Thomas D. Rea, MD, MPH; John C. Breitner, MD; Bruce M. Psaty, MD, PhD; Annette L. Fitzpatrick, PhD; Oscar L. Lopez, MD; Anne B. Newman, MD, MPH; William R. Hazzard, MD; Peter P. Zandi, PhD, MPH; Gregory L. Burke, MD, MS; Constantine G. Lyketsos, MD, MHS;
Background: Statins (3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia.
Objective: To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs).
Design: Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 partici- pants free of dementia at baseline.
Main Outcome Measures: Using Cox proportional hazards regression analysis, we estimated the risk of in- cident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses in- cluded the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach.
Results: Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause de- mentia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer dis- ease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzhei- mer disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary analyses, cur- rent use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all- cause dementia and 0.56 (95% CI, 0.35-0.92) for any Alz- heimer disease.
Conclusions: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.