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使用生存分析方法对阿尔茨海默病进展进行事件发生时间预测。

Time-to-event prediction using survival analysis methods for Alzheimer's disease progression.

作者信息

Sharma Rahul, Anand Harsh, Badr Youakim, Qiu Robin G

机构信息

The Pennsylvania State University Malvern Pennsylvania USA.

出版信息

Alzheimers Dement (N Y). 2021 Dec 31;7(1):e12229. doi: 10.1002/trc2.12229. eCollection 2021.

Abstract

INTRODUCTION

Many research studies have well investigated Alzheimer's disease (AD) detection and progression. However, the continuous-time survival prediction of AD is not yet fully explored to support medical practitioners with predictive analytics. In this study, we develop a survival analysis approach to examine interactions between patients' inherent temporal and medical patterns and predict the probability of the AD next stage progression during a time period. The likelihood of reaching the following AD stage is unique to a patient, helping the medical practitioner analyze the patient's condition and provide personalized treatment recommendations ahead of time.

METHODOLOGIES

We simulate the disease progression based on patient profiles using non-linear survival methods-non-linear Cox proportional hazard model (Cox-PH) and neural multi-task logistic regression (N-MTLR). In addition, we evaluate the concordance index (C-index) and Integrated Brier Score (IBS) to describe the evolution to the next stage of AD. For personalized forecasting of disease, we also developed deep neural network models using the dataset provided by the National Alzheimer's Coordinating Center with their multiple-visit details between 2005 and 2017.

RESULTS

The experiment results show that our N-MTLR based survival models outperform the CoxPH models, the best of which gives Concordance-Index of 0.79 and IBS of 0.09. We obtained 50 critical features out of 92 by applying recursive feature elimination and random forest techniques on the clinical data; the top ones include normal cognition and behavior, criteria for dementia, community affairs, etc. Our study demonstrates that selecting critical features can improve the effectiveness of probabilities at each time interval.

CONCLUSIONS

The proposed deep learning-based survival method and model can be used by medical practitioners to predict the patients' AD shift efficiently and recommend personalized treatment to mitigate or postpone the effects of AD. More generally, our proposed survival analysis approach for predicting disease stage shift can be used for other progressive diseases such as cancer, Huntington's disease, and scleroderma, just to mention a few, using the corresponding clinical data.

摘要

引言

许多研究对阿尔茨海默病(AD)的检测和进展进行了充分调查。然而,AD的连续时间生存预测尚未得到充分探索,无法通过预测分析为医学从业者提供支持。在本研究中,我们开发了一种生存分析方法,以检查患者内在的时间和医学模式之间的相互作用,并预测一段时间内AD下一阶段进展的概率。达到下一AD阶段的可能性因患者而异,有助于医学从业者分析患者状况并提前提供个性化治疗建议。

方法

我们使用非线性生存方法——非线性Cox比例风险模型(Cox-PH)和神经多任务逻辑回归(N-MTLR),基于患者档案模拟疾病进展。此外,我们评估一致性指数(C-index)和综合Brier评分(IBS)来描述向AD下一阶段的进展。为了进行疾病的个性化预测,我们还使用了美国国家阿尔茨海默病协调中心提供的数据集,该数据集包含2005年至2017年间的多次就诊详细信息,开发了深度神经网络模型。

结果

实验结果表明,我们基于N-MTLR的生存模型优于CoxPH模型,其中最佳模型的一致性指数为0.79,IBS为0.09。通过对临床数据应用递归特征消除和随机森林技术,我们从92个特征中获得了50个关键特征;其中最重要的包括正常认知和行为、痴呆标准、社区事务等。我们的研究表明,选择关键特征可以提高每个时间间隔概率的有效性。

结论

所提出的基于深度学习的生存方法和模型可供医学从业者使用,以有效预测患者的AD转变,并推荐个性化治疗以减轻或推迟AD的影响。更一般地说,我们提出的用于预测疾病阶段转变的生存分析方法可用于其他进行性疾病,如癌症、亨廷顿病和硬皮病等,只需使用相应的临床数据即可。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/849a/8719343/a5988b851312/TRC2-7-e12229-g002.jpg

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