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

Abstract

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.

Figure 1

Adjusted HR and 95% confidence interval of statin therapy for AD by age-at-entry based on Cox models adjusted for cohort, gender, race, years of education, CASI score at baseline, comorbid vascular diseases, BMI, history of cigarette smoking and other LLA use. HR: hazard ration; AD: Alzheimer’s disease; CASI: Cognitive Abilities Screening Instrument (score range 0 – 100); BMI: body mass index; LLA: other lipid lowering agent.

Figure 2

Adjusted HR and 95% confidence interval of statin therapy for AD by age-at-entry and APOE allele ε2/ε2 or ε2/ε3 (circle), ε3/ε3 (triangle) and ε2/ε4, ε3/ε4, or ε4/ε4 ('x') based on stratified Cox models adjusted for cohort, gender, race, years of education, CASI score at baseline, comorbid vascular diseases, BMI, history of cigarette smoking and other LLA use, with strata defined by 5 category age. HR: hazard ration; AD: Alzheimer’s disease; CASI: Cognitive Abilities Screening Instrument (score range 0 – 100); BMI: body mass index; LLA: other lipid lowering agent.