Common infections and neuroimaging markers of dementia in three UK cohort studies

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (N _main = 2632; N _{APOE-interaction} = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = −3.89 mL [−5.81, −1.97], P _adjusted < 0.05); these were largely attenuated in fully adjusted models (β = −1.59 mL [−3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication.