Journal
ALZHEIMERS & DEMENTIA
Volume 19, Issue 5, Pages 1876-1887Publisher
WILEY
DOI: 10.1002/alz.12819
Keywords
African American; Alzheimer's disease; angiotensin II receptor blockers; insurance claim data; Mendelian randomization; pharmacoepidemiology; telmisartan
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The study found that moderate to high exposure to telmisartan was significantly associated with a reduced incidence of Alzheimer's disease in African Americans, but not in non-Hispanic European Americans. The medication possession ratio and average hypertension daily dosage of telmisartan were significantly associated with a stronger reduction in the incidence of both Alzheimer's disease and dementia in African Americans.
Introduction African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. Methods We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age >= 60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. Results We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs . Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. Discussion Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. Highlights Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-gamma agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.
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