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.
翻译:阿尔茨海默氏老年痴呆病是一种渐进形式的痴呆症,它导致记忆、思维和行为问题。它往往从乙型氨基和妥的异常聚集和沉积开始,然后是神经损伤,如河马坎皮的萎缩,导致阿尔茨海默氏病(AD)。本文的目的是绘制AD的遗传成像临床临床-临床路径图,以便根据阿尔茨海默氏疾病神经成像倡议(ADNI)数据集划定驱动疾病不断上升的基因调节脑部变化。我们开发了一种新型的两步方法,以划分高维2D河马峰表面暴露和Tau的沉积,然后是阿尔茨海默氏病的认知程度,同时在基线中考虑到超高的地表临床和遗传共变异因素。分析结果表明,两个河马峰的每一种像的放射距离与以观察到的临床和遗传变异体为条件的行为赤字的严重性有负联系。这些协会在Cornu Ammonis区域1 (CA1) 和亚马斯区域3 (CA2) 和亚克鲁姆次区域(CA3) 区域(CAMA2) 和亚区域较强。