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

Abstract

INTRODUCTIONWe 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.METHODSWe 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 (Nmain = 2632; NAPOE‐interaction = 1810).RESULTSSeropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = −3.89 mL [−5.81, −1.97], Padjusted < 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.DISCUSSIONWe did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication.

No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts

“…This stratified method can be more robust to possible population structure that may introduce confounding (21,22) but omits many participants, and in our research this only allowed participants closely clustering with “European” reference panel populations to be included. Analyses were conducted using multivariable logistic regression including genetic PCs (derived in our previous work (9)), age, sex, and genotyping batch (for UKB only) as covariates. Findings were meta-analysed using random-effects models.…”

“…The study workflow is summarised in Figure 1. As detailed previously (9), we conducted analyses using three population-based UK cohorts: UKB, NSHD, and SABRE. UKB is a large study including >500,000 participants who were approximately were aged 39-73 years at baseline assessments in 2006-10 (10).…”

“…All participants provided written informed consent, and all cohorts were granted ethical 2.2 Genetic data and quality control (QC) Details of genotyping and basic QC of genetic data can be found elsewhere (9,10,13). We used metrics indicative of poor sample quality or sample mix-up to define the analytical subset (excluding those with discordant genetic and self-reported sex, or outliers in heterozygosity and missing rates).…”

“…Serum immunoglobulin G antibody titers ("seroreactivity") against a range of antigens for pathogens of interest were quantified using a multiplex serology platform (German Cancer Research Center (DKFZ), Heidelberg), as described previously (9). In brief, 21 pathogens were assayed among 9,689 participants at baseline or instance 1 in the UKB; 18 pathogens among 1,813 NSHD participants at the age 60-64 visit; and the same 18 pathogens among 1,423 SABRE participants at visit 2.…”