The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.
The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.
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DOI：
10.1371/journal.pone.0157514
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Löwe LC;Gaser C;Franke K;Alzheimer’s Disease Neuroimaging Initiative
在当今的老龄化社会中，老年人的疾病越来越受到人们的关注。研究中的一个重要问题是轻度认知障碍（MCI）和阿尔茨海默病（AD）及其原因，诊断，治疗和疾病预测。我们应用脑年龄差距估计（BrainAGE）方法来研究载脂蛋白E（APOE）基因型对结构性脑老化的影响，利用来自阿尔茨海默病神经影像学倡议（ADNI）数据库的405名受试者的纵向磁共振成像（MRI）数据。我们测试了诊断组内APOE ε4携带者和非携带者之间神经解剖学老化的差异，以及在约3年随访期间个体脑老化的纵向变化。我们进一步研究了BrainAGE和APOE状态的组合是否可以提高MCI患者转化为AD的预测准确性。在所有等位基因亚组以及ε4携带者和非携带者中分析了APOE状态对从MCI转化为AD的影响。正常对照组、稳定型MCI（sMCI）和进行性MCI（pMCI）组及AD组的BrainAGE评分差异有统计学意义。在APOE ε4携带状态以及pMCI和AD组中观察到BrainAGE变化率随时间的差异。在基线和随访期间，BrainAGE评分与APOE ε4携带者和非携带者的神经心理学测试评分显著相关，尤其是在pMCI和AD患者中。与神经心理学测试分数相比，使用BrainAGE分数预测转换是最准确的，即使患者的APOE状态未知。为了评估个体患AD的风险以及预测从MCI向AD的转化，BrainAGE方法被证明是一种有用且准确的工具，即使患者的APOE状态信息缺失。
In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient’s APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient’s APOE status is missing.