Data_Sheet_1_Prior infections are associated with smaller hippocampal volume in older women.docx

Accumulating evidence suggests that infections may play a major role in Alzheimer's disease (AD), however, mechanism is unclear, as multiple pathways may be involved. One possibility is that infections could contribute to neurodegeneration directly by promoting neuronal death. We explored relationships between history of infections and brain hippocampal volume (HV), a major biomarker of neurodegeneration, in a subsample of the UK Biobank (UKB) participants. Infectious disease diagnoses were based on ICD10 codes. The left/right HV was measured by the magnetic resonance imaging (MRI) in cubic millimeters and normalized. Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found that HV was significantly lower in women aged 60–75, as well as 65–80, years, with history of infections, compared to same age women without such history. The effect size increased with age faster for the left vs. right HV. Results for males didn't reach statistical significance. Results of our study support a major role of adult infections in neurodegeneration in women. The detrimental effect of infections on HV became stronger with age, in line with declining resilience and increasing brain vulnerability to stressors due to aging. The faster increase in the effect size observed for the left vs. right HV may indicate that female verbal memory degrades faster over time than visual-spatial memory. The observed sex difference may reflect a higher vulnerability of female brain to infection-related factors, which in turn may contribute to a higher risk of AD in women compared to men.