Perioperative Anticholinergic Medication Use and Incident Dementia among Older Surgical Patients: a Retrospective Cohort Study using Real-World Data.

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.
Competing Interests: Declarations. Conflicts of interest: Z.B.M. has a financial interest in DigiCare Realized and could benefit from the results of this research. M.B. serves as a Chief Scientific Officer and Co-Founder of Blue Agilis, and is the Chief Health Officer of DigiCare Realized. He has equity interest in Blue Agilis, DigiCare Realized, Preferred Population Health Management LLC, and MyShift (previously known as RestUp, LLC). He serves as an advisory board member for Acadia Pharmaceuticals, Eisai, Biogen, and Genentech. These conflicts have been reviewed by Indiana University and have been appropriately managed to maintain objectivity. The remaining authors declare no competing interests. Funding: This study was supported by National Institute on Aging no. K23AG071945. Ethics approval: The protocol for this retrospective cohort study was reviewed and approved by the Indiana University Institutional Review Board (no. 15767) prior to initiation. Consent to participate: Not applicable. Consent for publication: Not applicable. Data availability: The data that support the findings of this study are available from the Regenstrief Institute, but restrictions apply to the availability of these data, which were used under a research agreement for the current study and are therefore not publicly available. Code availability: Not applicable. Author contributions: All authors contributed to the study concept and design. Data analysis was performed by E.H. The first draft of the manuscript was written by E.H. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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