Early biomarker predicts cognitive impairment after out-of-hospital cardiac arrest

Routine early measurement of neurofilament light chain could help improve prediction of cognitive impairment after out-of-hospital cardiac arrest, according to a study presented today at ESC Acute CardioVascular Care 2026, the annual congress of the Association for Acute CardioVascular Care (ACVC), a branch of the European Society of Cardiology (ESC). 

After an out-of-hospital cardiac arrest, the brain is highly susceptible to injury and a range of tests are used by clinicians to predict if survivors have brain damage.

Currently, we measure neuron-specific enolase in the blood as a marker of brain injury but there are concerns about its reliability as factors other than brain damage can lead to high levels. Another blood biomarker, neurofilament light chain, has potentially better diagnostic performance than neuron-specific enolase. We compared neurofilament light chain and neuron-specific enolase for the prediction of long-term cognitive function in survivors of out-of-hospital cardiac arrest." 

Doctor Martin Meyer, study presenter, Rigshospitalet – Copenhagen University, Denmark

The study analyzed blood samples from participants in the Blood Pressure and Oxygenation Targets after Cardiac Arrest (BOX) trial who had been resuscitated from out-of-hospital cardiac arrest and were comatose on hospital admission. Levels of neurofilament light chain and levels of neuron-specific enolase were measured in samples taken 48 hours after cardiac arrest. 

Data on cognitive function, assessed by the Montreal Cognitive Assessment (MoCA) score months after the cardiac arrest, were available for a subset of survivors who had both neurofilament light chain and neuron-specific enolase measurements. 

The key finding of the investigation is that neurofilament light chain levels at 48 hours were inversely correlated with MoCA score, i.e. higher blood levels of neurofilament light chain were indicative of worse long-term cognitive function. 

In contrast, no association was observed for neuron-specific enolase levels at 48 hours and cognitive function at follow-up. 

Summing up the findings, Doctor Meyer concluded: "Neurofilament light chain levels measured early after cardiac arrest, while patients were still admitted to hospital, were related to long-term cognitive function. This association with cognitive function was not observed with neuron-specific enolase testing.

The introduction of routine early neurofilament light chain measurement could potentially assist in the identification of patients at high risk, helping to optimize decision-making about other tests and scans, improve the targeting of rehabilitation and enable clinicians to better inform patients and their families about expectations for the future." Further validation and standardisation of neurofilament light chain assays are now needed.