BMJ. 2012 Sep 27;345:e6231. doi: 10.1136/bmj.e6231.
Benzodiazepine use and risk of dementia: prospective population based study.
Source
Université Bordeaux Segalen, F-33000 Bordeaux, France.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.Pub
Benzodiazepine use and risk of dementia: prospective population based study
This study demonstrates a clear association between the use of
benzodiazepines and a subsequent diagnosis of dementia but it does not
demonstrate causality.
Sleep disturbance is a common feature across many forms of neurodegenerative disease (1) and may precede a diagnosis of dementia by some years. A clear example of this is the strong association between a developing a REM sleep behavioural disorder (RBD) and alpha-synucleinopathies, including Dementia with Lewy bodies. The ten year risk of a significant neurodegenerative disease following ‘idiopathic’ RBD has been estimated at around 40% (2). Benzodiazepines remain a commonly used treatment for sleep disturbance and the introduction of benzodiazepines between years three and five of the study may indicate the onset of dementia pathology without the diagnosis being made until later.
Furthermore psychiatric symptoms and disorders other than depression (the only one considered in the analysis), including anxiety are common and may lead to the introduction of a benzodiazepine. These may therefore also herald the emergence of a neurodegenerative disorder or other dementia long before a formal diagnosis of dementia is made.
The authors admit that the indications for the introduction of a benzodiazepine may be prodromal symptoms of dementia but argue against this reverse causality confounding their results. They use a three year run-in time and exclude participants who have been exposed to benzodiazepines prior to or during this. This allows for adjustment for pre-existing factors already treated with benzodiazepines but not the emergence of new ones. The increase in association strength of new use of benzodiazepines and dementia diagnosis after about seven years of follow up does not differentiate between benzodiazepine use or any underlying symptomatic risk factors for dementia being treated. Similarly the lack of increase of association strength amongst cohorts of new benzodiazepines users at later stages of the study cannot be used to make inferences about the underlying causality. The small sample sizes and wide confidence intervals for hazard ratio for each subsequent cohort precludes significant comparisons of risk between them.
This paper raises an important issue but does not provide evidence of a causal link between benzodiazepines and dementia. It must be treated with caution, especially in view of the potential harm or anxiety induced by such reports or sudden changes in prescription practice.
BMJ
Sleep disturbance is a common feature across many forms of neurodegenerative disease (1) and may precede a diagnosis of dementia by some years. A clear example of this is the strong association between a developing a REM sleep behavioural disorder (RBD) and alpha-synucleinopathies, including Dementia with Lewy bodies. The ten year risk of a significant neurodegenerative disease following ‘idiopathic’ RBD has been estimated at around 40% (2). Benzodiazepines remain a commonly used treatment for sleep disturbance and the introduction of benzodiazepines between years three and five of the study may indicate the onset of dementia pathology without the diagnosis being made until later.
Furthermore psychiatric symptoms and disorders other than depression (the only one considered in the analysis), including anxiety are common and may lead to the introduction of a benzodiazepine. These may therefore also herald the emergence of a neurodegenerative disorder or other dementia long before a formal diagnosis of dementia is made.
The authors admit that the indications for the introduction of a benzodiazepine may be prodromal symptoms of dementia but argue against this reverse causality confounding their results. They use a three year run-in time and exclude participants who have been exposed to benzodiazepines prior to or during this. This allows for adjustment for pre-existing factors already treated with benzodiazepines but not the emergence of new ones. The increase in association strength of new use of benzodiazepines and dementia diagnosis after about seven years of follow up does not differentiate between benzodiazepine use or any underlying symptomatic risk factors for dementia being treated. Similarly the lack of increase of association strength amongst cohorts of new benzodiazepines users at later stages of the study cannot be used to make inferences about the underlying causality. The small sample sizes and wide confidence intervals for hazard ratio for each subsequent cohort precludes significant comparisons of risk between them.
This paper raises an important issue but does not provide evidence of a causal link between benzodiazepines and dementia. It must be treated with caution, especially in view of the potential harm or anxiety induced by such reports or sudden changes in prescription practice.
BMJ
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