APOE ε4 modifies the relationship between infectious burden and poor cognition

Objective We investigated whether APOE ε4 is an effect modifier of the association between infectious burden (IB) and poor cognition in a multiethnic cohort, the Northern Manhattan Study. Methods IB was assessed by a quantitative weighted index of exposure to common pathogens associated with vascular risk, infectious burden index (IBI), and by serology for individual infections. Cognition was assessed by completion of the Mini-Mental State Examination at baseline and a full neuropsychological test battery after a median follow-up of approximately 6 years. Adjusted linear and logistic regressions estimated the association between IBI and cognition, with a term included for the interaction between APOE ε4 and IBI. Results Among those with full neuropsychological test results (n = 569), there were interactions between IBI and APOE ε4 (p = 0.07) and herpes simplex virus 1 (HSV-1) and APOE ε4 (p = 0.02) for processing speed. IBI was associated with slower processing speed among non–ε4 carriers (β = -0.08 per SD change in IBI, 95% confidence interval [CI] -0.16 to -0.01), but not among APOE ε4 carriers (β = 0.06 per SD change in IBI, 95% CI –0.08 to 0.19). HSV-1 positivity was associated with slower processing speed among non–ε4 carriers (β = -0.24, 95% CI -0.45 to -0.03), but not among APOE ε4 carriers (β = 0.27, 95% CI -0.09 to 0.64). Conclusions Potential effect modification by the APOE ε4 allele on the relationship of infection, and particularly viral infection, to cognitive processing speed warrants further investigation.