Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease.
Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease.
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将多基因危险评分与体积磁共振成像和认知测量相结合，可以改善从轻度认知障碍到阿尔茨海默病进展的预测。
DOI：
10.3389/fnins.2018.00260
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发表时间：
2018
影响因子：
4.3
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Kauppi K;Fan CC;McEvoy LK;Holland D;Tan CH;Chen CH;Andreassen OA;Desikan RS;Dale AM;Alzheimer's Disease Neuroimaging Initiative
改善对轻度认知功能障碍（MCI）老年人阿尔茨海默病（AD）进展的预测具有高度的临床和社会意义。我们最近开发了一种多基因危险评分（PHS），预测AD发病年龄高于和超过APOE。在这里，我们使用来自阿尔茨海默病神经影像学倡议（ADNI）的数据，以进一步探索PHS预测MCI老年人AD发展的潜在临床效用。我们研究了PHS单独和结合基线结构磁共振成像（MRI）数据对简易精神状态检查（MMSE）表现的预测价值。在生存分析中，PHS显著预测了120个月内从MCI进展为AD的时间（p = 1.07e-5），PHS的预测性显著高于单独使用APOE（p = 0.015）。与没有PHS的模型相比，将PHS与基线脑萎缩评分和/或MMSE评分相结合显著改善了预测（三因素模型p = 4.28e-17）。与仅使用萎缩评分和MMSE相比，在模型中包括PHS也提高了预测模型的准确性、灵敏度和曲线下面积。此外，使用线性混合效应模型，PHS改善了基线MCI患者36个月内临床痴呆评分总和（CDR-SB）评分和MMSE变化的预测，超过了APOE和基线脑萎缩水平。这些结果说明了PHS用于评估MCI个体中AD进展风险的潜在临床实用性，无论是单独使用还是与前驱疾病的临床指标（包括认知功能和局部脑萎缩的指标）联合使用。
Improved prediction of progression to Alzheimer's Disease (AD) among older individuals with mild cognitive impairment (MCI) is of high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age of AD onset above and beyond APOE. Here, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to further explore the potential clinical utility of PHS for predicting AD development in older adults with MCI. We examined the predictive value of PHS alone and in combination with baseline structural magnetic resonance imaging (MRI) data on performance on the Mini-Mental State Exam (MMSE). In survival analyses, PHS significantly predicted time to progression from MCI to AD over 120 months (p = 1.07e-5), and PHS was significantly more predictive than APOE alone (p = 0.015). Combining PHS with baseline brain atrophy score and/or MMSE score significantly improved prediction compared to models without PHS (three-factor model p = 4.28e-17). Prediction model accuracies, sensitivities and area under the curve were also improved by including PHS in the model, compared to only using atrophy score and MMSE. Further, using linear mixed-effect modeling, PHS improved the prediction of change in the Clinical Dementia Rating—Sum of Boxes (CDR-SB) score and MMSE over 36 months in patients with MCI at baseline, beyond both APOE and baseline levels of brain atrophy. These results illustrate the potential clinical utility of PHS for assessment of risk for AD progression among individuals with MCI both alone, or in conjunction with clinical measures of prodromal disease including measures of cognitive function and regional brain atrophy.
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DOI：
10.3233/jad-161070
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Marioni RE;Campbell A;Hagenaars SP;Nagy R;Amador C;Hayward C;Porteous DJ;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
2.8
作者：
Brewer JB
通讯作者：
Brewer JB
影响因子：
9.9
作者：
Vemuri, P.;Wiste, H. J.;Jack, C. R., Jr.
通讯作者：
Jack, C. R., Jr.
影响因子：
3.7
作者：
Ridge PG;Mukherjee S;Crane PK;Kauwe JS;Alzheimer’s Disease Genetics Consortium
通讯作者：
Alzheimer’s Disease Genetics Consortium
影响因子：
4
作者：
Dukart, Juergen;Sambataro, Fabio;Bertolino, Alessandro
通讯作者：
Bertolino, Alessandro