Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study

Saarelainen, Laura; Tolppanen, Anna‐Maija; Koponen, Marjaana; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi

doi:10.1002/gps.4821

Cited by 27 publications

(17 citation statements)

References 42 publications

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“…; Saarelainen et al . ). Importantly, these studies and our findings suggest that further research is needed to clarify how altered GABA A R subunit expression, composition and pharmacology in AD patients might change GABAergic drug responses (Govindpani et al .…”

Section: Discussionmentioning

confidence: 97%

GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

Kwakowsky

Guzmán

Pandya

et al. 2018

Journal of Neurochemistry

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Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA type A receptors (GABA Rs) are severely affected in Alzheimer's disease (AD). However, the distribution and subunit composition of GABA Rs in the AD brain are not well understood. This is the first comprehensive study to show brain region- and cell layer-specific alterations in the expression of the GABA R subunits α1-3, α5, β1-3 and γ2 in the human AD hippocampus, entorhinal cortex and superior temporal gyrus. In late-stage AD tissue samples using immunohistochemistry we found significant alteration of all investigated GABA Rs subunits except for α3 and β1 that were well preserved. The most prominent changes include an increase in GABA R α1 expression associated with AD in all layers of the CA3 region, in the stratum (str.) granulare and hilus of the dentate gyrus. We found a significant increase in GABA R α2 expression in the str. oriens of the CA1-3, str. radiatum of the CA2,3 and decrease in the str. pyramidale of the CA1 region in AD cases. In AD there was a significant increase in GABA R α5 subunit expression in str. pyramidale, str. oriens of the CA1 region and decrease in the superior temporal gyrus. We also found a significant decrease in the GABA R β3 subunit immunoreactivity in the str. oriens of the CA2, str. granulare and str. moleculare of the dentate gyrus. In conclusion, these findings indicate that the expression of the GABA R subunits shows brain region- and layer-specific alterations in AD, and these changes could significantly influence and alter GABA R function in the disease. Cover Image for this issue: doi: 10.1111/jnc.14179.

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Section: Discussionmentioning

confidence: 97%

GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

Kwakowsky

Guzmán

Pandya

et al. 2018

Journal of Neurochemistry

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“…Notwithstanding, and seeing the possible consequences derived from their intake, there needs to be a significant increase in awareness about their risks. In fact, there have been some studies reporting that the consumption of BZDs favors the appearance of cognitive affectations and increases the number of deaths in patients with AD (Imfeld et al, 2015;Saarelainen et al, 2017;Grande et al, 2019). Yet, as we have already assessed, there is controversy, and other researchers defend that BDZs have no such detrimental effects (Picton and Pharm, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, AD patients treated with BZDs showed a risk of mortality up to 41% higher than those who did not use such drugs. Z-drugs did not increase the risk of death, but authors suggested that they could not be considered safer in persons with dementia (Saarelainen et al, 2018).…”

Section: Case-control Studiesmentioning

confidence: 99%

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

Ettcheto

Olloquequi

Busquets

et al. 2020

Front. Aging Neurosci.

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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.

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“…In this study, and the community outreach study, documentation was found to be significantly poor for side effects, however, checking the records revealed some information about some side effects such like falls, respiratory and GIT problems, although we could not ascertain the cause. Some studies showed a relationship between benzodiazepines, opioids and anticholinergics use in old age population with cognitive and behavioral disorders [17]. A systematic review linking psychotropic drugs with falls in older people found that there is a small, but consistent, association between the use of most classes of psychotropic drugs and falls.…”

Section: Discussionmentioning

confidence: 99%

Use of Benzodiazepines and Hypnotic Medications in Psychiatry Older Adult Outpatients

2018

IJCR

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Benzodiazepines have anxiolytic, hypnotic, anticonvulsant, and muscle-relaxing properties, therefore, a widely prescribed treatment for anxiety and insomnia. They bind to gamma-aminobutyric acid type A (GABAA) receptors, which are responsible for most of the inhibitory neurotransmission in the central nervous system and these receptors are a major target of alcohol, barbiturates, muscle relaxants, and other medications with sedative effects, resulting in tolerance and dependence [1]. Benzodiazepines are categorized into short (15 to 30 minutes), intermediate (30 to 60 minutes), and long-acting agents (one hour or longer). Benzodiazepines are frequently prescribed for elderly patients living in the community and for those in hospitals and institutions. Prolonged use of benzodiazepines is particularly likely in old age for the treatment not only of insomnia and anxiety, but also of a wide range of nonspecific symptoms. Long term users are likely to have multiple concomitant physical and psychological health problems [2]. Benzodiazepines produce dependence, reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behavior, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60 [3]. According to Maudsley guidelines, benzodiazepines use in elderly are poorly supported for their link to cognitive decline, increase

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Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study

Abstract: Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.

Cited by 27 publications

References 42 publications

GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

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

Use of Benzodiazepines and Hypnotic Medications in Psychiatry Older Adult Outpatients

Contact Info

Product

Resources

About

Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study

Abstract: Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.

Cited by 27 publications

References 42 publications

GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

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

Use of Benzodiazepines and Hypnotic Medications in Psychiatry Older Adult Outpatients

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Product

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GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus

GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus