Petra Steinacker1, Sarah Anderl-Straub1, Janine Diehl-Schmid1, Elisa Semler1, Ingo Uttner1, Christine A F von Arnim1, Henryk Barthel1, Adrian Danek1, Klaus Fassbender1, Klaus Fliessbach1, Hans Foerstl1, Timo Grimmer1, Hans-Jürgen Huppertz1, Holger Jahn1, Jan Kassubek1, Johannes Kornhuber1, Bernhard Landwehrmeyer1, Martin Lauer1, Juan Manuel Maler1, Benjamin Mayer1, Patrick Oeckl1, Johannes Prudlo1, Anja Schneider1, Alexander E Volk1, Jens Wiltfang1, Matthias L Schroeter1, Albert C Ludolph1, Markus Otto2. 1. From the Department of Neurology (P.S., S.A.-S., E.S., I.U., C.A.F.v.A., J. Kassubek, B.L., P.O., A.C.L., M.O.) and Institute of Epidemiology and Medical Biometry (B.M.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., T.G.), Klinikum Rechts der Isar, Technical University of Munich; Department of Nuclear Medicine (H.B.), Leipzig University Hospital; Department of Neurology (A.D.), Ludwig-Maximilians-University, Munich; Department of Neurology (K.F.), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K.F.), University of Bonn, Germany; Swiss Epilepsy Center (H.-J.H.), Zurich, Switzerland; Department of Psychiatry and Psychotherapy (H.J.), University Medical Center Hamburg-Eppendorf, Hamburg; AMEOS Klinikum (H.J.), Heiligenhafen; Department of Psychiatry and Psychotherapy (J. Kornhuber, J.M.M.), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; Department of Neurology (J.P.), University of Rostock; DZNE (J.P.), Rostock; Department of Neurodegenerative Diseases and Geriatric Psychiatry (A.S.), University Hospital Bonn; DZNE (A.S.), Bonn; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (J.W.), University Medical Center Göttingen; DZNE (J.W.), Göttingen, Germany; iBiMED (J.W.), Medical Sciences Department, University of Aveiro, Portugal; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig; and Max Planck Institute for Human Cognitive and Brain Sciences (M.L.S.), Leipzig, Germany. 2. From the Department of Neurology (P.S., S.A.-S., E.S., I.U., C.A.F.v.A., J. Kassubek, B.L., P.O., A.C.L., M.O.) and Institute of Epidemiology and Medical Biometry (B.M.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., T.G.), Klinikum Rechts der Isar, Technical University of Munich; Department of Nuclear Medicine (H.B.), Leipzig University Hospital; Department of Neurology (A.D.), Ludwig-Maximilians-University, Munich; Department of Neurology (K.F.), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K.F.), University of Bonn, Germany; Swiss Epilepsy Center (H.-J.H.), Zurich, Switzerland; Department of Psychiatry and Psychotherapy (H.J.), University Medical Center Hamburg-Eppendorf, Hamburg; AMEOS Klinikum (H.J.), Heiligenhafen; Department of Psychiatry and Psychotherapy (J. Kornhuber, J.M.M.), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; Department of Neurology (J.P.), University of Rostock; DZNE (J.P.), Rostock; Department of Neurodegenerative Diseases and Geriatric Psychiatry (A.S.), University Hospital Bonn; DZNE (A.S.), Bonn; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (J.W.), University Medical Center Göttingen; DZNE (J.W.), Göttingen, Germany; iBiMED (J.W.), Medical Sciences Department, University of Aveiro, Portugal; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig; and Max Planck Institute for Human Cognitive and Brain Sciences (M.L.S.), Leipzig, Germany. markus.otto@uni-ulm.de.
Abstract
OBJECTIVE: To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). METHODS: Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. RESULTS: At baseline, serum NfL level correlated with CSF NfL (bvFTD r = 0.706, p < 0.0001; AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p <0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006; [follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001; 95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001; [follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. CONCLUSIONS: As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.
OBJECTIVE: To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). METHODS: Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. RESULTS: At baseline, serum NfL level correlated with CSF NfL (bvFTD r = 0.706, p < 0.0001; AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p <0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006; [follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001; 95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001; [follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. CONCLUSIONS: As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.
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