Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study

Keenan A. Walker, Rebecca F. Gottesman, Aozhou Wu, David S Knopman, Alden L. Gross, Thomas H. Mosley, Elizabeth Selvin, B. Gwen Windham

Research output: Contribution to journalArticle

17 Scopus citations


OBJECTIVE: To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline. METHODS: Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language. RESULTS: A total of 12,336 participants (baseline age 56.8 [5.7], 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting. CONCLUSIONS: Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.

Original languageEnglish (US)
Pages (from-to)e1256-e1267
Issue number11
StatePublished - Mar 12 2019

ASJC Scopus subject areas

  • Clinical Neurology

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    Walker, K. A., Gottesman, R. F., Wu, A., Knopman, D. S., Gross, A. L., Mosley, T. H., Selvin, E., & Windham, B. G. (2019). Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study. Neurology, 92(11), e1256-e1267.