Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium

Abstract

Background: Delirium is associated with new-onset dementia, suggesting that delirium pathophysiology involves neuronal injury. Neurofilament light (NFL) is a sensitive biomarker for neuroaxonal injury. Methods: NFL was measured in cerebrospinal fluid (CSF) (n = 130), preoperative serum (n = 192), and postoperative serum (n = 280) in hip fracture patients, and in CSF (n = 123) and preoperative serum (n = 134) in cognitively normal older adults undergoing elective surgery. Delirium was diagnosed with the Confusion Assessment Method. Results: Median serum NFL (pg/mL) was elevated in delirium in hip fracture patients (94 vs. 54 pre- and 135 vs. 92 postoperatively, both p < 0.001). Median CSF NFL tended to be higher in hip fracture patients with delirium (1,804 vs. 1,636, p = 0.074). Serum and CSF NFL were positively correlated (ρ = 0.56, p < 0.001). Conclusion: Our findings support an association between neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.

Association of Plasma Neurofilament Light with Postoperative Delirium

“…A number of prior studies have found associations of NfL with delirium. A study of patients presenting with hip fractures found that those with delirium had significantly higher preoperative and postoperative serum NfL compared with patients without delirium 44 . Likewise, our study found similar associations, and our cohort of elective surgical patients eliminates potential confounding effects associated with hip fracture.…”

“…A study of patients presenting with hip fractures found that those with delirium had significantly higher preoperative and postoperative serum NfL compared with patients without delirium. 44 Likewise, our study found similar associations, and our cohort of elective surgical patients eliminates potential confounding effects associated with hip fracture. In another study, NfL was found to be increased after cardiopulmonary bypass, with the highest postoperative levels among those with delirium.…”

Impact of parturition on maternal cardiovascular and neuronal integrity in a high risk cohort – a prospective cohort study

“…Interestingly, postoperative NfL levels in non-pregnant surgical patients increase significantly over preoperative values, in a range very similar to the almost 2-fold increase we identified, suggesting that general anesthesia and surgery are associated with at least short-term neuronal damage [42, 43]. Given that none of our women underwent general anesthesia but 91% had epidural anesthesia and that NfL levels did not differ between women delivering spontaneously compared to those delivering by caesarean we conclude that giving birth per se has a negative impact on neuronal integrity.…”

Delirium

“…Dementia after delirium might be associated with new pathological signatures rather than with exacerbation of amyloidβ and tau pathology, consistent with a new brain injury occurring during delirium 77 . This idea is supported by emerging clinical studies showing elevation of the axonal injury marker neurofilament light chain in medical and surgical patients with delirium [355][356][357] , markers of synaptic damage in patients with delirium after infection 188 and the finding of persistent cognitive deficits and hippocampal atrophy in intensive care unit patients with delirium at 6-24 months after discharge 358 . Animal model studies previously demonstrated new neuronal death 84 and tau and synaptic pathology 359 after systemic lipopolysaccharide administration and surgical challenges in animals with prior neurodegenerative disease.…”