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An Increased Risk of Reversible Dementia May Occur After Zolpidem Derivative Use in the Elderly Population: A Population-Based Case-Control Study
Open accessAbstract
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.
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Prescription of zolpidem is currently not recommended for individuals older than 65 by the American Geriatric Society.
“Prescription of zolpidem is currently not recommended for individuals older than 65 by the American Geriatric Society93,94.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [93]
The Discussion describes risks of zolpidem use in older adults, and the conclusion calls for careful evaluation and follow-up. Neither passage states an American Geriatrics Society recommendation against prescribing it to people over 65; searches for that recommendation and the Beers criteria found no such statement in our copy. (LLM, conf=0.74)
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Brandt, J., & Leong, C. (2017) · Drugs in R&D · doi:10.1007/s40268-017-0207-7 · Cited by 356
Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep
Hauglund, N. L., Andersen, M., Tokarska, K., Radovanovic, T., Kjaerby, C., Sørensen, F. L., Bojarowska, Z., Untiet, V., Ballestero, S. B., Kolmos, M. G., et al. (2025) · Cell · doi:10.1016/j.cell.2024.11.027 · Cited by 349
Metadata
- Authors
- Shih, H.-I., Lin, C.-C., Tu, Y.-F., Chang, C.-M., Hsu, H.-C., Chi, C.-H., & Kao, C.-H.
- Affiliations
- China Medical University (TW)
- National Cheng Kung University Hospital (TW)
- Corresponding author
- Kao, Chia-Hung
- Venue
- Medicine
- Published
- 2015-05
- Volume
- 94
- Issue
- 17
- Pages
- e809
- ISSN
- 0025-7974 (ISSN-L)
- PMC
- PMC4603066
- OpenAlex
- W2322484035
- Cited by
- 55
- References
- 2
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 7
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nd
- Locations
- Medicine (publishedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Funders
- Taiwan Biobank
- Academia Sinica (BM 104010092)
- China Medical University Hospital (BM104010092)
- National Research Program for Biopharmaceuticals (MOST 103-2325-B-039 -006)
- China Medical University
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- zolpidem, dementia, Alzheimer's disease, reversible dementia, older adults, cumulative dose, dose-response relationship, benzodiazepine-like drugs, hypertension, diabetes mellitus, stroke, drug safety
- MeSH terms
- Zolpidem, Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Dose-Response Relationship, Drug, Female, Humans, Hypnotics and Sedatives, Male, Pyridines, Retrospective Studies, Risk Factors, Taiwan, Comorbidity, Case-Control Studies
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