Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis
Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis
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DOI：
10.1136/jnnp.2010.231555
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发表时间：
2011-10-01
影响因子：
11
通讯作者：
Visser, Pieter Jelle
中科院分区：
文献类型：
--
作者：
Elias-Sonnenschein, Lyzel S.;Viechtbauer, Wolfgang;Visser, Pieter Jelle
研究背景识别阿尔茨海默病（AD）高危人群中的轻度认知功能障碍（MCI）患者对预后和早期干预具有重要意义。APOE-β 4等位基因是已知的AD最强的遗传危险因素。作者进行了一项荟萃分析，以建立从MCI进展到AD型dementia.Methods的APOE-β 4等位基因的预测准确性，作者纳入了35个前瞻性队列研究与MCI的主题，包括6095名受试者，其中1236进展到AD型痴呆后，2.9年的后续行动。OR、灵敏度、特异性、阳性和阴性预测值的合并估计值（PPV和NPV）以及阳性和阴性似然比结果携带APOE-β 4等位基因的MCI患者进展为AD型痴呆的OR为2.29（95%CI 1.88 ~ 2.80），敏感性为0.53（95%CI 0.46 ~ 0.61），特异性为0.67（95% CI 0.62 - 0.71），PPV为0.57（95% CI 0.48 - 0.66），NPV为0.75（95% CI 0.70 - 0.80），LR+为1.60（95% CI 1.48 - 1.72），LR-为0.75（95% CI 0.67 - 0.82）。Meta回归分析显示，敏感性、特异性和NPV与年龄、APOE-β 4等位基因背景患病率或随访时间长短有关。结论APOE-β 4等位基因与MCI进展为AD型痴呆的风险中度增加相关。由于敏感性和阳性预测值较低，基因分型对AD型痴呆的临床预测价值有限。对于旨在预防MCI进展为AD型痴呆的试验，APOE基因分型可能有助于选择进展为AD型痴呆风险较高的受试者。
Background The identification of subjects with mild cognitive impairment (MCI) at high risk for Alzheimer's disease (AD) is important for prognosis and early intervention. The APOE-epsilon 4 allele is the strongest known genetic risk factor for AD. The authors performed a meta-analysis to establish the predictive accuracy of the APOE-epsilon 4 allele for progression from MCI to AD-type dementia.Methods The authors included 35 prospective cohort studies of subjects with MCI, including 6095 subjects, of whom 1236 progressed to AD-type dementia after 2.9 years of follow-up. Pooled estimates of the OR, sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) were obtained using random-effects models.Results The OR for subjects with MCI who are carriers of APOE-epsilon 4 allele to progress to AD-type dementia was 2.29 (95% CI 1.88 to 2.80), the sensitivity was 0.53 (95% CI 0.46 to 0.61), the specificity was 0.67 (95% CI 0.62 to 0.71), the PPV was 0.57 (95% CI 0.48 to 0.66), the NPV was 0.75 (95% CI 0.70 to 0.80), the LR+ was 1.60 (95% CI 1.48 to 1.72), and the LR- was 0.75 (95% CI 0.67 to 0.82). Meta-regression showed that sensitivity, specificity and NPV were dependent on age, APOE-epsilon 4 allele background prevalence or follow-up length.Conclusions The APOE-epsilon 4 allele is associated with a moderately increased risk for progression from MCI to AD-type dementia. The low sensitivity and PPV makes genotyping of limited value for predicting AD-type dementia in clinical practice. For trials aiming to prevent progression from MCI to AD-type dementia, APOE genotyping may be useful in selecting subjects with a higher risk for progression to AD-type dementia.