Biomarkers of neurodegeneration and neural injury as potential predictors for delirium

Abstract

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 (Aβ)42, Aβ40, 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, Aβ40 and Aβ42.ConclusionsThese preliminary findings suggest that plasma GFAP, a marker of astroglial activation, may be worth further investigation as a predictive risk marker for delirium.

Neurofilament Light Chain as a Potential Biomarker for Perioperative Neurocognitive Disorders: A Systematic Review and Meta-Analysis

“…After screening the titles and abstracts, 624 studies were found to be potentially eligible. Finally, 12 studies [22,24,[29][30][31][32][33][34][35][36][37][38] were selected based on the exclusion criteria (Figure 1). All reviewers agreed to include these 12 papers.…”

“…The demographic and clinical characteristics of the included studies are presented in Table 1. Nine studies [22,24,[29][30][31][32][33][34][35] involved patients with POD, three studies [36][37][38] focused on patients with POCD, and one study considered patients with pre-existing cognitive impairment [36]. CSF NfL detection was reported in six studies [24,29,[35][36][37][38], whereas four studies [24,29,35,37] discussed the correlation between CSF and blood NfL levels.…”

“…Nine studies [22,24,[29][30][31][32][33][34][35] involved patients with POD, three studies [36][37][38] focused on patients with POCD, and one study considered patients with pre-existing cognitive impairment [36]. CSF NfL detection was reported in six studies [24,29,[35][36][37][38], whereas four studies [24,29,35,37] discussed the correlation between CSF and blood NfL levels. Furthermore, five studies [24,[31][32][33][34] examined preoperative blood NfL levels as a risk factor for subsequent POD and presented the results as odds ratios (ORs) and 95% confidence intervals (CIs).…”

“…CSF NfL detection was reported in six studies [24,29,[35][36][37][38], whereas four studies [24,29,35,37] discussed the correlation between CSF and blood NfL levels. Furthermore, five studies [24,[31][32][33][34] examined preoperative blood NfL levels as a risk factor for subsequent POD and presented the results as odds ratios (ORs) and 95% confidence intervals (CIs).…”

“…Recent studies have found that elevated CSF/blood NfL levels are associated with postoperative cognitive changes [22,23]. However, these results have been inconsistent, with opposing results observed under similar experimental conditions and designs [22,24]. Consequently, we performed a meta-analysis of the relationship between CSF/blood NfL levels and PND to determine the predictive and diagnostic value of NfL for this condition and summarise the correlation between NfL levels in CSF and blood in surgical patients based on existing studies.…”