Serum neurofilament light chain protein as a biomarker for delirium
Research type
Research Study
Full title
Serum neurofilament light chain protein as a prognostic biomarker for delirium in critically ill patients
IRAS ID
278187
Contact name
Valerie Page
Contact email
Sponsor organisation
West Hertfordshire Hospitals NHS Trust
Duration of Study in the UK
0 years, 10 months, 25 days
Research summary
Summary of Research
When patients are critically ill they will often become acutely confused, this temporary problem with brain function is called delirium. An episode of delirium will make any existing cognitive impairment worse and accelerate dementia. Delirium is the number one predictive factor for patients developing cognitive impairment.
There is no blood test for delirium. Other conditions i.e. cancer have biomarkers, substances in the blood that tell us about the presence of cancer that are used clinically and in research to monitor patients progress and response to treatment. A substance called neurofilament light protein is present in the blood in neurodegenerative conditions such as dementia, multiple sclerosis and traumatic brain injury and it can predict disease progression.
We have 400 serum samples from blood samples taken from 142 patients recruited to a completed trial, Modifying Delirium Using Simvastatin, undertaken in adult intensive care patients at Watford General Hospital. They were stored for use in future research. They were taken at intervals while patients were on intensive care. We will test these serum samples for levels of neurofilament light protein. We want to find out what the levels are of this protein in patients when they have delirium and when they recover. Also if the amount of this protein is related to how long a patient had delirium, if they survived or had cognitive decline.
If neurofilament light protein is shown to be a biomarker it will be invaluable in future research trials, in monitoring response to treatment and diagnosis of delirium.Summary of Results
In this study we have shown a positive association between plasma NfL levels on admission and delirium days plus deep sedation days in a general adult critical care population. Patients with higher plasma NfL levels on admission and day three had more days in delirium or deep sedation as well as poorer outcomes either as a hospital stay of 14 days or more and/or death by six months following recruitment. Baseline NfL levels were high across all age groups with only 20 patients (14%) with plasma NfL levels in normal range, suggesting that most of the patients suffered from conditions that impacted neuronal integrity. We were unable to show an association between critical care plasma NfL levels and long-term cognitive outcomes probably due to the small number of patients with follow-up data.
Our findings suggest that while plasma NfL on day three of intensive care admission has potential to predict risk of delirium lasting seven days or more, mortality or prolonged hospital stay repeated measures in the hospital stay are unlikely to add any more useful information. Routine delirium screening will enable clinicians to determine the progress of acute cognitive recovery.
Measuring plasma NfL levels, however, at three- and or six-month follow-up with cognitive assessments would be informative in interventional delirium research and useful in monitoring long-term clinical recovery. We need to know more however about the dynamics of NfL and how long after neuronal damage and release of NfL into the blood that the levels plateau and then fall. Only then can we determine the utility, if any, of serum NfL as an early response to intervention biomarker.
Measurement of plasma NfL within three days of admission may be a useful enrichment strategy for future delirium interventional trials in the critically ill.REC name
Wales REC 5
REC reference
20/WA/0204
Date of REC Opinion
21 Jul 2020
REC opinion
Favourable Opinion