Sex-specific associations of inflammation markers with cognitive decline

Background/objective: Inflammation is implicated in cognitive decline; however, there is a paucity of data for African American populations and for sex-specific associations. Design: Prospective cohort study. Setting: Genetic Epidemiology Network of Arteriopathy/Genetics of Microangiopathic Brain Injury studies. Participants: African-American sibships (N = 1010). Measurements: Neurocognitive tests assessed global cognition and four cognitive domains: processing speed, memory, language, and executive function at two time points over seven years. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor receptor (TNFR)-1 and TNFR2 were measured at study baseline. Linear mixed models were used to investigate the association between inflammation markers and cognitive decline. Results: Among men, a one SD increase in CRP was associated with an increased rate of decline over 7 years in global cognitive Z-score (adjusted difference in slopes = −0.31, p = 0.006) and in processing speed Z-score (adjusted difference in slopes = −0.10, p = 0.02), but not declines in memory, language, or executive function Z-scores. Also among men, a one SD increase in IL-6 was associated with an increased decline rate in global cognitive Z-score (adjusted difference in slopes = −0.33, p = 0.002) and in processing speed Z-score (adjusted difference in slopes = −0.12, p = 0.007). There was no difference in decline rates by CRP or IL-6 level in adjusted analyses among women for any cognitive scores. Among men and women combined, a one SD increase in baseline sTNFR1 was associated with a faster rate of decline in memory Z-score (adjusted difference in slopes = −0.09, p = 0.02). Baseline sTNFR2 levels did not significantly predict rate of cognitive decline in any cognitive domains. Conclusions: Circulating markers of CRP and IL-6 may be differential risk factors for men and women in relation to cognitive decline. A novel inflammation marker, sTNFR1, may be a useful predictor of memory decline in older adults.