Several studies have found associations between inflammatory biomarker levels and cognitive ability. This study tested the relationship between polymorphisms in genes that are associated with or encode the biomarkers and cognitive ability and estimated lifetime cognitive change. Data came from the aspirin for asymptomatic atherosclerosis trial (n = 2091, mean age = 67.2 years ). Twelve single nucleotide polymorphisms (SNPs) were genotyped from five genes (IL-1alpha, IL-1beta, IL-6, HNF-1A and F13A1). Cognition was assessed via administration of a five-test battery of psychometric tests, which were used to derive a general intelligence factor, g. A vocabulary-based cognitive test was also administered and adjusted for in the analysis to enable an estimation of lifetime cognitive change. Age- and sex-adjusted analyses yielded one weakly significant association between the IL-1alpha rs2856838 SNP and a measure of mental flexibility/processing speed (P = 0.044). Adjustment for the vocabulary-based scores resulted in a single, significant association between the IL-1alpha rs3783546 SNP and a measure of processing speed (P = 0.048). There is little evidence to suggest an association between SNPs in the inflammation-related genes IL-1alpha, IL-1beta, IL-6, TCF-1 and F13A1 and cognition in an elderly population of community-dwelling Scottish citizens.