Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment

Abstract

The association between cerebrovascular disease pathology (measured by white matter hyperintensities, WMH) and brain atrophy in early Alzheimer's disease (AD) remain to be elucidated. Thus, we investigated how WMH influence neurodegeneration and cognition in prodromal and clinical AD. We examined 51 healthy controls, 35 subjects with mild cognitive impairment (MCI), and 30 AD patients. We tested how total and regional WMH is related to specific grey matter volume (GMV) reductions in MCI and AD compared to controls. Stepwise regression analysis was further performed to investigate the association of GMV and regional WMH volume with global cognition. We found that total WMH volume was highest in AD but showed the strongest association with lower GMV in MCI. Frontal and parietal WMH had the most extensive influence on GMV loss in MCI. Additionally, parietal lobe WMH volume (but not hippocampal atrophy) was significantly associated with global cognition in MCI while smaller hippocampal volume (but not WMH volume) was associated with lower global cognition in AD. Thus, although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI. Our study thus highlights the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.

Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

“…This finding has also been echoed in another local study, which found an association between WMH and MTA among patients with clinically diagnosed amnestic deficits [14]. We have also previously demonstrated that regional WMH is associated with greater grey matter atrophy in patients with mild cognitive impairment [36]. The present study suggests the direct effect of CVD on clinical symptoms of AD and MTA, in the absence of amyloid pathology.…”

White Matter Hyperintensity Load Drives Differential Grey Matter Changes in Mild Cognitive Impairment

“…The nding of widespread negative association between WMH load and GMV at both the voxel-wise and ROI level at high WMH load evidenced in our study is supported by numerous prior studies (11,(15)(16)(17)(18)(19)(20)(21)(22)26). However, the mechanisms underlying this relationship need to be examined further.…”

“…This relationship thus needs further elucidation in early disease stages. While our previous work has also shown that derogatory in uences of WMH on GMV are most widespread at the MCI stage, compared to both cognitively normal and AD stages (26), the possible differential effects of WMH load on GMV in the cognitively normal and MCI remain to be elucidated.…”

“…Age at visit and sex were added as covariates to the analysis. The GM clusters showing signi cant effect of WMH were examined using a threshold of uncorrected p < 0.001 and a minimum cluster size of 100 voxels (26,48). Signi cant GM clusters were identi ed using the Automated Anatomical Labelling atlas.…”

“…Our results highlight variable relationships between WMH and GMV, dependent on the amount of cerebral WMH burden and their subsequent association with cognition in participants with MCI, indicating that such associations cannot be assumed to be linear in nature. This variable relationship may have important implications in the clinical management of MCI patients with varying loads of WMH.Cerebral WMH has been associated with several mechanisms including small vessel cerebrovascular disease, GM atrophy and neuroin ammation(15,21,26,51,52). It has been widely assumed that irrespective of the underlying mechanism, increasing WMH load will result in progressive increase in GMV loss.…”