Longitudinal and concurrent C-reactive protein and diet associations with cognitive function in the population-based Tromso study

Background: Immune dysregulation has been implicated in Alzheimer's disease; however, precise mechanisms and timing have not been established. Objective: To investigate the concurrent and longitudinal associations of serum C-reactive protein (CRP) and dietary inflammatory index (DII) with cognitive decline as observed in Alzheimer's disease. Methods: The study was based on 7613 individuals who participated in Troms & oslash;6 (2007-2008) and Troms & oslash;7 (2015-2016). We analyzed the relationship between CRP levels, DII, and cognitive function cross-sectionally using linear regression. We used mediation analysis to examine if CRP mediates the effects of DII on cognitive function. Further, we related baseline serum CRP to cognitive function and to change in cognitive function after 7 years of follow up. We used linear mixed models to relate changes in CRP levels to changes in cognitive function measured at two time points with 7 years apart. Results: Both CRP level and DII were cross-sectionally inversely associated with cognitive function (psychomotor speed, executive function). There was no prospective relationship between CRP level at baseline and cognitive function after 7 years of follow up. Increase in CRP levels was associated with decrease in cognitive function (psychomotor speed, executive function, and verbal memory) observed between two measurements 7 years apart. The mediation model did not show convincing evidence of a mediating effect of CRP in the association between diet and cognitive function. Conclusions: After comprehensive analysis of associations between CRP, DII and cognitive function, we conclude that CRP is likely to reflect the changes in inflammatory environment occurring in parallel with cognitive decline.