TOPLINE:

Patients with dementia aged 50 years or older who continued the use of acetylcholinesterase (AChE) inhibitors had a lower risk for delirium diagnosed during hospitalisation than those who discontinued treatment earlier.

METHODOLOGY:

• Using data from multiple linked national registries in Denmark, researchers conducted a nationwide population-based cohort study to evaluate the 3-year risk for a hospital discharge diagnosis of delirium in patients with dementia who continued AChE inhibitor treatment vs those who discontinued the treatment after the first prescription.
• The analysis included 45,651 patients with dementia aged 50 years or older who initiated AChE inhibitor treatment between 2005 and 2024; of these, 41,291 (median age, 80 years; 61% women) continued treatment and 4360 (median age, 81 years; 58% women) discontinued treatment earlier.
• The continuation of AChE inhibitor treatment was defined as redeeming a second prescription for AChE inhibitors within 90 days of the initial prescription, and discontinuation was defined as not redeeming another prescription within 90 days.
• The primary outcome was a hospital discharge diagnosis of delirium, registered during an inpatient admission.
• Follow-up began 90 days after their first prescription and continued for up to 3 years.

TAKEAWAY:

• Delirium occurred less frequently among patients who continued AChE inhibitor treatment than among those who discontinued treatment earlier (incidence rate, 66 vs 112 events per 10,000 person-years).
• After propensity score weighting, patients who continued AChE inhibitors had a 28% lower risk for delirium than those who discontinued treatment earlier (hazard ratio [HR], 0.72; 95% CI, 0.54-0.96).
• Among patients with Alzheimer's dementia, the continuation of AChE inhibitor treatment was also associated with a lower risk for delirium than early discontinuation (HR, 0.68; 95% CI, 0.48-0.96).
• A negative control outcome — bleeding peptic ulcer — showed no association with the continued use of AChE inhibitors, supporting that the observed delirium benefit was not driven by potential residual confounding.

IN PRACTICE:

"Clinically, [the study] findings suggest that beyond managing cognitive impairment of dementia, AChEIs [AChE inhibitors] may reduce the risk of a severe neuropsychiatric complication with substantial prognostic implications. The findings may provide additional rationale for maintaining AChEI treatment in dementia care, particularly in situations where discontinuation is being considered due to perceived intolerance or marginal benefit considerations," the authors wrote.

SOURCE:

This study was led by Martin Torp Rahbek, Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark. It was published online on April 28, 2026, in Alzheimer's Research & Therapy.

LIMITATIONS:

The study lacked data on the severity of dementia, neuropsychiatric symptoms, and behavioural disturbances at treatment initiation. The reliance on hospital discharge coding may have led to the misclassification and underascertainment of delirium. Treatment exposure was defined using prescription redemption, which could not have confirmed actual drug intake.

DISCLOSURES:

This study did not disclose any funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.