Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife
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
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
in standardized scores (mean = 0, SD = 1) of
memory, reasoning, and verbal fluency using mixed models. Mini-Mental
(MMSE) was administered in 2002–2004 and
2007–2009; decline ≥3 points was modeled with logistic regression.
adjusted for baseline age, sex, education, and
ethnicity; further analyses were also adjusted for smoking, obesity,
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,
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.
Received November 8, 2013.
Accepted in final form March 10, 2014.
© 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.
Volume and page numbers
83 , 486 -493
Open Access article; © 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.