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Published

Neurofilament, but not Alzheimer disease biomarkers in the acute phase correlate with cognitive performance after cardiac arrest

Authors

Johannes Lorentzson, Gisela Lilja, Erik Blennow Nordström, Kaj Blennow, Henrik Zetterberg, Christian Hassager, Matt P Wise, Andrea L Benedet, Tommaso Pellis, Hans Friberg, Nicholas Ashton, Marion Moseby Knappe

Abstract

Resusc Plus. 2025 Jul 8;25:101025. doi: 10.1016/j.resplu.2025.101025. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Biomarkers serve as a quantitative measure of brain injury and may predict cognitive outcome after cardiac arrest. This study investigates the association and predictive accuracy of acute changes in Alzheimer disease-associated biomarkers to cognitive outcome in cardiac arrest survivors.

METHODS: Retrospective study of the Target Temperature Management after Out-of-Hospital cardiac arrest trial. Serum from adult cardiac arrest survivors was sampled prospectively at 24, 48, and 72 h post-arrest and analyzed for peak-levels of Alzheimer disease markers (p-tau181, total tau, amyloid β [Aβ40 and Aβ42]), and the neurodegenerative biomarker neurofilament light (NfL). Cognitive outcome was evaluated blinded from biomarker results using four performance-based assessments at 6 months post-arrest. Spearman correlations were calculated. Area Under the Receiver Operating Characteristics curves (AUC) were calculated for biomarkers discriminatory ability for binary results of cognitive performance.

RESULTS: 206/342 (60 %) survivors from participating sites were included. Median was age 62 (IQR 53-69), 86 % male, 15 (7 %) had Mini-Mental State Examination (MMSE) scores < 24. Alzheimer disease biomarkers exhibited at best small correlations to cognitive outcomes (rho = -0.22 to 0.18). The correlation between outcome instruments and NfL was rho = -0.32 to -0.20 (p < 0.01). Discriminatory ability of cognitive impairment for acute changes in Alzheimer disease biomarkers was AUC 0.44-0.68 (95 % CI 0.29-0.82), and AUC 0.66-0.86 (95 % CI 0.59-0.95) for NfL.

CONCLUSION: In contrast to tau- and amyloid-related biomarkers, NfL could be more useful for predicting cognitive function in cardiac arrest survivors. Low participation by survivors with severe brain injury may have influenced results.

PMID:40703816 | PMC:PMC12284371 | DOI:10.1016/j.resplu.2025.101025

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg