Raskind Murray A, Peskind Elaine R, Truyen Luc, Kershaw Paul, Damaraju ChandrasekharRao Venkata
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and VISN 20 Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle 98108, USA.
Arch Neurol. 2004 Feb;61(2):252-6. doi: 10.1001/archneur.61.2.252.
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.
To report the long-term cognitive effects of galantamine hydrobromide given continuously for 36 months in AD patients.
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.
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.
Patients treated continuously with galantamine for 36 months increased a mean +/- 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.
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.
阿尔茨海默病（AD）会导致数年的渐进性认知和功能衰退。尽管胆碱酯酶抑制剂在为期3至6个月的研究中已证明有效，但对于长期治疗知之甚少。
报告在AD患者中连续36个月给予氢溴酸加兰他敏的长期认知效果。
受试者为194名美国轻至中度AD患者，他们在两项双盲安慰剂对照试验中的任何一项中被随机分配接受连续加兰他敏治疗。受试者随后接受了长达36个月的开放标签连续加兰他敏治疗。
将对认知的影响分析为阿尔茨海默病评估量表11项认知子量表得分相对于研究入组基线的变化。将加兰他敏治疗组受试者的认知衰退与接受12个月安慰剂治疗的临床相似AD患者历史对照样本以及未经治疗患者36个月的数学预测衰退进行比较。将完成整个36个月试验的患者（n = 119）的认知衰退率与在长期开放标签延长期因任何原因退出的患者（n = 75）进行比较。还对36个月完成者进行了反向应答者分析。
连续36个月接受加兰他敏治疗的患者在阿尔茨海默病评估量表11项认知子量表上平均增加了10.2±0.9分——认知衰退比未治疗患者预测的要小得多（约50%）。在36个月前停止加兰他敏治疗的患者在停药前的衰退速度与完成36个月治疗的患者相似。与未治疗患者的预测相比，连续接受加兰他敏治疗长达36个月的患者中近80%似乎显示出认知益处。
连续36个月加兰他敏治疗的认知衰退明显小于轻度至中度痴呆未治疗患者的预测认知衰退。因此，加兰他敏的认知益处似乎至少持续36个月。这些发现表明加兰他敏可减缓AD的临床进展。
