Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study

Mooijaart, S.P., Sattar, N. , Trompet, S., Lucke, J., Stott, D.J. , Ford, I. , Jukema, J.W., Westendorp, R.G.J. and de Craen, A.J.M. (2013) Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study. Journal of Internal Medicine, 274(1), pp. 77-85. (doi:10.1111/joim.12052)

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Abstract

<p>Background: 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.</p> <p>Methods: 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).</p> <p>Results: 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).</p> <p>Conclusions: 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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Ford, Professor Ian and Sattar, Professor Naveed
Authors: Mooijaart, S.P., Sattar, N., Trompet, S., Lucke, J., Stott, D.J., Ford, I., Jukema, J.W., Westendorp, R.G.J., and de Craen, A.J.M.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Internal Medicine
ISSN:0954-6820
ISSN (Online):1365-2796

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