论文标题
用应用于阿尔茨海默氏病的遗传成像 - 临床途径
Mapping the Genetic-Imaging-Clinical Pathway with Applications to Alzheimer's Disease
论文作者
论文摘要
阿尔茨海默氏病是痴呆症的一种进步形式，导致记忆，思维和行为问题。它通常始于β淀粉样蛋白和tau的异常聚集和沉积，其次是神经元损害，例如海马萎缩，导致阿尔茨海默氏病（AD）。本文的目的是绘制AD的遗传成像 - 临床途径，以描绘基于阿尔茨海默氏病神经成像计划（ADNI）数据集的遗传调节的大脑变化，这些变化驱动疾病进展。我们开发了一种新型的两步方法，用于描述高维2D海马表面暴露与阿尔茨海默氏病评估量表（ADAS）认知评分之间的关联，同时考虑到基线时超高维临床和遗传协变量。分析结果表明，两个海马的每个像素的径向距离与在观察到的临床和遗传协变量上有条件的行为缺陷的严重程度负相关。与Cornu Ammonis区域2（CA2）和Cornu Ammonis区域3（CA3）子区域相比，这些关联在Cornu氨区（CA1）和下区域更强。
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 beta amyloid and tau, followed by neuronal damage such as atrophy of the hippocampi, leading to Alzheimer's 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 Alzheimer's 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 Alzheimer's 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.
