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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