The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case-control study

Acta Psychiatr Scand. 2018 Aug;138(2):91-100. doi: 10.1111/acps.12909. Epub 2018 May 31.

Abstract

Objective: To assess the association between benzodiazepine and related drug (BZDR) use and risk of Alzheimer's disease (AD) with cumulative consumption and duration of use based models.

Method: A nationwide nested case-control study of all Finnish community-dwelling persons who received clinically verified AD diagnosis in 2005-2011 (N = 70 719) and their matched controls (N = 282 862). AD diagnosis was based on DSM-IV and NINCDS-ADRDA criteria. BZDR purchases were extracted from the Prescription Register since 1995. The association between BZDR use and AD was assessed using conditional logistic regression with 5-year lag time between exposure and outcome.

Results: Benzodiazepine and related drug use was associated with modestly increased risk of AD (adjusted OR 1.06, 95% CI 1.04-1.08). A dose-response relationship was observed with both cumulative consumption and duration. Adjustment for other psychotropics removed the cumulative dose-response relationship by attenuating the ORs in the highest dose category.

Conclusion: Benzodiazepine and related drug use in general was associated with modestly increased risk of AD. No major differences were observed between different subcategories of BZDRs (i.e. benzodiazepines, Z drugs, short-/medium-acting or long-acting BZDRs). As dose-response relationship abolished after adjustment for other psychotropics, it is possible that the association may partially be due to antidepressants and/or antipsychotics, or concomitant use of these medications.

Keywords: Alzheimer; dementia; pharmacoepidemiology; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / epidemiology
  • Antipsychotic Agents / adverse effects
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Case-Control Studies
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dose-Response Relationship, Drug
  • Female
  • Finland / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Risk Factors
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / etiology*

Substances

  • Antipsychotic Agents
  • Benzodiazepines