{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:13:39Z","timestamp":1791490419630,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R35AG071476"],"award-info":[{"award-number":["R35AG071476"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG071018"],"award-info":[{"award-number":["R01AG071018"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2023,5]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>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.<\/jats:p><\/jats:sec>Methods<\/jats:title>We conducted race\u2010conscious pharmacoepidemiologic studies of 5.62 million older individuals (age \u226560) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan\u2013Meier analysis, and log\u2010rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD.<\/jats:p><\/jats:sec>Results<\/jats:title>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\u20130.91, p<\/jats:italic>\u2010value = 0.0022), but not in the non\u2010Hispanic EAs (HR = 0.97, 95% CI: 0.89\u20131.05, p<\/jats:italic>\u2010value = 0.4110). Sensitivity and sex\u2010\/age\u2010stratified 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\u2010wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA\u2010specific beneficial effects of telmisartan for AD.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD.<\/jats:p><\/jats:sec>Highlights<\/jats:title>\nTelmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs).<\/jats:p><\/jats:list-item>\nTelmisartan is the only angiotensin II receptor blockers having PPAR\u2010\u03b3 agonistic properties with beneficial anti\u2010diabetic and renal function effects, which mitigate AD risk in AAs.<\/jats:p><\/jats:list-item>\nMendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12819","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T07:22:37Z","timestamp":1667546557000},"page":"1876-1887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Population\u2010based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans"],"prefix":"10.1002","volume":"19","author":[{"given":"Pengyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hou","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhu","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noll","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Purdue University West Lafayette Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Pieper","sequence":"additional","affiliation":[{"name":"Harrington Discovery Institute University Hospitals Cleveland Medical Center Cleveland Ohio USA"},{"name":"Department of Psychiatry Case Western Reserve University Cleveland Ohio USA"},{"name":"Geriatric Psychiatry GRECC Louis Stokes Cleveland VA Medical Center Cleveland Ohio USA"},{"name":"Institute for Transformative Molecular Medicine School of Medicine Case Western Reserve University Cleveland Ohio USA"},{"name":"Department of Neuroscience Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Leverenz","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Ohio USA"},{"name":"Lou Ruvo Center for Brain Health Neurological Institute Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Cummings","sequence":"additional","affiliation":[{"name":"Chambers\u2010Grundy Center for Transformative Neuroscience Department of Brain Health School of Integrated Health Sciences University of Nevada Las Vegas Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixiong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland Ohio USA"},{"name":"Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Ohio USA"},{"name":"Case Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2003.5.1\/hhippius"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","unstructured":"Asher Mullard.Controversial Alzheimer's drug approval could affect other diseases.2021;2021.","DOI":"10.1038\/d41586-021-01763-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179573520907397"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12328"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4471"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12509"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt269"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21709"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.41"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00838-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000152888.26576.37"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2018.06.021"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30267-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0000000000000308"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.21442"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.3536"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.16879"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02989"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10150917"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2016.09.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12023"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-014-0239-7"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.45"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-016-0165-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2012.08.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S206770"},{"key":"e_1_2_8_29_1","unstructured":"GaspariniA SalmasianH Williman J.Comorbidity: computing comorbidity scores. Accessed July 31 2022.https:\/\/cran.r\u2010project.org\/web\/packages\/comorbidity\/comorbidity.pdf"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.34059"},{"key":"e_1_2_8_31_1","unstructured":"Centers for Disease Control and Prevention (CDC).Alcohol\u2010related ICD codes.2021;2021. Accessed July 31 2022.https:\/\/www.cdc.gov\/alcohol\/ardi\/alcohol\u2010related\u2010icd\u2010codes.html"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-020-0117-1"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab071"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq433"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002496"},{"key":"e_1_2_8_36_1","unstructured":"HansenB FredricksonM BucknerJ et\u00a0al.Optmatch: functions for optimal matching. Accessed July 31 2022.https:\/\/rdrr.io\/cran\/optmatch\/"},{"key":"e_1_2_8_37_1","unstructured":"HoD ImaiK KingG et\u00a0al.MatchIt: nonparametric preprocessing for parametric causal inference. Accessed July 31 2022.https:\/\/www.jstatsoft.org\/article\/view\/v042i08"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"e_1_2_8_39_1","first-page":"471","article-title":"Nonparametric estimation from incomplete observations","author":"Kaplan E","year":"1958","journal-title":"J Am Stat Assoc"},{"key":"e_1_2_8_40_1","first-page":"163","article-title":"Evaluation of survival data and two new rank order statistics arising in its consideration","volume":"50","author":"Mantel N","year":"1966","journal-title":"Cancer Chemother Rep"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-020-00642-8"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00713-x"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00931-x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1055"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4197"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00776-w"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0311-9"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14156-4"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05116-5"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16969-0"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.09.015"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.07.014"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2016.1252380"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mbp.0000172708.97534.15"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.204"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0407-x"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07867-7"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2352"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017080856"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13418"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp471"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24439"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2017.01.006"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4499-5"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00934-0"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00951-z"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00043-0"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17049"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.05.023"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-013-0321-y"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111441"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b12-00387"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-102"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00138-z"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0212117"}],"container-title":["Alzheimer's & Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12819","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12819","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:36:16Z","timestamp":1759941376000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":78,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/alz.12819"],"URL":"https:\/\/doi.org\/10.1002\/alz.12819","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]},"assertion":[{"value":"2022-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}