Biomarkers of neurodegeneration and neural injury as potential predictors for delirium

ObjectivesDetermine if biomarkers of Alzheimer's disease and neural injury may play a role in the prediction of delirium risk.MethodsIn a cohort of older adults who underwent elective surgery, delirium case-no delirium control pairs (N = 70, or 35 matched pairs) were matched by age, sex and vascular comorbidities. Biomarkers from CSF and plasma samples collected prior to surgery, including amyloid beta (A beta)42, A beta 40, total (t)-Tau, phosphorylated (p)-Tau181, neurofilament-light (NfL), and glial fibrillary acid protein (GFAP) were measured in cerebrospinal fluid (CSF) and plasma using sandwich enzyme-linked immunosorbent assays (ELISAs) or ultrasensitive single molecule array (Simoa) immunoassays.ResultsPlasma GFAP correlated significantly with CSF GFAP and both plasma and CSF GFAP values were nearly two-fold higher in delirium cases. The median paired difference between delirium case and control without delirium for plasma GFAP was not significant (p = 0.074) but higher levels were associated with a greater risk for delirium (odds ratio 1.52, 95% confidence interval 0.85, 2.72 per standard deviation increase in plasma GFAP concentration) in this small study. No matched pair differences or associations with delirium were observed for NfL, p-Tau 181, A beta 40 and A beta 42.ConclusionsThese preliminary findings suggest that plasma GFAP, a marker of astroglial activation, may be worth further investigation as a predictive risk marker for delirium. Delirium is a common complication of hospitalization associated with poor outcomes, but the underlying pathophsysiology of this condition is poorly understoodThere is a close interrelationship between delirium and dementia, therefore CSF and blood biomarkers for Alzheimer's Disease and neural injury might be associated with deliriumWe found that plasma and CSF glial fibrillary acid protein (GFAP), a marker of reactive gliosis known to be elevated in neurodegeneration, appears to be related to delirium risk, with a nearly two-fold greater odds of deliriumFurther larger studies are needed to understand the potential role of GFAP as a predictive risk marker for delirium