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

Summary

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.

Received November 8, 2013.
Accepted in final form March 10, 2014.

© 2014 American Academy of Neurology

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