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Delirium is associated with incident dementia across the multimorbidity spectrum: a population-based cohort study

Penfold, R. S.; MacRae, C. E.; Sampson, E. L.; Anand, A.; Davis, D.; Ely, W.; Guthrie, B.; MacLullich, A. M.

2025-10-08 geriatric medicine
10.1101/2025.10.06.25337244 medRxiv
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BackgroundDelirium is strongly associated with subsequent dementia, but this is often assumed to reflect underlying associations of baseline health with dementia. We examined the associations of delirium on admission with incident dementia across the spectrum of multimorbidity. MethodsRetrospective population-based cohort study using linked primary care and hospital data for emergency admissions aged [≥]65 years in Lothian, Scotland, from 1 Apr 2017 to 1 Apr 2020. Delirium on admission was assessed at the bedside for all patients using the 4AT (www.the4AT.com). Associations of delirium, multimorbidity, and their interaction with incident dementia and mortality were examined using Fine-Gray competing-risks regression and Cox proportional hazards models. ResultsOf 23,558 people without pre-existing dementia (mean age 78.9 years, 54% female), 4135 (18%) had an admission with delirium. Delirium was associated with higher incident dementia risk. The relative risk was highest in those without multimorbidity (adjusted Hazard Ratio (aHR) 3.38, 95% CI 2.46-4.63) and decreased with an increasing number of long-term conditions. Delirium was also associated with increased mortality, regardless of multimorbidity. In those without multimorbidity, delirium was associated with higher early mortality ([≤]90 days: aHR 4.23, 95% CI 3.27 to 5.49) and late mortality (>90 days: aHR 1.64, 95% CI 1.33 to 2.03). ConclusionDelirium is strongly associated with incident dementia in older adults across the multimorbidity spectrum, with the highest relative risk in people without multimorbidity. Findings support routine delirium assessment on hospital admission for all older adults and highlight need to further investigate neurodegenerative mechanisms in delirium.

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