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Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort
AbuAlrob MA, Itbaisha A, Abujwaid YK, Abulehia A, Hussein A, Mesraoua B.. Journal of Alzheimer's disease reports, 2025-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Alzheimer's disease (AD) is a leading cause of dementia with societal and economic burdens. While recent therapies offer disease-modifying potential, concerns remain about efficacy and safety. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), used in type 2 diabetes, show neuroprotective effects via reduced neuroinflammation and amyloid burden. Objective To evaluate whether GLP-1RA use is associated with a reduced risk of incident dementia in adults aged ≥50 years using real-world data. Methods We conducted a retrospective cohort study using the TriNetX platform, analyzing records from 142 healthcare organizations. Adults aged ≥50 were included, comparing GLP-1RA users (liraglutide, semaglutide, dulaglutide, exenatide, albiglutide) to non-users. Propensity-score matching balanced demographics and comorbidities. Incident dementia, defined by ICD-10 codes, was analyzed with Cox proportional-hazards models. Results Matched cohorts (n = 147,505 each) had similar baseline characteristics. Dementia incidence was lower in GLP-1RA users (0.20% versus 0.44%), with a hazard ratio of 0.30 (95% CI 0.28-0.33; p < 0.001). Conclusions GLP-1RA use was associated with a 70% reduced dementia risk, warranting further clinical evaluation.
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APA 7th
AbuAlrob, M. A., Itbaisha, A., Abujwaid, Y. K., Abulehia, A., Hussein, A., & Mesraoua, B. (2025). Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort. Journal of Alzheimer's disease reports. https://doi.org/10.1177/25424823251388650
Vancouver
AbuAlrob MA, Itbaisha A, Abujwaid YK, Abulehia A, Hussein A, Mesraoua B. Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort. Journal of Alzheimer's disease reports. 2025. doi:10.1177/25424823251388650. PMID: 41122341.
BibTeX
@article{abualrob2025-41122341,
author = {AbuAlrob, M. A. and Itbaisha, A. and Abujwaid, Y. K. and Abulehia, A. and Hussein, A. and Mesraoua, B.},
title = {{Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort}},
journal = {Journal of Alzheimer's disease reports},
year = {2025},
doi = {10.1177/25424823251388650},
pmid = {41122341},
url = {https://doi.org/10.1177/25424823251388650}
}
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Key findings
- Objective To evaluate whether GLP-1RA use is associated with a reduced risk of incident dementia in adults aged ≥50 years using real-world data.
- Results Matched cohorts (n = 147,505 each) had similar baseline characteristics.
- Dementia incidence was lower in GLP-1RA users (0.20% versus 0.44%), with a hazard ratio of 0.30 (95% CI 0.28-0.33; p < 0.001).
- Conclusions GLP-1RA use was associated with a 70% reduced dementia risk, warranting further clinical evaluation.
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Study details
- Study designcohort study
- Participants147,505
- Effect size0.20%; 0.44%
- Evidence strengthModerate
How this study scored 76/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for 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 44 of the 58 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease reports) |
| 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 | 4 / 4 | 147,505 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 41122341) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 44 of the 58 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
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