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.
U2 - 10.1136/jnnp-2018-319784
DO - 10.1136/jnnp-2018-319784
M3 - Article
C2 - 31123142
AN - SCOPUS:85066140649
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 -