Age-varying association between statin use and incident Alzheimer's disease

Ge Li, Jane B. Shofer, Isaac C. Rhew, Walter A. Kukull, Elaine R. Peskind, Wayne McCormick, James D. Bowen, Gerard D. Schellenberg, Paul K. Crane, John C.S. Breitner, Eric B. Larson

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


OBJECTIVES: To determine whether risk reduction of statins for Alzheimer's disease (AD) varies by age or presence of apolipoprotein E (APOE) ε4 allele. DESIGN: A cohort of cognitively intact elderly participants was assessed biennially for dementia and AD. SETTING: Community based. PARTICIPANTS: Three thousand three hundred ninety-two members of a health maintenance organization (HMO) aged 65 and older and without dementia. MEASUREMENTS: Statin use was identified from the HMO pharmacy database, and proportional hazards models were applied with statin use as a time-dependent covariate to assess the association between statins and AD and the modifying effects of age and the APOE ε4 allele. RESULTS: Over an average of 6.1 years of follow-up of 3,099 participants, 263 participants developed probable AD. The adjusted hazard ratio (aHR) for statin use was 0.62 (95% confidence interval (CI)=0.40-0.97) for AD in models including demographic characteristics and vascular risk factors as covariates. The strength of the association between statins and AD diminished with age (statin-by-age at entry interaction P=.04); the aHR in those younger than 80 was 0.44 (95% CI=0.25-0.78), versus 1.22 (95% CI=0.61-2.42) for aged 80 and older. The interaction term for statin use-by-APOE ε4 was not significant (P=.65). CONCLUSION: This enlarged study confirms earlier findings that statin therapy in early old age, but not in late age, may be associated with a lower risk of AD. The relationship between statin use and AD was consistent across APOE genotypes.

Original languageEnglish (US)
Pages (from-to)1311-1317
Number of pages7
JournalJournal of the American Geriatrics Society
Issue number7
StatePublished - Jul 2010
Externally publishedYes


  • APOE genotype
  • Alzheimer's disease
  • old age
  • statin

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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