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Population-Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study
Desai RJ, Varma VR, Mahesri M, Lee SB, Freedman A, Gerhard T, Segal J, Vine S et al.. Clinical pharmacology and therapeutics, 2025-02-11
Topic: Amyloid, tau and blood-test diagnosis
We evaluated whether drugs approved for other indications that also target metabolic drivers of Alzheimer's disease and related dementia (ADRD) pathogenesis are associated with delayed onset of ADRD. Using routinely collected healthcare data from two population-based data sources from the US (Medicare) and UK (CPRD), we conducted active comparator, new-user cohort studies. Four alternate analytic and design specifications were implemented: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month 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 [0.75-0.88] in Analysis 1, 0.98 [0.92-1.06] in Analysis 2, 0.83 [0.75-0.91] in Analysis 3, 0.75 [0.65-0.85] in Analysis 4). Amiloride vs. triamterene, although less precise, also suggested a potential reduction in risk in 3 out of 4 analyses (0.86 [0.66-1.11] in Analysis 1, 0.98 [0.79-1.23] in Analysis 2, 0.74 [0.54-1.00] in Analysis 3, 0.61 [0.36-1.05] 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.
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APA 7th
Desai, R. J., Varma, V. R., Mahesri, M., Lee, S. B., Freedman, A., Gerhard, T., et al. (2025). Population-Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study. Clinical pharmacology and therapeutics. https://doi.org/10.1002/cpt.3583
Vancouver
Desai RJ, Varma VR, Mahesri M, Lee SB, Freedman A, Gerhard T, et al. Population-Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study. Clinical pharmacology and therapeutics. 2025. doi:10.1002/cpt.3583. PMID: 39935003.
BibTeX
@article{desai2025-39935003,
author = {Desai, R. J. and Varma, V. R. and Mahesri, M. and Lee, S. B. and Freedman, A. and Gerhard, T. and Segal, J. and Vine, S. and others},
title = {{Population-Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study}},
journal = {Clinical pharmacology and therapeutics},
year = {2025},
doi = {10.1002/cpt.3583},
pmid = {39935003},
url = {https://doi.org/10.1002/cpt.3583}
}
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Key findings
- We evaluated whether drugs approved for other indications that also target metabolic drivers of Alzheimer's disease and related dementia (ADRD) pathogenesis are associated with delayed onset of ADRD.
- Future replication studies should be considered to validate our findings.
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Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical pharmacology and therapeutics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39935003) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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