Systemic markers of inflammation and cognitive decline in old age

J Am Geriatr Soc. 2007 May;55(5):708-16. doi: 10.1111/j.1532-5415.2007.01159.x.


Objectives: To investigate whether higher circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and alpha1-antichymotrypsin (ACT) are associated with worse cognitive function and decline in old age.

Design: Two independent population-based cohort studies.

Setting: The Rotterdam Study (mean follow-up 4.6 years) and the Leiden 85-plus Study (maximal follow-up 5 years).

Participants: Three thousand eight hundred seventy-four individuals, mean age 72, from the Rotterdam Study, and 491 individuals, all aged 85, from the Leiden 85-plus Study.

Measurements: Both studies assessed global cognition, executive function, and memory. Linear regression analyses were used in the current study to investigate the associations between inflammatory markers and cognitive function and decline.

Results: In the Rotterdam Study, higher levels of CRP and IL-6 were cross-sectionally associated with worse global cognition and executive function (P<.05). ACT was not associated with cognitive function. In the Leiden 85-plus Study, estimates were similar for CRP, although not statistically significant. Higher IL-6 levels were related to a steeper annual decline in memory function in the longitudinal analysis in the Leiden 85-plus Study (P<.05). The effect of higher IL-6 levels on global and memory function decline was stronger in apolipoprotein E (APOE) epsilon4 carriers (P-interaction=.01) than in those who were not (P-interaction=.05). In the Rotterdam Study, higher IL-6 levels were related to a steeper annual decline in global cognition in APOE epsilon4 carriers only.

Conclusion: Systemic markers of inflammation are only moderately associated with cognitive function and decline and tend to be stronger in carriers of the APOE epsilon4 allele. Systemic markers of inflammation are not suitable for risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / analysis
  • Apolipoprotein E4 / genetics
  • Biomarkers / blood*
  • C-Reactive Protein / analysis*
  • Cognition Disorders / blood
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation
  • Inflammation Mediators / blood
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • alpha 1-Antichymotrypsin / blood*


  • Apolipoprotein E4
  • Biomarkers
  • Inflammation Mediators
  • Interleukin-6
  • alpha 1-Antichymotrypsin
  • C-Reactive Protein