Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Lieke H. H. Meeter, Rebecca M. E. Steketee, Dina Salkovic, Maartje E. Vos, Murray Grossman, Corey T. McMillan, David J. Irwin, Adam L. Boxer, Julio C. Rojas, Nicholas T. Olney, Anna Karydas, Bruce L. Miller, Yolande A. L. Pijnenburg, Frederik Barkhof, Raquel Sánchez-Valle, Albert Lladó, Sergi Borrego-Ecija, Janine Diehl-Schmid, Timo Grimmer, Oliver Goldhardt & 27 others Alexander F. Santillo, Oskar Hansson, Susanne Vestberg, Barbara Borroni, Alessandro Padovani, Daniela Galimberti, Elio Scarpini, Jonathan D. Rohrer, Ione O. C. Woollacott, Matthis Synofzik, Carlo Wilke, Alexandre de Mendonca, Rik Vandenberghe, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Wiro J. Niessen, Janne M. Papma, Harro Seelaar, Lize C. Jiskoot, Frank Jan de Jong, Laura Donker Kaat, Marta del Campo, Charlotte E. Teunissen, Esther E. Bron, Esther van den Berg, John C. van Swieten

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
Publication statusPublished - 2019

Cite this

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. ; Olney, Nicholas T. ; Karydas, Anna ; Miller, Bruce L. ; Pijnenburg, Yolande A. L. ; Barkhof, Frederik ; Sánchez-Valle, Raquel ; Lladó, Albert ; Borrego-Ecija, Sergi ; Diehl-Schmid, Janine ; Grimmer, Timo ; Goldhardt, Oliver ; Santillo, Alexander F. ; Hansson, Oskar ; Vestberg, Susanne ; Borroni, Barbara ; Padovani, Alessandro ; Galimberti, Daniela ; Scarpini, Elio ; Rohrer, Jonathan D. ; Woollacott, Ione O. C. ; Synofzik, Matthis ; Wilke, Carlo ; de Mendonca, Alexandre ; Vandenberghe, Rik ; Benussi, Luisa ; Ghidoni, Roberta ; Binetti, Giuliano ; Niessen, Wiro J. ; Papma, Janne M. ; Seelaar, Harro ; Jiskoot, Lize C. ; de Jong, Frank Jan ; Donker Kaat, Laura ; del Campo, Marta ; Teunissen, Charlotte E. ; Bron, Esther E. ; van den Berg, Esther ; van Swieten, John C. / Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia. In: Journal of Neurology, Neurosurgery and Psychiatry. 2019.
@article{c606486af97245e8ab2a7d6b5e113ada,
title = "Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia",
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 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.",
author = "Meeter, {Lieke H. H.} and Steketee, {Rebecca M. E.} and Dina Salkovic and Vos, {Maartje E.} and Murray Grossman and McMillan, {Corey T.} and Irwin, {David J.} and Boxer, {Adam L.} and Rojas, {Julio C.} and Olney, {Nicholas T.} and Anna Karydas and Miller, {Bruce L.} and Pijnenburg, {Yolande A. L.} and Frederik Barkhof and Raquel S{\'a}nchez-Valle and Albert Llad{\'o} and Sergi Borrego-Ecija and Janine Diehl-Schmid and Timo Grimmer and Oliver Goldhardt and Santillo, {Alexander F.} and Oskar Hansson and Susanne Vestberg and Barbara Borroni and Alessandro Padovani and Daniela Galimberti and Elio Scarpini and Rohrer, {Jonathan D.} and Woollacott, {Ione O. C.} and Matthis Synofzik and Carlo Wilke and {de Mendonca}, Alexandre and Rik Vandenberghe and Luisa Benussi and Roberta Ghidoni and Giuliano Binetti and Niessen, {Wiro J.} and Papma, {Janne M.} and Harro Seelaar 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.}",
year = "2019",
doi = "10.1136/jnnp-2018-319784",
language = "English",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",

