Grey and White Matter Changes at Different Stages of Alzheimer's Disease

Abstract

This study investigates abnormalities of grey (GM) and white matter (WM) in Alzheimer's disease (AD), by modeling the AD pathological process as a continuous course between normal aging and fully developed dementia, with amnesic mild cognitive impairment (aMCI) as an intermediate stage. All subjects (9 AD, 16 aMCI patients, and 13 healthy controls) underwent a full neuropsychological assessment and an MRI examination at 3 Tesla, including a volumetric scan and diffusion tensor (DT)-MRI. The volumes were processed to perform a voxel-based morphometric analysis of GM and WM volume, while DT-MRI data were analyzed using tract based spatial statistics, to estimate changes in fractional anisotropy and mean diffusivity data. GM and WM volume and mean diffusivity and fractional anisotropy were compared across the three groups, and their correlation with cognitive functions was investigated. While AD presented a pattern of widespread GM atrophy, tissue loss was more subtle in patients with aMCI. WM atrophy was mainly located in the temporal lobe, but evidence of WM microscopic damage, assessed by DT-MRI, was also observable in the thalamic radiations and in the corpus callosum. Memory and executive functions correlated with either GM volume or fractional anisotropy in fronto-temporal areas. In conclusion, this study shows a comprehensive assessment of the brain tissue damage across AD evolution, providing insights on different pathophysiological mechanisms (GM atrophy, Wallerian degeneration, and brain disconnection) and their possible association with clinical aspects of cognitive decline.

Short‐term white matter alterations in Alzheimer's disease characterized by diffusion tensor imaging

“…Additionally, the ROI analysis revealed significant alterations in FA in the body and splenium of the corpus callosum, as well as the right superior longitudinal fasciculus. Previous studies that have assessed cross-sectional differences in FA between Alzheimer's disease and healthy controls have consistently revealed decreases in FA in the corpus callosum, SLF, and cingulum [32][33][34][35][36][37] -which agrees with our findings. The longitudinal alterations in these diffusion metrics are consistent with previous work done that identified FA and MD changes in the genu and body of the corpus callosum, fornix, and left cingulum over a 12-month follow-up DTI study, 8 highlighting that these regions are still vulnerable to change even in progressive mild-moderate Alzheimer's disease.…”

Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer’s Disease

“…Despite its precise anatomical-functional localization being still under debate [24,25,41,44,45], constructional apraxia is generally observed in patients with parietal [39] or frontal lobe [23] damages. For example, in a previous volumetric study we found grey matter atrophy restricted in the parietal, occipital and temporal brain areas of patients with AD and evidence of constructional apraxia [4]. The present study suggested a direct involvement of the FAT in different aspects of constructional apraxia abilities as measured by Copy of drawings tasks and by Raven's Coloured Matrices.…”

“…In its typical form, AD presents with a distinct pattern of grey (GM) and white matter (WM) brain tissue damage [2], supporting the existence of a disconnection syndrome [2,3] in addition to regional GM loss. Several previous studies used diffusion tensor imaging (DTI) to investigate the role of structural brain disconnection in AD at different clinical stages [4,5].…”

“…FAT is considered as a part of a "motor stream" mainly involved in speech production [19] and complementing the dorsal and ventral language streams [20]. Microstructural abnormalities in several WM tracts have been described in AD brains [4,6,7], whose involvement is likely to affect broader networks.…”

Currently Available Neuroimaging Approaches in Alzheimer Disease (AD) Early Diagnosis

“…The genu has a lower AF compared to the splenium. Several major white matter fibre bundles, including those connecting to the hippocampal structures, pass through the genu of the CC (Serra et al, 2010). Anatomical localization of AF reductions in amnestic MCI (aMCI) seems to be a robust finding across a variety of approaches.…”