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

Erik Blennow Nordström; Gisela Lilja; Susann Ullén; Kaj Blennow; Hans Friberg; Christian Hassager; Jesper Kjærgaard; Niklas Mattsson-Carlgren; Marion Moseby-Knappe; Niklas Nielsen; Susanna Vestberg; Henrik Zetterberg; Tobias Cronberg

doi:10.1080/02699052.2022.2048693

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

Erik Blennow Nordström, Gisela Lilja, Susann Ullén, Kaj Blennow, Hans Friberg, Christian Hassager, Jesper Kjærgaard, Niklas Mattsson-Carlgren, Marion Moseby-Knappe, Niklas Nielsen, Susanna Vestberg, Henrik Zetterberg, Tobias Cronberg

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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.

Originalspråk	engelska
Sidor (från-till)	800-809
Tidskrift	Brain Injury
Volym	36
Nummer	6
Tidigt onlinedatum	2022
DOI	https://doi.org/10.1080/02699052.2022.2048693
Status	Published - 2022 juni 13

Bibliografisk information

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.

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Neurologi
Tillämpad psykologi

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10.1080/02699052.2022.2048693Licens: CC BY-NC-ND

1 Doktorsavhandling (sammanläggning)

Neurocognitive function following out-of-hospital cardiac arrest
Blennow Nordström, E., 2022, Lund: Lund University, Faculty of Medicine. 105 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

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1 Avslutade

Neurocognitive function following out-of-hospital arrest
Blennow Nordström, E., Cronberg, T., Lilja, G., Vestberg, S. & Nielsen, N.
2016/01/01 → 2022/11/11
Projekt: Avhandling

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Blennow Nordström, E., Lilja, G., Ullén, S., Blennow, K., Friberg, H., Hassager, C., Kjærgaard, J., Mattsson-Carlgren, N., Moseby-Knappe, M., Nielsen, N., Vestberg, S., Zetterberg, H., & Cronberg, T. (2022). Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest. Brain Injury, 36(6), 800-809. https://doi.org/10.1080/02699052.2022.2048693

@article{55a0380486ce4699bd0d1353a3062488,

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

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 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.",

keywords = "biomarker, cardiovascular disease, cognitive impairment, heart arrest, Hypoxic-ischemic encephalopathy",

author = "{Blennow Nordstr{\"o}m}, Erik and Gisela Lilja and Susann Ull{\'e}n and Kaj Blennow and Hans Friberg and Christian Hassager and Jesper Kj{\ae}rgaard and Niklas Mattsson-Carlgren and Marion Moseby-Knappe and Niklas Nielsen and Susanna Vestberg and Henrik Zetterberg and Tobias Cronberg",

note = "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: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2022",

month = jun,

day = "13",

doi = "10.1080/02699052.2022.2048693",

language = "English",

volume = "36",

pages = "800--809",

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Blennow Nordström, E , Lilja, G, Ullén, S, Blennow, K, Friberg, H, Hassager, C, Kjærgaard, J, Mattsson-Carlgren, N , Moseby-Knappe, M , Nielsen, N , Vestberg, S, Zetterberg, H & Cronberg, T 2022, 'Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest', Brain Injury, vol. 36, nr. 6, s. 800-809. https://doi.org/10.1080/02699052.2022.2048693

TY - JOUR

T1 - Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest

AU - Blennow Nordström, Erik

AU - Lilja, Gisela

AU - Ullén, Susann

AU - Blennow, Kaj

AU - Friberg, Hans

AU - Hassager, Christian

AU - Kjærgaard, Jesper

AU - Mattsson-Carlgren, Niklas

AU - Moseby-Knappe, Marion

AU - Nielsen, Niklas

AU - Vestberg, Susanna

AU - Zetterberg, Henrik

AU - Cronberg, Tobias

N1 - 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.

PY - 2022/6/13

Y1 - 2022/6/13

N2 - 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.

AB - 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.

KW - biomarker

KW - cardiovascular disease

KW - cognitive impairment

KW - heart arrest

KW - Hypoxic-ischemic encephalopathy

U2 - 10.1080/02699052.2022.2048693

DO - 10.1080/02699052.2022.2048693

M3 - Article

C2 - 35253570

AN - SCOPUS:85126049647

SN - 0269-9052

VL - 36

SP - 800

EP - 809

JO - Brain Injury

JF - Brain Injury

IS - 6

ER -

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

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Bibliografisk information

Ämnesklassifikation (UKÄ)

FN:s Globala mål

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Forskningsoutput

Neurocognitive function following out-of-hospital cardiac arrest

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Neurocognitive function following out-of-hospital arrest

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