Geroscience. 2025 Nov 14. doi: 10.1007/s11357-025-02009-6. Online ahead of print.
ABSTRACT
Postoperative delirium is a potentially devastating complication of surgery that commonly affects older adults. Neurofilament light chain (NfL) is a biomarker of neuronal injury with reported associations with the development of postoperative delirium. Previous studies suggest that nighttime dexmedetomidine may help prevent delirium following cardiac surgery. However, the mechanisms involved in the delirium-sparing properties of dexmedetomidine treatment remain unclear. This study investigated circulating NfL levels as an objective molecular biomarker associated with postoperative delirium and investigated whether nighttime dexmedetomidine moderates the association between NfL and delirium severity. Serum collected from participants aged 60 years and older who underwent cardiac surgery in the Minimizing ICU Neurological Dysfunction with Dexmedetomidine Induced Sleep (MINDDS) trial were analyzed for NfL concentrations using single-molecule immunoassays (n = 355 patients with preoperative NfL and delirium severity scores). Delirium assessments were performed using the Confusion Assessment Method (CAM). The primary outcome was the peak CAM-Severity score observed within 3 days after surgery. The analysis investigated the associations between preoperative and postoperative NfL levels and delirium severity, and whether nighttime dexmedetomidine modified these associations. Elevated preoperative NfL was associated with increased delirium incidence (odds ratio = 1.62, 95% confidence interval [1.22-2.14], p = 0.001). A one-standard-deviation increase in preoperative NfL was associated with a 0.32-point increase in CAM-S (95% confidence interval [0.14-0.50], p = 0.001). Dexmedetomidine significantly attenuated the association between preoperative NfL levels and delirium severity suggesting that dexmedetomidine may intervene early in the disease process to mitigate neuronal damage in older adults following surgery. This study provides insight into the use of preoperative NfL levels to predict delirium risk and reveals a novel interaction between dexmedetomidine treatment and delirium severity.
PMID:41236671 | DOI:10.1007/s11357-025-02009-6
