The Association Between the Use of Zolpidem and the Risk of Alzheimer's Disease Among Older People

J Am Geriatr Soc. 2017 Nov;65(11):2488-2495. doi: 10.1111/jgs.15018. Epub 2017 Sep 7.


Objectives: To evaluate the association between zolpidem use and the risk of Alzheimer's disease among older people.

Design: A retrospective cohort study using data from 2001 to 2011 from the National Health Insurance Research Database.

Setting: Taiwan.

Participants: A total of 6,922 patients aged 65 years or older enrolled from January 2002 to December 2004 (the enrollment period).

Intervention (exposure): Zolpidem users were identified as patients who used zolpidem during the enrollment period. The index date was the date of the first zolpidem prescription. Dosage of zolpidem use was defined using cumulative defined daily dose (cDDD) based on the cumulative dosage that patients took within one year after the index date (grouped as: less than 28, 28-90, 91-180, and more than 180 cDDD).

Measurements: The occurrence of Alzheimer's disease was defined as the time period from the end of one year after the index date to the date of the Alzheimer's disease diagnosis. The propensity score was used to adjust the measured confounders of Alzheimer's disease. Cox proportional hazards models were used to evaluate the association between zolpidem use and the incidence of Alzheimer's disease.

Results: Zolpidem users with a high cumulative dose (>180 cDDD) in the first year after initiation had a significantly greater risk of Alzheimer's disease than non-zolpidem users (HR = 2.97, 95% CI = 1.61-5.49) and low cumulative dose (<28 cDDD) users (HR = 4.18, 95% CI = 1.77-9.86).

Conclusion: We found the use of a high cumulative dose of zolpidem was associated with an increased risk of Alzheimer's disease among older people living in Taiwan. It is advised to use caution when considering long-term use of zolpidem in older patients.

Keywords: Alzheimer's disease; National Health Insurance Research Database (NHIRD); Taiwan; hypnotics; zolpidem.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / epidemiology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects*
  • Male
  • National Health Programs
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Risk Factors
  • Sleep Wake Disorders / drug therapy
  • Taiwan
  • Zolpidem


  • Hypnotics and Sedatives
  • Pyridines
  • Zolpidem