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Benzodiazepine use and risk of Alzheimer's disease: case-control study
Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, Pariente A, Bégaud B.. BMJ (Clinical research ed.), 2014-09-09
Topic: Amyloid, tau and blood-test diagnosis
Objectives To investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment. Design Case-control study. Setting The Quebec health insurance program database (RAMQ). Participants 1796 people with a first diagnosis of Alzheimer's disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09. Main outcome measure The association between Alzheimer's disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life. Results Benzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose 180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones). Conclusion Benzodiazepine use is associated with an increased risk of Alzheimer's disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern.
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APA 7th
Billioti de Gage, S., Moride, Y., Ducruet, T., Kurth, T., Verdoux, H., Tournier, M., et al. (2014). Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ (Clinical research ed.). https://doi.org/10.1136/bmj.g5205
Vancouver
Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ (Clinical research ed.). 2014. doi:10.1136/bmj.g5205. PMID: 25208536.
BibTeX
@article{billiotidegage2014-25208536,
author = {Billioti de Gage, S. and Moride, Y. and Ducruet, T. and Kurth, T. and Verdoux, H. and Tournier, M. and Pariente, A. and Bégaud, B.},
title = {{Benzodiazepine use and risk of Alzheimer's disease: case-control study}},
journal = {BMJ (Clinical research ed.)},
year = {2014},
doi = {10.1136/bmj.g5205},
pmid = {25208536},
url = {https://doi.org/10.1136/bmj.g5205}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Results Benzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60).
- Conclusion Benzodiazepine use is associated with an increased risk of Alzheimer's disease.
- The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia.
Why it matters
In Quebec health-insurance records of adults over 66, the 1,796 people diagnosed with Alzheimer's were more likely than 7,184 matched controls to have started a benzodiazepine at least five years earlier (adjusted odds ratio 1.51; 1.43 after also accounting for anxiety, depression and insomnia), and the link was stronger for long-term use. The authors say this "reinforces the suspicion of a possible direct association" but that benzodiazepine use "might also be an early marker" of a condition that raises dementia risk — so it shows an association, not that the drugs cause Alzheimer's.
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Study details
- Study designcase-control study
- Participants1,796
- Evidence strengthModerate
How this study scored 69/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (BMJ (Clinical research ed.)) |
| Journal's citation record | 3 / 4 | BMJ: journal h-index 413 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| 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 | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,796 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 6 / 7 | Cited 559 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 39.9 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 6 / 6 | Cited 43.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 3 / 4 | Cited 77 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Bernard Bégaud: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25208536) |
| Free to read | 2 / 2 | Free to read |
| Total | 69 / 100 | — |
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