Erkinjuntti Timo, Kurz Alexander, Gauthier Serge, Bullock Roger, Lilienfeld Sean, Damaraju ChandrasekharRao Venkata
Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland.
Lancet. 2002 Apr 13;359(9314):1283-90. doi: 10.1016/S0140-6736(02)08267-3.
Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer's disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer's disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer's disease combined with cerebrovascular disease.
Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician's interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward.
Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated.
Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.
血管性痴呆是第二常见的痴呆形式，血管因素在许多阿尔茨海默病患者的痴呆发展过程中起作用。加兰他敏通过抑制乙酰胆碱酯酶和调节烟碱样受体来增强乙酰胆碱反应。它已在阿尔茨海默病患者中显示出广泛、持续的益处。我们研究了加兰他敏对诊断为可能的血管性痴呆或阿尔茨海默病合并脑血管疾病患者的影响。
在一项多中心、双盲、为期6个月的试验中，符合条件的患者被随机分配接受24毫克/天的加兰他敏（n = 396）或安慰剂（n = 196）。主要终点是认知（阿尔茨海默病评估量表，认知分量表[ADAS-cog]）和整体功能（基于临床医生访谈的变化印象加照顾者意见[CIBIC-plus]）。次要终点包括对日常生活活动和行为症状的评估。对患者进行不良事件监测。分析基于观察到的病例或末次观察向前结转。
加兰他敏在ADAS-cog方面显示出比安慰剂更高的疗效（加兰他敏变化-1.7[标准误0.4]，而安慰剂为1.0[0.5]；治疗效果为2.7分；p<0.0001），在CIBIC-plus方面也是如此（213例[74%]患者保持稳定或改善，而安慰剂组为95例[59%]，p = 0.0001）。与安慰剂相比，日常生活活动和行为症状也有显著改善（分别为p = 0.002和p = 0.016）。加兰他敏耐受性良好。
加兰他敏在这组痴呆患者的认知和非认知能力的所有关键领域均显示出治疗效果。
