Key result
Moderate to high telmisartan exposure linked to ~23% lower Alzheimer's incidence in African Americans.
Why the study?
African Americans and European Americans differ in Alzheimer's disease prevalence, risk factors, and presentation, yet African Americans are less likely to enroll in clinical trials.
Does moderate/high telmisartan exposure reduce the incidence of Alzheimer's disease in older African Americans?
Observational (n=5,620,000)
Does moderate/high telmisartan exposure reduce the incidence of Alzheimer's disease in older African Americans?
Telmisartan exposure is associated with a significantly reduced risk of Alzheimer's disease specifically in African Americans, suggesting a potential race-specific neuroprotective benefit.
Telmisartan should not yet alter AD prevention strategies; leaves open hypothesis of race-specific benefit pending randomized confirmation.
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-γ 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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Zhang et al. (2022) conducted an observational in Alzheimer's disease (n=5,620,000). Telmisartan vs. Low/no telmisartan exposure was evaluated on Incidence of Alzheimer's disease (HR 0.77, 95% CI 0.65-0.91, p=0.0022). Moderate to high telmisartan exposure was associated with a reduced incidence of Alzheimer's disease in African Americans compared to low or no exposure (HR 0.77; 95% CI 0.65-0.91; P=0.0022).
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