Benzodiazepine use associated with increased risk of Alzheimer's disease

Patients who had taken benzodiazepines for at least 3 months had a 50% increased risk of Alzheimer's disease, a recent study of older patients found.

Researchers conducted a case-control study using Quebec's health insurance program database to find a random sample of community-dwelling adults age 66 years or older from 2000 to 2009. The study included 1,796 people with a first diagnosis of Alzheimer's disease and health data from at least 6 years before diagnosis, matched with 7,184 controls by sex, age, and duration of follow-up. Any exposure to benzodiazepines was categorized by the cumulative number of prescribed daily doses (1 to 90, 91 to 180, more than 180) and the drug elimination half-life. Results appeared online Sept. 9 at The BMJ.

Ever using benzodiazepines was associated with an increased risk of Alzheimer's disease (adjusted odds ratio [OR], 1.51; 95% CI, 1.36 to 1.69). Adjustment for anxiety, depression, and insomnia slightly altered this result, but it remained significant (OR, 1.43; 95% CI, 1.28 to 1.60). No association was found for a cumulative dose of less than 91 prescribed daily doses. The association with Alzheimer's increased from an OR of 1.32 with 91 to 180 prescribed daily doses (95% CI, 1.01 to 1.74) to an OR of 1.84 with more than 180 prescribed daily doses (95% CI, 1.62 to 2.08). Drug half-life showed a similar trend (OR, 1.43 [95% CI, 1.27 to 1.61] for short-acting drugs and OR, 1.70 [95% CI, 1.46 to 1.98] for long-acting ones).

The researchers noted that the stronger association for long-term exposures reinforces the suspicion of a possible direct association, although benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. The results provide “arguments for carefully evaluating the indications for use of this drug class,” the authors wrote.

An editorial echoed the possibility of reverse effect, that is, that older adults who received a diagnosis of dementia are more likely to take benzodiazepines and other potentially inappropriate medications. “Currently, there is no standardized approach to help to identify and monitor the cognitive side effects of drug treatments,” the editorial stated. “As a result, potential long term consequences of drugs such as benzodiazepines remain hidden and contribute to a growing burden of cognitive impairment among older adults. Identification of drugs with adverse cognitive effects requires dedicated monitoring of cognitive function, which is often absent from routine hospital and ambulatory clinical care.”