Antihypertensive drugs decrease risk of Alzheimer disease

Abstract

Objectives: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or b-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI).Methods: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n 5 1,928) or MCI (n 5 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders.Results: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio 5 0.38, 95% CI 0.20-0.73).Conclusions: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI. Observational studies suggest protective effects of antihypertensive medications on risk of dementia 1-6 independently or in addition to their ability to control blood pressure, and that these effects may be specific to the class of drugs to which they belong. A postmortem study of subjects with Alzheimer disease (AD) dementia showed that treated hypertensive subjects had less AD dementia neuropathology than untreated hypertensive and normotensive subjects, 7 while imaging studies showed preserved hippocampus in normotensive and treated hypertensive subjects. 8,9 However, clinical trials evaluating antihypertensive medications for dementia prevention found no risk reduction, 10-12 which could be explained by dementia being a secondary outcome and therefore insufficiently powered. Additionally, the majority of these studies were confounded by combined antihypertensive medication use 11,13-16 to achieve acceptable blood pressure. There are few studies with equivocal evidence regarding the role of hypertension (HTN) and no randomized clinical trials evaluating the effects of antihypertensive medications on progression of mild cognitive impairment (MCI) to dementia.

P2‐083: Age of Onset of Hypertension and Risk of Dementia in the Oldest‐old: The 90+ Study

“…Studies of younger elderly have reported lower dementia risk in people taking different classes of anti-hypertensive medications [34][35][36]. These studies, however, have not included the oldest-old and we did not find similar effects (data not shown).…”

Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

“…In addition, clinical studies reported that for each 10mmHg decrease in systolic blood pressure or diastolic blood pressure there was a significant reduction in risk of conversion from any type MCI to dementia 27 ; and that systolic or diastolic blood pressure readings did not predict conversion from aMCI to AD 32 and treatment with a diuretic was associated with a lower risk of conversion from any type MCI to AD, compared with no antihypertensive treatment 33 .…”

Antihypertensive drug use and risk of cognitive decline in the very old

“…Relationships between blood pressure lowering and dementia risk are less well understood [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], particularly in very old age [3]. Systematic reviews [10][11][12], clinical trials [13,14,19] and observational studies [15][16][17][18][20][21][22] variably report antihypertensive drug use as associated with decreased risk of dementia/cognitive decline [14][15][16][17][18][19][20][21], increased risk [22], or no impact [10][11][12][13]. The majority of double-blind randomized placebo controlled trials show no relationships.…”