{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:35:11Z","timestamp":1791560111821,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>During hospital admissions, patients with dementia are at risk for developing delirium, an acute state of brain failure associated with significant morbidity. There are currently no pharmacologic tools to treat or prevent delirium. Decreased cholinergic signaling plays a role in the pathophysiology of both disorders. Whether enhanced pre\u2010hospital cholinergic signaling in patients with dementia improves outcomes during critical illness remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We utilized the Medical Information Mart for Intensive Care III (MIMIC\u2010III) database to determine whether pre\u2010hospital donepezil use was associated with improved outcomes during critical illness in dementia patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 2734 subjects with dementia admitted to the intensive care unit (ICU; 447 received donepezil). After adjusting for confounders, patients with dementia who were receiving donepezil had a significantly reduced in\u2010hospital and 90\u2010day mortality, ICU length of stay, and duration of mechanical ventilation. Donepezil use was associated with, and its benefit was mediated by, reduced delirium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Patients with dementia who are treated with donepezil have improved outcomes during critical illness and reductions in delirium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>No pharmacologic treatments exist to reduce delirium in patients with dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Donepezil improves outcomes during critical illness in patients with dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Improved outcomes are mediated by a reduction in hospital delirium.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Future studies in patients with dementia should prospectively evaluate donepezil in the prevention of 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