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Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Meeter, Lieke H.H.; Steketee, Rebecca M.E.; Salkovic, Dina; Vos, Maartje E.; Grossman, Murray; McMillan, Corey T.; Irwin, David J.; Boxer, Adam L.; Rojas, Julio C. and Olney, Nicholas T., et al. (2019) In Journal of Neurology, Neurosurgery and Psychiatry
Abstract

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with... (More)

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs=-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs=-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.

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Journal of Neurology, Neurosurgery and Psychiatry
pages
8 pages
publisher
BMJ Publishing Group
external identifiers
  • scopus:85066140649
ISSN
0022-3050
DOI
10.1136/jnnp-2018-319784
language
English
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yes
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2f67232d-cdb3-453f-88e0-fc4b043cb14b
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2019-06-12 19:02:54
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2019-07-02 04:47:56
@article{2f67232d-cdb3-453f-88e0-fc4b043cb14b,
  abstract     = {<p>Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p&lt;0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (r<sub>s</sub>=-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r<sub>s</sub>=-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.</p>},
  author       = {Meeter, Lieke H.H. and Steketee, Rebecca M.E. and Salkovic, Dina and Vos, Maartje E. and Grossman, Murray and McMillan, Corey T. and Irwin, David J. and Boxer, Adam L. and Rojas, Julio C. and Olney, Nicholas T. and Karydas, Anna and Miller, Bruce L. and Pijnenburg, Yolande A.L. and Barkhof, Frederik and Sánchez-Valle, Raquel and Lladó, Albert and Borrego-Ecija, Sergi and Diehl-Schmid, Janine and Grimmer, Timo and Goldhardt, Oliver and Santillo, Alexander F. and Hansson, Oskar and Vestberg, Susanne and Borroni, Barbara and Padovani, Alessandro and Galimberti, Daniela and Scarpini, Elio and Rohrer, Jonathan D. and Woollacott, Ione O.C. and Synofzik, Matthis and Wilke, Carlo and De Mendonca, Alexandre and Vandenberghe, Rik and Benussi, Luisa and Ghidoni, Roberta and Binetti, Giuliano and Niessen, Wiro J. and Papma, Janne M. and Seelaar, Harro and Jiskoot, Lize C. and De Jong, Frank Jan and Donker Kaat, Laura and Del Campo, Marta and Teunissen, Charlotte E. and Bron, Esther E. and Van Den Berg, Esther and Van Swieten, John C.},
  issn         = {0022-3050},
  language     = {eng},
  month        = {05},
  pages        = {8},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Neurology, Neurosurgery and Psychiatry},
  title        = {Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia},
  url          = {http://dx.doi.org/10.1136/jnnp-2018-319784},
  year         = {2019},
}