The pathophysiology of delirium is incompletely understood including what molecular pathways are involved in brain vulnerability to delirium. We determined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study.


Inclusion criteria were patients ≥65 years of age, undergoing elective noncardiac surgery with a hospital stay of ≥ two days. Concentrations of preoperative plasma P-tau181, neurofilament light chain (NfL), amyloid b1-42 (Ab42), and glial fibrillary acidic protein (GFAP) concentrations were measured with digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. We did a propensity score matching on age and sex with nearest neighbor such that each patient in the delirium group was matched on age and sex with a patient in the no delirium group.


Our initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 years, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no delirium (n=102) and a delirium (n=102) groups matched on age and sex using the propensity score method. Of the four biomarkers assayed, the median value for NfL was 32.05 pg/ml for the delirium group vs. 23.7 pg/ml in the no delirium group. The distribution of biomarker values significantly differed between the delirium and no delirium groups (p-value =0.02 by the Kolmogorov-Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml.


These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma NfL biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline.