Plasma Glial Fibrillary Acidic Protein and p-Tau217: Potential Biomarkers of Delirium in Older Adults

Abstract Objective Delirium is a common complication of hospitalization among older adults, and is associated with cognitive decline, but the underlying mechanisms are poorly understood. Delirium and dementia are closely interrelated; therefore, blood biomarkers for Alzheimer’s disease (AD) and neural injury may yield insight to potential mechanisms in delirium. Methods Data were obtained from the Successful Aging after Elective Surgery (SAGES) study (n = 530). Glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis elevated in neurodegeneration and neural injury, and tau phosphorylated at residue 217 (p-Tau217), a marker of AD pathology, were measured from plasma collected prior to surgery. Post-operative delirium incidence and severity were assessed using the Confusion Assessment Method (CAM) and CAM-S (0-19, 19 worst), respectively. Results Higher GFAP (4th vs. 1st quartile) was associated with delirium incidence (relative risk (RR) 1.7, 95% confidence interval (CI): 1.1-2.8) and greater CAM-S severity (adjusted mean difference=0.5, 95% CI: 0.1-1.0). p-Tau217 did not significantly predict delirium incidence, though higher levels were associated with greater severity (adjusted mean CAM-S difference 1st to 4th quartile=0.6, 95% CI: 0.1-1.0). Interpretation High pre-operative plasma GFAP was associated with higher delirium incidence and severity, whereas high p-Tau217 was associated only with higher severity. Overall, GFAP appears to be a stronger risk marker than p-Tau217 for delirium. Further work is needed to establish whether astrocytosis contributes to delirium pathophysiology.