Insights on benzodiazepines' potential in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most frequent type of dementia characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. AD is associated with the disturbances of various neurotransmitters including gamma-aminobutyric acid (GABA). Of note, GABA is reduced in AD, and restoration of GABA effect by benzodiazepines (BDZs) may improve AD outcomes. However, BDZs may adversely affect cognitive functions chiefly in elderly AD patients with sleep disorders. Besides, there is a controversy regarding the use of BDZs in AD. Consequently, the objective of the present review was to disclose the possible role of BDZs on the pathogenesis of AD that might be beneficial, neutral, or detrimental effects on AD. Prolonged use of intermediate-acting BDZ lorazepam exerts amnesic effects due to attenuation of synaptic plasticity and impairment of recognition memory. However, BDZs may have a protective effect against the development of AD by reducing tau phosphorylation, neuroinflammation, and progression of AD neuropathology. On the other side, other findings highlighted that extended use of BDZs was not associated with the development of AD. In conclusion, there are controversial points concerning the use of BDZs and the risk for the progression of AD. Thus, preclinical, and clinical studies are essential in this regard.

Keywords: Alzheimer's disease; Benzodiazepines; Cognitive dysfunction; Gamma-aminobutyric acid.