Early Stage Diagnosis of Alzheimer’s Disease Employing DTI-Derived Biomarkers

Abstract

INTRODUCTION: Dementia is the major healthcare issue in 21th century(1) causing progressive cognitive decline in aging population. Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder(2). Mild Cognitive Impairment (MCI) usually represents a transitional phase between normal aging and AD(3). In spite of vast investigations; there is still no reliable cure for AD(4) mainly because etiopathogenesis of AD still remains unclear due to its multifactorial nature. The limbic system consisting Gray Matter (GM) structures and their White Matter (WM) connections, play key roles in memory(5). Literatures regarding structural Magnetic Resonance Imaging (MRI) have highlighted atrophy in GMs, including the hippocampus. Diffusion Tensor Imaging (DTI) is a variant of MRI sensitive to microscopic WM changes not detectable with standard MRI. DTI-based WM studies indicated widespread alterations including cingulum bundle(6). Studies have shown that WM damage has been correlated with atrophy in anatomically connected GM areas in AD patients(7). Despite growing diffusion imaging evidence of AD-related WM changes, it is not clear which of the brain’s systems and related DTI measures are the most sensitive for differential diagnosis. In this study, we employ a system-based evaluation and hypothesis that the alterations of the DTI metrics of the limbic-associated GMs and WMs can differentiate AD