Risk of Dementia in Long-Term Benzodiazepine Users: Evidence from a Meta-Analysis of Observational Studies
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초록
Background and Purpose There is conflicting evidence in the literature on the association between benzodiazepines (BDZs) and the risk of dementia. This meta-analysis aimed to determine the relationship between the long-term usage of BDZs and the risk of dementia. Methods The PubMed and Embase databases were systematically searched for relevant publications up to September 2017. The literature search focused on observational studies that analyzed the relationship between the long-term use of BDZs and the risk of dementia. Pooled rate ratios (RRs) with 95% confidence interval (CI) were assessed using a random-effects model. The robustness of the results was checked by performing subgroup and sensitivity analyses. Results Ten studies were included: six case–control and four cohort studies. The pooled RR for developing dementia was 1.51 (95% CI=1.17–1.95, p=0.002) in patients taking BDZ. The risk of dementia was higher in patients taking BDZs with a longer half-life (RR=1.16, 95% CI= 0.95–1.41, p=0.150) and for a longer time (RR=1.21, 95% CI=1.04–1.40, p=0.016). Conclusions This meta-analysis that pooled ten studies has shown that BDZ significantly increases the risk of dementia in the elderly population. The risk is higher in patients taking BDZ with a longer half-life (>20 hours) and for a longer duration (>3 years).
Abstract
Background and Purpose There is conflicting evidence in the literature on the association between benzodiazepines (BDZs) and the risk of dementia. This meta-analysis aimed to determine the relationship between the long-term usage of BDZs and the risk of dementia. Methods The PubMed and Embase databases were systematically searched for relevant publications up to September 2017. The literature search focused on observational studies that analyzed the relationship between the long-term use of BDZs and the risk of dementia. Pooled rate ratios (RRs) with 95% confidence interval (CI) were assessed using a random-effects model. The robustness of the results was checked by performing subgroup and sensitivity analyses. Results Ten studies were included: six case–control and four cohort studies. The pooled RR for developing dementia was 1.51 (95% CI=1.17–1.95, p=0.002) in patients taking BDZ. The risk of dementia was higher in patients taking BDZs with a longer half-life (RR=1.16, 95% CI= 0.95–1.41, p=0.150) and for a longer time (RR=1.21, 95% CI=1.04–1.40, p=0.016). Conclusions This meta-analysis that pooled ten studies has shown that BDZ significantly increases the risk of dementia in the elderly population. The risk is higher in patients taking BDZ with a longer half-life (>20 hours) and for a longer duration (>3 years).
참고문헌 (29)
- Griffin CE 3rd, "Benzodiazepine pharmacology and central nervous system-mediated effects", Ochsner J, 13, pp.214~223 (2013)
- Gallacher J, "Benzodiazepine use and risk of dementia : evidence from the caerphilly prospective study(CaPS)", J Epidemiol Community Health, 66, pp.869~873 (2012)
- Wu CS, "Effect of benzodiazepine discontinuation on dementia risk", Am J Geriatr Psychiatry, 19, pp.151~159 (2011)
- Wu CS, "The association between dementia and long-term use of benzodiazepine in the elderly : nested case-control study using claims data", Am J Geriatr Psychiatry, 17, pp.614~620 (2009)
- Lagnaoui R, "Benzodiazepine use and risk of dementia : a nested case-control study", J Clin Epidemiol, 55, pp.314~318 (2002)
- Billioti de Gage S, "Benzodiazepine use and risk of dementia: prospective population based study", BMJ, 345, pp.e6231~ (2012)
- Gomm W, "Regular benzodiazepine and z-substance use and risk of dementia : an analysis of German claims data", J Alzheimers Dis, 54, pp.801~808 (2016)
- Gray SL, "Benzodiazepine use and risk of incident dementia or cognitive decline : prospective population based study", BMJ, 352, pp.i90~ (2016)
- Shash D, "Benzodiazepine, psychotropic medication, and dementia : a population-based cohort study", Alzheimers Dement, 12, pp.604~613 (2016)
- Imfeld P, "Benzodiazepine use and risk of developing Alzheimer’s disease or vascular dementia : a case-control analysis", Drug Saf, 38, pp.909~919 (2015)
- Chan TT, "Association between high cumulative dose of benzodiazepine in Chinese patients and risk of dementia : a preliminary retrospective casecontrol study", Psychogeriatrics, 17, pp.310~316 (2017)
- Altman DG, "Interaction revisited : the difference between two estimates", BMJ, 326, pp.219~ (2003)
- Begg CB, "Operating characteristics of a rank correlation test for publication bias", Biometrics, 50, pp.1088~1101 (1994)
- Golder S, "Comparison of pooled risk estimates for adverse effects from different observational study designs : methodological overview", PLoS One, 8, pp.e71813~ (2013)
- Imbimbo BP, "γ-secretase inhibitors and modulators for the treatment of Alzheimer’s disease : disappointments and hopes", Curr Top Med Chem, 11, pp.1555~1570 (2011)
- Doody RS, "A phase 3 trial of semagacestat for treatment of Alzheimer’s disease", N Engl J Med, 369, pp.341~350 (2013)
- May PC, "GYKI 52466 protects against non-NMDA receptor-mediated excitotoxicity in primary rat hippocampal cultures", Neurosci Lett, 152, pp.169~172 (1993)
- Jo S, "GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease", Nat Med, 20, pp.886~896 (2014)
- Pariente A, "The benzodiazepine-dementia disorders link : current state of knowledge", CNS Drugs, 30, pp.1~7 (2016)
- Zhang Y, "Benzodiazepine use and cognitive decline in elderly with normal cognition", Alzheimer Dis Assoc Disord, 30, pp.113~117 (2016)
- Amieva H, "Prodromal Alzheimer’s disease : successive emergence of the clinical symptoms", Ann Neurol, 64, pp.492~498 (2008)
- Taragano FE, "Mild behavioral impairment and risk of dementia : a prospective cohort study of 358 patients", J Clin Psychiatry, 70, pp.584~592 (2009)
- Lyketsos CG, "Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment : results from the cardiovascular health study", JAMA, 288, pp.1475~1483 (2002)
- Pariente A, "Benzodiazepines and injurious falls in community dwelling elders", Drugs Aging, 25, pp.61~70 (2008)
- Rossat A, "Association between benzodiazepines and recurrent falls : a crosssectional elderly population-based study", J Nutr Health Aging, 15, pp.72~77 (2011)
- Díaz-Gutiérrez MJ, "Relationship between the use of benzodiazepines and falls in older adults : a systematic review", Maturitas, 101, pp.17~22 (2017)
- Fastbom J, "Benzodiazepines may have protective effects against Alzheimer disease", Alzheimer Dis Assoc Disord, 12, pp.14~17 (1998)
- Chen PL, "Risk of dementia in patients with insomnia and long-term use of hypnotics : a populationbased retrospective cohort study", PLoS One, 7, pp.e49113~ (2012)
- Billioti de Gage S, "Benzodiazepine use and risk of Alzheimer’s disease: casecontrol study", BMJ, 349, pp.g5205~ (2014)
