Benzodiazepines, Related Drugs Associated With Modestly Increased Risk for Alzheimer Disease

Results of a Finnish study published in Acta Psychiatrica Scandinavica show that use of benzodiazepines and related drugs is associated with a modestly increased risk of developing Alzheimer disease. However, the cumulative dose-response relationship was eliminated after adjusting for use of other psychotropics, suggesting that the association may at least in part be caused by these other medications or by the underlying disease for which they were prescribed.

Use of benzodiazepine and related drugs is common among older people. Evidence has demonstrated short-term negative effects on memory and cognition, and long-term use has been hypothesized to accelerate cognitive decline and increase the risk for dementia.

Researchers set out to assess the effect of dose, half-life, cumulative consumption, and duration, as well as individual associations of benzodiazepines and related drugs, on the risk for the subsequent development of Alzheimer disease.

Vesa Tapiainen, Bachelor of Medicine, School of Pharmacy, University of Eastern Finland in Kuopio, Finland, and colleagues conducted a nationwide nested case-control study of all community-dwelling individuals in Finland who had received a clinical diagnosis of Alzheimer disease between 2005 and 2011 (n=70,719) and matched controls (n=282,862). Benzodiazepine purchases were derived from the Prescription Register from 1995 onward. The investigators assessed the relationship between benzodiazepine use and Alzheimer disease using conditional logistic regression with a 5-year lag time between exposure and outcome.

The association between use of these drugs and Alzheimer disease was modest (odds ratio 1.06). Although the investigator observed a dose-response relationship for both cumulative consumption and duration in the unadjusted analysis, after adjustment for use of other psychotropic medications, the differences between the highest and lowest dose category were eliminated. 

The authors noted that assuming there was no uncontrolled bias or confounding, 5.7% of cases of Alzheimer disease that occur among benzodiazepine users are attributable to drug exposure. Limitations of the study included the recording of only reimbursed drug purchases by the Prescription Register, which may have underestimated benzodiazepine use, and that information on drug use in hospitals was not available.

The authors noted concerns that given the frequent use of benzodiazepines among older people, even a small increase in absolute risk may be a serious matter on a population level.

Reference

Tapiainen V, Taipale H, Tanskanen A, Tiihone J, Hartikainen S, Tolppanen A-M. The risk of Alzheimer’s disease associated with benzodiazepines and related drugs: a nested case-control study [published online May 31, 2018]. Acta Psychiatr Scand. doi:10.1111/acps.12909