Neurodegeneration biofluid markers and postoperative delirium: Results from a prospective cohort study

Objectives Blood biomarkers are emerging as new tools for the diagnosis of age-related cognitive disorders, and they may help to elucidate the pathophysiology of postoperative delirium. We conducted an exploratory prospective cohort study to evaluate whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium. Methods Inclusion criteria were patients ≥ 65 years of age, undergoing elective noncardiac surgery. Incidence of delirium was determined by the Confusion Assessment Method score. Delirium severity was determined with the Memorial Delirium Assessment Scale and Confusion Assessment Method scores. Concentrations of preoperative plasma phosphorylated tau 181, neurofilament light chain, amyloid beta (amyloid β 1–40 , and amyloid β 1–42 ), and glial fibrillary acidic protein were measured with a single molecule array and compared between groups with or without delirium. After propensity matching for age and sex, relationships between delirium and individual or joint biomarker levels were assessed using logistic regression. Biomarker relationships with longitudinal change in delirium severity were assessed with mixed effects models. Results After matching for age and sex, the sample size of 235 was reduced to 168, with an incidence of postoperative delirium in this final analytic cohort of 33.3% (56/168 patients). By bi-variate analysis, phosphorylated tau 181, amyloid β 1–40 , amyloid β 1–42 , and amyloid β 1–42 /amyloid β 1–40 showed preoperative differences between the patients with vs . without delirium. In the joint logistic regression analysis with multiple biomarkers, amyloid β 1–40 was associated with postoperative delirium. When stratified by the sample’s storage time (< 10 years vs . ≥ 10 years), amyloid β 1–40 , amyloid β 1–42 , amyloid β 1–42 /amyloid β 1–40 , and phosphorylated tau 181 had significantly different mean values. Based on biomarker-wise logistic regression, amyloid β 1–40 and amyloid β 1–42 were associated with increased risk of postoperative delirium. Delirium severity was associated with five of the seven biomarkers: amyloid β 1–40 , amyloid β 1–42 , amyloid β 1–42 /amyloid β 1–40 , phosphorylated tau 181, and neurofilament light chain. Conclusions Preoperative concentrations of blood amyloid β, tau, and neurodegeneration markers are associated with the incidence and severity of postoperative delirium in older individuals. The postoperative delirium represents an acute expression of chronic neurodegenerative stress, and the pathophysiological link could be explored with established neurodegeneration biomarkers.