Supplemental data at Neurology.org

Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife 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 theWhitehall 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 5 0, SD 5 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 base-line 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]20.14, 20.03) lower in participants with high compared to low IL-6. In longitudinal analysis, 10-year decline in reasoning was greater (ptrend5 0.01) among participants with high IL-6 (20.35; 95% CI 20.37, 20.33) than those with low IL-6 (20.29; 95 % CI 20.31, 20.27). In addition, partic-ipants 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. Neurology ® 2014;83:486–493 GLOSSARY CHD 5 coronary heart disease; CI 5 confidence interval; CRP 5 C-reactive protein; CVD 5 cardiovascular disease; IL-6 5 interleukin-6; IQR 5 interquartile range; MMSE 5 Mini-Mental State Examination