title: Reverse causation in the association between C-reactive protein and fibrinogen levels and cognitive abilities in an aging sample.
abstract: OBJECTIVE
  To test the hypothesis that increased levels of inflammatory and hemostatic markers are associated with poorer cognitive performance and to assess the influence of childhood intelligence quotient (IQ) and current cardiovascular disease (CVD) risk factors on this relationship. Blood inflammatory markers have been shown to predict late-life cognition, although the mechanism through which this occurs is unknown.
  
  
  METHODS
  Levels of the biomarkers C-reactive protein and fibrinogen were measured in 1053 Scottish participants (50.2% female) from the Lothian Birth Cohort 1936 ranging in age from 67 to 71 years. Biomarker levels were tested for their association with diverse cognitive abilities.
  
  
  RESULTS
  Significant cross-sectional associations were found between the biomarkers and various cognitive abilities: their effect size was around 1% of the variance and was in the direction of higher marker levels conferring poorer cognitive performance. With the exception of the reaction time measures (and fibrinogen), these associations could be explained by childhood IQ, CVD risk factors, or both. Importantly, both the inflammatory markers at age 70 years were associated (p < .001) with childhood IQ.
  
  
  CONCLUSIONS
  Whereas inflammatory marker levels predict contemporaneous general cognitive ability, the results support a model of reverse causation because childhood IQ predicts late-life inflammation. This might be through its association with later life CVD risk factors or because it is a measure of system integrity. Unlike general cognitive ability, the association between inflammatory markers (particularly fibrinogen) and processing speed was maintained in the presence of childhood IQ and/or CVD risk factor adjustments. This might also reflect variation in physiological integrity.
authors.affiliation: Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gow
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood* / Q000523:psychology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015984:Causality; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006305:Health Status Indicators; D006487:Hemostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000523:psychology; D007360:Intelligence; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011930:Reaction Time; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D005340:Fibrinogen; D002097:C-Reactive Protein