SERUM NEUROFILAMENT LIGHT CHAIN PREDICTS PROGRESSIVE MICROSTRUCTURAL DAMAGE AND PSYCHOMOTOR SPEED DECLINE IN CEREBRAL SMALL VESSEL DISEASE

2018 ◽  
Author(s):  
Nils Peters
Keyword(s):  
Light Chain ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Psychomotor Speed ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease ◽  
Microstructural Damage

scholarly journals Serum Neurofilament Light Chain Levels Are Related to Small Vessel Disease Burden

2018 ◽  
Vol 20 (2) ◽  
pp. 228-238 ◽  
Author(s):  
Marco Duering ◽  
Marek J. Konieczny ◽  
Steffen Tiedt ◽  
Ebru Baykara ◽  
Anil Man Tuladhar ◽  
...  
Keyword(s):  
Light Chain ◽  
Disease Burden ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease

scholarly journals Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2108-2114 ◽  
Author(s):  
Thomas Gattringer ◽  
Daniela Pinter ◽  
Christian Enzinger ◽  
Thomas Seifert-Held ◽  
Markus Kneihsl ◽  
...  
Keyword(s):  
Single Molecule ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Reader response: Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2018 ◽  
Vol 90 (24) ◽  
pp. 1126.2-1126
Author(s):  
Stefanie Schreiber ◽  
Vincent Scheumann ◽  
Valentina Perosa ◽  
Stefan Vielhaber ◽  
Anne Assmann
Keyword(s):  
Reader Response ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Neurofilament Light ◽  
Vessel Disease

scholarly journals White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

Stroke ◽  
2016 ◽  
Vol 47 (6) ◽  
pp. 1679-1684 ◽  
Author(s):  
Marco Pasi ◽  
Inge W.M. van Uden ◽  
Anil M. Tuladhar ◽  
Frank-Erik de Leeuw ◽  
Leonardo Pantoni
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Microstructural Damage

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

2020 ◽  
Vol 22 (3) ◽  
pp. 369-376
Author(s):  
Nils Peters ◽  
Esther van Leijsen ◽  
Anil M. Tuladhar ◽  
Christian Barro ◽  
Marek J. Konieczny ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Analysis Of Covariance ◽  
Small Vessel ◽  
Cognitive Measures ◽  
Neurofilament Light ◽  
Baseline Serum ◽  
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 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.

scholarly journals Structural network changes in cerebral small vessel disease

2019 ◽  
Vol 91 (2) ◽  
pp. 196-203 ◽  
Author(s):  
Anil M Tuladhar ◽  
Jonathan Tay ◽  
Esther van Leijsen ◽  
Andrew J Lawrence ◽  
Ingeborg Wilhelmina Maria van Uden ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Psychomotor Speed ◽  
Network Efficiency ◽  
Vessel Disease ◽  
Global Efficiency ◽  
Structural Network ◽  
Imaging Markers

ObjectivesTo investigate whether longitudinal structural network efficiency is associated with cognitive decline and whether baseline network efficiency predicts mortality in cerebral small vessel disease (SVD).MethodsA prospective, single-centre cohort consisting of 277 non-demented individuals with SVD was conducted. In 2011 and 2015, all participants were scanned with MRI and underwent neuropsychological assessment. We computed network properties using graph theory from probabilistic tractography and calculated changes in psychomotor speed and overall cognitive index. Multiple linear regressions were performed, while adjusting for potential confounders. We divided the group into mild-to-moderate white matter hyperintensities (WMH) and severe WMH group based on median split on WMH volume.ResultsThe decline in global efficiency was significantly associated with a decline in psychomotor speed in the group with severe WMH (β=0.18, p=0.03) and a trend with change in cognitive index (β=0.14, p=0.068), which diminished after adjusting for imaging markers for SVD. Baseline global efficiency was associated with all-cause mortality (HR per decrease of 1 SD 0.43, 95% CI 0.23 to 0.80, p=0.008, C-statistic 0.76).ConclusionDisruption of the network efficiency, a metric assessing the efficiency of network information transfer, plays an important role in explaining cognitive decline in SVD, which was however not independent of imaging markers of SVD. Furthermore, baseline network efficiency predicts risk of mortality in SVD that may reflect the global health status of the brain in SVD. This emphasises the importance of structural network analysis in the context of SVD research and the use of network measures as surrogate markers in research setting.

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