Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

Abstract

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. INTRODUCTIONDementia, including Alzheimer's disease, is one of the major threats to public health as people age. Dementia is also an important economic cost to society because affected people may spend extended periods in nursing homes. The causes of dementia, and Alzheimer's disease in particular, are complex, but evidence increasingly points to three main risk factors-age, the accumulation of amyloid β in the brain, and the deterioration of the cardiovascular system. Cardiovascular dysfunction is also strongly related to other forms of dementia. Studies have found that cardiovascular risk factors in mid-life, such as hypercholesterolaemia, hypertension, and diabetes contribute to the development of dementia.1-5 Drugs used to treat these risk factors may also reduce the incidence of dementia.

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Similar beneficial effects in reducing the incidence and/or AD progression, has been found in a clinical trial with angiotensin 1 (AT-1) receptor blocker (Li et al 2010). Although experiments in animal AD models are limited, the results support the findings from clinical trials.…”

Antihypertensive medication use and risk of cognitive impairment

“…20 ARB treatment has also been linked to a reduced risk of Alzheimer disease among persons with a history of CVD, as compared with other cardiovascular drugs; however, this analysis used administrative data without validated outcome assessment and did not assess BB use specifically. 29 In an autopsy series of hypertensive subjects, ARB use was associated with less Alzheimerrelated pathology but more strokes, as compared with other antihypertensive and no drug treatment, although BB use alone was not evaluated. 30 Clinical trial data are similarly limited.…”

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

“…Medication with ARBs has been associated with decreased incidence of dementia [109,110]. Epidemiological analyses revealed that a group of patients that took ARBs, displayed significantly reduced incidence and progression of AD and dementia than those treated with a comparable antihypertensive agent, ACE inhibitor [109].…”

“…Medication with ARBs has been associated with decreased incidence of dementia [109,110]. Epidemiological analyses revealed that a group of patients that took ARBs, displayed significantly reduced incidence and progression of AD and dementia than those treated with a comparable antihypertensive agent, ACE inhibitor [109]. In vivo animal studies revealed that oral or intranasal administration of some ARBs, including valsartan, olmesartan, and losartan, reduced Aβ levels and ameliorated spatial learning and memory deficits in mouse models of Aβ pathology [111,112].…”