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Statin Use and the Risk of Incident Dementia
The Cardiovascular Health Study
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;
Charles Bernick, MD;
Lewis H. Kuller, MD, DrPH
Arch Neurol. 2005;62:1047-1051.
Background Statins (3-hydroxy-3-methylglutaryl coenzyme 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 participants free of dementia at baseline.
Main Outcome Measures Using Cox proportional hazards regression analysis, we estimated the risk of incident 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 included 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 dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer 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, current 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 Alzheimer 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.
Author Affiliations: Departments of Medicine (Drs Rea, Breitner, Psaty, and Hazzard) and Epidemiology (Drs Psaty and Fitzpatrick), University of Washington, and Veterans Administration Puget Sound Healthcare System (Drs Breitner and Hazzard), Seattle; Departments of Neurology, Psychiatry, and Psychology (Dr Lopez), Medicine (Dr Newman), and Epidemiology (Drs Newman and Kuller), University of Pittsburgh School of Medicine, Pittsburgh, Pa; Department of Mental Health, Bloomberg School of Public Health (Dr Zandi), and Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine (Dr Lyketsos), The Johns Hopkins University, Baltimore, Md; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (Dr Burke); and Division of Neurology, University of Nevada, Las Vegas (Dr Bernick).
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