Risk of dementia in patients with insomnia and long-term use of hypnotics: a population-based retrospective cohort study

PLoS One. 2012;7(11):e49113. doi: 10.1371/journal.pone.0049113. Epub 2012 Nov 7.


Background: Hypnotics have been reported to be associated with dementia. However, the relationship between insomnia, hypnotics and dementia is still controversial. We sought to examine the risk of dementia in patients with long-term insomnia and the contribution of hypnotics.

Methods: Data was collected from Taiwan's Longitudinal Health Insurance Database. The study cohort comprised all patients aged 50 years or older with a first diagnosis of insomnia from 2002 to 2007. The comparison cohort consisted of randomly selected patients matched by age and gender. Each patient was individually tracked for 3 years from their insomnia index date to identify whether the patient had a first diagnosis of dementia. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: We identified 5693 subjects with long-term insomnia and 28,465 individuals without. After adjusting for hypertension, diabetes mellitus, hyperlipidemia, and stroke, those with long-term insomnia had significantly higher risks of dementia (HR, 2.34; 95% CI, 1.92-2.85). Patients with long-term insomnia and aged 50 to 65 years had a higher increased risk of dementia (HR, 5.22; 95% CI, 2.62-10.41) than those older than 65 years (HR, 2.33; 95% CI, 1.90-2.88). The use of hypnotics with a longer half-life and at a higher prescribed dose predicted a greater increased risk of dementia.

Conclusions: Patients with long-term use of hypnotics have more than a 2-fold increased risk of dementia, especially those aged 50 to 65 years. In addition, the dosage and half-lives of the hypnotics used should be considered, because greater exposure to these medications leads to a higher risk of developing dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Dementia* / chemically induced
  • Dementia* / epidemiology
  • Dementia* / etiology
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Sleep Initiation and Maintenance Disorders* / complications
  • Sleep Initiation and Maintenance Disorders* / drug therapy
  • Taiwan


  • Hypnotics and Sedatives

Grant support

This study was supported in part by grants from the following organizations: Taiwan National Science Council (100-2314-B-075-002-); Taipei Veterans General Hospital (VGHUST101-G7-1-2, V101C-105); NSC support for the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan (NSC100-2911-I-008-001); the Brain Research Center, National Yang-Ming University; and the Ministry of Education “Aim for the Top” University Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.