Is delirium after stroke associated with dysregulation of Hypothalamic pituitary axis?

Delirium after stroke is a serious condition associated with poorer longer term cognition. However the mechanism of delirium is poorly understood. The aberrant stress response has been postulated as a mechanism for delirium. Aim To explore the relationship between cortisol dysregulation and delirium over the first year after stroke in a prospective cohort study of patients admitted to an acute stroke unit. Methods Consecutive patients admitted to an acute stroke unit over a one year period were identified and recruited if they were aged 65 or over and not taking steroids. Patients with incapacity were included if proxy consent could be obtained. Baseline data included stroke severity, cognition, illness severity, and pre-stroke cognition. Patients were assessed at 1, 3, 5, 7, 14, 21, 28 days, 4 months and 12 months for delirium. Salivary samples were taken morning and evening for cortisol analysis. Results Of the 831 patients screened, 304 met inclusion criteria and of these 95 agreed to participant. Twenty-six (27%) had delirium at some point during the 12 months follow-up. Delirium was associated with increasing age (mean age 83.5 years vs 74 years, p<0.001), being female (62% vs 23%, p=0.013), not independent in pre-stroke activities of daily living (35% vs 33%), higher IQCODE score median 3.56 vs 3.19), worse stroke severity (median National Institute of Stroke Scale 5 vs 8.5) p=0.009) and having had a total anterior circulation stroke (p<0.001). Univariable analyses identified several associations between delirium and cortisol in the first 28 days but not at 4 or 12 months. However, on multivariable analyses there were no significant associations between delirium and cortisol at any time point e.g. odds ratio for median 9am cortisol 0.95 (95% CI 0.89 to 1.01, p=0.08). Conclusion There was no independent association between delirium and cortisol dysregulation after stroke. If an association does exist, it is likely to be small. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Dr Barugh was funded by a Research Training Fellowship from the Dunhill Medical Trust. Alasdair MacLullich, Amanda Barugh, Susan Shenkin and Michael Allerhand were members of the Centre for Cognitive Ageing and Cognitive Epidemiology funded by BBSCR, ESRC, MRC as part of the Lifelong Health and Well-being Initiative. ### 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: Scotland A Research Ethics committee 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 Additional data may be available on request