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

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=70719) and their matched controls (N=282862). 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.