Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies
Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies
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DOI：
10.1176/appi.ajp.159.5.738
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发表时间：
2002-05-01
影响因子：
17.7
通讯作者：
Reiman, EM
中科院分区：
文献类型：
--
作者：
Alexander, GE;Chen, K;Reiman, EM
目的：众所周知，在精神静息状态（眼耳遮蔽）下，通过[F - 18]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）评估的阿尔茨海默病患者的局部脑葡萄糖代谢率，为阿尔茨海默病痴呆提供了一种敏感的体内代谢指标。然而，很少有研究评估阿尔茨海默病所致痴呆患者局部脑葡萄糖代谢的纵向下降情况；此外，现有的研究没有使用最近开发的脑成像算法来描述阿尔茨海默病在整个大脑中的进展情况，并且没有考虑局部脑葡萄糖代谢在检验治疗减缓痴呆进展能力方面的统计效力。
方法：作者使用FDG PET和一种脑成像算法来研究局部脑葡萄糖代谢的横断面降低情况、1年随访后局部脑葡萄糖代谢的纵向下降情况，以及这种方法在评估轻至中度痴呆的阿尔茨海默病患者治疗效果方面的效力。最初对14名阿尔茨海默病患者和34名年龄和性别相似的健康对照受试者进行了PET扫描。1年后对患者进行了重复扫描。对在1年期间局部脑葡萄糖代谢（毫克/100克每分钟）显示最大下降的体素进行了功效分析，以估计在1年的双盲、安慰剂对照治疗研究中检测到显著治疗反应所需的样本量。
结果：阿尔茨海默病患者在顶叶、颞叶、枕叶、额叶和后扣带回皮质的葡萄糖代谢明显低于健康对照受试者。1年后，阿尔茨海默病患者在顶叶、颞叶、额叶和后扣带回皮质的葡萄糖代谢显著下降。利用左额叶皮质的最大葡萄糖代谢降低情况，我们估计在1年的双盲、安慰剂对照治疗研究中，每组仅需36名患者，即可在单侧显著性p≤0.005且功效为80%的情况下检测到33%的治疗反应。
结论：这些发现表明，在精神静息期间通过FDG PET评估的脑代谢是阿尔茨海默病1年期间疾病进展的敏感标志物。这些发现也支持将FDG PET用作结果测量指标来检验治疗减缓阿尔茨海默病进展能力的可行性。
Objective: It is well established that regional cerebral metabolic rates for glucose assessed by [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with Alzheimer's disease in the mental resting state (eyes and ears covered) provide a sensitive, in vivo metabolic index of Alzheimer's disease dementia. Few studies, however, have evaluated longitudinal declines in regional cerebral glucose metabolism in patients with dementia caused by Alzheimer's disease, in addition, the available studies have not used recently developed brain mapping algorithms to characterize the progression of Alzheimer's disease throughout the brain, and none considered the statistical power of regional cerebral glucose metabolism in testing the ability of treatments to attenuate the progression of dementia.Method: The authors used FDG PET and a brain mapping algorithm to investigate cross-sectional reductions in regional cerebral glucose metabolism, longitudinal decline in regional cerebral glucose metabolism after a 1-year follow-up, and the power of this method to evaluate treatments for Alzheimer's disease in patients with mild to moderate dementia. PET scans were initially acquired in 14 patients with Alzheimer's disease and 34 healthy comparison subjects of similar age and sex. Repeat scans were obtained in the patients 1 year later. Power analyses for voxels showing maximal decline over the 1-year period in regional cerebral glucose metabolism (mg/100 g per minute) were computed to estimate the sample sizes needed to detect a significant treatment response in a 1-year, double-blind, placebo-controlled treatment study.Results: The patients with Alzheimer's disease had significantly lower glucose metabolism than healthy comparison subjects in parietal, temporal, occipital, frontal, and posterior cingulate cortices, One year later, the patients, with Alzheimer's disease had significant declines in glucose metabolism in parietal, temporal, frontal, and posterior cingulate cortices. Using maximal glucose metabolism reductions in the left frontal cortex, we estimated that as few as 36 patients per group would be needed to detect a 33% treatment response with one-tailed significance of pless than or equal to0.005 and 80% power in a 1-year, double-blind, placebo-controlled treatment study.Conclusions: These findings indicate that brain metabolism as assessed by FDG PET during mental rest is a sensitive marker of disease progression in Alzheimer's disease over a 1-year period. These findings also support the feasibility of using FDG PET as an outcome measure to test the ability of treatments to attenuate the progression of Alzheimer's disease.