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Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.
The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.
Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).
The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).
While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”
The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”
The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.
As more and more individuals are living well into their 80s and 90s, we can expect an increase in the burden of neurodegenerative illness including Alzheimer’s disease. This study showed that the likelihood of developing Alzheimer’s later in life was associated with prolonged exposure to benzodiazepines and to their duration of action. Monitoring cognitive side effects of medications is difficult and proving cause and effect can be challenging. For me, this reiterates the need to complete “medication reconciliation” at each patient encounter. Doing so may prevent duplication from different providers, maintains an up to date medication list, and most importantly, reassesses the need for continuation of medications being prescribed. In addition, before prescribing a medication, carefully consider the potential side effects and long-term consequences.
Dr. W. Michael Alberts, FCCP
As more and more individuals are living well into their 80s and 90s, we can expect an increase in the burden of neurodegenerative illness including Alzheimer’s disease. This study showed that the likelihood of developing Alzheimer’s later in life was associated with prolonged exposure to benzodiazepines and to their duration of action. Monitoring cognitive side effects of medications is difficult and proving cause and effect can be challenging. For me, this reiterates the need to complete “medication reconciliation” at each patient encounter. Doing so may prevent duplication from different providers, maintains an up to date medication list, and most importantly, reassesses the need for continuation of medications being prescribed. In addition, before prescribing a medication, carefully consider the potential side effects and long-term consequences.
Dr. W. Michael Alberts, FCCP
As more and more individuals are living well into their 80s and 90s, we can expect an increase in the burden of neurodegenerative illness including Alzheimer’s disease. This study showed that the likelihood of developing Alzheimer’s later in life was associated with prolonged exposure to benzodiazepines and to their duration of action. Monitoring cognitive side effects of medications is difficult and proving cause and effect can be challenging. For me, this reiterates the need to complete “medication reconciliation” at each patient encounter. Doing so may prevent duplication from different providers, maintains an up to date medication list, and most importantly, reassesses the need for continuation of medications being prescribed. In addition, before prescribing a medication, carefully consider the potential side effects and long-term consequences.
Dr. W. Michael Alberts, FCCP
Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.
The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.
Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).
The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).
While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”
The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”
The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.
Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.
The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.
Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).
The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).
While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”
The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”
The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.