Mapping the Genetic-Imaging-Clinical Pathway with Applications to Alzheimer's Disease

Mapping the Genetic-Imaging-Clinical Pathway with Applications to Alzheimer's Disease

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 (...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Statistical Association 2022, Vol.117 (540), p.1656-1668
Main Authors: Yu, Dengdeng, Wang, Linbo, Kong, Dehan, Zhu, Hongtu
Format: Article
Language:eng
Subjects:
2D Surface
Alzheimer's disease
Atrophy
Behavioral deficits
Confounders
Dementia
Hippocampus
Mapping
Medical imaging
Neuroimaging
Patient care planning
Regression analysis
Statistical methods
Statistics
Variable selection
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0162-1459
1537-274X