Abstract
BackgroundStatins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.MethodsWe analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.ResultsWe observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, p < 0.0001) and 0.91 (CI 0.80–1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, p < 0.0001).ConclusionSimvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.
Highlights
Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3methylglutaryl-coenzyme A reductase
We found that simvastatin is associated with a significant reduction in incident dementia and atorvastatin is associated with a more modest reduction that is of borderline significance
We examined the number of hospitalizations and the Charlson Index during the study period, which is an index providing a general assessment of chronic disease [22]
Summary
Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3methylglutaryl-coenzyme A reductase. Some studies suggest that medications used to treat these risk factors are associated with a reduced incidence of dementia [5,6,7,8,9,10]. Subsequent studies using a cross-sectional analytic method consistently observed a reduced prevalence and incidence of dementia among statin users (reviewed by Sjogren et al[16]). The cross-sectional nature of these studies raises concerns based on the potential for unanticipated biases including confounding by indication. These concerns have prompted investigators to pursue other strategies to test whether statins might protect against dementia
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