These authors contributed equally to this work.
Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study
Article first published online: 11 MAR 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 274, Issue 1, pages 77–85, July 2013
How to Cite
on behalf of The PROSPER Study Group (Leiden University Medical Center, Leiden; Netherlands Consortium for Healthy Aging, The Netherlands; BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; Leiden University Medical Center, Leiden, The Netherlands; University of Glasgow, Glasgow; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK). Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study J Intern Med 2013; 274: 77‒85, , , , , , , ,
- Issue published online: 11 JUN 2013
- Article first published online: 11 MAR 2013
- Accepted manuscript online: 18 FEB 2013 03:15AM EST
- Bristol-Myers Squibb, USA
Inflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin-6 (IL-6) has a role in cardiovascular disease, but the association of IL-6 concentration and the functional IL-6 -174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL-6 and the -174 promoter polymorphism, and increased cognitive decline in old age.
Over 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL-6 and genotype of the IL-6 -174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL-6. A cognitive test battery was administered at baseline and repeatedly during follow-up (mean 39 months).
In the cross-sectional analysis of 5653 participants, higher IL-6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL-6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL-6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL-6 concentrations, the IL-6 -174 CC genotype was associated with worse performance on the Stroop test (P = 0.045).
Higher circulating levels of IL-6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL-6 pathway in cognitive decline.