Increased risk of dementia diagnosis, benzodiazepine exposure in seniors with anxiety

Research from Saint Louis University School of Medicine finds that among patients 65 and older, a diagnosis of anxiety was significantly associated with an increased risk of dementia diagnosis, and benzodiazepine exposure was associated with a 28% increased risk of dementia. However, when benzodiazepines were prescribed to patients with an anxiety disorder, there was no significant association between these medications and incident dementia.

The study, “Anxiety Disorders, Benzodiazepine Prescription and Incident Dementia,” was published online July 28 in the Journal of the American Geriatrics Society.

Jay A. Brieler, M.D., associate professor of family and community medicine at SLU, is the paper’s first author. Jeffrey Scherrer, Ph.D., professor of family and community medicine and a member of the AHEAD Institute, is the senior author.

The study’s authors found while there is an association between anxiety and dementia, and an association between benzodiazepines and dementia, there is no association between these medications and dementia when prescribed to persons with an anxiety disorder.

It is unknown whether treating late-life anxiety disorders with benzodiazepines exposes patients to additional risks of dementia. Anxiety in older adults can be linked with cardiovascular disease, diabetes, depression, social withdrawal, physical inactivity, sleep disturbance, smoking, obesity, alcohol consumption and chronic disease burden.

Benzodiazepine prescriptions for older patients is controversial. Their use has been associated with short term cognitive impairment, falls, and fractures. Per Dr. Brieler,

“As a clinician who frequently treats patients with anxiety disorders, recent studies suggesting benzodiazepine use could contribute to dementia were very concerning to me,” Brieler said. “I had the assumption that if a benzodiazepine was used and side effects occurred, simply stopping the medication would remedy the problem over time.

“The difficult issue with those studies is that anxiety itself is also associated with dementia. It was still unclear from the literature whether the disease or the treatment was the culprit. Based on our work, it appears that both are playing a part, but it remains uncertain how the two interact with each other.”

This retrospective cohort study reviewed the electronic health data of 72,496 patients from 2014-21.

The de-identified medical record data was obtained from the Saint Louis University-SSM Healthcare System’s Virtual Data Warehouse (VDW). The VDW, created and maintained by the Advanced HEAlth Data (AHEAD) Research Institute at Saint Louis University, captures clinical encounters starting from Jan. 1, 2008, from academic and non-academic ambulatory and inpatient settings in the Midwest.

The VDW includes more than 5 million patients from birth to 90 years of age who have utilized services in the healthcare system since 2008.

Eligible patients were 65 years of age or older, had clinic encounters before and after index and were free of dementia for two years prior to index date. Of the cohort, 85.6% were white and 59.9% were female. The median age was 74.

Five million Americans 65 or older had an Alzheimer’s or related dementia diagnosis in 2014, which is expected to double by 2060.

“This study is a great example of using real-world clinical data to examine research questions that otherwise would not be practical to investigate,” Scherrer said. “We do not have the resources to follow tens of thousands of patients over time. We overcame that obstacle by using the VDW and expertise available in the AHEAD Institute.”

Takeaways

• Anxiety was associated with a 19% increased risk of incident dementia independent of sustained benzodiazepine use.
• Sustained benzodiazepine use was associated with a 28% increased risk of dementia.
• Sustained benzodiazepine use among those with anxiety disorder did not lower or increase the risk of dementia.
• Literature determining an independent association between anxiety and benzodiazepines with incident dementia is inclusive.

The authors recommend further studies to determine if the association with incident dementia varies across other anxiety medications.

Funds to maintain the Virtual Data Warehouse came from the Saint Louis University Research Institute. Saint Louis University is a member of the Health Care Systems Research Network.

Other authors include Joanne Salas, MPH, of the Department of Family and Community Medicine at Saint Louis University, Harry S. Truman Veterans Administration Medical Center, Columbia, Mo., and the Advanced HEAlth Data (AHEAD) Research Institute at SLU; Matthew E. Amick, Poorva Sheth, Elizabeth A. Keegan-Garrett, M.D., of the Department of Family and Community Medicine at Saint Louis University; and John Morley, MBBCh., of the AHEAD Institute at SLU.