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A case-control study published in The British Medical Journal has reported a link between benzodiazepines and Alzheimer’s disease.

While there is currently no effective treatment for Alzheimer’s disease, there are a growing number of studies aimed at investigating the possible causes and risk factors for developing Alzheimer’s disease. A recent study, published in The British Medical Journal on September 9, 2014, is a case-control study that examines the relationship between benzodiazepines and risk of Alzheimer’s disease.

Benzodiazepine drugs are prescribed primarily for the treatment of anxiety and insomnia, and their use in elderly populations can range up to 43%. Benzodiazepines increase the activity of GABA neurotransmitters in the brain, (which are inhibitory neurotransmitters), ultimately acting to have an inhibitory or calming effect. Different types of benzodiazepines have either short, intermediate, or long-acting effects. The shorter acting benzodiazepines are better suited for treating insomnia, while the longer acting benzodiazepines are better suited for treatment of anxiety. Some examples of benzodiazepines include: alprazolam (Xanax), lorazepam (Ativan), bromazepam (Lectopam), oxazepam (Serax), diazepam (Valium), and temazepam (Restoril).

There is evidence that benzodiazepines have negative effects on memory and cognition, however there is some dispute as to whether use of these drugs increases risk of dementia. The question the authors set out to answer was whether there was an association between use of benzodiazepines and the risk of Alzheimer’s disease, and whether this was a dose effect. The case-control study included an elderly population, aged 66 years or older, living in Quebec, Canada. To be included in the study, the patients were required to have their first diagnosis of Alzheimer’s disease during the study period, without having a prior diagnosis of any other form of dementia, or associated treatment. Each patient was matched with four controls, matched for sex, age group, and duration of follow up. In total, 1796 patients were analysed as cases, with 7184 matched controls. Of the participants followed during the study, 49.8% of those who developed Alzheimer’s disease (compared with 40% of the controls) had taken benzodiazepines. In addition, 32.9% of patients with Alzheimer’s disease (compared with 21.8% of control patients) had a recorded long-term use of benzodiazepines. The study reported a significant increase in risk of Alzheimer’s disease (43-51%) with the use of benzodiazepines at any time, and increasing risk with increased exposure to the drug. In support of these findings, the study also reported a stronger association of Alzheimer’s disease with long acting benzodiazepines compared to short acting benzodiazepines.

The study also adjusted for potential confounding factors due to suggestions that symptoms of depression, anxiety, or sleep disorders could potentially be precursors to dementia. Adjustment for these confounding factors did not significantly change the results of the study.

The authors suggest that an experimental approach in animal models should be undertaken in order to investigate the biological mechanism(s) that may play a role in the link between benzodiazepines and Alzheimer’s disease. Additionally, as a result of the findings of the study, the authors suggest that physicians carefully consider the risks versus benefits of benzodiazepines before prescribing to patients, and support the current international recommendations for short-term use, no longer than three months in duration.

 

Dikeos DG, Theleritis CG, Soldatos CR (2008). “Benzodiazepines: effects on sleep”.

In Pandi-Perumal SR, Verster JC, Monti JM, Lader M, Langer SZ (eds.). “Sleep Disorders: Diagnosis and Therapeutics.”Informa Healthcare. pp. 220–2.

De Gage, SB, Moride, Y, Ducruet, T, Kurth, T,Verdoux, H, Tournier, M, Pariente, A, Bégaud, B. “Benzodiazepine use and risk of Alzheimer’s disease: case-control study” BMJ 2014;349:g5205

Image courtesy of David Castillo Dominici at FreeDigitalPhotos.net

 

 

Written by Deborah Tallarigo, PhD

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