Benzodiazepine Use and Risk of Developing Alzheimer's Disease: A Case-Control Study Based on Swiss Claims Data

CNS Drugs. 2017 Mar;31(3):245-251. doi: 10.1007/s40263-016-0404-x.


Background: A possible association between benzodiazepine use and Alzheimer's disease (AD) has been hypothesized in previous studies.

Objectives: Using claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between previous benzodiazepine use and the risk of AD.

Methods: We conducted a matched case-control study and identified 1438 incident AD cases between 2013 and 2014 based on recorded first-time use of drugs used to treat AD [i.e., acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate receptor antagonist memantine] and matched one control to each case on age, sex, index date, and residence (canton). Because the initiation of benzodiazepine use shortly before the AD diagnosis date may occur as a result of symptomatic treatment of prodromal symptoms of early major neurocognitive disorder, we introduced an induction period of 2 years before the AD diagnosis date. Additionally, we categorized medication use by duration of use prior to the index date using prescriptions. We applied conditional logistic regression analyses to calculate odds ratios with 95% confidence intervals and adjusted for use of antidepressants.

Results: The crude odds ratio (95% confidence interval) of developing AD for patients starting benzodiazepine treatment was 1.71 (1.17-2.99) in the year before diagnosis and 1.19 (0.82-1.72) in the third year before diagnosis. After accounting for benzodiazepine use initiated during the prodromal phase, benzodiazepine use was not associated with an increased risk of developing AD; long-term benzodiazepine use (≥30 prescriptions) yielded an adjusted odds ratio of 0.78 (0.53-1.14).

Conclusions: After taking into consideration a possible protopathic bias in the 2 years preceding the AD diagnosis date, benzodiazepine use was not associated with an increased risk of developing AD.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / epidemiology*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Case-Control Studies
  • Female
  • Humans
  • Insurance, Health
  • Male
  • Middle Aged
  • Nootropic Agents / therapeutic use
  • Odds Ratio
  • Risk
  • Switzerland


  • Antidepressive Agents
  • Nootropic Agents
  • Benzodiazepines