Role of white matter alteration in the relationship between regional microbleeds and cognitive impairment in cerebral amyloid angiopathy

Abstract

AbstractBackgroundPathophysiology of cognitive decline in CAA is multifactorial, because microbleeds, white matter hyperintensities, and combined concomitant parenchymal Alzheimer’s disease (AD) pathology have been suggested to cause cognitive impairment. The mechanism by which microbleeds affect cognitive impairment is still under investigation. We aimed to investigate the mechanism of how microbleeds contribute to cognitive impairment, in association with white matter tract abnormalities or cortical thickness in CAA with significant amyloid deposition.MethodWe retrospectively investigated 30 patients with probable CAA according to Boston criteria and 30 patients with Alzheimer’s disease (AD), all of whom showed severe amyloid deposition on amyloid PET (Aβ+). Age, sex, and clinical deteriorating scale were matched. Using MRI, cortical thickness and white matter tract abnormalities as fractional anisotropy (FA) were obtained. We compared cortical thickness, FA, and cognitive scores of five domains between Aβ+ CAA and Aβ+ AD. Using path analysis, we investigated the correlation between number of regional microbleeds, cortical thickness, FA, and cognitive impairments.ResultBoth CAA and AD group showed similar cortical amyloid deposition in AD related regions such as precuneus, and posterior cingulate cortex suggesting that CAA in this study might have AD pathology. Patients with Aβ+ CAA presented with significantly lower FA in clusters of posterior area than patients with Aβ+ AD (FWE‐corrected p value <0.05) Importantly, total number of microbleeds were associated with decreased FA in tapetum of corpus callosum (r=‐0.429, p<0.001), which were consequently associated with visuospatial function (r=0.466, p<0.001). Cortical thickness was not significantly different between CAA and AD, and it did not mediate the association between regional microbleeds and cognition.ConclusionThis study suggests that lobar microbleeds may impact cognitive decline through the mediation of white matter tract abnormalities in CAA.