Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults

Abstract

With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults.

The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay.

Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P = .16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P = .22). The C-allele carriers performed worse on a measure of executive functioning (P = .035) and had lower global cognitive scores (P = .045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P < .05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group.

These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.