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Benjamin Wolozin, MD, PhD; Wendy Kellman; Paul Ruosseau, MD; Gastone G. Celesia, MD; George Siegel, MD

Arch Neurol. 2000;57:1439-1443.

Context  Increasing evidence suggests that cholesterol plays a role in the pathophysiology of Alzheimer disease (AD). For instance, an elevated serum cholesterol level has been shown to be a risk factor for AD.

Objective  To determine whether patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), which are a group of medicines that inhibit the synthesis of cholesterol, have a lower prevalence of probable AD.

Design  The experiment uses a cross-sectional analysis comparing the prevalence of probable AD in 3 groups of patients from hospital records: the entire population, patients receiving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (hereafter referred to as the statins), and patients receiving medications used to treat hypertension or cardiovascular disease.

Patients  The subjects studied were those included in the computer databases of 3 different hospitals for the years October 1, 1996, through August 31, 1998.

Main Outcome Measures  Diagnosis of probable AD.

Results  We find that the prevalence of probable AD in the cohort taking statins during the study interval is 60% to 73% (P<.001) lower than the total patient population or compared with patients taking other medications typically used in the treatment of hypertension or cardiovascular disease.

Conclusions  There is a lower prevalence of diagnosed probable AD in patients taking 2 different 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors—lovastatin and pravastatin. While one cannot infer causative mechanisms based on these data, this study reveals an interesting association in the data, which warrants further study.

From the Departments of Pharmacology (Dr Wolozin), Neurology (Drs Celesia and Seigel), and Biochemistry (Dr Siegel and Ms Kellman), Loyola University Medical Center, Maywood, Ill; Department of Neurology, Edward Hines Jr Veterans Affairs Hospital, Hines, Ill (Dr Siegel); and Department of Geriatrics and Extended Care Medicine, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Ariz (Dr Rousseau). Drs Wolozin and Siegel have applied for a patent on the use of lovastatin and pravastatin in treating Alzheimer disease.

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