Age-Varying Association Between Statin Use and Incident Alzheimer's Disease

• Published in: Journal of the American Geriatrics Society (JAGS) 2010-07, Vol.58 (7), p.1311-1317
• Main Authors: Li, Ge, Shofer, Jane B., Rhew, Isaac C., Kukull, Walter A., Peskind, Elaine R., McCormick, Wayne, Bowen, James D., Schellenberg, Gerard D., Crane, Paul K., Breitner, John C.S., Larson, Eric B.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Age Factors; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer Disease - prevention & control; Alzheimer's disease; APOE genotype; Apolipoprotein E4 - genetics; Biological and medical sciences; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; General aspects; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Incidence; Male; Medical sciences; Neurology; old age; Organic mental disorders. Neuropsychology; Proportional Hazards Models; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Factors; statin
• ISSN: 0002-8614; 1532-5415
• DOI: 10.1111/j.1532-5415.2010.02906.x

OBJECTIVES: To determine whether risk reduction of statins for Alzheimer's disease (AD) varies by age or presence of apolipoprotein E (APOE) ɛ4 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 ɛ4 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 ɛ4 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.