Nancy A West1, Iftikhar J Kullo2, M Caroline Morris3, Thomas H Mosley4. 1. Department of Internal Medicine, Division of Epidemiology, University of Utah, Salt Lake City, UT, United States of America. Electronic address: nancy.west@utah.edu. 2. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America. 3. School of Medicine, University of Mississippi Medical Center, Jackson, MS, United States of America. 4. Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, United States of America.
Abstract
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.
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.