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.