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

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 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.

Methods: In 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.

Findings: RAS-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.

Conclusion: Hypertension 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.