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Psychoneuroendocrinology. 2008 Nov;33(10):1322-34. doi: 10.1016/j.psyneuen.2008.07.006. Epub 2008 Sep 5.

Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study.

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  • 1International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK.



To assess whether C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with low cognitive performance and decline in middle-aged adults.


The Whitehall II study; an ongoing large-scale, prospective occupational cohort study of employees from 20 London-based white-collar Civil Service departments.


Data from more than 3000 males and 1200 female employees.


Inflammatory makers measured in 1991-1993 and five cognitive tests (short-term verbal memory, inductive reasoning (AH4-I), vocabulary (Mill Hill), and phonemic and semantic fluency) performed in 1997-1999 and 2002-2004. Performance in the lowest sex-specific quintile indicated low cognitive performance or decline. Covariates included sociodemographics, health behaviours and health conditions.


In age-adjusted analyses both CRP and IL-6 were associated with all cognitive measures in 1997-1999, even though the association with memory was not consistent. After extensive adjustment raised CRP levels were only associated with poor cognitive performance on the AH4-I (OR=1.38; 95% CI: 1.05-1.82) and Mill Hill (OR=1.52; 95% CI: 1.14-2.03) and IL-6 on semantic fluency (OR=1.27; 95% CI: 1.14-2.03). Associations were more evident in men than in women. No clear relationship was observed for decline.


Our results suggest that raised levels of inflammatory markers in midlife are moderately associated with lower cognitive status, but little with cognitive decline.

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