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

J Am Geriatr Soc. 2010 Jul;58(7):1311-7. doi: 10.1111/j.1532-5415.2010.02906.x. Epub 2010 Jun 1.


Objectives: To determine whether risk reduction of statins for Alzheimer's disease (AD) varies by age or presence of apolipoprotein E (APOE) epsilon4 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 epsilon4 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 epsilon4 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / prevention & control
  • Apolipoprotein E4 / genetics*
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Incidence
  • Male
  • Proportional Hazards Models
  • Risk Factors


  • Apolipoprotein E4
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors