Preoperative Biofluid Biomarkers for Predicting Postoperative Neurocognitive Disorders in Older Adults: A Systematic Review

Preoperative biofluid biomarkers reflecting pathophysiological, neuronal injury, and inflammation as well as those for Alzheimer's disease (AD) may be valuable tools for the risk stratification of perioperative neurocognitive disorders (PNDs) in older adults. We summarized current evidence relating these preoperative biomarkers to PND beyond 7 days, in older surgical participants aged ≥60 years. Studies that evaluated the association of preoperative biomarkers with cognitive decline as an outcome, beyond 7 days, were identified through searches of 6 databases and 3 trial registries to 17 January 2024. Preclinical studies, intracranial surgical, or studies with participants aged <60 years were excluded. Studies varied widely in the assessment of PND, so a wide range of cognitive outcomes was accepted, including those using the term postoperative cognitive dysfunction (POCD) to define cognitive decline. The pooled incidence of POCD utilizing a binary cognitive outcome was summarized. Fifteen studies involving 2103 participants were included. Marked heterogeneity was evident in the cognitive outcome metrics, assessment timeframes, limiting a quantitative synthesis. Of the 9 studies using binarized cognitive outcomes, the incidence of POCD was 23.4% (95% confidence interval [CI], 6.6-46.2) at <3 months, 11.4% (95% CI, 8.1-15.0) at 3 to <12 months, and 6.9% (95% CI, 1.9-14.5) at ≥12 months postoperatively. Of the 15 studies, 9 described blood-based biomarkers, 4 described cerebrospinal fluid (CSF) biomarkers, and 2 measured both blood and CSF markers. The biomarkers evaluated reflected the pathogenic indicators neuronal injury (9 studies), inflammation (5 studies) and of amyloid (5 studies), and Tau (1 study). The studies included were of medium to high quality. Evidence was the most promising for amyloid biomarkers, with 4 of 5 included studies demonstrating associations of lower preoperative biofluid amyloid biomarker levels with increased risk of POCD. In conclusion, preoperative biofluid amyloid biomarkers may hold potential utility for the prediction of POCD, although current evidence remains limited. Other potential preoperative biomarkers for POCD included p-Tau181 and Neurofilament Light, however small sample sizes, study heterogeneity, and conflicting results limited conclusions drawn. Standardized cognitive outcome metrics and common assessment timeframes are additionally required in future studies to ascertain the prognostic utility of these biomarkers for POCD.