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.

Highlights

  • An estimated 5.5 million Americans have Alzheimer’s disease (AD), which is the most common cause of dementia [1]

  • Antihypertensive (AHT) medications are commonly prescribed for adults with chronic high blood pressure, spanning six different widely used therapeutic classes: two renin-angiotensin system (RAS) acting classes (angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs)), and four classes that work primarily via non-RAS mechanisms (beta blockers (BBLs), calcium channel blockers (CCBs), loop diuretics (LDs), and thiazide-like diuretics (TDs))

  • We examined differences within RAS-acting AHTs by comparing ACEIs and ARBs, and whether associations vary by sex and race/ethnicity in multivariable regressions that control for age, sex, race, education, income, comorbidities, health care utilization tendencies, and statin use

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Summary

Background

Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and 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

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