Associations between depression symptom burden and delirium risk: a prospective cohort study

BACKGROUND AND OBJECTIVES Delirium and depression are increasingly common in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer’s disease (AD), functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older individuals during hospitalization. RESEARCH DESIGN AND METHODS 319,141 UK biobank participants between 2006-2010 (mean 58y [range 37-74, SD=8], 54% female) reported frequency (0-3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12y median follow-up. 40,451 (mean age 57±8; range 40-74y) had repeat assessment on average 8y after their first. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium during hospitalization. RESULTS 5,753 (15 per 1000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR=1.16, [95% confidence interval 1.08–1.25], p <0.001), modest (scores 3-5, 1.30 [1.19–1.43], p <0.001) and severe (scores ≥ 5, 1.38 [1.24–1.55], p <0.001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across hospitalization settings (e.g., surgical, medical, or critical care) and specialty (e.g., neuropsychiatric, cardiorespiratory or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03–1.88], p =0.03) independent of baseline depression burden. The association was strongest in those over 65y at baseline ( p for interaction <0.001). DISCUSSION AND IMPLICATIONS Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may be warranted for delirium prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the BrightFocus Foundation Alzheimers Disease Research Program (grant number: A2020886S) to [PL]; Alzheimers Association Research Fellowship (grant number AARFD-22-928372) to [CG]; National Institutes of Health (grant numbers RF1AG064312, R01AG083799) to [KH]; National Institutes of Health (grant number R03AG067985) to [LG]; and the Alzheimers Association Clinician Scientist Fellowship (grant number AACSF-23-1148490) to [LG]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank received National Research Ethics Approval, and participants gave written informed consent. This study was conducted under the terms of UK Biobank access number 40556 and Mass General Brigham IRB approval (#2020P002097) which gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available from the UK Biobank after submitting an application. The syntax for conducting the analysis is available upon reasonable request.