Use of Benzodiazepines and Risk of Incident Dementia: A Retrospective Cohort Study

Previous findings regarding the association between benzodiazepine exposure and dementia have conflicted, though many have not accounted for anticholinergic exposure. The goal of this study was to evaluate the association of benzodiazepine exposure with the risk of developing dementia, accounting for the anticholinergic burden.

Using a retrospective cohort design, we identified veterans 65 or older without dementia during a 10-year baseline period and then followed participants for 5 years to evaluate the risk of dementia diagnosis. The primary exposure was cumulative benzodiazepine exposure. Cox proportional hazards survival model was used to examine the association between benzodiazepine exposure and dementia, adjusting for anticholinergic burden and other demographic and clinical characteristics associated with increased dementia risk.

Of the 528 006 veterans in the study cohort, 28.5% had at least one fill for a benzodiazepine. Overall, 7.9% developed a diagnosis of dementia during the observation period. Compared to veterans with no exposure to benzodiazepines, the adjusted hazard ratios for dementia risk were 1.06 (95% confidence interval [CI] 1.02-1.10) for low benzodiazepine exposure, 1.05 (95% CI 1.01-1.09) for medium benzodiazepine exposure, and 1.05 (95% CI 1.02-1.09) for high benzodiazepine exposure.

Cumulative benzodiazepine exposure was minimally associated with increased dementia risk when compared with nonuse but did not increase in a dose-dependent fashion with higher exposure. Veterans with low benzodiazepine exposure had essentially the equivalent risk of developing dementia as veterans with high exposure. While benzodiazepines are associated with many side effects for older adults, higher cumulative use does not appear to increase dementia risk.