Cohort Analysis of the Association of Delirium Severity With Cerebrospinal Fluid Amyloid-Tau-Neurodegeneration Pathologies

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 = .710) and pTau (p = .01, r = .667) but not NfL (p = .09, ρ = .491) or Ab42/40-ratio (p = .18, ρ = .394). Sensitivity analysis with exclusion of participants with putative spinal cord ischemia shifted the NfL result to significance (p < .001, ρ = .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.

Keywords: Biology of aging; Biomarkers; Dementia.

© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Descriptive plots for the time course of cerebrospinal fluid changes for each biomarker by participant, (A) pTau, (B) tTau, (C) NfL, and (D) Ab42/40-ratio. Ab42/40-ratio = amyloid-β 42/40 ratio; NfL = neurofilament light; pTau = phosphorylated tau; tTau = total tau.

Figure 2.

Peak delirium severity correlates with peak postoperative changes in cerebrospinal fluid tTau (A) and pTau (B) but not NfL (C) or Ab42/40-ratio (D). The y-axis is on a log(10) scale. Ab42/40-ratio = amyloid-β 42/40 ratio; DRS = Delirium Rating Scale; NfL = neurofilament light; pTau = phosphorylated tau; tTau = total tau.

Figure 3.

Peak delirium severity did not correlate with changes in plasma tTau (A), pTau (B), NfL (C), or Ab42/40-ratio (D). The y-axis is on a log(10) scale. Ab42/40-ratio = amyloid-β 42/40 ratio; DRS = Delirium Rating Scale; NfL = neurofilament light; pTau = phosphorylated tau; tTau = total tau.

Figure 4.

Peak changes in cerebrospinal fluid biomarkers, tTau (A), pTau (B), NfL (C), or Ab42/40-ratio (D), were not associated with delirium incidence. The y-axis is on a log(10) scale. Ab42/40-ratio = amyloid-β 42/40 ratio; NfL = neurofilament light; pTau = phosphorylated tau; tTau = total tau.