AIMS: Frailty and poor sleep are both risk factors for delirium, but their joint and interactive associations with incident delirium are unknown. The study aimed to examine the associations of frailty status and sleep quality with incident delirium. METHODS: A total of 346,846 participants from the UK Biobank without delirium, dementia, or cognitive impairment at baseline were included. Incident delirium cases were identified through the International Classification of Diseases, Tenth Revision codes. A modified-version Fried phenotype was utilized to evaluate frailty status. A sleep score comprising five sleep characteristics was used to quantify sleep quality. Cox proportional hazard models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations. Also, their interactions on delirium incidence on the multiplicative and additive scales were quantified. RESULTS: During a median follow-up of 13.8 years, 6554 (1.9%) cases of incident delirium were documented. Prefrail and frail individuals had a 34% (HR = 1.34
95% CI: 1.27-1.41) and 98% (HR = 1.98
95% CI: 1.78-2.19) increased risk of delirium, respectively, compared with nonfrail controls. Each 1-point increment in frailty score was associated with a 25% (HR = 1.25
95% CI: 1.21-1.28) increased risk of delirium. Healthy sleep significantly counteracted the increased risk of delirium due to frailty (P for multiplicative interaction = 0.026). In the poor and healthy sleep stratification, the corresponding HRs (95% CIs) were 2.07 (1.86-2.31) and 1.28 (0.83-1.97), respectively. Moreover, we observed the highest delirium risk in frail individuals with poor sleep quality (HR = 2.08
95% CI: 1.83-2.35), with evidence of an additive interaction. CONCLUSIONS: Both physical frailty and poor sleep are significantly associated with higher delirium risk. Achieving healthy sleep could not only lower the risk of delirium but also greatly offset the adverse impact of frailty on delirium.