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

Neurology. 2019 Mar 12;92(11):e1256-e1267. doi: 10.1212/WNL.0000000000007094. Epub 2019 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / metabolism
  • Cognition*
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / metabolism*
  • Cohort Studies
  • Executive Function
  • Factor VIII / metabolism
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Language
  • Leukocyte Count
  • Longitudinal Studies
  • Male
  • Memory
  • Middle Aged
  • von Willebrand Factor / metabolism


  • von Willebrand Factor
  • Factor VIII
  • Fibrinogen
  • C-Reactive Protein