The association of genetic variants in interleukin-1 genes with cognition: Findings from the cardiovascular health study

The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta = 0.47, 95%CI = 0.09, 0.85, p = 0.016; rs4251961: beta = − 0.36, 95%CI = − 0.13,−0.60, p = 0.0027; rs931471: beta = 0.39, 95%CI = 0.13, 0.65, p = 0.0032), and the IL1B gene for African Americans (rs1143627: beta = 1.6, 95%CI = 0.48, 2.8; p = 0.006 and rs1143634: beta = 2.09, 95%CI = 0.39, 3.8; p = 0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.

► We evaluated variation in interleukin-1 genes with cognitive trajectories of older adults.
► SNP signals were found in IL1RA for Caucasians, and IL1B for African Americans.
► Most SNP associations with cognition were found with baseline, rather than annual change.
► Interleukin-1 associations are likely to underlie a dementing process.
► Cognitive reserve may be a modifier of these interleukin-1 gene associations.