Perioperative Anticholinergic Medication Use and Incident Dementia Among Older Surgical Patients: A Retrospective Cohort Study using Real-World Data

Abstract

Background: Inpatient anticholinergic medications have been associated with a higher likelihood of postoperative delirium in older adults. However, it remains unclear whether administering anticholinergic medications after surgery adversely affects long-term cognitive function. Objective: We aimed to evaluate the relationship between in-hospital anticholinergic medications and time to incident dementia in a cohort of older surgical patients. We also sought to determine whether the association between in-hospital anticholinergic drugs and dementia differed by sex and prehospital anticholinergic exposure. Methods: This was a retrospective analysis of electronic health record data from a regional health information exchange. The study population included patients aged 50 years and older who underwent major surgery requiring an inpatient stay between 2014 and 2021. Orders for anticholinergic medications were identified using the anticholinergic cognitive burden (ACB) scale. A Cox proportional hazards model was used to estimate the association between inpatient orders for strong anticholinergics and incident dementia after hospital discharge. Cause-specific hazards were modeled. Stratification and relative excess risk due to interaction (RERI) were used to investigate multiplicative and additive interaction, respectively. Results: In total, 66,420 surgical encounters were analyzed. Approximately 90% of patients received one or more strong anticholinergics during hospitalization, and 3806 patients developed dementia during a median follow-up of 3.4 years. The median time to dementia was 2.2 years. Each one-order increase in inpatient anticholinergic medications was associated with a 0.60% increase in dementia risk (HR 1.006; 95% CI 1.003-1.008). This association was stronger among patients who were prescribed anticholinergics before hospitalization (RERI 0.10; 95% CI 0.08-1.12; p = 0.0122). Conclusions: Perioperative anticholinergics may increase the risk of dementia after major surgery. Avoiding these medications in hospitalized older adults may improve long-term cognitive outcomes.