title: Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife.
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.
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France. Archana.Singh-Manoux@inserm.fr.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Aline
authors.initials: A
authors.lastname: Dugravot
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Eric
authors.initials: E
authors.lastname: Brunner
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Martin
authors.initials: M
authors.lastname: Shipley
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.affiliation: From INSERM (A.S.-M., A.D., A.E.), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif Cedex, France; Department of Epidemiology and Public Health (A.S.-M., E.B., M. Kumari, M.S., A.E., M. Kivimaki), University College London, UK; Centre de Gérontologie (A.S.-M.), Hôpital Ste Périne, AP-HP; and University Versailles St-Quentin en Yvelines (A.D.), France.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein