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Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife

Singh-Manoux, A; Dugravot, A; Brunner, E; Kumari, M; Shipley, M; Elbaz, A; Kivimaki, M; (2014) Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurology , 86 (6) pp. 486-493. 10.1212/WNL.0000000000000665. Green open access

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Abstract

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.

Type: Article
Title: Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000000665
Publisher version: http://dx.doi.org/10.1212/WNL.0000000000000665
Additional information: © 2014 American Academy of Neurology. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/1434277
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