Prins Niels D, van der Flier Wiesje A, Knol Dirk L, Fox Nick C, Brashear H Robert, Nye Jeffrey S, Barkhof Frederik, Scheltens Philip
Alzheimer Centre, Department of Neurology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, the Netherlands ; Alzheimer Research Center, Gebouw Cronenburg, Cronenburg 75, 1081 GM Amsterdam, the Netherlands.
Department of Epidemiology & Biostatistics, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
Alzheimers Res Ther. 2014 Jul 21;6(4):47. doi: 10.1186/alzrt275. eCollection 2014.
The aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype.
We used data from the Galantamine-International-11 (Gal-Int-11) trial, a 24-month, randomized, double blind, placebo-controlled, flexible-dose (16 to 24 mg daily) study in patients with MCI. Brain magnetic resonance imaging (MRI), including a 3-dimensional T1-weighted gradient echo volumetric sequence, was performed at screening and at 24 months. We recorded whole brain and hippocampal volumes, and calculated annual atrophy rates. Linear regression analysis was used to calculate adjusted mean differences in the rate of whole brain and hippocampal atrophy, between MCI patients treated with galantamine and with placebo. Additionally, we performed stratified analyses according to APOE genotype.
Data from 364 MCI patients with 24-month MRI data (galantamine, n = 176; placebo, n = 188) were included in the volumetric analysis. Subjects treated with galantamine demonstrated a lower rate of whole brain atrophy compared to those treated with placebo (adjusted mean difference 0.18% per year (95% confidence interval (CI) 0.04; 0.30)). Stratified analyses according to APOE genotype, showed that this effect was confined to patients who carried an APOE ϵ4 allele (adjusted mean difference 0.28% per year (95% CI 0.07; 0.50)). Rates of hippocampal atrophy did not differ significantly between study groups.
Patients with MCI who were treated with galantamine demonstrated a lower rate of whole brain atrophy, but not of hippocampal atrophy, over a 24-month treatment period, compared to those treated with placebo. This protective effect of galantamine on whole brain atrophy rate in MCI was only present in APOE ϵ4 carriers.
本研究旨在评估加兰他敏（一种乙酰胆碱酯酶抑制剂和烟碱受体变构调节剂）对轻度认知障碍（MCI）患者脑萎缩的影响，并评估载脂蛋白E（APOE）基因型对效应的修饰作用。
我们使用了加兰他敏国际-11（Gal-Int-11）试验的数据，这是一项针对MCI患者进行的为期24个月的随机、双盲、安慰剂对照、灵活剂量（每日16至24毫克）研究。在筛查时和24个月时进行了脑磁共振成像（MRI），包括三维T1加权梯度回波容积序列。我们记录了全脑和海马体积，并计算了年萎缩率。采用线性回归分析计算加兰他敏治疗组和安慰剂治疗组MCI患者全脑和海马萎缩率的调整后平均差异。此外，我们根据APOE基因型进行了分层分析。
364例有24个月MRI数据的MCI患者（加兰他敏组，n = 176；安慰剂组，n = 188）的数据纳入了容积分析。与安慰剂治疗组相比，加兰他敏治疗组患者的全脑萎缩率较低（调整后平均差异为每年0.18%（95%置信区间（CI）0.04；0.30））。根据APOE基因型进行的分层分析表明，这种效应仅限于携带APOE ε4等位基因的患者（调整后平均差异为每年0.28%（95%CI 0.07；0.50））。研究组之间海马萎缩率无显著差异。
与安慰剂治疗组相比，接受加兰他敏治疗的MCI患者在24个月的治疗期内全脑萎缩率较低，但海马萎缩率无差异。加兰他敏对MCI患者全脑萎缩率的这种保护作用仅在APOE ε4携带者中存在。
