默病已彻底走出其“小众范畴”，并被认定为一项（重点）公共卫生问题。在过去15年里，针对这种疾病已取得了相当大的进展，在以下领域取得了进步：对潜在病因发病机制、遗传和生化机制的认识；症状学、临床和辅助临床方法；早期诊断中心和多学科护理网络的建立；可供患者使用或目前正在研发的治疗方法。四种现有的乙酰胆碱酯酶抑制剂已被证实对轻度至中度阿尔茨海默病患者有症状缓解作用，现在又有了美金刚（易倍申），一种N-甲基-D-天冬氨酸（NMDA）受体的非竞争性激动剂。阿尔茨海默病的一种致病机制似乎是谷氨酸能神经元的活动亢进。多项临床前研究表明，美金刚（易倍申）通过调节NMDA受体来抑制阿尔茨海默病中的谷氨酸能亢进。自20世纪90年代初以来，多项针对中度至重度阿尔茨海默病患者（3＜简易精神状态检查表＜或 =14）的对照临床试验证明了美金刚在认知标准（严重痴呆的认知评估）（严重损害量表——SIB）、功能标准（功能评估阶段——FAST）和整体临床标准（基于临床医生访谈的变化印象——CIBIC Plus）方面的疗效。这些研究的数据以及自1982年以来美金刚在德国的临床经验证实了该药物在推荐剂量（10至30毫克/天）下使用的安全性和良好的耐受性。美金刚治疗通过减轻护理人员的负担和推迟患者入住机构护理，降低了该疾病的总体成本。这些不同的研究已使美金刚在这一特定适应症上获得了欧洲药品管理局的批准。目前正在评估美金刚在轻度至中度阿尔茨海默病中的疗效。初步结果似乎也有利于该药物在某些形式的血管性痴呆中的疗效。最后，该药物与抗乙酰胆碱酯酶药物联合使用的良好安全性概况为阿尔茨海默病的联合治疗开辟了一个现实的前景。
