The cognitive benefits of galantamine are sustained for at least 36 months - A long-term extension trial
The cognitive benefits of galantamine are sustained for at least 36 months - A long-term extension trial
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DOI：
10.1001/archneur.61.2.252
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发表时间：
2004-02-01
影响因子：
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通讯作者：
Damaraju, CV
中科院分区：
文献类型：
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作者：
Raskind, MA;Peskind, ER;Damaraju, CV
背景：阿尔茨海默病（AD）会导致多年的认知和功能下降。虽然胆碱酯酶抑制剂已在持续3至6个月的研究中证明了疗效，但对长期治疗知之甚少。目的：报告连续36个月给予加兰他敏对AD患者的长期认知影响。参与者：受试者为194例轻度至中度AD的美国患者，他们被随机分配至2个双盲安慰剂-对照试验。受试者随后接受开放标签连续加兰他敏治疗长达36 months.Main结果测量：对认知的影响进行了分析，作为阿尔茨海默病评估量表11项认知子量表评分从研究招募基线的变化。将加兰他敏治疗受试者的认知功能下降与接受安慰剂治疗12个月的AD患者的临床相似历史对照样本进行比较，并与36个月内未治疗患者的数学预测下降进行比较。将完成整个36个月试验的患者（n= 119）的认知下降率与长期开放标签扩展期间因任何原因退出的患者（n = 75）进行比较。倒置应答者分析也进行了36个月的completers.Results：连续治疗加兰他敏36个月的患者增加了平均+/-SE的10.2+/-0.9点的阿尔茨海默氏病评估量表-11项认知子量表-一个实质上较小的认知下降（约50%）比未治疗患者的预测。在36个月前停止加兰他敏治疗的患者与完成36个月治疗的患者在停药前的下降率相似。几乎80%的患者连续接受加兰他敏长达36个月似乎表现出认知的好处相比，预测为untreated patients.Conclusions：认知下降超过36个月的连续加兰他敏治疗大大低于预测的认知下降未治疗的轻度至中度痴呆患者。因此，加兰他敏的认知益处似乎可持续至少36个月。这些发现表明加兰他敏减缓了AD的临床进展。
Background: Alzheimer disease (AD) causes progressive cognitive and functional decline over years. Although cholinesterase inhibitors have demonstrated efficacy in studies lasting 3 to 6 months, little is known about long-term therapy.Objective: To report the long-term cognitive effects of galantamine hydrobromide given continuously for 36 months in AD patients.Participants: Subjects were 194 US patients with mild to moderate AD who had been randomized to continuous galantamine therapy in either of 2 double-blind placebo-controlled trials. Subjects subsequently received open-label continuous galantamine therapy for up to 36 months.Main Outcome Measures: Effects on cognition were analyzed as change from study enrollment baseline in scores on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale. Cognitive decline in galantamine-treated subjects was compared with that in a clinically similar historical control sample of AD patients who had received placebo for 12 months and with the mathematically predicted decline of untreated patients over 36 months. The rate of cognitive decline of patients who completed the entire 36-month trial (n= 119) was compared with that of patients who withdrew for any reason during the long-term open-label extension (n = 75). An inverted responder analysis was also performed in 36-month completers.Results: Patients treated continuously with galantamine for 36 months increased a meant+/-SE of 10.2+/-0.9 points on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale-a substantially smaller cognitive decline (approximately 50%) than that predicted for untreated patients. Patients discontinuing galantamine therapy before 36 months had declined at a similar rate before discontinuation as those completing 36 months of treatment. Almost 80% of patients who received galantamine continuously for up to 36 months seemed to demonstrate cognitive benefits compared with those predicted for untreated patients.Conclusions: Cognitive decline over 36 months of continuous galantamine treatment was substantially less than the predicted cognitive decline of untreated patients with mild to moderate dementia. Thus, the cognitive benefits of galantamine seemed to be sustained for at least 36 months. These findings suggest that galantamine slows the clinical progression of AD.