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Using routinely collected healthcare data from two population\u2010based data sources from the US (Medicare) and UK (CPRD), we conducted active comparator, new\u2010user cohort studies. Four alternate analytic and design specifications were implemented: (1) an as\u2010treated follow\u2010up approach, (2) an as\u2010started follow\u2010up approach incorporating a 6\u2010month induction period, (3) incorporating a 6\u2010month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Of the 10 drug pairs evaluated, hydrochlorothiazide vs. dihydropyridine CCBs showed meaningful reductions in 3 out of 4 analyses that addressed specific biases including informative censoring, reverse causality, and outcome misclassification (pooled hazard ratios [95% confidence intervals] across Medicare and CPRD: 0.81 [0.75\u20130.88] in Analysis 1, 0.98 [0.92\u20131.06] in Analysis 2, 0.83 [0.75\u20130.91] in Analysis 3, 0.75 [0.65\u20130.85] in Analysis 4). Amiloride vs. triamterene, although less precise, also suggested a potential reduction in risk in 3 out of 4 analyses (0.86 [0.66\u20131.11] in Analysis 1, 0.98 [0.79\u20131.23] in Analysis 2, 0.74 [0.54\u20131.00] in Analysis 3, 0.61 [0.36\u20131.05] in Analysis 4). Other analyses suggested likely no major differences in risk (probenecid, salbutamol, montelukast, propranolol\/carvedilol, and anastrozole) or had limited precision precluding a definitive conclusion (semaglutide, ciloztozol, levetiracetam). Future replication studies should be considered to validate our findings.<\/jats:p>","DOI":"10.1002\/cpt.3583","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:19:22Z","timestamp":1739319562000},"page":"1039-1050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population\u2010Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-7273","authenticated-orcid":false,"given":"Rishi J.","family":"Desai","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine, Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay 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