}

Meeter, LHH, Steketee, RME, Salkovic, D, Vos, ME, Grossman, M, McMillan, CT, Irwin, DJ, Boxer, AL, Rojas, JC, Olney, NT, Karydas, A, Miller, BL, Pijnenburg, YAL, Barkhof, F, Sánchez-Valle, R, Lladó, A, Borrego-Ecija, S, Diehl-Schmid, J, Grimmer, T, Goldhardt, O, Santillo, AF, Hansson, O, Vestberg, S, Borroni, B, Padovani, A, Galimberti, D, Scarpini, E, Rohrer, JD, Woollacott, IOC, Synofzik, M, Wilke, C, de Mendonca, A, Vandenberghe, R, Benussi, L, Ghidoni, R, Binetti, G, Niessen, WJ, Papma, JM, Seelaar, H, Jiskoot, LC, de Jong, FJ, Donker Kaat, L, del Campo, M, Teunissen, CE, Bron, EE, van den Berg, E & van Swieten, JC 2019, 'Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia' Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2018-319784

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.; Olney, Nicholas T.; Karydas, Anna; Miller, Bruce L.; Pijnenburg, Yolande A. L.; Barkhof, Frederik; Sánchez-Valle, Raquel; Lladó, Albert; Borrego-Ecija, Sergi; Diehl-Schmid, Janine; Grimmer, Timo; Goldhardt, Oliver; Santillo, Alexander F.; Hansson, Oskar; Vestberg, Susanne; Borroni, Barbara; Padovani, Alessandro; Galimberti, Daniela; Scarpini, Elio; Rohrer, Jonathan D.; Woollacott, Ione O. C.; Synofzik, Matthis; Wilke, Carlo; de Mendonca, Alexandre; Vandenberghe, Rik; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Niessen, Wiro J.; Papma, Janne M.; Seelaar, Harro; Jiskoot, Lize C.; de Jong, Frank Jan; Donker Kaat, Laura; del Campo, Marta; Teunissen, Charlotte E.; Bron, Esther E.; van den Berg, Esther; van Swieten, John C.

In: Journal of Neurology, Neurosurgery and Psychiatry, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

AU - Meeter, Lieke H. H.

AU - Steketee, Rebecca M. E.

AU - Salkovic, Dina

AU - Vos, Maartje E.

AU - Grossman, Murray

AU - McMillan, Corey T.

AU - Irwin, David J.

AU - Boxer, Adam L.

AU - Rojas, Julio C.

AU - Olney, Nicholas T.

AU - Karydas, Anna

AU - Miller, Bruce L.

AU - Pijnenburg, Yolande A. L.

AU - Barkhof, Frederik

AU - Sánchez-Valle, Raquel

AU - Lladó, Albert

AU - Borrego-Ecija, Sergi

AU - Diehl-Schmid, Janine

AU - Grimmer, Timo

AU - Goldhardt, Oliver

AU - Santillo, Alexander F.

AU - Hansson, Oskar

AU - Vestberg, Susanne

AU - Borroni, Barbara

AU - Padovani, Alessandro

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Rohrer, Jonathan D.

AU - Woollacott, Ione O. C.

AU - Synofzik, Matthis

AU - Wilke, Carlo

AU - de Mendonca, Alexandre

AU - Vandenberghe, Rik

AU - Benussi, Luisa

AU - Ghidoni, Roberta

AU - Binetti, Giuliano

AU - Niessen, Wiro J.

AU - Papma, Janne M.

AU - Seelaar, Harro

AU - Jiskoot, Lize C.

AU - de Jong, Frank Jan

AU - Donker Kaat, Laura

AU - del Campo, Marta

AU - Teunissen, Charlotte E.

AU - Bron, Esther E.

AU - van den Berg, Esther

AU - van Swieten, John C.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066140649&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31123142

U2 - 10.1136/jnnp-2018-319784

DO - 10.1136/jnnp-2018-319784

M3 - Article

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

ER -