Patterns of disruption of white matter integrity in mild cognitive impairment and Alzheimer’s disease with and without vascular comorbidities

Abstract

AbstractBackgroundAlzheimer’s disease (AD) has been primarily been considered a grey matter disease. Recent studies, however, indicate the presence of white matter abnormalities in AD. This study’s aim was to investigate the patterns of white matter disruption in people with mild cognitive impairment (MCI) and AD dementia with vascular comorbidities (obesity, diabetes and hypertension).MethodDiffusion Tensor Imaging (DTI) was used to appraise white matter integrity using diffusion indices such as axial diffusivity (AxD) and mean diffusivity (MD). Participants were stratified according to presence or absence of vascular comorbidities and group status (controls n = 13, MCI n = 13 and AD n = 13). The vascular comorbidities were binarized into High Risk (either one or more vascular risks) or Low Risk (no vascular risks). Each pathological group was compared to Low‐Risk controls who served as the reference sample. Both groups were matched by age. For each of the group comparisons, there were 13 participants for each condition with the exception of the Low‐Risk AD group comparison where there were only 7 participants for both conditions. Between group differences in diffusion indices were measured using voxel‐wise whole brain approach using tract based spatial statistics (TBSS). A non‐parametric unpaired T‐Test was conducted between each group and the reference sample while controlling for location (site of recruitment), total intracranial volume and years of education.ResultThe results indicate that vascular comorbidity primarily affects the right projection fibres, forceps major, posterior areas of the corpus callosum such as the splenium as well as right fornix/stria terminalis. In the absence of comorbidities, in MCI and AD white matter is compromised in commissural fibres such as genu and body of the corpus callosum along with forceps minor.ConclusionThese results suggest that microstructural differences are more visible than macrostructural changes in AD. The results suggests that late myelinating fibres are more prone to damage to both neurodegeneration and vascular risks. In addition, the splenium of the corpus callosum is affected at a more severe stage in AD but is also affected by the presence of vascular risks.