Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia

Author(s):Show less -

Ettcheto, Miren ^{[1, 2, 3, 4]} ; Olloquequi, Jordi ^[5] ; Sanchez-Lopez, Elena ^{[1, 6, 7]} ; Busquets, Oriol ^{[1, 2, 3, 4]} ; Cano, Amanda ^{[1, 6, 7]} ; Regina Manzine, Patricia ^[8] ; Beas-Zarate, Carlos ^[9] ; Castro-Torres, Ruben D. ^[9] ; Luisa Garcia, Maria ^{[1, 6, 7]} ; Bullo, Monica ^{[3, 10, 11]} ; Auladell, Carme ^{[1, 2, 12]} ; Folch, Jaume ^{[1, 3]} ; Camins, Antoni ^{[1, 2, 4, 5]}

Affiliation:Show less -

^[1] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid - Spain

^[2] Univ Barcelona, Inst Neurociencies, Barcelona - Spain

^[3] Univ Rovira & Virgili, Fac Med & Cieincies Salut, Dept Bioquim & Biotecnol, Reus - Spain

^[4] Univ Barcelona, Fac Farm & Ciencies Alimentac, Dept Farmacol Toxicol & Quim Terapeut, Barcelona - Spain

^[5] Univ Autonoma Chile, Inst Ciencias Biomed, Fac Ciencias Salud, Lab Cellular & Mol Pathol, Talca - Chile

^[6] Univ Barcelona, Fac Farm & Ciencies Alimentac, Unitat Farm Tecnol Farmaceut & Fisicoquim, Barcelona - Spain

^[7] Univ Barcelona, Inst Nanosci & Nanotechnol IN2UB, Barcelona - Spain

^[8] Fed Univ Sao Carlos UFSCar, Dept Gerontol, Sao Carlos - Brazil

^[9] CUCBA, Inst Neurobiol, Dept Biol Celular & Mol, Lab Regenerac & Desarrollo Neural, Guadalajara - Mexico

^[10] IISPV, Reus - Spain

^[11] Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid - Spain

^[12] Univ Barcelona, Fac Biol, Dept Biol Cellular Fisiol & Immunol, Barcelona - Spain

• Document type: Review article
• Source: FRONTIERS IN AGING NEUROSCIENCE; v. 11, JAN 8 2020.
• Web of Science Citations: 0

Abstract

Benzodiazepines (BZDs) and Z-drugs are compounds widely prescribed in medical practice due to their anxiolytic, hypnotic, and muscle relaxant properties. Yet, their chronic use is associated with cases of abuse, dependence, and relapse in many patients. Furthermore, elderly people are susceptible to alterations in pharmacodynamics, pharmacokinetics as well as to drug interaction due to polypharmacy. These situations increase the risk for the appearance of cognitive affectations and the development of pathologies like Alzheimer's disease (AD). In the present work, there is a summary of some clinical studies that have evaluated the effect of BZDs and Z-drugs in the adult population with and without AD, focusing on the relationship between their use and the loss of cognitive function. Additionally, there is an assessment of preclinical studies focused on finding molecular proof on the pathways by which these drugs could be involved in AD pathogenesis. Moreover, available data (1990-2019) on BZD and Z-drug use among elderly patients, with and without AD, was compiled in this work. Finally, the relationship between the use of BZD and Z-drugs for the treatment of insomnia and the appearance of AD biomarkers was analyzed. Results pointed to a vicious circle that would worsen the condition of patients over time. Likewise, it put into relevance the need for close monitoring of those patients using BZDs that also suffer from AD. Consequently, future studies should focus on optimizing strategies for insomnia treatment in the elderly by using other substances like melatonin agonists, which is described to have a much more significant safety profile. (AU)

• FAPESP's process: 17/13224-5 - Study of the JNK1 pathway as a selective target for the treatment of cognitive metabolic disorder: ADAM10 protein analysis
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/26084-1 - Evaluation of platelet ADAM10 in non-Alzheimer's dementias
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships in Brazil - Post-Doctoral