Mapping the Genetic-Imaging-Clinical Pathway with Applications to Alzheimer’s Disease
基于ADNI数据，提出两步法分析海马表面与认知评分的关系，发现海马CA1和下托区域与行为缺陷严重程度负相关更强。
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.