1 Center for the Assessment of Pharmaceutical Practices and Pharmaceutical Assessment, Management and Policy Program, Department of Health Policy and Management, Boston University School of Public Health, Boston, MA, USA, 2 Center for Health Quality Outcomes and Economic Research, Veteran Affairs Medical Center, Bedford, MA, 3 Department of Surgery, Massachusetts General Hospital, Boston, MA, 4 Division of Research, Epidemiology, Etiology and Prevention, Kaiser Permanente, Oakland, CA, USA, 5 Aging Research Center, Karolinska Institute, Stockholm, Sweden, 6 MAVERIC, VA Cooperative Studies Program, Boston, MA, 7 Department of Pharmacology and Department of Neurology, Boston University School of Medicine, Boston, MA 02118-2526, USA

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases.

Design Prospective cohort analysis.

Setting Administrative database of the US Veteran Affairs, 2002-6.

Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease.

Main outcome measures Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the "cardiovascular comparator") over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia.

Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease.

Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population