{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:53:08Z","timestamp":1790117588994,"version":"4.0.1"},"reference-count":102,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,13]],"date-time":"2018-10-13T00:00:00Z","timestamp":1539388800000},"content-version":"vor","delay-in-days":285,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DA035778"],"award-info":[{"award-number":["P30 DA035778"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared the effect of aHTN drugs on Mini\u2010Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combination of diuretics, calcium channel blockers, and renin\u2010angiotensin\u2010aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (\u0394\u03b2\u00a0=\u00a0+1.46,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001). aHTN medications slow down cognitive decline in ChEI users (\u0394\u03b2\u00a0=\u00a0+0.56,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.006), but not in non\u2010ChEI users (\u0394\u03b2\u00a0=\u00a0\u22120.31,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.53).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>aHTN and ChEI drugs showed synergistic effects. A combination of diuretics, renin\u2010angiotensin\u2010aldosterone system blockers, and calcium channel blockers had the slowest cognitive decline. The chemogenomics systems pharmacology\u2013identified molecular targets provide system pharmacology interpretation of the synergism of the drugs in clinics. The results suggest that improving vascular health is essential for AD treatment and provide a novel direction for AD drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.trci.2018.09.001","type":"journal-article","created":{"date-parts":[[2018,10,13]],"date-time":"2018-10-13T21:38:13Z","timestamp":1539466693000},"page":"542-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease"],"prefix":"10.1002","volume":"4","author":[{"given":"Ziheng","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levent","family":"Kirisci","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh Pittsburgh PA USA"},{"name":"Department of Clinical Pharmacy Zhongshan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Klunk","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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