{"doi":"10.1002/alz.12819","title":"Population‐based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans","abstract":"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.","journal":"Alzheimer s & Dementia","year":2022,"id":250830,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105382,"name":"Yuan Hou","orcid":null,"position":1,"is_corresponding":false},{"id":328942,"name":"Wanzhu Tu","orcid":"0000-0002-4236-9135","position":2,"is_corresponding":false},{"id":651140,"name":"Noll L. Campbell","orcid":"0000-0002-8933-9339","position":3,"is_corresponding":false},{"id":247916,"name":"Andrew A. Pieper","orcid":"0000-0001-6299-6577","position":4,"is_corresponding":false},{"id":108604,"name":"James B. Leverenz","orcid":"0000-0002-0896-0749","position":5,"is_corresponding":false},{"id":324302,"name":"Sujuan Gao","orcid":"0000-0002-6741-6380","position":6,"is_corresponding":false},{"id":2716,"name":"Jeffrey L. Cummings","orcid":"0000-0001-8944-4158","position":7,"is_corresponding":false},{"id":69831,"name":"Feixiong Cheng","orcid":"0000-0002-1736-2847","position":8,"is_corresponding":false},{"id":12547,"name":"Pengyue Zhang","orcid":"0000-0002-7381-9303","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T00:24:32.960657Z","pmid":"36331056","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}