Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke

Abstract

Background: It is important to predict poststroke cognitive outcome to guide individualized treatment and prevention strategy. We aimed to evaluate the predictive value of the combination of a serum biomarker for axonal damage (neurofilament light chain [NfL]) and neuroimaging markers (volume of infarction and white matter hyperintensities [WMH]) for neuronal abnormality in poststroke cognitive outcome. Methods: A total of 1028 patients were screened; among them, 144 patients with acute ischemic stroke (stroke group) and 30 patients without stroke (control group) were enrolled. Serum NfL levels of samples obtained from both groups were measured through single molecule array assay. Neuroimaging markers of neuroaxonal injury, including infarct volume and WMH in the stroke group were quantified on magnetic resonance images using an in-house MATLAB code (MATLAB 2017; MathWorks). The primary outcome was the functional independence measure (FIM) cognitive subscores on discharge. We assessed the association of serum NfL levels and neuroimaging markers with cognitive outcome. The prognosis value of the combination of serum NfL levels and imaging markers for predicting FIM cognitive subscores on discharge was calculated using the area under curve (AUC) of the receiver operating characteristic. Results: Serum NfL levels of the stroke group were 9-fold higher than those of the control group (1449.7 vs 157.2 pg/mL, n = 144/30, P < .001). There was a correlation of serum NfL levels with infarct volume ( r = 0.530, P < .001) and functional outcome, including FIM cognitive subscores ( r = −0.387, P < .001) and FIM motor subscores on admission ( r = −0.306, P < .001), but not with WMH volume after adjusting for infarct volume ( r = −0.196, P = .245). Serum NfL levels on admission independently predicted poststroke FIM cognitive subscores on discharge (AUC = 0.672, P < .001). The predictive value for poststroke cognitive outcome was improved by combining serum NfL levels with infarct and WMH volume (AUC = 0.760, P < .001). Conclusion: The combination of serum NfL levels with volume of infarct and WMH shows an improved predictive value for cognitive function during acute rehabilitation phase after stroke, providing a promising panel of biomarkers for prognosis and guidance of treatment.