CNS Drugs

, Volume 30, Issue 1, pp 1–7 | Cite as

The Benzodiazepine–Dementia Disorders Link: Current State of Knowledge

  • Antoine Pariente
  • Sophie Billioti de Gage
  • Nicholas Moore
  • Bernard Bégaud
Current Opinion

Abstract

The short-term effects of benzodiazepines on memory are well established and are suspected in the long term. Eleven studies have been published so far concerning benzodiazepine use and the risk of dementia disorders; nine of these studies concluded these drugs have a deleterious effect, one found a protective effect, and one (the most recently published) observed no effect. The positive association found in some studies could be due to a reverse causation bias since the main indications for benzodiazepines (e.g. sleep disorders, anxiety) can also be prodromes of dementia disorders. This bias is less likely for treatments started more than 10 years before the diagnosis. Among others, three mechanisms could underlie the potential influence of benzodiazepines on the development of dementia disorders. First, benzodiazepines can decrease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) and γ-secretase activity and slow down the accumulation of Aβ oligomers in the brain. This potential positive effect has never been confirmed; the same is true for the prevention of excitotoxicity through benzodiazepine anti-glutamatergic action. Second, since astrocytes located in the area of amyloid plaques could have gamma-aminobutyric acid (GABA)-secreting activity, patients with pre-dementia lesions could be at increased risk of presenting with more pronounced deleterious cognitive effects of benzodiazepines. Finally, owing to the neural compensation and cognitive reserve concepts, some subjects could cope with initial lesions by using/developing alternative networks. By lowering the brain activation level, benzodiazepines could limit this capacity. In conclusion, it is essential that animal studies explore the mechanistic hypotheses of this association found by most of the pharmacoepidemiological studies conducted on this topic.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Antoine Pariente
    • 1
    • 2
  • Sophie Billioti de Gage
    • 1
  • Nicholas Moore
    • 1
    • 2
  • Bernard Bégaud
    • 1
    • 2
  1. 1.INSERM, U657-PharmacoepidemiologyUniversité de BordeauxBordeaux cedexFrance
  2. 2.Department of Clinical PharmacologyUniversity Hospital of BordeauxBordeauxFrance

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