Yu Dengdeng, Wang Linbo, Kong Dehan, Zhu Hongtu
Department of Mathematics, University of Texas at Arlington.
Department of Statistical Sciences, University of Toronto.
J Am Stat Assoc. 2022;117(540):1656-1668. doi: 10.1080/01621459.2022.2087658. Epub 2022 Jul 19.
Alzheimer's disease is a progressive form of dementia that results in problems with memory, thinking, and behavior. It often starts with abnormal aggregation and deposition of amyloid and tau, followed by neuronal damage such as atrophy of the hippocampi, leading to Alzheimers Disease (AD). The aim of this paper is to map the genetic-imaging-clinical pathway for AD in order to delineate the genetically-regulated brain changes that drive disease progression based on the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset. We develop a novel two-step approach to delineate the association between high-dimensional 2D hippocampal surface exposures and the Alzheimers Disease Assessment Scale (ADAS) cognitive score, while taking into account the ultra-high dimensional clinical and genetic covariates at baseline. Analysis results suggest that the radial distance of each pixel of both hippocampi is negatively associated with the severity of behavioral deficits conditional on observed clinical and genetic covariates. These associations are stronger in Cornu Ammonis region 1 (CA1) and subiculum subregions compared to Cornu Ammonis region 2 (CA2) and Cornu Ammonis region 3 (CA3) subregions. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
阿尔茨海默病是一种渐进性痴呆，会导致记忆、思维和行为方面的问题。它通常始于淀粉样蛋白和tau蛋白的异常聚集和沉积，随后出现神经元损伤，如海马体萎缩，进而导致阿尔茨海默病（AD）。本文旨在绘制AD的基因-影像-临床路径，以便根据阿尔茨海默病神经影像倡议（ADNI）数据集，描绘驱动疾病进展的基因调控脑变化。我们开发了一种新颖的两步法，以描绘高维二维海马表面暴露与阿尔茨海默病评估量表（ADAS）认知评分之间的关联，同时考虑基线时的超高维临床和基因协变量。分析结果表明，在观察到的临床和基因协变量条件下，两个海马体每个像素的径向距离与行为缺陷的严重程度呈负相关。与海马角2区（CA2）和海马角3区（CA3）亚区域相比，这些关联在海马角1区（CA1）和下托亚区域更强。本文的补充材料，包括可用于重现该工作的材料的标准化描述，可作为在线补充材料获取。
