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

Delirium after stroke is a serious condition associated with worse long-term cognition. However, the mechanism of delirium is not well 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 1 year period were identified and recruited if they were aged age ≥ 60 years 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 9 am 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.