Preclinical Alzheimer's disease (AD), the earliest stage in the AD continuum, can last fifteen to twenty years, with cognitive decline trajectories nonlinear and heterogeneous between subjects. Characterizing cognitive decline in the preclinical phase of AD is critical for the development of early intervention strategies when disease-modifying therapies may be most effective. In the last decade, there has been an increased interest in the application of change point (CP) models to longitudinal cognitive outcomes. Because patients' change points can vary greatly, it is essential to model this variation. In this paper, we introduce a BAyesian Bent-Line Regression model longitudinal data on cognitive function in middle-aged adults with a high risk of AD. We provide an approach for estimating the fixed (group-level) and random (person-level) CPs, slopes pre- and post-CP, and intercepts at CP for cognition. Our model not only estimates the individual cognitive trajectories but also the distributions of the cognitive bent line curves at each age, enabling researchers and clinicians to estimate subjects' quantiles. Simulation studies show that the estimation and inferential procedures perform reasonably well in finite samples. The practical use is illustrated by an application to a longitudinal cognitive composite in the Wisconsin Registry for Alzheimer's Prevention (WRAP).
翻译:创伤性阿尔茨海默氏病(AD)是AD连续体中最早的阶段,它可以持续15至20年,其认知下降轨迹不线性,各学科之间各有差异。在疾病改良疗法可能最为有效时,确定AD前期认知下降对于制定早期干预战略至关重要。在过去十年中,人们越来越关注将改变点模型(CP)应用于纵向认知结果。由于病人的变化点可以大相径庭,它对于模拟这种变异至关重要。在本文中,我们引入了关于中年成年人认知功能的BAJyesian Bent-Line Regrestition模型纵向数据,该模型具有高度的ADD风险。我们提供了一种方法,用于估计固定(群体级)和随机(人级)CP、斜坡前和后CP,以及CP用于纵向认知结果。我们的模型不仅估计了个人认知轨迹,而且还可以模拟这种变异的分布。在每一个年龄,使研究人员和临床医生能够估计对象的认知功能功能。我们提供了一个方法,用以进行长期的SDiscialimrealalalal Ex压测算。