Depression symptoms and risk for delirium during hospitalization and after surgery

Abstract Background Delirium is an acute neuropsychiatric disorder associated with increased risks of Alzheimer’s disease (AD) and death; it is characterized by acute confusion commonly after stressors during hospitalization and after surgery. The long‐term relationship between depressive symptoms and risk for delirium during hospitalization and after surgery remains unclear. Method 372,893 UK biobank participants between 2006‐2010 (mean 57.9y [SD = 8.0], 54.0% female) reported frequency (never‐0, occasional‐1, often‐2, always‐3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, followed by at least one hospitalization or surgical event during follow‐up until 2020. A depression score (0‐12) was generated as the sum of the four symptoms. This was further categorized into none (0), mild (1‐2), modest (3‐5), and severe (≥6) symptoms. Delirium was determined using ICD‐10 coding from hospitalization records. Cox proportional hazards models were used to assess the predictive value of the depression score/categories for delirium risk. Result 5,919 (16 per 1000) newly developed delirium (median 12 years follow‐up). Increased risk for delirium during hospitalization was seen for mild (HR = 1.14, 95% CI: 0.98–1.41, p<0.001), modest (HR = 1.25, 95%CI: 1.14–1.37, p<0.001) and severe (HR = 1.29, 95%CI 1.15–1.45, p<0.001) depressive symptoms, compared to those with none, after controlling for demographics, lifestyle factors, cardiovascular risk, morbidity burden, and cognition. These findings were consistent for postoperative delirium. In sensitivity analysis, the risk of delirium in the modest/severe groups was significantly stronger in those ≥65y (HR 1.70, 95% CI: 1.56 – 1.86) than in those <65y (1.36, 95% CI: 1.24 –1.48) compared to none/mild groups (p for interaction <0.0001). A follow‐up cohort (n = 225) were reassessed for depressive symptoms 4 years later. A worsening depression score (>1 point increase), compared to no change/improved score, was associated with a 39% increased risk (HR 1.39, 95%CI: 1.03–1.99, p = 0.03) independent of baseline depression scores. Conclusion Greater depression symptoms predicted delirium risk during hospitalization. A more recent cohort showed that worsening trajectory of depression conferred additional risk compared to those with no change/improved score. Increased awareness for subclinical depression/anxiety symptoms may be warranted for better design of therapies/strategies to identify those at increased risk for delirium.