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. 2014 Aug 5;83(6):486-93.
doi: 10.1212/WNL.0000000000000665. Epub 2014 Jul 2.

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

Archana Singh-Manoux  1 , Aline Dugravot  2 , Eric Brunner  2 , Meena Kumari  2 , Martin Shipley  2 , Alexis Elbaz  2 , Mika Kivimaki  2
Affiliations

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

Archana Singh-Manoux et al. Neurology. .

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.

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Figures

Figure
Figure. Study profile
CRP = C-reactive protein.
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References

    1. Duong T, Nikolaeva M, Acton PJ. C-reactive protein-like immunoreactivity in the neurofibrillary tangles of Alzheimer's disease. Brain Res 1997;749:152–156 - PubMed
    1. Iwamoto N, Nishiyama E, Ohwada J, Arai H. Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections. Neurosci Lett 1994;177:23–26 - PubMed
    1. Gorelick PB. Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials. Ann NY Acad Sci 2010;1207:155–162 - PubMed
    1. Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam Study. Arch Neurol 2004;61:668–672 - PubMed
    1. Tan ZS, Beiser AS, Vasan RS, et al. Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology 2007;68:1902–1908 - PubMed

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