Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife.
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ABSTRACT: Objective
Peripheral inflammatory markers are elevated in patients with dementia. In order to assess their etiologic role, we examined whether interleukin-6 (IL-6) and C-reactive protein (CRP) measured in midlife predict concurrently assessed cognition and subsequent cognitive decline.Methods
Mean value of IL-6 and CRP, assessed on 5,217 persons (27.9% women) in 1991-1993 and 1997-1999 in the Whitehall II longitudinal cohort study, were categorized into tertiles to examine 10-year decline (assessments in 1997-1999, 2002-2004, and 2007-2009) in standardized scores (mean = 0, SD = 1) of memory, reasoning, and verbal fluency using mixed models. Mini-Mental State Examination (MMSE) was administered in 2002-2004 and 2007-2009; decline ≥3 points was modeled with logistic regression. Analyses were adjusted for baseline age, sex, education, and ethnicity; further analyses were also adjusted for smoking, obesity, Framingham cardiovascular risk score, and chronic diseases (cancer, coronary heart disease, stroke, diabetes, and depression).Results
In cross-sectional analysis, reasoning was 0.08 SD (95% confidence interval [CI] -0.14, -0.03) lower in participants with high compared to low IL-6. In longitudinal analysis, 10-year decline in reasoning was greater (ptrend = 0.01) among participants with high IL-6 (-0.35; 95% CI -0.37, -0.33) than those with low IL-6 (-0.29; 95% CI -0.31, -0.27). In addition, participants with high IL-6 had 1.81 times greater odds ratio of decline in MMSE (95% CI 1.20, 2.71). CRP was not associated with decline in any test.Conclusions
Elevated IL-6 but not CRP in midlife predicts cognitive decline; the combined cross-sectional and longitudinal effects over the 10-year observation period corresponded to an age effect of 3.9 years.
SUBMITTER: Singh-Manoux A
PROVIDER: S-EPMC4141998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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