Abstract
BACKGROUND: Delirium is a common complication of hospitalization with poor outcomes, but its underlying pathophysiology is poorly understood. We investigated the association of preoperative glial fibrillary acidic protein (GFAP), a biomarker of reactive astrocytosis, with delirium incidence and severity.
METHODS: Data were obtained from the ongoing prospective Successful Aging after Elective Surgery (SAGES) study. GFAP was measured in preoperative plasma (n = 529). Post-operative delirium incidence and severity were measured using the Confusion Assessment Method (CAM) and CAM-S (0-19, 19 worst), respectively. A multivariable generalized linear model (GLM) with log link and binary or Poisson error distribution was used to estimate the relative risk of delirium by GFAP quartile scale, and GLM with identity link was used to examine the association of preoperative GFAP and delirium severity.
RESULTS: Overall mean preoperative GFAP value was 289.6 ± 153.3 pg/ml; mean value by quartile (Q) was 148.1 ± 28.6 pg/ml for Q1, 220.5 ± 19.8 pg/ml for Q2, 298.2 ± 28.4 pg/ml for Q3, and 503.4 ± 128.3 pg/ml for Q4. Delirium incidence by GFAP level was 16% in Q1, 24% in Q2, 25% in Q3, and 28% in Q4 (Cochran Trend test P-value = 0.031; adjusted P-value = 0.205). Higher GFAP levels (4th vs. 1st quartile) were associated with greater risk of incident delirium (adjusted relative risk 1.70, 95% confidence interval (CI): 1.01-2.86) and greater delirium severity (adjusted mean difference 0.86, 95% CI: 0.004-1.71).
CONCLUSIONS: High preoperative plasma GFAP was associated with increased delirium incidence and severity, suggesting GFAP may serve as a risk marker for delirium. Brain vulnerability in the setting of astrocytosis may contribute to delirium pathophysiology.