Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease
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 longitud...
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| Format: | Article |
| Language: | English |
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Korean Stroke Society
2020-09-01
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| Series: | Journal of Stroke |
| Subjects: | |
| Online Access: | http://www.j-stroke.org/upload/pdf/jos-2019-02845.pdf |
| _version_ | 1818280333681885184 |
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| author | Nils Peters Esther van Leijsen Anil M. Tuladhar Christian Barro Marek J. Konieczny Michael Ewers Philippe Lyrer Stefan T. Engelter Jens Kuhle Marco Duering Frank-Erik de Leeuw |
| author_facet | Nils Peters Esther van Leijsen Anil M. Tuladhar Christian Barro Marek J. Konieczny Michael Ewers Philippe Lyrer Stefan T. Engelter Jens Kuhle Marco Duering Frank-Erik de Leeuw |
| author_sort | Nils Peters |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T23:47:34Z |
| format | Article |
| id | doaj.art-b7c7e2220e2b4b6684fc2c5abad0d161 |
| institution | Directory Open Access Journal |
| issn | 2287-6391 2287-6405 |
| language | English |
| last_indexed | 2024-12-12T23:47:34Z |
| publishDate | 2020-09-01 |
| publisher | Korean Stroke Society |
| record_format | Article |
| series | Journal of Stroke |
| spelling | doaj.art-b7c7e2220e2b4b6684fc2c5abad0d1612022-12-22T00:06:49ZengKorean Stroke SocietyJournal of Stroke2287-63912287-64052020-09-0122336937610.5853/jos.2019.02845340Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel DiseaseNils Peters0Esther van Leijsen1Anil M. Tuladhar2Christian Barro3Marek J. Konieczny4Michael Ewers5Philippe Lyrer6Stefan T. Engelter7Jens Kuhle8Marco Duering9Frank-Erik de Leeuw10 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 Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The NetherlandsBackground 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.http://www.j-stroke.org/upload/pdf/jos-2019-02845.pdfstrokedementiasmall vessel diseasesneurofilamentmagnetic resonance imagingbiomarkers |
| spellingShingle | Nils Peters Esther van Leijsen Anil M. Tuladhar Christian Barro Marek J. Konieczny Michael Ewers Philippe Lyrer Stefan T. Engelter Jens Kuhle Marco Duering Frank-Erik de Leeuw Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease Journal of Stroke stroke dementia small vessel diseases neurofilament magnetic resonance imaging biomarkers |
| title | Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease |
| title_full | Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease |
| title_fullStr | Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease |
| title_full_unstemmed | Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease |
| title_short | Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease |
| title_sort | serum neurofilament light chain is associated with incident lacunes in progressive cerebral small vessel disease |
| topic | stroke dementia small vessel diseases neurofilament magnetic resonance imaging biomarkers |
| url | http://www.j-stroke.org/upload/pdf/jos-2019-02845.pdf |
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