Circulating interleukin‐6 concentration and cognitive decline in old age: the PROSPER study. (11th March 2013)

• Record Type: Journal Article
• Authors: Mooijaart, S. P.; Sattar, N.; Trompet, S.; Lucke, J.; Stott, D. J.; Ford, I.; Jukema, J. W.; Westendorp, R. G. J.; de, A. J. M.
• Is Part Of: Journal of internal medicine. Volume 274:Number 1(2013:Jul.)
• Page Start: 77
• Page End: 85
• Publication Date: 2013-03-11
• Subjects: Internal medicine -- Periodicals; Medicine -- Periodicals; 616
• DOI: 10.1111/joim.12052
• Languages: English
• ISSNs: 0954-6820

Abstract

<abstract abstract-type="main" id="joim12052-abs-0001"> <title>Abstract</title> <sec id="joim12052-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>IL‐6</italic> ‐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> </sec> <sec id="joim12052-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>IL‐6</italic> ‐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> </sec> <sec id="joim12052-sec-0003" sec-type="section"> <title>Results</title> <p>In the cross‐sectional analysis of 5653 participants, higher IL‐6 concentration was associated with worse executive cognitive function (<italic>P </italic><<italic> </italic>0.001), independent of cardiovascular disease status and risk factors. No association was found between IL‐6 concentration and memory function (<italic>P </italic>><italic> </italic>0.14). In the prospective analysis, higher IL‐6 concentration was associated with an increased rate of cognitive decline in both executive function (<italic>P </italic>=<italic> </italic>0.002) and memory function (<italic>P </italic>=<italic> </italic>0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL‐6 concentrations, the <italic>IL‐6</italic> ‐174 CC genotype was associated with worse performance on the Stroop test (<italic>P </italic>=<italic> </italic>0.045).</p> </sec> <sec id="joim12052-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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> </sec> </abstract>