CSF neurofilament light chain concentration in patients with delirium following hip fracture: a multicenter prospective study

Abstract Background Studies suggest delirium is associated with neuronal injury, which may further raise mortality risk. Neuronal injury can be assessed by measuring neurofilament light chain (NFL) concentrations in cerebrospinal fluid (CSF). This study aimed to investigate the association of CSF-NfL with delirium and mortality in patients with hip fracture. Methods The study comprised two prospective cohorts of 548 hip fracture patients with per-operative CSF samples. CSF-NfL concentrations were measured using a commercial ELISA. Delirium was assessed daily from admission until the fifth postoperative day and survival censored at one year. The multivariable analyses (Logistic and Cox regression) were adjusted for age, sex, glomerular filtration rate, dementia status, comorbidity, and Activities of Daily Living. Additionally, Cox regression was adjusted for delirium. Results In total, 259 (52%) patients developed delirium. In univariate analysis, CSF-NfL was higher among patients with delirium (2116 pg/ml versus 1366 pg/ml, odds ratio (OR) 2.21, (95% confidence interval (CI) [1.75,2,78], P < 0.001). In adjusted analysis, CSF-NfL was not significant (OR 1.29, [0.92,1.81], P = 0.128) and only remained significantly associated with delirium in the subgroup of patients without dementia (OR 1.84, [1.17, 2.89], P = 0.007). In unadjusted analysis of mortality, CSF-NfL was significantly associated with death at one year (hazard ratio (HR) 1.60, [1.37, 1.87], P < 0.001) but not in adjusted analysis (HR 1.03 [0.84, 1.26], P = 0.736). Conclusions Our findings show that CSF-NfL concentrations were associated with delirium in patients without pre-existing dementia, suggesting possible undiagnosed dementia or, less likely, delirium-related neuronal injury. The CSF-NfL-associated mortality hazard was non-significant after adjustment, mainly for delirium. Thus, the clinical context must be considered when studying CSF-NfL and delirium.