4 modifies the relationship between infectious burden and poor cognition.

Objective: We investigated whether 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 and IBI.

Results: Among those with full neuropsychological test results (n = 569), there were interactions between IBI and 4 ( = 0.07) and herpes simplex virus 1 (HSV-1) and 4 ( = 0.02) for processing speed. IBI was associated with slower processing speed among non-4 carriers (β = -0.08 per SD change in IBI, 95% confidence interval [CI] -0.16 to -0.01), but not among 4 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-4 carriers (β = -0.24, 95% CI -0.45 to -0.03), but not among 4 carriers (β = 0.27, 95% CI -0.09 to 0.64).

Conclusions: Potential effect modification by the 4 allele on the relationship of infection, and particularly viral infection, to cognitive processing speed warrants further investigation.