An Increased Risk of Reversible Dementia May Occur After Zolpidem Derivative Use in the Elderly Population: A Population-Based Case-Control Study

Shih, Hsin-I; Lin, Che-Chen; Tu, Yi-Fang; Chang, Chia-Ming; Hsu, Hsiang-Chin; Chi, Chih-Hsien; Kao, Chia-Hung

Section Editor(s): Barkin., Robert

doi: 10.1097/MD.0000000000000809
Article: Observational Study

Abstract: We evaluate the effects of zolpidem use to develop dementia or Alzheimer disease from the Taiwan National Health Insurance Research Database (NHIRD).

A retrospective population-based nested case–control study. Newly diagnosed dementia patients 65 years and older and controls were sampled. A total of 8406 dementia and 16,812 control subjects were enrolled from Taiwan NHIRD during 2006 to 2010. The relationships between zolpidem use and dementia were measured using odds and adjusted odds ratios. The relationship between the average cumulative doses for zolpidem and dementia was also analyzed.

Zolpidem alone or with other underlying diseases, such as hypertension, diabetes, and stroke, was significantly associated with dementia after controlling for potential confounders, such as age, sex, coronary artery disease, diabetes, anti-hypertension drugs, stroke, anticholesterol statin drugs, depression, anxiety, benzodiazepine, anti-psychotic, and anti-depressant agents’ use (Adjusted OR = 1.33, 95% CI 1.24–1.41). Zolpidem use also has significant dose–response effects for most of the types of dementia. In patient with Alzheimer diseases, the effects of zolpidem among patients with Alzheimer's disease remained obscure. The adjusted OR for patients whose cumulative exposure doses were between 170 and 819 mg/year (adjusted OR: 1.65, 95% CI 1.08–2.51, P = 0.0199) was significant; however, the effects for lower and higher cumulative dose were not significant.

Zolpidem used might be associated with increased risk for dementia in elderly population. Increased accumulative dose might have higher risk to develop dementia, especially in patients with underlying diseases such as hypertension, diabetes, and stroke.

From the Department of Emergency Medicine, National Cheng Kung University Hospital (H-IS, H-CH); Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (H-IS, C-HC); Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Y-FT); Management Office for Health Data, China Medical University Hospital, Taichung (C-CL); Department of Internal Medicine, Division of Geriatrics and Gerontology, National Cheng Kung University Hospital (C-MC); Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan (C-MC); Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University (C-HK); and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (C-HK).

Correspondence: Chia-Hung Kao, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan (e-mail: d10040@mail.cmuh.org.tw).

Abbreviations: AORs = adjusted odds ratios, ATC = anatomical therapeutic chemical, BZD = benzodiazepine, CI = confidence interval, GABA = γ-aminobutyric acid, ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification, NHIRD = National Health Insurance Research Database = OR, odds ratio.

Contributors: conception/design: H-IS, C-HK; provision of study materials: Y-FT, C-MC, H-CH, C-HC; collection and/or assembly of data: C-CL, C-HK; data analysis and interpretation: H-IS, C-HK;

manuscript writing: All authors; final approval of manuscript: all authors.

This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212–113002); China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103–2325-B-039 -006); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and Health, and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW104-TDU-B-212–124–002, Taiwan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.

The authors report no conflicts of interest.

This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

Received March 4, 2015

Received in revised form April 1, 2015

Accepted April 1, 2015

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