Angiotensin Receptor Blocker Use May Decrease the Incidence and Progression of Alzheimer’s Disease and Dementia in Older Men but the Strength of the Evidence Is Questionable

Abstract

ANGIOTENSIN RECEPTOR BLOCKER USE MAY DECREASE THE INCIDENCE AND PROGRESSION OF ALZHEIMER’S DISEASE AND DEMENTIA IN OLDER MEN BUT THE STRENGTH OF THE EVIDENCE IS QUESTIONABLE Multiple longitudinal studies suggest that elevated blood pressure (BP) in midlife is associated with deterioration of cognitive function later in life, and prospective, randomized, placebo-controlled studies have suggested that treatment of hypertension may reduce the incidence and severity of dementia. Whether certain antihypertensive agents provide additional benefits independent of their BP-lowering ability in reducing the incidence and progression of dementia in general, and Alzheimer’s disease (AD) in particular, has been the subject of considerable debate. A few studies in both humans and animals have suggested that angiotensin receptor blockers (ARBs) may preserve cognitive function independent of and in addition to their effects on BP. The current prospective, observational study analyzed information from the Veteran’s Administration (VA) healthcare system decision support database in a large population with uniform healthcare coverage. It asked whether, as compared to the angiotensin converting enzyme inhibitor (ACEI) lisinopril or other cardiovascular (CV) disease medications, use of ARBs is associated with a decrease in the incidence and progression of dementia and AD. Investigators identified patients who as of October 2002 were 65 years of age or older from a database of over 7.3 million people. Patients were divided into those who did (progression analysis) or did not yet (incidence analysis) have a diagnosis of AD or dementia as of October 2002. In each of these groups, 3 different cohorts were analyzed and compared: (1) those taking ARBs (overall sample size of more than 11,500 patients), (2) those taking the ACEI lisinopril (overall sample size of more than 91,000 patients), and (3) those taking other CV drugs (excluding ARBs, ACEIs, and statins) as defined by VA formulary classification (more than 696,000 patients). Drug use from any of those 3 classes was determined based on a ‘‘drug possession ratio’’ of at least 80% and no exposure to other study drug classes during an index period of 6 months from October 2002. Drug use after entry into the study was in no way restricted by the investigators and was completely at the discretion of the treating physicians. For patients with a known history of dementia or AD at study entry (progression analysis), the primary endpoints evaluated were time to admission to a nursing home and death. For patients without a known history of dementia or AD at study entry (incidence analysis), time to diagnosis of either condition were the primary endpoints. Data on endpoints were collected over a 5-year time span (fiscal year 2002–2006). Since raw BP data were not in the VA decision support database at the time of this study, the investigators determined mean BP for each cohort on the basis of a subsample from the VA health systems vertically integrated service network. To account for potential confounding variables, multiple statistical models including various CV From the Division of General Internal Medicine ⁄ Division of Cardiology, University of Nevada School of Medicine; the Risk Reduction Center, Saint Mary’s Regional Medical Center, Reno, NV; the Primary Care Service Line, Ralph H. Johnson VA Medical Center; and the Division of General Internal Medicine ⁄Geriatrics, Medical University of South Carolina, Charleston, SC Address for correspondence: Michael J. Bloch, MD, Risk Reduction Center, Saint Mary’s Regional Medical Center, 645 North Arlington Street, Suite 460, Reno, NV 89503 E-mail: mbloch@aol.com