A Systematic Review and Meta-Analysis of the Risk of Dementia Associated with Benzodiazepine Use, After Controlling for Protopathic Bias

@article{Penninkilampi2018ASR,
  title={A Systematic Review and Meta-Analysis of the Risk of Dementia Associated with Benzodiazepine Use, After Controlling for Protopathic Bias},
  author={Ross Penninkilampi and Guy D. Eslick},
  journal={CNS Drugs},
  year={2018},
  volume={32},
  pages={485-497}
}
BackgroundBenzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings.ObjectiveThe aim of our study was to investigate the risk of dementia associated with the use of benzodiazepines in elderly… 
History of Benzodiazepine Prescriptions and Risk of Dementia: Possible Bias Due to Prevalent Users and Covariate Measurement Timing in a Nested Case-Control Study
TLDR
The findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.
Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies
TLDR
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), found anxiety is significantly associated with an increased risk of all-cause dementia.
Is there a link between the use of benzodiazepines and related drugs and dementia? A systematic review of reviews
TLDR
Although hampered by the heterogeneity between the studies, the present findings suggest an association between BZDs/BZRDs use and increased risk of dementia in older adults.
Association between Anxiety and Vascular Dementia Risk: New Evidence and an Updated Meta-Analysis
TLDR
It is indicated that anxiety is associated with an increased risk of vascular dementia (VaD), and treating and preventing it might reduce the prevalence and incidence of VaD.
The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies
TLDR
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 impairing in BzD abusers but not in B ZD regular users.
Benzodiazepine and Z-Drug Use and the Risk of Developing Dementia
TLDR
It was found that the incidence of dementia was not higher among all BZDR users and short half-life BZDs and Z-drugs increased the risk of dementia at the highest doses, especially in female patients, showing a dose-response relationship.
Impact of benzodiazepine consumption reduction on future burden of dementia
TLDR
A modest but significant reduction in future dementia burden could be obtained by applying current recommendation for duration of benzodiazepine use, using a Monte Carlo approach based on an illness-death model.
Association between Development of Dementia and Use of Benzodiazepines: A Systematic Review and Meta‐Analysis
TLDR
The objective was to identify whether an association between the use of benzodiazepines and the development of dementia exists and whether such an association exists.
Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use.
TLDR
No evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer's disease is found; however, one cannot rule out effects owing to small numbers.
...
...

References

SHOWING 1-10 OF 60 REFERENCES
Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis
TLDR
The results suggest that benzodiazepine use is significantly associated with dementia risk, however, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable.
Association between Benzodiazepine Use and Dementia: A Meta-Analysis
TLDR
Long-term benzodiazepine users have an increased risk of dementia compared with never users, however, findings should be treated with caution due to limited studies and potential reverse causation.
Is there really a link between benzodiazepine use and the risk of dementia?
TLDR
The body of evidence seems sufficient for avoiding prescriptions or renewals that are not fully justified and indiscriminate long-term use and if the causal nature of this association remains unproved, the reviewed material provides arguments for evoking a causal link.
Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies
TLDR
Findings from prospective studies carried out in general population samples exploring whether exposure to benzodiazepines is associated with an increased risk of incident cognitive decline may be due to methodological differences, especially regarding the definitions of exposure and cognitive outcome.
Benzodiazepine use and risk of dementia: a nested case-control study.
Benzodiazepine Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis
TLDR
After taking a prodromal phase into consideration, benzodiazepine use was not associated with an increased risk of developing Alzheimer’s disease or vascular dementia or VaD.
Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS)
TLDR
The taking of benzodiazepines is associated with an increased risk of dementia, and men exposed in earlier phases showed a greater association than more recent exposure, counter to what one would expect if this was due to reverse causation.
Effect of benzodiazepine discontinuation on dementia risk.
TLDR
The risk of dementia was high for current users and decreased as the duration of BZD discontinuation lengthened, and further investigations are needed to replicate this association and explore the underlying mechanism that links long-term BzD use, BZd discontinuation, and the pathogenesis of neurocognitive dysfunction.
Association between Benzodiazepine Use and Dementia: Data Mining of Different Medical Databases
TLDR
Benzodiazepine use was found to be associated with dementia in analyses using the FAERS database and the Canada Vigilance Adverse Reaction Online Database andMulti-methodological approaches using different methods, algorithms, and databases suggest that long-term use of benzodiazepines and long-acting benzodiazines are strongly associated with an increased risk of dementia.
The association between dementia and long-term use of benzodiazepine in the elderly: nested case-control study using claims data.
TLDR
Long-term use of BZDs should be avoided among the elderly, who may be at a higher risk for developing dementia, in addition to other health problems, including cardiovascular and psychiatric diseases.
...
...