title: Systemic markers of inflammation and cognitive decline in old age.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Two independent population-based cohort studies.
  
  
  METHODS
  The Rotterdam Study (mean follow-up 4.6 years) and the Leiden 85-plus Study (maximal follow-up 5 years).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. m.vanmeeteren@lumc.nl
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.forename: Sjoerd M
authors.initials: SM
authors.lastname: Euser
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Witteman
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Jelle
authors.initials: J
authors.lastname: Jolles
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000032:analysis / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000514:alpha 1-Antichymotrypsin / Q000097:blood*
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D000514:alpha 1-Antichymotrypsin; D002097:C-Reactive Protein