{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:30:48Z","timestamp":1777397448066,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>P-glycoprotein (P-gp) is linked to Alzheimer's disease (AD), as P-gp contributes to clearance of amyloid-\u03b2 (A\u03b2) from the CNS. Thus, other P-gp substrates (Pgp-S) could affect A\u03b2 clearance, either negatively through competitive inhibition or positively via cooperative transport, impacting risk for AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We probed impacts of Pgp-S on AD risk by querying AD rates among individuals prescribed medications that are considered Pgp-S.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort study was performed using the PharMetrics Plus database (IQVIA), encompassing 70,340 users of prescription drugs identified as Pgp-S and 352,382 Pgp-S non-users. Users and non-users were matched by age, sex, and geographical region. Cox regression models afforded adjustments for covariates and comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pgp-S use was generally associated with a significant reduction in the hazard ratio of AD in both crude (HR\u2009=\u20090.89, 95% CI\u2009=\u20090.79\u20130.99) and matched (HR\u2009=\u20090.87; 95% CI\u2009=\u20090.78\u20130.98) analyses. AD risk was higher among subsets diagnosed with comorbidities: depression (HR\u2009=\u20094.44; 95% CI, 3.99\u20134.94), stroke (HR\u2009=\u20091.98, 95% CI\u2009=\u20091.63\u20132.41), and hypertension (HR\u2009=\u20091.24, 95% CI\u2009=\u20091.13\u20131.36). In an analysis of individual drugs, digoxin (OR = 0.52, 95% CI, 0.34\u20130.77), atorvastatin (OR = 0.80, 95% CI, 0.73\u20130.87), omeprazole (OR = 0.83, 95% CI, 0.73\u20130.94), and prednisone (OR = 0.64, 95% CI, 0.46\u20130.86) were associated with significantly decreased odds of incident AD; rivaroxaban (OR = 1.29, 95% CI\u2009=\u20090.97\u20131.68) and mirabegron (OR = 1.45, 95% CI\u2009=\u20090.86\u20132.28) trended toward increased risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings suggest an association between Pgp-S use and AD, but limitations of the study design impel additional work to confirm the direction of impact for individual drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251351629","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T02:57:20Z","timestamp":1750733840000},"page":"1063-1073","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Prescription-based association of P-glycoprotein substrates with Alzheimer's disease risk: A nested case-control study"],"prefix":"10.1177","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4618-5133","authenticated-orcid":false,"suffix":"Jr","given":"Joseph","family":"Asante","sequence":"first","affiliation":[{"name":"Graduate Program in Bioinformatics, University of Arkansas at Little Rock, Little Rock, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-500X","authenticated-orcid":false,"given":"Corey L","family":"Nagel","sequence":"additional","affiliation":[{"name":"College of Nursing, University of Arkansas for Medical Sciences, Little Rock, AR, USA"},{"name":"Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-6480","authenticated-orcid":false,"given":"Steven W","family":"Barger","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA"},{"name":"Department of Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, USA"},{"name":"Geriatric Research, Education &amp; Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25247"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160314151012"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-023-00470-z"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15148"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00113.x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200210000-00005"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205043332225"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.061754"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-802851-3.00007-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.834661"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1303111"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1358568"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2021-217090"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2299"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025815"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00130.x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1316"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2012.02.002"},{"key":"e_1_3_4_20_2","unstructured":"IQVIA. 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