Benzodiazepine Use and Risk of Dementia
Benzodiazepine Use and Risk of Dementia
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.
Primarily indicated for treating the symptoms of anxiety and sleep disorders over short periods, benzodiazepines are widely prescribed in developed countries. In France, 30% of people aged 65 years and over use benzodiazepines. They are used by more than 20% of people aged 65 and over in Canada and Spain and by around 15% of those in Australia. Benzodiazepine use is less widespread but still high in elderly people in the United States and the United Kingdom. Consumption of benzodiazepines is often chronic, and many people take them for years despite the existence of good practice guidelines suggesting that the duration should be limited to a few weeks.
The short term effects of benzodiazepines on cognition are well known. They are mediated through an agonist action on receptors of γ aminobutyric acid A, a major inhibitory neurotransmitter in the brain. However, the long term adverse effects of benzodiazepines on cognition are still debated.
Studies focusing on the association between benzodiazepine use and dementia or cognitive decline in elderly people have shown conflicting results. Some found an increased risk of dementia or cognitive impairment in benzodiazepine users, whereas others were not conclusive or reported a potential protective effect. In previous studies, the timing of exposure to benzodiazepines in relation to the outcome event allowed for the possibility of reverse causation. Insomnia, depression, and anxiety (the main indications for prescribing benzodiazepines) can be prodromal symptoms of dementia.
Dementia is already responsible for a major societal burden worldwide. With more than 81 million cases expected in 2040, this burden will become even greater in the coming decades. As treatment options remain limited, identifying factors contributing to dementia is critical. The objective of this study was to assess the association between starting benzodiazepines and risk of subsequent dementia in a well defined population based cohort of elderly people with available follow-up of up to 20 years.
Abstract and Introduction
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.
Introduction
Primarily indicated for treating the symptoms of anxiety and sleep disorders over short periods, benzodiazepines are widely prescribed in developed countries. In France, 30% of people aged 65 years and over use benzodiazepines. They are used by more than 20% of people aged 65 and over in Canada and Spain and by around 15% of those in Australia. Benzodiazepine use is less widespread but still high in elderly people in the United States and the United Kingdom. Consumption of benzodiazepines is often chronic, and many people take them for years despite the existence of good practice guidelines suggesting that the duration should be limited to a few weeks.
The short term effects of benzodiazepines on cognition are well known. They are mediated through an agonist action on receptors of γ aminobutyric acid A, a major inhibitory neurotransmitter in the brain. However, the long term adverse effects of benzodiazepines on cognition are still debated.
Studies focusing on the association between benzodiazepine use and dementia or cognitive decline in elderly people have shown conflicting results. Some found an increased risk of dementia or cognitive impairment in benzodiazepine users, whereas others were not conclusive or reported a potential protective effect. In previous studies, the timing of exposure to benzodiazepines in relation to the outcome event allowed for the possibility of reverse causation. Insomnia, depression, and anxiety (the main indications for prescribing benzodiazepines) can be prodromal symptoms of dementia.
Dementia is already responsible for a major societal burden worldwide. With more than 81 million cases expected in 2040, this burden will become even greater in the coming decades. As treatment options remain limited, identifying factors contributing to dementia is critical. The objective of this study was to assess the association between starting benzodiazepines and risk of subsequent dementia in a well defined population based cohort of elderly people with available follow-up of up to 20 years.
