Abstract The underlying mechanisms of the neuropsychiatric syndrome delirium are still unknown, but neuroinflammation is a central hypothesis. Chitinase-3-like-protein-1 (YKL-40/CHI3L1) is considered a marker of neuroinflammation when measured in cerebrospinal fluid (CSF). The aim of this study was to examine concentrations of CSF YKL-40 in patients with and without delirium, to enhance the understanding of delirium pathophysiology. A total of 545 hip fracture patients were included from two similar cohorts. CSF samples were collected in conjunction with spinal anaesthesia for hip fracture surgery. The patients were screened for delirium both pre- and postoperatively. Those with delirium were further divided into subgroups based on whether they developed it before surgery (prevalent delirium) or after surgery (incident delirium). Among patients without delirium, those who met some, but not all diagnostic criteria, were classified as having subsyndromal delirium. Prefracture cognitive function was assessed, and American Society of Anaesthesiologists physical status score was included as a marker of comorbidity. In total, 257 (47%) of the patients developed delirium. These patients were older and had a higher prevalence of dementia and severe systemic diseases. Among the patients without dementia, those with delirium had higher median concentration of CSF YKL-40 compared with those without delirium (first cohort: 175 versus 132 ng/mL, P = 0.01, second cohort: 243 versus 174 ng/mL, P 0.001). No association was found among the patients with dementia. The results remained consistent when adjusting for age and comorbidity. No difference in median CSF YKL-40 concentration was found between patients who had delirium at the time of surgery (prevalent delirium) and those who developed it afterwards (incident delirium). Our findings support the hypothesis of neuroinflammation as a mechanism for delirium in patients without dementia.
Berntsen et al. (2026) studied this question.