title: Long-term systemic inflammation and cognitive impairment in a population-based cohort.
abstract: OBJECTIVE
  Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results.
  
  
  METHODS
  Prospective population-based cohort.
  
  
  METHODS
  Epidemiology of Hearing Loss Study participants.
  
  
  METHODS
  Individuals without cognitive impairment in 1998-2000 (N = 2,422; 1,947 with necessary data).
  
  
  METHODS
  Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998-2000, 2003-2005, and 2009-2010. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988-1990, 1998-2000, and 2009-2010; tumor necrosis factor-alpha was measured from 1998-2000.
  
  
  RESULTS
  Participants with high CRP in 1988-1990 and 1998-2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26-0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09-10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009-2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04-1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06-1.65).
  
  
  CONCLUSIONS
  With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed.
authors.affiliation: Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin, Madison, Wisconsin; Institute on Aging, University of Wisconsin, Madison, Wisconsin.
authors.forename: Margarete A
authors.initials: MA
authors.lastname: Wichmann
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Cruickshanks
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.forename: Rick
authors.initials: R
authors.lastname: Chappell
authors.forename: Mary E
authors.initials: ME
authors.lastname: Fischer
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Carla R
authors.initials: CR
authors.lastname: Schubert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis*; D003072:Cognition Disorders / Q000453:epidemiology*; D015331:Cohort Studies; D003704:Dementia / Q000453:epidemiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014922:Wisconsin / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: cognition; dementia; epidemiology; inflammation; population-based