Ma Yan, Zhang Shuo, Li Jing, Zheng Dong-Ming, Guo Yang, Feng Juan, Ren Wei-Dong
From the Department of Ultrasound (YM, JL, WDR), Department of Neurology (SZ, DMZ, YG, JF), Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Medicine (Baltimore). 2014 Dec;93(27):e150. doi: 10.1097/MD.0000000000000150.
In the past decade, amyloid deposition has been shown to begin many years before the clinical symptoms of dementia in mild cognitive impairment (MCI) due to Alzheimer disease (AD). Longitudinal studies with different follow-up durations have suggested that C-Pittsburgh compound B positron emission tomography (C-PIB-PET) may play a role in stratifying patients with MCI into risk levels for developing AD. However, the predictive accuracy of amyloid imaging for the progression from MCI to AD with different follow-up durations has not yet been systematically evaluated. A formal systematic evaluation of the sensitivity, specificity, and other properties of C-PIB-PET was performed.This study aimed to systematically review and meta-analyze published data on the diagnostic performance of C-PIB-PET for predicting conversion to AD in patients with MCI and to determine whether long-term follow-up has a positive effect on predictive accuracy. Relevant studies were systematically identified through electronic searches, which were performed in MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (Ovid SP), and LILACS (Bireme). The methodological quality of each study was assessed by QUADAS-2. Sensitivities and specificities of C-PIB-PET in individual studies were calculated, and the studies underwent meta-analysis with a random-effects model. A summary receiver-operating characteristic curve (SROC) was constructed with the Moses-Shapiro-Littenberg method. Pooled estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and the SROC curve of each subgroup were determined. Heterogeneity was tested, and potential sources for heterogeneity were explored by assessing whether certain covariates significantly influenced the relative DOR.Eleven eligible studies consisting of a total of 352 patients with MCI at baseline were included. Overall, the studies were of moderate-to-high methodological quality. The sensitivity and specificity of C-PIB-PET for predicting conversion to AD ranged from 83.3% to 100% and 41.1% to 100%, respectively, with pooled estimates of 94.7% (95% confidence interval [CI]: 89.8%-97.7%) and 57.2% (95% CI: 50.1%-64.2%), respectively . Moderate heterogeneity was observed for specificity between the included studies (I = 42.1%). The pooled estimates for the long-term follow-up subgroup were 95.5% sensitivity (95% CI: 84.5%-99.4%) and 72.4% specificity (95% CI: 59.1%-83.3.8%), whereas the pooled estimates for the short-term follow-up subgroup were 94.4% sensitivity (95% CI: 88.2%-97.9%) and 51.0% specificity (95% CI: 42.6%-59.5%). Homogeneity in each subgroup was significantly higher than that of the included studies, and most diagnostic indicators in the long-term follow-up subgroup were far superior to those in the short-term follow-up subgroup or the entire group. Not all of the methodological quality scores of studies included in this systematic review were high. Current evidence suggests that prolongation of the follow-up duration tended to yield greater accuracy of C-PIB-PET for predicting the progression from MCI to AD. In particular, the specificity, which reflects the exploratory nature of the use of amyloid imaging to identify the process of MCI to AD, was improved with a longer follow-up period.
在过去十年中,研究表明,在阿尔茨海默病(AD)所致轻度认知障碍(MCI)中,淀粉样蛋白沉积在痴呆临床症状出现多年前就已开始。不同随访时长的纵向研究表明,碳-匹兹堡化合物B正电子发射断层扫描(C-PIB-PET)可能在将MCI患者分层为发生AD的风险水平方面发挥作用。然而,不同随访时长下淀粉样蛋白成像对MCI进展为AD的预测准确性尚未得到系统评估。本研究对C-PIB-PET的敏感性、特异性及其他特性进行了正式的系统评价。本研究旨在系统回顾和荟萃分析已发表的关于C-PIB-PET预测MCI患者转化为AD的诊断性能的数据,并确定长期随访是否对预测准确性有积极影响。通过电子检索系统识别相关研究,检索在MEDLINE(OvidSP)、EMBASE(OvidSP)、BIOSIS Previews(ISI Web of Knowledge)、科学引文索引(ISI Web of Knowledge)、PsycINFO(Ovid SP)和拉丁美洲及加勒比地区卫生科学数据库(LILACS,Bireme)中进行。采用QUADAS-2评估每项研究的方法学质量。计算各研究中C-PIB-PET的敏感性和特异性,并采用随机效应模型对研究进行荟萃分析。采用Moses-Shapiro-Littenberg方法构建汇总的受试者工作特征曲线(SROC)。确定各亚组的敏感性、特异性、阳性似然比(LR+)、阴性似然比(LR-)、诊断比值比(DOR)的合并估计值以及SROC曲线。检验异质性,并通过评估某些协变量是否显著影响相对DOR来探索异质性的潜在来源。纳入了11项符合条件的研究,共352例基线时患有MCI的患者。总体而言,这些研究的方法学质量为中到高。C-PIB-PET预测转化为AD 的敏感性和特异性分别在83.3%至100%和41.1%至100%之间,合并估计值分别为94.7%(95%置信区间[CI]:89.8%-97.7%)和57.2%(95%CI:50.1%-64.2%)。纳入研究之间特异性存在中度异质性(I² = 42.1%)。长期随访亚组的合并估计值为敏感性95.5%(95%CI:84.5%-99.4%)和特异性7%.4%(95%CI:59.1%-83.3%),而短期随访亚组的合并估计值为敏感性94.4%(95%CI:88.2%-97.9%)和特异性51.0%(95%CI:42.6%-59.5%)。各亚组的同质性显著高于纳入研究,长期随访亚组的大多数诊断指标远优于短期随访亚组或整个组。本系统评价纳入的研究并非所有方法学质量评分都很高。目前的证据表明,延长随访时长往往会使C-PIB-PET预测MCI进展为AD的准确性更高。特别是,反映使用淀粉样蛋白成像识别MCI进展为AD过程探索性的特异性,在随访期较长时有所提高。