Longitudinal measurement of serum neurofilament light chain in patients with CADASIL

Abstract

Introduction: Serum neurofilament light chain (NfL) levels have been shown to be strongly associated with MRI markers of cerebral small vessel disease, cognitive deficits, and disability in cross-sectional studies of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate the longitudinal changes in serum NfL levels and their correlation with disease progression in patients with CADASIL. Methods: We prospectively enrolled a group of CADASIL patients and assessed their clinical symptoms, cognitive function, brain MRI, and serum NfL levels at baseline and after a three-year follow-up. We measured cortical thickness, white matter hyperintensity volume, number of lacunar infarctions, and number of cerebral microbleeds on brain MRI. Global cognitive function was evaluated using the Seoul Neuropsychological Screening Battery dementia version (SNSB-D), with a maximum score of 300. We used linear mixed-effects models to investigate associations between changes in serum NfL levels and changes in cognitive function and MRI markers. Results: At baseline, we examined 59 CADASIL patients between October 2018 and August 2019, and 51 patients completed the three-year follow-up, including clinical assessment, brain MRI, and serum NfL measurement. At baseline, the log-transformed serum NfL level showed significant correlations with age, glomerular filtration rate, SNSB-D score, and cortical thickness (Figure 1). During the three-year follow-up, there was a significant increase in mean serum NfL levels (19.04 ± 1.90 pg/ml vs. 30.84 ± 3.41 pg/ml, P<0.001) (Figure 2). Changes in serum NfL levels were also significantly associated with age, changes in SNSB-D score, and cortical thickness. After adjusting for age, changes in serum NfL levels could predict changes in cortical thickness (P<0.001) or SNSB-D score (P <0.001) (Figure 3). Discussion: Over a three-year follow-up period, changes in serum NfL levels were strongly correlated with changes in global cognitive function and cortical thickness measured on brain MRI. Longitudinal measurements of serum NfL could serve as a valuable blood biomarker for monitoring disease progression in patients with CADASIL.