Benzodiazepine use and risk of dementia: prospective population based study

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6231 (Published 27
September 2012)
Cite this as: BMJ 2012;345:e6231

Sophie Billioti de Gage, PhD student12,
Bernard Bégaud, professor123,
Fabienne Bazin, researcher12,
Hélène Verdoux, professor124,
Jean-François Dartigues, professor153,
Karine Pérès, researcher15,
Tobias Kurth, director of research167,
Antoine Pariente, associate professor123

Author Affiliations

Correspondence to: S Billioti de Gage or B Bégaud, Université
Bordeaux Segalen, INSERM U657, 146 rue Léo Saignat, F-33076, Bordeaux
cedex, France sophie.billiotidegage@u-bordeaux2.fr or
bernard.begaud@u-bordeaux2.fr

Accepted 4 September 2012

Abstract

Objective To evaluate the association between use of benzodiazepines
and incident dementia.

Design Prospective, population based study.

Setting PAQUID study, France.

Participants 1063 men and women (mean age 78.2 years) who were free of
dementia and did not start taking benzodiazepines until at least the
third year of follow-up.

Main outcome measures Incident dementia, confirmed by a neurologist.

Results During a 15 year follow-up, 253 incident cases of dementia
were confirmed. New use of benzodiazepines was associated with an
increased risk of dementia (multivariable adjusted hazard ratio 1.60,
95% confidence interval 1.08 to 2.38). Sensitivity analysis
considering the existence of depressive symptoms showed a similar
association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis
pooled cohorts of participants who started benzodiazepines during
follow-up and evaluated the association with incident dementia. The
pooled hazard ratio across the five cohorts of new benzodiazepine
users was 1.46 (1.10 to 1.94). Results of a complementary nested
case-control study showed that ever use of benzodiazepines was
associated with an approximately 50% increase in the risk of dementia
(adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users.
The results were similar in past users (odds ratio 1.56, 1.23 to 1.98)
and recent users (1.48, 0.83 to 2.63) but reached significance only
for past users.

Conclusions In this prospective population based study, new use of
benzodiazepines was associated with increased risk of dementia. The
result was robust in pooled analyses across cohorts of new users of
benzodiazepines throughout the study and in a complementary
case-control study. Considering the extent to which benzodiazepines
are prescribed and the number of potential adverse effects of this
drug class in the general population, indiscriminate widespread use
should be cautioned against.