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Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest

Blennow Nordström, Erik LU orcid ; Lilja, Gisela LU ; Ullén, Susann LU ; Blennow, Kaj LU ; Friberg, Hans LU ; Hassager, Christian ; Kjærgaard, Jesper ; Mattsson-Carlgren, Niklas LU orcid ; Moseby-Knappe, Marion LU and Nielsen, Niklas LU , et al. (2022) In Brain Injury 36(6). p.800-809
Abstract

Objective: To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods: An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results: Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and... (More)

Objective: To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods: An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results: Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1–2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]–TSQ) to strong (CPC–MMSE). Conclusions: The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarker, cardiovascular disease, cognitive impairment, heart arrest, Hypoxic-ischemic encephalopathy
in
Brain Injury
volume
36
issue
6
pages
800 - 809
publisher
Taylor & Francis
external identifiers
  • scopus:85126049647
  • pmid:35253570
ISSN
0269-9052
DOI
10.1080/02699052.2022.2048693
project
Neurocognitive function following out-of-hospital arrest
language
English
LU publication?
yes
additional info
Funding Information: K.B. has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, all unrelated to the present work. J.K. is supported by a grant from NovoNordisk foundation (grant number NNF17OC0028706), for work outside the present manuscript. H.Z. has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, all unrelated to the present work. H.Z. is a Wallenberg Scholar. All other authors report no conflicts of interest with respect to the research, authorship, and/or publication of this article. The study sponsors had no involvement in the study design; in the collection, analyses and interpretation of the data; in the writing of the manuscript or in the decision to submit the manuscript for publication. Publisher Copyright: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
id
55a03804-86ce-4699-bd0d-1353a3062488
date added to LUP
2022-03-21 10:22:18
date last changed
2025-01-02 06:13:59
@article{55a03804-86ce-4699-bd0d-1353a3062488,
  abstract     = {{<p>Objective: To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods: An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results: Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1–2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]–TSQ) to strong (CPC–MMSE). Conclusions: The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.</p>}},
  author       = {{Blennow Nordström, Erik and Lilja, Gisela and Ullén, Susann and Blennow, Kaj and Friberg, Hans and Hassager, Christian and Kjærgaard, Jesper and Mattsson-Carlgren, Niklas and Moseby-Knappe, Marion and Nielsen, Niklas and Vestberg, Susanna and Zetterberg, Henrik and Cronberg, Tobias}},
  issn         = {{0269-9052}},
  keywords     = {{biomarker; cardiovascular disease; cognitive impairment; heart arrest; Hypoxic-ischemic encephalopathy}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{800--809}},
  publisher    = {{Taylor & Francis}},
  series       = {{Brain Injury}},
  title        = {{Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest}},
  url          = {{http://dx.doi.org/10.1080/02699052.2022.2048693}},
  doi          = {{10.1080/02699052.2022.2048693}},
  volume       = {{36}},
  year         = {{2022}},
}