The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity

Abstract

BackgroundAntihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management.MethodsIn a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities.FindingsRAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women.ConclusionHypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance.

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

“…Given the availability of potentially beneficial therapeutics and the lack of successful interventions for AD ( Edwards Iii et al, 2019 ), antihypertensive drugs have been explored as AD treatments. A retrospective cohort analysis of patients taking antihypertensive RAS-acting medicines, including angiotensin-converting enzyme inhibitors (ACEIs) and Ang II receptor blockers (ARBs), reported that AD incidence was lower in women (both Caucasian and African American) and Caucasian men taking ARBs compared with their counterparts not taking RAS-acting drugs ( Barthold et al, 2018 ). Furthermore, a meta-analysis found that controlling blood pressure with antihypertensive drugs in and of itself may have positive outcomes for cognitive function ( Ding et al, 2020 ).…”

Antihypertensive agents in Alzheimer’s disease: beyond vascular protection

“…Studies should include individuals with preclinical or early prodromal AD and plan a long follow-up period. As the association between antihypertensive drugs and AD may depend on sex, ethnicity and genetic background (APOE status), future therapeutic strategies will probably be personalized [148]. Recent evidence of the efficacy of polypills associating two antihypertensive drugs (diuretic and ACE inhibitor), statin, and aspirin came from a pragmatic trial in Iran, showing a reduction of the risk of major cardiovascular events.…”

Association of Angiotensin II–Stimulating Antihypertensive Use and Dementia Risk

“…6 Subclasses most consistently associated with reduced dementia risk compared to other antihypertensives are angiotensin receptor blockers, certain calcium channel blockers, and diuretics. [6][7][8][9][10][11][12][13][14] The mechanisms underlying these differential effects are currently unclear. [6][7][8][9][10][11][12]15 They may be related to the renin-angiotensin system (RAS; Figure 1).…”