Abstract

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 β amyloid and tau, followed by neuronal damage such as atrophy of the hippocampi, leading to Alzheimer’s disease (AD). The aim of this article 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. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

摘要

阿尔茨海默病是一种进行性痴呆症，会导致记忆、思维和行为问题。它通常始于β淀粉样蛋白和tau蛋白的异常聚集和沉积，随后出现海马萎缩等神经元损伤，从而导致阿尔茨海默病（AD）。本文的目的是根据阿尔茨海默病神经影像计划 (ADNI) 数据集绘制 AD 的基因-影像-临床路径图，以描述驱动疾病进展的基因调节大脑变化。我们开发了一种新颖的两步方法来描述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，同时考虑基线的超高维临床和遗传协变量。分析结果表明，两个海马体每个像素的径向距离与观察到的临床和遗传协变量的行为缺陷的严重程度呈负相关。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 Ammonis 区域 1 (CA1) 和下托子区域中更强。本文的补充材料（包括可用于复制作品的材料的标准化描述）可作为在线补充材料获得。