title: The role of peripheral inflammatory markers in dementia and Alzheimer's disease: a meta-analysis.
abstract: BACKGROUND
  Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD).
  
  
  METHODS
  The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic.
  
  
  RESULTS
  Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16).
  
  
  CONCLUSIONS
  An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
authors.affiliation: San Francisco VA Medical Center, 4150 Clement St., VAMC 116H, San Francisco, CA 94121, USA. alain.koyama@va.gov
authors.forename: Alain
authors.initials: A
authors.lastname: Koyama
authors.forename: Jacqueline
authors.initials: J
authors.lastname: O'Brien
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weuve
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Metti
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D003625:Data Collection; D003704:Dementia / Q000209:etiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein