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; 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

doi:10.1136/jnnp-2018-319784

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

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

Erasmus University Rotterdam
University of Pennsylvania
University of California at San Francisco
University College London
Hospital Clinic de Barcelona
August Pi i Sunyer Biomedical Research Institute
Technical University of Munich
Lund University
University of Brescia
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
International Centre for Rural Health of the San Paolo Hospital
UCL Institute of Neurology
University of Tübingen
University of Bonn and German Center for Neurodegenerative Diseases (DZNE)
University of Lisbon
KU Leuven
IRCCS Centro San Giovanni di Dio Fatebenefratelli - Brescia
Delft University of Technology
Leiden University
Vrije Universiteit (VU) Amsterdam and VU Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

7 Downloads (Pure)

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 (r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r s =-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 language	English
Pages (from-to)	997-1004
Number of pages	8
Journal	Journal of Neurology, Neurosurgery and Psychiatry
Volume	90
Issue number	9
DOIs	https://doi.org/10.1136/jnnp-2018-319784
Publication status	Published - 1 Sept 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1136/jnnp-2018-319784

Clinical-value-of-cerebrospinal-fluid-neurofilament-light-chain-in-semantic-dementia.pdfFinal published version, 1.29 MBLicence: CC BY

Cite this

Meeter, L. H. H., Steketee, R. M. E., Salkovic, D., Vos, M. E., Grossman, M., McMillan, C. T., Irwin, D. J., Boxer, A. L., Rojas, J. C., Olney, N. T., Karydas, A., Miller, B. L., Pijnenburg, Y. A. L., Barkhof, F., Sánchez-Valle, R., Lladó, A., Borrego-Ecija, S., Diehl-Schmid, J., Grimmer, T., ... van Swieten, J. C. (2019). Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia. Journal of Neurology, Neurosurgery and Psychiatry, 90(9), 997-1004. https://doi.org/10.1136/jnnp-2018-319784

@article{b63695ec1d254eb6a5b54d01fa82506a,

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 (r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r s =-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.\}",

note = "Funding Information: Funding This study was funded by a Memorabel grant from Deltaplan Dementie (The Netherlands Organisation for health Research and Development, and alzheimer Nederland grant number 7330598105), National Institutes of health (Grants aG010124, aG032953, aG043503, Ns088341, aG017586, aG052943, aG038490), the Wyncote Foundation, Dana Foundation, Brightfocus Foundation, penn Institute on aging, pla estrat{\`e}gic de recerca i innovaci{\'o} en salut 2016-2020, catalan Department of health (grant number sLT002/16/00408), Italian Ministry of health (Ricerca corrente) and the German Federal Ministry of education and Research (FTLDc 01GI1007a). Ms was supported by the else Kr{\"o}ner-Fresenius-stiftung. cW was supported by the Vaillant stiftung Competing interests The authors report no conflicts of interest relevant to this study. LhhM is supported by alzheimer Nederland (grant number We.09 2014 04). aLB and JcR are supported by the NIh (U54Ns092089, R01aG031278, R01aG038791, R01aG032306, R01aG022983) and the association for Frontotemporal Degeneration. aLB, JcR and LDK are supported by the Bluefield project to cure Frontotemporal Dementia. The Dementia Research centre is supported by alzheimer{\textquoteright}s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIhR Queen square Dementia Biomedical Research Unit, the NIhR UcL/h Biomedical Research centre and the Leonard Wolfson experimental Neurology centre (LWeNc) clinical Research Facility as well as an alzheimer{\textquoteright}s society grant (as-pG-16-007). JDR is supported by an MRc clinician scientist Fellowship (MR/M008525/1) and has received funding from the NIhR Rare Disease Translational Research collaboration (BRc149/Ns/Mh). IOcW is supported by an MRc clinical Research Training Fellowship (MR/M018288/1). as is supported by the swedish society for Medical Research. ceT is supported by ZonMW Memorabel program (grant number 733050206). Jcvs is supported by the Dioraphte Foundation. Publisher Copyright: {\textcopyright} {\textcopyright} Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = sep,

day = "1",

doi = "10.1136/jnnp-2018-319784",

language = "English",

volume = "90",

pages = "997--1004",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

number = "9",

}

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, vol. 90, no. 9, pp. 997-1004. https://doi.org/10.1136/jnnp-2018-319784

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.

N1 - Funding Information: Funding This study was funded by a Memorabel grant from Deltaplan Dementie (The Netherlands Organisation for health Research and Development, and alzheimer Nederland grant number 7330598105), National Institutes of health (Grants aG010124, aG032953, aG043503, Ns088341, aG017586, aG052943, aG038490), the Wyncote Foundation, Dana Foundation, Brightfocus Foundation, penn Institute on aging, pla estratègic de recerca i innovació en salut 2016-2020, catalan Department of health (grant number sLT002/16/00408), Italian Ministry of health (Ricerca corrente) and the German Federal Ministry of education and Research (FTLDc 01GI1007a). Ms was supported by the else Kröner-Fresenius-stiftung. cW was supported by the Vaillant stiftung Competing interests The authors report no conflicts of interest relevant to this study. LhhM is supported by alzheimer Nederland (grant number We.09 2014 04). aLB and JcR are supported by the NIh (U54Ns092089, R01aG031278, R01aG038791, R01aG032306, R01aG022983) and the association for Frontotemporal Degeneration. aLB, JcR and LDK are supported by the Bluefield project to cure Frontotemporal Dementia. The Dementia Research centre is supported by alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIhR Queen square Dementia Biomedical Research Unit, the NIhR UcL/h Biomedical Research centre and the Leonard Wolfson experimental Neurology centre (LWeNc) clinical Research Facility as well as an alzheimer’s society grant (as-pG-16-007). JDR is supported by an MRc clinician scientist Fellowship (MR/M008525/1) and has received funding from the NIhR Rare Disease Translational Research collaboration (BRc149/Ns/Mh). IOcW is supported by an MRc clinical Research Training Fellowship (MR/M018288/1). as is supported by the swedish society for Medical Research. ceT is supported by ZonMW Memorabel program (grant number 733050206). Jcvs is supported by the Dioraphte Foundation. Publisher Copyright: © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/9/1

Y1 - 2019/9/1

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 (r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r s =-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 (r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r s =-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/pages/publications/85066140649

U2 - 10.1136/jnnp-2018-319784

DO - 10.1136/jnnp-2018-319784

M3 - Article

C2 - 31123142

SN - 0022-3050

VL - 90

SP - 997

EP - 1004

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 9

ER -

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this