E-Mail karger@karger.com Systematic Review Neuroepidemiology 2016;47:181–191 DOI: 10.1159/000454881 Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis Md. Mohaimenul Islam   a, b Usman Iqbal   c Bruno Walther   c Suleman Atique   a, b Navneet Kumar Dubey   d Phung-Anh Nguyen   a, b Tahmina Nasrin Poly   f Jakir Hossain Bhuiyan Masud   a, b Yu-Chuan (Jack) Li   a, b, e Syed-Abdul Shabbir   a, b a  Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, b  International Center for Health Information Technology (ICHIT), c  Aster Program in Global Health and Development, College of Public Health, and d  Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, and e  Chair, Department of Dermatology, Wan Fang Hospital, Taipei, and f  Department of Microbiology and Immunology, Tzu Chi University, Hualien, Taiwan and sensitivity analyses. Odds of dementia were 78% high- er in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33–2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66– 3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34–1.65 and OR 1.43; 95% CI 1.16–1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associ- ated with increased risk of dementia but negative associa- tion was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical het- erogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our 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 confound- ing variable. Therefore, more research is needed. © 2016 S. Karger AG, Basel Key Words Benzodiazepines · Dementia · Diabetic · Hypertension · Heterogeneity Abstract Background: Benzodiazepines are a widely used medica- tion in developed countries, particularly among elderly pa- tients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evi- dence from observational studies that evaluated the asso- ciation between benzodiazepines use and dementia risk. Summary: We performed a systematic review and meta- analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All con- trol observational studies that compared dementia out- come in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identi- fied) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis Received: October 7, 2016 Accepted: December 1, 2016 Published online: December 24, 2016 Dr. Syed-Abdul Shabbir, MD, MSc, PhD Assistant Professor and Health IT consultant, Graduate Institute of Biomedical Informatics College of Medical Science and Technology, Taipei Medical University 250 Wu-Hsing St., Taipei 110 (Taiwan) E-Mail drshabbir  @  tmu.edu.tw © 2016 S. Karger AG, Basel www.karger.com/ned