Reverse causation in the association between c-reactive protein and fibrinogen levels and cognitive abilities in an aging sample

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. Keywords: inflammation, hemostasis, cognitive ability, processing speed, cognitive aging, normal population.