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:

• Hypoxic-ischemic encephalopathy
• heart arrest
• cognitive impairment
• biomarker
• cardiovascular disease

Disclosure statement

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.

Additional information

Funding

This work was supported by the the Swedish state under the agreement between the Swedish government and the County Councils – the ALF-agreement [ALFGBG-715986,ALFGBG-720931];The Swedish Research Council;The Swedish Society of Medicine;The County Council of Skane;The Segerfalk Foundation;The Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research;The Koch Foundation;The Tryg Foundation;The Swedish Heart and Lung Association;The Royal Swedish Academy of Sciences;The Skane University Hospital Psychology Research and Development Grant;The Skane University Hospital Foundations;The Swedish Heart-Lung Foundation;The Gyllenstiernska-Krapperup Foundation;AFA Insurance Foundation;Academy of Caring Sciences at Skane University Hospital.