Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease

Journal of Stroke

Nils Peters¹  Philippe Lyrer¹  Stefan T. Engelter¹  Esther van Leijsen²  Marco Duering²  Anil M. Tuladhar²  Frank-Erik de Leeuw²  Marek J. Konieczny³  Michael Ewers³  Christian Barro⁴  Jens Kuhle⁴ 

[1] Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland;Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands;Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany;Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland;

关键词: stroke;    dementia;    small vessel diseases;    neurofilament;    magnetic resonance imaging;    biomarkers;   

DOI  :  10.5853/jos.2019.02845

来源: DOAJ

【 摘 要 】

Background and Purpose Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) cross-sectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally. Methods From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA). Results Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=–0.159; 95% confidence interval [CI], –0.242 to –0.068; P=0.001; executive function β=–0.095; 95% CI, –0.170 to –0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age. Conclusions Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly.

【 授权许可】

Unknown