学习阿尔茨海默病临床前阶段生物标记物轨迹和变化点的贝叶斯半参数模型。

IF 1.4 4区 数学 Q3 BIOLOGY
Biometrics Pub Date : 2024-03-27 DOI:10.1093/biomtc/ujae048
Kunbo Wang, William Hua, MeiCheng Wang, Yanxun Xu
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引用次数: 0

摘要

轻度认知障碍(MCI)是阿尔茨海默病(AD)的早期症状之一,可能在神经病理学异常出现 10 年或更长时间后才出现,这一点已成为共识。因此,了解阿尔茨海默病生物标志物的发展过程,并在患者认知能力正常的情况下揭示大脑改变何时开始于临床前阶段,对于有效的早期检测和治疗开发至关重要。在本文中,我们开发了一种贝叶斯半参数框架,在异质性人群中,该框架可联合建模AD生物标志物的纵向轨迹与相对于症状发作的变化点,该变化点会受到左截断和右删减的影响。此外,与大多数现有方法假设所考虑人群中的每个人最终都会发病不同,我们的方法考虑到了某些个体即使经过长时间随访也可能从未出现 MCI 或 AD 的可能性。我们通过模拟研究对所提出的模型进行了评估,并利用正常人认知能力下降生物标志物(BIOCARD)研究的数据集检测了一个重要的注意力缺失症生物标志物 ptau181,从而证明了该模型的临床实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Bayesian semi-parametric model for learning biomarker trajectories and changepoints in the preclinical phase of Alzheimer's disease.

It has become consensus that mild cognitive impairment (MCI), one of the early symptoms onset of Alzheimer's disease (AD), may appear 10 or more years after the emergence of neuropathological abnormalities. Therefore, understanding the progression of AD biomarkers and uncovering when brain alterations begin in the preclinical stage, while patients are still cognitively normal, are crucial for effective early detection and therapeutic development. In this paper, we develop a Bayesian semiparametric framework that jointly models the longitudinal trajectory of the AD biomarker with a changepoint relative to the occurrence of symptoms onset, which is subject to left truncation and right censoring, in a heterogeneous population. Furthermore, unlike most existing methods assuming that everyone in the considered population will eventually develop the disease, our approach accounts for the possibility that some individuals may never experience MCI or AD, even after a long follow-up time. We evaluate the proposed model through simulation studies and demonstrate its clinical utility by examining an important AD biomarker, ptau181, using a dataset from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study.

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来源期刊
Biometrics
Biometrics 生物-生物学
CiteScore
2.70
自引率
5.30%
发文量
178
审稿时长
4-8 weeks
期刊介绍: The International Biometric Society is an international society promoting the development and application of statistical and mathematical theory and methods in the biosciences, including agriculture, biomedical science and public health, ecology, environmental sciences, forestry, and allied disciplines. The Society welcomes as members statisticians, mathematicians, biological scientists, and others devoted to interdisciplinary efforts in advancing the collection and interpretation of information in the biosciences. The Society sponsors the biennial International Biometric Conference, held in sites throughout the world; through its National Groups and Regions, it also Society sponsors regional and local meetings.
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