Neurofilament, but not Alzheimer disease biomarkers in the acute phase correlate with cognitive performance after cardiac arrest
Lorentzson, Johannes ; Lilja, Gisela LU ; Blennow Nordström, Erik LU
; Blennow, Kaj
LU
; Zetterberg, Henrik
LU
; Hassager, Christian
; Wise, Matt P.
; Benedet, Andrea L.
LU
; Pellis, Tommaso
and Friberg, Hans
LU
, et al.
(2025)
In Resuscitation Plus
25.
- 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... (More)
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.
(Less)- Abstract (Swedish)
- 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... (More) - 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. (Less)
- author
- Lorentzson, Johannes
; Lilja, Gisela
LU
; Blennow Nordström, Erik
LU
; Blennow, Kaj
LU
; Zetterberg, Henrik
LU
; Hassager, Christian
; Wise, Matt P.
; Benedet, Andrea L.
LU
; Pellis, Tommaso
and Friberg, Hans
LU
, et al. (More)
- Lorentzson, Johannes
; Lilja, Gisela
LU
; Blennow Nordström, Erik
LU
; Blennow, Kaj
LU
; Zetterberg, Henrik
LU
; Hassager, Christian
; Wise, Matt P.
; Benedet, Andrea L.
LU
; Pellis, Tommaso
; Friberg, Hans
LU
; Ashton, Nicholas
and Moseby Knappe, Marion
LU
(Less)
- organization
- publishing date
- 2025-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amyloid beta, Cognitive impairment, Neurofilament light, Neuroprognostication, OHCA, Tau, OHCA, Neuroprognostication, Amyloid beta, Tau, Neurofilament light, Cognitive impairment
- in
- Resuscitation Plus
- volume
- 25
- article number
- 101025
- publisher
- Elsevier
- external identifiers
-
- scopus:105010606468
- pmid:40703816
- ISSN
- 2666-5204
- DOI
- 10.1016/j.resplu.2025.101025
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s)
- id
- fc75d111-282b-4072-8ea0-1bc4b9ed944d
- date added to LUP
- 2025-07-25 14:19:45
- date last changed
- 2025-08-22 17:05:05
@article{fc75d111-282b-4072-8ea0-1bc4b9ed944d,
abstract = {{<p>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.</p><p>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-tau<sup>181</sup>, 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.</p><p>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.</p><p>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.</p>}},
author = {{Lorentzson, Johannes and Lilja, Gisela and Blennow Nordström, Erik and Blennow, Kaj and Zetterberg, Henrik and Hassager, Christian and Wise, Matt P. and Benedet, Andrea L. and Pellis, Tommaso and Friberg, Hans and Ashton, Nicholas and Moseby Knappe, Marion}},
issn = {{2666-5204}},
keywords = {{Amyloid beta; Cognitive impairment; Neurofilament light; Neuroprognostication; OHCA; Tau; OHCA; Neuroprognostication; Amyloid beta; Tau; Neurofilament light; Cognitive impairment}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Resuscitation Plus}},
title = {{Neurofilament, but not Alzheimer disease biomarkers in the acute phase correlate with cognitive performance after cardiac arrest}},
url = {{http://dx.doi.org/10.1016/j.resplu.2025.101025}},
doi = {{10.1016/j.resplu.2025.101025}},
volume = {{25}},
year = {{2025}},
}