Age-varying association between statin use and incident Alzheimer's disease.
OBJECTIVE
To determine whether risk reduction of statins for Alzheimer's disease (AD) varies by age or presence of apolipoprotein E (APOE) epsilon4 allele.


METHODS
A cohort of cognitively intact elderly participants was assessed biennially for dementia and AD.


METHODS
Community based.


METHODS
Three thousand three hundred ninety-two members of a health maintenance organization (HMO) aged 65 and older and without dementia.


METHODS
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).


CONCLUSIONS
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.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. gli@u.washington.edu
Ge
G
Li
Jane B
JB
Shofer
Isaac C
IC
Rhew
Walter A
WA
Kukull
Elaine R
ER
Peskind
Wayne
W
McCormick
James D
JD
Bowen
Gerard D
GD
Schellenberg
Paul K
PK
Crane
John C S
JC
Breitner
Eric B
EB
Larson
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D053327:Apolipoprotein E4 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015994:Incidence; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors
D053327:Apolipoprotein E4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors