title: Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study.
abstract: OBJECTIVE
  To assess the association between statin therapy and risk of Alzheimer disease (AD) in a prospective cohort study with documented statin exposure and incident dementia.
  
  
  METHODS
  This is a prospective, cohort study of statin use and incident dementia and probable AD. A cohort of 2,356 cognitively intact persons, aged 65 and older, were randomly selected from a health maintenance organization (HMO), and were assessed biennially for dementia. Statin use was identified using the HMO pharmacy database. A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin-dementia/AD association.
  
  
  RESULTS
  Among 312 participants with incident dementia, 168 had probable AD. The unadjusted hazard ratios (HRs) with statin use were 1.33 (95% CI 0.95 to 1.85) for all-cause dementia and 0.90 (CI 0.54 to 1.51) for probable AD. Adjusted corresponding HRs were 1.19 (CI 0.82 to 1.75) and 0.82 (CI 0.46 to 1.46). A subgroup analysis of participants with at least one APOE-epsilon4 allele who entered the study before age 80 produced an adjusted HR of 0.33 (CI 0.10 to 1.04).
  
  
  CONCLUSIONS
  Employing time-dependent proportional hazards modeling, the authors found no significant association between statin use and incident dementia or probable AD. In contrast, when the data were analyzed, inappropriately, as a case-control study, the authors found an OR of 0.55 for probable AD, falsely indicating a protective effect of statins. Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings.
authors.affiliation: Department of Psychiatry and Behavioral Science, University of Washington, Seattle, USA. gli@u.washington.edu
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Higdon
authors.forename: W A
authors.initials: WA
authors.lastname: Kukull
authors.forename: E
authors.initials: E
authors.lastname: Peskind
authors.forename: K
authors.initials: K
authors.lastname: Van Valen Moore
authors.forename: D
authors.initials: D
authors.lastname: Tsuang
authors.forename: G
authors.initials: G
authors.lastname: van Belle
authors.forename: W
authors.initials: W
authors.lastname: McCormick
authors.forename: J D
authors.initials: JD
authors.lastname: Bowen
authors.forename: L
authors.initials: L
authors.lastname: Teri
authors.forename: G D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: E B
authors.initials: EB
authors.lastname: Larson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology*; D015331:Cohort Studies; D016208:Databases, Factual; D003704:Dementia / Q000453:epidemiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors