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

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 11C-PK11195 positron emission tomography and dynamic contrast enhanced MRI respectively. RESULTS: Greater 11C-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 11C-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 recognised interaction between vascular and neurodegenerative pathology.