Benzodiazepine use linked with Alzheimer’s disease

1. There was an increased risk of Alzheimer’s disease among older adults who had ever used benzodiazepines, and an even higher risk for those who had used benzodiazepines for greater than the recommended 3 months.

2. The use of long-acting benzodiazepines was more strongly associated with Alzheimer’s disease than short-acting benzodiazepines.

Evidence Rating Level: 3 (Average)        

Study Rundown: Dementia affects over 30 million people worldwide and is a common cause of morbidity and disability in older adults. Benzodiazepines are commonly used medications for treatment of anxiety disorders and insomnia, especially among elderly patients. The short-term negative effects of benzodiazepines on memory and cognition are well known, but the link between long-term benzodiazepine use and development of Alzheimer’s disease is less well studied. This study aimed to evaluate the relationship between benzodiazepine use and Alzheimer’s disease by comparing Canadian prescription drug claims records between older adults who had been diagnosed with Alzheimer’s (cases) and those who had not (controls). The study found that Alzheimer’s was more common in adults with previous benzodiazepine use, and that the association was even higher if a patient had used benzodiazepines for greater than 3 months. The authors also found that long-acting benzodiazepines had a stronger association with Alzheimer’s than shorter-acting benzodiazepines.

Two strengths of this study include a longer follow-up period than previous studies (five years), and controls for potential confounders by matching cases and controls on several variables while also adjusting for other many potential confounders in the multivariate regression. A limitation of this study was that benzodiazepine use was determined based on prescription claims, which do not always accurately reflect medication use. Additionally, although the researchers found a dose-response relationship, in that longer benzodiazepine use held higher risk of Alzheimer’s, this does not necessarily imply causality. This study has important implications for public health as it encourages physicians to consider limiting the use of benzodiazepines to the 3 months recommended by international guidelines given the possible long-term effects on memory and cognition.

Click to read the study in the BMJ

Click to read an accompanying editorial in the BMJ

Relevant Reading: Effect of Benzodiazepine Discontinuation on Dementia Risk

In-Depth [retrospective case-control]: This study was a retrospective case-control study based on elderly adult patients (age >66) in the Quebec public drug plan database. 1,796 people were selected as cases based on a recorded ICD-9 diagnosis code of Alzheimer’s disease. The cases were matched with 7,184 controls on sex, age group, and duration of follow-up. Benzodiazepine use was quantified using prescription drug claims. 49.8% of patients with Alzheimer’s disease had ever used benzodiazepines compared to 40% of controls. Researchers used a multivariate conditional logistic regression to determine the association between Alzheimer’s disease and benzodiazepine use in the last five years before Alzheimer’s diagnosis. Potential confounders controlled for in the regression included high blood pressure, stroke, hypercholesterolemia, diabetes, anxiety, depression, and insomnia. Ever having used a benzodiazepine was associated with 1.5 times the odds of Alzheimer’s disease (CI95% 1.36-1.69). The risk of Alzheimer’s disease increased with longer exposure, with odds of 1.32 (CI95% 1.01-1.74) for 3-6 months use and 1.84 (CI95% 1.62-2.08) for greater than 6 months use. Less than 3 months of daily doses, a low level of prescription, had to association with Alzheimer’s. Additionally, a greater risk of developing Alzheimer’s disease was found for long acting benzodiazepines (1.70, CI95% 1.46-1.98) than for short acting ones (1.43, CI95% 1.27-1.61).

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