Evidence map›Paper›PMID 25208536›Full record

ArticleBMJ (Clinical research ed.)2014

Benzodiazepine use and risk of Alzheimer's disease: case-control study.

Sophie Billioti de Gage, Yola Moride, Thierry Ducruet, Tobias Kurth, Hélène Verdoux, Marie Tournier, Antoine Pariente, Bernard Bégaud

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ (Clinical research ed.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02478593 (Impact of Patient Education on Benzodiazepine Use in the Elderly), which is not on this map. Cited by 222 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
222citing papers in PubMed, 16 pooled it
39.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02478593 nawithdrawnnot on this mapstarted 2015, after this paper: background citation

Impact of Patient Education on Benzodiazepine Use in the Elderly

TypeinterventionalSponsorUniversity of VermontRan2015 to 2019Enrolled0ConditionsAnxiety, InsomniaArmsEducational booklet
3 · Its place in the literature

Who cites it

222 citing papers in PubMed, 16 syntheses or guidelines pooled it, 545 citations in OpenAlex.

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  4. Use of Drugs Affecting GABAMolecular neurobiology · 2025
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162 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Sophie Billioti de GageINSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France sophie.billioti-de-gage@u-bordeaux.fr.
Yola MorideResearch Center, University of Montreal Hospital Center, Montreal, Canada Faculty of Pharmacy, University of Montreal, Montreal, Canada.
Thierry DucruetResearch Center, University of Montreal Hospital Center, Montreal, Canada.
Tobias KurthInserm Research Center for Epidemiology and Biostatistics, U897-Team Neuroepidemiology, F-33000 Bordeaux, France University of Bordeaux, College of Health Sciences, F-33000 Bordeaux, France.
Hélène VerdouxINSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France Centre Hospitalier Charles Perrens, F-33000 Bordeaux, France.
Marie TournierINSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France Centre Hospitalier Charles Perrens, F-33000 Bordeaux, France.
Antoine ParienteINSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France.
Bernard BégaudINSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France.
Bordeaux Population Health · FRUniversité de Montréal · CAInserm · FRUniversité de Bordeaux · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo 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.

designCase-control study.

settingThe Quebec health insurance program database (RAMQ).

participants1796 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 measureThe 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.

resultsBenzodiazepine 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 <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >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).

conclusionBenzodiazepine 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.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAnxiety DisordersBenzodiazepinesCase-Control StudiesDepressive DisorderFemaleHumansMaleQuebecRisk FactorsSleep Initiation and Maintenance DisordersBenzodiazepines

Identifiers

PMID25208536
PMCPMC4159609
OpenAlexW2000736071

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.