Cortical Microstructural Alterations in Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Abstract

In Alzheimer’s disease (AD), neurodegenerative processes are ongoing for years prior to the time that cortical atrophy can be reliably detected using conventional neuroimaging techniques. Recent advances in diffusion-weighted imaging have provided new techniques to study neural microstructure, which may provide additional information regarding neurodegeneration. In this study, we used neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model, in order to investigate cortical microstructure along the clinical continuum of mild cognitive impairment (MCI) and AD dementia. Using gray matter-based spatial statistics (GBSS), we demonstrated that neurite density index (NDI) was significantly lower throughout temporal and parietal cortical regions in MCI, while both NDI and orientation dispersion index (ODI) were lower throughout parietal, temporal, and frontal regions in AD dementia. In follow-up ROI analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) within the same brain regions, differences in NODDI metrics remained, even after controlling for cortical thickness. Moreover, for participants with MCI, gray matter NDI—but not cortical thickness—was lower in temporal, parietal, and posterior cingulate regions. Taken together, our results highlight the utility of NODDI metrics in detecting cortical microstructural degeneration that occurs prior to measurable macrostructural changes and overt clinical dementia.

Detection of gray matter microstructural changes in Alzheimer’s disease continuum using fiber orientation

“…To test the sensitivity of radiality, we sought to identify the earliest stage of AD. Interestingly, our CN vs. EMCI radiality analysis did not show a biphasic trajectory, as discussed in a previous work [34]. Thus, we conducted an additional analysis on amyloid-negative CN and amyloid-positive CN (Supp Fig.…”

Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

“…Typical MRI-based measures are derived from T1-weighted imaging and include whole brain atrophy [64], gray matter atrophy, and regional atrophy (e.g., medial temporal areas, hippocampus, and hippocampal subfields [65]), as well as surface-based cortical thickness [66]. Advances in neuroimaging acquisition and modelling of water diffusion have also facilitated the characterization of cortical microstructure, which may provide a sensitive measure of neurodegeneration that precedes overt cell loss [67]. Clinically, volumetric imaging is already used to monitor progression of neurodegeneration; multi-shell diffusion-weighted imaging is available as part of commercial scanning packages, but would need specialized processing for interpretation of neurodegeneration in the context of AD.…”

APOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults

“…In addition, NODDI yields the orientation dispersion index (ODI) that reflects the spatial configuration of neurite structures (Table 2). Recent studies reported ICSF and ODI reductions in grey and white matter of patients with MCI, LOAD and young onset AD [52][53][54] . For instance, Fu et al (2019) found decreased ICSF and ODI in the corpus callosum in MCI and LOAD patients, while Colgan et al 55 reported positive correlations between ICSF and histological measurements of hyperphosphorylated tau protein in the hippocampus of rTg4510 mice.…”