Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Neuropsychiatr Dis Treat. 2011;7:565-76. doi: 10.2147/NDT.S24196. Epub 2011 Sep 30.
In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.
Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog), functional rating (Instrumental Activities of Daily Living Scale [IADL]), and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups.
After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ɛ4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46%) received higher doses of galantamine compared with dropouts.
AD patients who received long-term galantamine treatment were cognitively and globally stabilized. Subgroup response analysis identified a better short-term response in older patients with lower cognitive and functional abilities at baseline, a faster pretreatment progression rate, and a lower incidence of the APOE ɛ4 allele. The galantamine dose was higher in the population of completers.
在缺乏阿尔茨海默病（AD）胆碱酯酶抑制剂长期安慰剂对照研究的情况下，对开放标签试验结果的分析变得至关重要。本研究旨在探讨加兰他敏治疗 3 年的效果，以及对治疗的反应和依从性亚组。
280 例临床诊断为 AD 的患者纳入前瞻性、开放标签、多中心瑞典阿尔茨海默病治疗研究，并接受加兰他敏治疗。疗效测量包括认知测试，即简易精神状态检查（MMSE）和阿尔茨海默病评估量表认知子量表（ADAS-cog）、功能评定（日常生活活动量表[IADL]）和总体评定。评估在治疗前和治疗后每 6 个月进行，为期 3 年。使用 K 均值聚类分析来识别反应亚组。
治疗 3 年后，MMSE 从基线的平均变化为 2.6 分，ADAS-cog 评分变化为 5.6 分。总体而言，一半的患者在两年内改善或保持不变。聚类分析确定了两个反应亚组。亚组 1 包括基线时 ADAS-cog 和 IADL 评分较低的患者。尽管亚组 1 的患者年龄较大、受教育程度较低，但与亚组 2 的患者相比，他们在 6 个月时的反应更好。亚组 2 包括基线时 ADAS-cog 和 IADL 评分较高的患者。亚组 2 的患者 APOE ε4 等位基因频率较高，预处理进展率较慢，且比亚组 1 的患者在研究中停留时间更长。3 年完成治疗者（n=129，46%）接受的加兰他敏剂量高于脱落者。
接受长期加兰他敏治疗的 AD 患者认知和总体上稳定。亚组反应分析表明，基线时认知和功能能力较低、预处理进展较快、APOE ε4 等位基因频率较低的老年患者短期反应更好。完成治疗者（n=129，46%）的加兰他敏剂量较高。
