Risk of Dementia in Long-Term Benzodiazepine Users: Evidence from a Meta-Analysis of Observational Studies

He, Qian; Chen, Xiaohua; Wu, Tang Na; Li, Liyuan; Fei, Xiaofan

doi:10.3988/jcn.2019.15.1.9

Cited by 68 publications

(63 citation statements)

References 28 publications

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“…Our results might be also influenced by the heterogeneous characteristics of the studies, although univariate meta-regressions showed that there were no significant associations between the outcome and several variables (i.e., age, gender, sample size, follow-up period or methodological quality). Despite the controversial effect of psychotropic drugs on dementia risk, [58][59][60][61], we did not take into account how taking psychotropic drugs could affect our results, because only one study assessed this variable [34]. Due to the fact that the included studies assessed risk of dementia across their entire follow-up periods, we are unable to pinpoint a time before dementia diagnosis when the association with anxiety may begin.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies

Santabárbara

Lipnicki

Olaya

et al. 2020

JCM

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Background: Anxiety has been suggested as a potentially modifiable risk factor for dementia, but results are still controversial. Our main objectives are to develop an updated meta-analysis of prospective population-based studies on the relationship between anxiety and risk of dementia, and to estimate the population fraction of dementia attributable to anxiety (PAF). Methods: We searched for cohort studies listed on PubMed or Web of Science from January 2018 to January 2020 that reported risk estimates for the association between anxiety and incident dementia. These were added to cohort studies published before January 2018 that were used in a previously published meta-analysis. Fully adjusted RRs were pooled using random effects models. We estimated the proportion of incident dementia attributable to anxiety by using PAF. Results: The meta-analysis included nine prospective cohorts from eight studies, representing 29,608 participants. The overall relative risk (RR) of dementia was 1.24 (95% CI: 1.06–1.46) and the PAF of dementia due to anxiety was 3.9%. Conclusions: Anxiety is significantly associated with an increased risk of all-cause dementia. The treatment or prevention of anxiety might help to reduce dementia incidence rates, but more research is needed to clarify whether anxiety is a cause of dementia rather than a prodrome.

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Section: Strengths and Limitationsmentioning

confidence: 99%

Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies

Santabárbara

Lipnicki

Olaya

et al. 2020

JCM

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“…Their main findings pointed to a significantly increased risk of dementia in the elderly population using BZDs. This effect was associated with the use of BZDs with a longer half-life and with a longer treatment duration (He et al, 2019).…”

Section: Meta-analysesmentioning

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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“…After searching the databases, we did not find a meta-analysis investigating the cognitive effects of BZD abuse. The most relevant studies are two systematic reviews and meta-analyses papers on dementia risk in the elderly with long-duration and high dosage BZD users (58,59). In 2015, Zhong and colleagues summarized six nested case-control or prospective cohort studies and concluded that higher dosage BZD users had an increased risk of dementia (59).…”

Section: Main Findings Of Bzd Abusementioning

confidence: 99%

“…In 2015, Zhong and colleagues summarized six nested case-control or prospective cohort studies and concluded that higher dosage BZD users had an increased risk of dementia (59). In 2019, He et al found that the risk of dementia was higher in patients taking BZD for a longer duration (>3 years) among six case-control and four cohort studies (58). Although long-term or high dosage use is not equivalent to dependence, BZD addiction is more likely to occur in long-term and high-dose users (60).…”

Section: Main Findings Of Bzd Abusementioning

confidence: 99%

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies

et al. 2020

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Objective: Benzodiazepines (BZD) are one of the most frequently prescribed drugs worldwide. However, the cognitive effects of benzodiazepines in the elderly are highly debated. This systematic review and meta-analysis aims to explore the following two questions in the elderly population: (i) Do BZD lead to any impairments in cognitive functions in elderly users? and (ii) Which specific cognitive domains are most affected by BZD use and abuse? Methods: First, we performed a literature search following the PRISMA guidelines. Electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane Library, and Web of Science were searched until May 14 th , 2020. After selecting the relevant articles, we integrated the results of the selected studies with a standardized cognitive classification method. Next, we performed meta-analyses with the random-effects model on the cognitive results. Finally, we specifically examined the cognitive impairments of BZD in the abuse subgroup. Results: Of the included studies, eight of the thirteen had meta-analyzable data. Compared to the controls, elderly BZD users had significantly lower digital symbol test scores (n=253; SMD:-0.61, 95% CI:-0.91 to 0.31, I² = 0%, p < 0.0001). There was no significant difference in Mini-Mental State Examination, Auditory Verbal Learning Test, and Stroop Color and Word Test scores between BZD users and controls. According to the subgroup analyses, BZD abusers performed significantly worse than controls in Mini-Mental State Examination (n=7726; SMD:-0.23, 95% CI:-0.44 to-0.03, I² = 86%, p = 0.02), while there was no significant difference between the regular BZD users and the controls (n=1536; SMD:-0.05, 95% CI:-0.59 to 0.48, I² = 92%, p =0.85). Conclusion: In the elderly population, the processing speed (digital symbol test scores) was significantly impaired in BZD users; global cognition (Mini-Mental State Examination scores) was significantly impaired in BZD abusers but not in BZD regular users. This study

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Risk of Dementia in Long-Term Benzodiazepine Users: Evidence from a Meta-Analysis of Observational Studies

Cited by 68 publications

References 28 publications

Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies

Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies

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

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies

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