title: Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study.
abstract: 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.
  
  
  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).
  
  
  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).
  
  
  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.
authors: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.p.mooijaart@lumc.nl
authors: S P
authors: SP
authors: Mooijaart
authors: N
authors: N
authors: Sattar
authors: S
authors: S
authors: Trompet
authors: J
authors: J
authors: Lucke
authors: D J
authors: DJ
authors: Stott
authors: I
authors: I
authors: Ford
authors: J W
authors: JW
authors: Jukema
authors: R G J
authors: RG
authors: Westendorp
authors: A J M
authors: AJ
authors: de Craen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood* / Q000235:genetics* / Q000517:prevention & control / Q000523:psychology; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D056344:Executive Function; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D015994:Incidence; D007249:Inflammation / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D007494:Ireland / Q000453:epidemiology; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017035:Pravastatin / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D017035:Pravastatin