Causal relationship between distinct sleep characteristics and delirium: A multivariable Mendelian randomization study

Delirium is a common neurological complication among hospitalized patients and has been closely linked to sleep disturbances. Dynamic changes in sleep rhythms are influenced by various sleep characteristics, which complicates the identification of the relationship between individual sleep features and the risk of delirium. Therefore, this study aimed to assess the potential causal relationships between distinct sleep characteristics and delirium, and to further investigate their independent effects. We obtained summary-level data on delirium and 10 distinct sleep characteristics. inverse-variance weighted (IVW) was employed as the primary analytical approach, supplemented by additional robust Mendelian randomization (MR) techniques. To ensure the robustness of the IVW results, heterogeneity tests and horizontal pleiotropy analyses were performed. Additionally, we employed a multivariable MR analysis to identify a direct causal relationship between the 2 conditions. The 2-sample MR analysis revealed that sleep duration (oversleepers) (OR = 5.561, 95% CI = 2.102-14.717, P < .001) and evening chronotype (OR = 1.879, 95% CI = 1.179-2.994, P = .008) were significantly associated with an increased risk of delirium. Conversely, getting up in the morning (OR = 0.544, 95% CI = 0.296-0.999, P = .049) and daytime dozing (OR = 0.134, 95% CI = 0.030-0.598, P = .008) appeared to be protective factors against delirium. The results of the reverse MR analysis showed that patients with delirium were more likely to exhibit a morning chronotype (OR = 0.998, 95% CI = 0.996-1.000, P < .020). Sensitivity analyses confirmed the robustness of the findings. Multivariable MR analysis further confirmed that evening chronotype remained causally associated with an elevated risk of delirium (OR = 3.860, 95% CI = 1.173-12.696, P = .026). Additionally, after adjusting for other sleep characteristics, daytime napping emerged as a significant risk factor for delirium (OR = 10.427, 95% CI = 1.246-87.287, P = .031). Various sleep characteristics exhibited both protective and detrimental effects on the risk of delirium. This study enhances our understanding of modifiable risk factors for delirium and offers new perspectives for its prevention strategies.