Pharmacoepidemiological Studies Using the Veterans Affairs Decision Support System

Abstract

Over the past decade, we have utilized the Veterans Affairs (VA) Decision Support System (DSS) database to identify medications that are associated with a reduced incidence and progression of dementia. Our studies identify two general classes of medications that are associated with reductions in the incidence of dementia, compared to a group of patients with similar cardiovascular risk profiles (Li et al., 2010; Wolozin et al., 2000; Wolozin et al., 2007). We have shown that simvastatin, a medication that blocks synthesis of cholesterol, is associated with a significant reduction in the hazard ratio for incident dementia (HR 0.46, CI 0.44 – 0.48 p<0.0001) (Wolozin et al., 2007). Simvastatin has two primary effects. One effect is to lower cholesterol and a second effect, which is observed only at higher doses of simvastatin, is to reduce inflammation (Wolozin et al., 2006). The second major class of medications that are associated with reduced progression of dementia fall in the general category of angiotensin receptor blocking medications, which includes lisinopril, candesartan and valsartan (Li et al., 2010). In this work, the reduction in dementia incidence (HR, 0.81, C.I., 0.68 – 0.96, p=0.016) was not as striking as for statins, but we also examined nursing home admissions, where we observed a strong effect (HR, 0.51, CI 0.36 – 0.72, p=0.0001). In addition, we observed additive effects when angiotensin receptor blockers (ARBs) were used in addition to Angiotensin Converting Enzyme (ACE) inhibitors (Li et al., 2010). Finally, we have also examined the influence of coronary artery bypass on the incidence of dementia (Lee et al., 2005). This work was recently expanded upon to include an examination of the putative role of gaseous anesthetics on the incidence of dementia (no evidence supporting such a hypothesis was observed) (Vanderweyde et al., 2010).