The Journals of Gerontology | July 14, 2021

Parker M, White M, Casey C, Kunkel D, Bo A, Blennow K, Zetterberg H, Pearce RA, Lennertz R and Sanders RD

J Gerontol A Biol Sci Med Sci. 2021

DOI: https://doi.org/10.1093/gerona/glab203

Abstract

Delirium is associated with cognitive decline and subsequent dementia, and rises in plasma total Tau (tTau) and neurofilament light (NfL), providing links to Amyloid-Tau-Neurodegeneration (ATN) pathophysiology. We investigated whether changes in delirium severity after surgery correlated with changes in cerebrospinal fluid (CSF) ATN biomarkers. Thirty-two thoracic vascular surgical patients were recruited into a prospective biomarker cohort study with assessment of delirium severity and incidence (NCT02926417). CSF (n = 54) and plasma (n = 118) samples were sent for biomarker analysis for tTau, phosphorylated tau-181 (pTau) (plasma n = 53), NfL, and amyloid-β 42/40 ratio (Ab42/40-ratio). The primary outcome was the correlation of preoperative to postoperative change in ATN biomarkers with the highest postoperative Delirium Rating Scale-98 score. CSF and plasma biomarkers all increased postoperatively (all P < .05, n = 13 paired preoperative-postoperative samples). Delirium severity was associated with peak changes in CSF tTau (P = .007, r = 0.710) and pTau (P = .01, r = 0.667) but not NfL (P = .09, rho = 0.491) or Ab42/40-ratio (P = 0.18, rho = 0.394). Sensitivity analysis with exclusion of subjects with putative spinal cord ischaemia shifted the NfL result to significance (P < .001, rho = .847). Our data show that changes in tau and biomarkers of neurodegeneration in the CSF are associated with delirium severity. These data should be considered hypothesis generating and future studies should identify if these changes are robust to confounding.