The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case–control study

Tapiainen, V.; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa; Tolppanen, Anna Maija

doi:10.1111/acps.12909

Cited by 41 publications

(45 citation statements)

References 32 publications

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“…The results suggested that both hypnotics should be considered risk factors for dementia in patients with long-term insomnia. Likewise, an association between higher prescribed dosages of BZDs and Zdrugs and risks of dementia was found, which is in agreement with previous studies (Tapiainen et al, 2018).…”

Section: Cohort Studiessupporting

confidence: 92%

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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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Section: Cohort Studiessupporting

confidence: 92%

“…Another study was performed in a wide population of Finland for 6 years (Tapiainen et al, 2018). Currently, this is the largest study assessing the effect of BZDs and Z-drugs on AD risk.…”

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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“…All other studies focused on the association between BZD and dementia risk. Eight case control studies (Billioti de Gage et al, ; Chan et al, ; Gomm et al, ; Imfeld, Bodmer, Jick, & Meier, ; Takada, Fujimoto, & Hosomi, ; Tapiainen et al, ; C.‐S. Wu, Ting, Wang, Chang, & Lin, ; C.‐S.…”

Section: Resultsmentioning

confidence: 99%

“…All other studies focused on the association between BZD and dementia risk. Eight case control studies (Billioti de Gage et al, 2014;Chan et al, 2017;Imfeld, Bodmer, Jick, & Meier, 2015;Takada, Fujimoto, & Hosomi, 2016;Tapiainen et al, 2018;C.-S. Wu, Ting, Wang, Chang, & Lin, 2011;C.-S. Wu, Wang, Chang, & Lin, 2009) and four cohort studies (Billioti de Gage et al, 2012;Gallacher et al, 2012;Gray et al, 2016;Shash et al, 2016) showed a significant association between chronic BZD use and increased risk of dementia.…”

Section: Benzodiazepinesmentioning

confidence: 99%

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Barus

Béné

Deguil

et al. 2019

British J Pharmacology

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Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. These drugs can be divided into drugs targeting CNS disorders (e.g., anticholinergic drugs, antiepileptics, antipsychotics, benzodiazepines, and opioids) and drugs targeting non‐CNS disorders (e.g., antidiabetics, antihypertensives, proton pump inhibitors, and statins). Furthermore, we sought to highlight the pharmacological mechanisms underlying their possible detrimental or beneficial effects on cognition. Anticholinergic and antiepileptic drugs were excluded from this review because their effects on cognition are well known. Studies investigating benzodiazepines have revealed an increased risk of dementia. Conclusions on dementia risk or cognitive impairment regarding opioids and antipsychotic drugs are difficult to draw. These different classes appear to impair cognition not by a single clear mechanism of action specific to each class but by several relatively interdependent and interconnected mechanisms (e.g., impaired neurotransmission, neuroinflammation, neuronal death, oxidative stress, or interactions with dementia‐related pathways). The dementia risk initially associated with the use of proton pump inhibitors might have been overestimated. In contrast, statins, antihypertensive medications, and antidiabetics could potentially decrease the risk of dementia and cognitive impairment by acting in ways opposite to the mechanisms cited above. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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“…In the present issue of Acta, a timely, well‐performed, register‐based nested case–control study finds that BZD use was associated with modestly increased odds of Alzheimer's disease with no clear dose–response relationship or difference between different types of BZD.…”

mentioning

confidence: 99%

Should benzodiazepines be avoided?

Jørgensen

Osler

2018

Acta Psychiatr Scand

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The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case–control study

Cited by 41 publications

References 32 publications

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

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

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Should benzodiazepines be avoided?

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