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

Journal of Stroke 2020년 22권 3호 p.369 ~ 376
Peters Nils, van Leijsen Esther, Tuladhar Anil M., Barro Christian, Konieczny Marek J., Ewers Michael, Lyrer Philippe, Engelter Stefan T., Kuhle Jens, Duering Marco, de Leeuw Frank-Erik,
소속 상세정보
 ( Peters Nils ) - University of Basel University Hospital Basel Department of Neurology
 ( van Leijsen Esther ) - Radboud University Medical Center Department of Neurology
 ( Tuladhar Anil M. ) - Radboud University Medical Center Department of Neurology
 ( Barro Christian ) - University Hospital of Basel Department of Medicine, Biomedicine and Clinical Research
 ( Konieczny Marek J. ) - Ludwig-Maximilians-University Munich University Hospital Institute for Stroke and Dementia Research
 ( Ewers Michael ) - Ludwig-Maximilians-University Munich University Hospital Institute for Stroke and Dementia Research
 ( Lyrer Philippe ) - University of Basel University Hospital Basel Department of Neurology
 ( Engelter Stefan T. ) - University of Basel University Hospital Basel Department of Neurology
 ( Kuhle Jens ) - University Hospital of Basel Department of Medicine, Biomedicine and Clinical Research
 ( Duering Marco ) - Radboud University Medical Center Department of Neurology
 ( de Leeuw Frank-Erik ) - Radboud University Medical Center Department of Neurology

Abstract


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.

키워드

Stroke; Dementia; Small vessel diseases; Neurofilament; Magnetic resonance imaging; Biomarkers

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