Fox N C, Black R S, Gilman S, Rossor M N, Griffith S G, Jenkins L, Koller M
Dementia Research Centre, Institute of Neurology, London, UK.
Neurology. 2005 May 10;64(9):1563-72. doi: 10.1212/01.WNL.0000159743.08996.99.
Alzheimer disease (AD) is characterized by progressive cerebral atrophy that may be measured using MRI. Reported are MRI findings of a Phase IIa immunotherapy trial in AD prematurely terminated owing to meningoencephalitis in a subset of patients.
To assess cerebral volume changes in patients immunized with AN1792 (beta-amyloid [Abeta] 1 to 42) who were antibody responders (anti-AN1792 IgG titer of > or =1:2,200) compared with placebo patients.
This randomized, multicenter, placebo-controlled, double-blind trial of AN1792 225 mug plus QS-21 50 mug included 372 patients with probable AD. Patients received one to three injections of AN1792/QS-21 or saline and were assessed for 12 months. Volumetric MRI was performed pre dose and at month 12 or early termination. Brain, ventricular, and hippocampal volume changes were measured from registered scan pairs.
Two hundred eighty-eight patients had paired scans (mean interval 10.9 months). Antibody responders (n = 45) had greater brain volume decrease (3.12 +/- 1.98 vs 2.04 +/- 1.74%; p = 0.007), greater ventricular enlargement as a percentage of baseline brain volume (1.10 +/- 0.75 vs 0.48 +/- 0.40%; p < 0.001), and a nonsignificant greater hippocampal volume decrease (3.78 +/- 2.63 vs 2.86 +/- 3.19%; p = 0.124) than placebo patients (n = 57). Increased losses in brain volume were not reflected in worsening cognitive performance; a composite z score across a Neuropsychological Test Battery showed differences favoring antibody responders over placebo (0.03 +/- 0.39 vs -0.24 +/- 0.45; p = 0.008).
A dissociation between brain volume loss and cognitive function was observed in AN1792/QS-21 antibody responders. The reasons for this remain unclear but include the possibility that volume changes were due to amyloid removal and associated cerebral fluid shifts.
阿尔茨海默病（AD）的特征是进行性脑萎缩，可通过磁共振成像（MRI）进行测量。本文报告了一项AD的IIa期免疫治疗试验的MRI结果，该试验因部分患者发生脑膜脑炎而提前终止。
评估与安慰剂组患者相比，接受AN1792（β-淀粉样蛋白[Abeta]1至42）免疫且产生抗体（抗AN1792 IgG滴度≥1:2200）的患者的脑容量变化。
这项随机、多中心、安慰剂对照、双盲的AN1792 225微克加QS-21 50微克试验纳入了372例可能患有AD的患者。患者接受一至三次AN1792/QS-21或生理盐水注射，并进行12个月的评估。在给药前以及第12个月或提前终止时进行容积MRI检查。从配准的扫描对中测量脑、脑室和海马的体积变化。
288例患者进行了配对扫描（平均间隔10.9个月）。产生抗体者（n = 45）的脑容量减少更多（3.12±1.98%对2.04±1.74%；p = 0.007），脑室扩大占基线脑容量的百分比更高（1.10±0.75%对0.48±0.40%；p < 0.001），海马体积减少虽无显著差异但也更大（3.78±2.63%对2.86±3.19%；p = 0.124），高于安慰剂组患者（n = 57）。脑容量损失增加并未反映在认知功能恶化上；一组神经心理测试的综合z评分显示，产生抗体者优于安慰剂组（0.03±0.39对-0.24±0.45；p = 0.008）。
在AN1792/QS-21产生抗体者中观察到脑容量损失与认知功能之间的分离。其原因尚不清楚，但包括体积变化可能是由于淀粉样蛋白清除和相关脑脊液移位的可能性。
Zotero 插件