Microglial reactivity predicts hippocampal, but not global, atrophy in cerebral small vessel disease

Abstract INTRODUCTION Cerebral small vessel disease (CSVD) is the most prevalent pathology underlying vascular dementia. Increased neuroinflammation and blood‐brain barrier (BBB) permeability have been implicated in CSVD pathogenesis. We determined whether microglial reactivity and BBB permeability at baseline predicted whole‐brain and hippocampal atrophy over one year, and cognitive impairment over four years. METHODS Seventy‐seven patients with CSVD were recruited to this prospective study. Baseline microglial reactivity and BBB permeability were determined using 11 C‐PK11195 positron emission tomography and dynamic contrast enhanced (DCE) MRI respectively. RESULTS Greater 11 C‐PK11195 binding at baseline was associated with hippocampal atrophy over one year ( p = 0.001), but not with global brain atrophy. Cox regression analyses showed no significant associations between 11 C‐PK11195 and cognitive impairment. There were no associations between BBB permeability with whole‐brain and hippocampal atrophy, or with cognitive impairment. DISCUSSION Our data suggests that microglial reactivity may play a role in hippocampal atrophy; potentially contributing to the increasingly recognized interaction between vascular and neurodegenerative pathology.