Alexander Gene E, Chen Kewei, Pietrini Pietro, Rapoport Stanley I, Reiman Eric M
Arizona Alzheimer's Research Center and Department of Psychiatry, Arizona State University, Tempe, 85287-1104, USA.
Am J Psychiatry. 2002 May;159(5):738-45. doi: 10.1176/appi.ajp.159.5.738.
It is well established that regional cerebral metabolic rates for glucose assessed by [(18)F]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.
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.
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 p</=0.005 and 80% power in a 1-year, double-blind, placebo-controlled treatment study.
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.
通过[（18）F]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）评估阿尔茨海默病患者静息状态（眼睛和耳朵遮盖）下的局部脑葡萄糖代谢率，已被充分证实可提供阿尔茨海默病痴呆的敏感活体代谢指标。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，现有研究未使用最近开发的脑图谱算法来描述阿尔茨海默病在全脑的进展情况，也没有一项研究考虑局部脑葡萄糖代谢在测试治疗减轻痴呆进展能力方面的统计效能。
作者使用FDG PET和一种脑图谱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，以及该方法评估轻度至中度痴呆的阿尔茨海默病患者治疗效果的效能。最初对14例阿尔茨海默病患者和34名年龄及性别相似的健康对照者进行PET扫描。1年后对患者进行重复扫描。对显示局部脑葡萄糖代谢（毫克/100克每分钟）在1年期间下降最大的体素进行效能分析，以估计在一项为期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。
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显著低于健康对照者。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。使用左侧额叶皮质最大葡萄糖代谢降低情况，我们估计在一项为期1年的双盲、安慰剂对照治疗研究中，每组仅需36例患者就能检测到具有单尾显著性p≤0.005且效能为80%的33%治疗反应。
这些发现表明，静息状态下通过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。这些发现还支持使用FDG PET作为结局指标来测试治疗减轻阿尔茨海默病进展能力的可行性。
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