Preoperative Neurofilament Light Associated With Postoperative Delirium in Hip Fracture Repair Patients Without Dementia

BACKGROUND: Delirium commonly occurs in older adults following surgery; although its pathophysiology is not fully understood, underlying neurodegeneration is a risk factor. OBJECTIVE: Examine the association of preoperative levels of markers of neuronal damage, neurofilament light (NfL) and phosphorylated tau (p-tau)₁₈₁, with postoperative delirium. METHODS: Preoperative cerebrospinal fluid (CSF) and plasma were obtained from 158 patients undergoing hip fracture repair and enrolled in the clinical trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients." Delirium diagnosis was adjudicated by a consensus panel. The association of plasma and CSF NfL and p-tau₁₈₁ levels with delirium incidence and severity were examined for the overall cohort and for a subgroup (n = 134) of patients without dementia. RESULTS: Patients who developed delirium were older, had lower Mini-Mental State Exam score, higher Clinical Dementia Rating and Geriatric Depression Scale scores at baseline; the overall incidence of delirium was 37.6% and 31.1% for the subgroup without dementia. Plasma and CSF p-tau₁₈₁ levels were not associated with delirium incidence or severity. CSF NfL levels were significantly associated with delirium severity, but not with incidence in the overall cohort. In the subgroup of patients without dementia, CSF NfL levels were significantly associated with increased odds of delirium incidence (odds ratio 4.74, 95% confidence level 1.21-18.59, P = 0.03) adjusted for age, sex, and Clinical Dementia Rating. CONCLUSIONS: CSF NfL was significantly associated with delirium incidence and severity in patients without dementia undergoing hip fracture repair. Results confirm prior studies suggesting NfL as an important marker of delirium risk and supports an association between pre-existing axonal injury and delirium. These results highlight delirium vulnerability in older hip fracture patients, even when clinical dementia is not identified.