Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors.

Humans Frontotemporal Dementia / diagnosis Amyloid beta-Peptides / cerebrospinal fluid Alzheimer Disease / diagnosis Intermediate Filaments Prospective Studies Neurofilament Proteins / cerebrospinal fluid Biomarkers tau Proteins / cerebrospinal fluid
Behavioural variant frontotemporal dementia Diagnosis Neurofilament Non-progressor Phenocopy Psychiatric

Journal

Journal of the neurological sciences
ISSN: 1878-5883
Titre abrégé: J Neurol Sci
Pays: Netherlands
ID NLM: 0375403

Informations de publication

Date de publication:
15 11 2022
Historique:
received: 19 06 2022
revised: 05 09 2022
accepted: 25 09 2022
pubmed: 7 10 2022
medline: 28 10 2022
entrez: 6 10 2022
Statut: ppublish

Résumé

Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative 'non-progressor' mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Cerebrospinal fluid (CSF) NfL, amyloid beta 1-42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow-up information, patients were categorised as Progressors or Non-Progressors: further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative causes). Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL, 95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau levels compared to Non-Progressor Revised Diagnoses. This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.

Sections du résumé

BACKGROUND
Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative 'non-progressor' mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay.
METHODS
Cerebrospinal fluid (CSF) NfL, amyloid beta 1-42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow-up information, patients were categorised as Progressors or Non-Progressors: further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative causes).
RESULTS
Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL, 95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau levels compared to Non-Progressor Revised Diagnoses.
CONCLUSION
This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.

Identifiants

DOI: 10.1016/j.jns.2022.120439 PMID: 36201960
pubmed: 36201960
pii: S0022-510X(22)00301-X
doi: 10.1016/j.jns.2022.120439
pii:
doi:

Substances chimiques

Amyloid beta-Peptides 0
Neurofilament Proteins 0
Biomarkers 0
tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

120439

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Auteurs

Dhamidhu Eratne (D)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia; National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. Electronic address: dhamidhu.eratne@mh.org.au.

Michael Keem (M)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

Courtney Lewis (C)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

Matthew Kang (M)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

Mark Walterfang (M)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia; National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.

Sarah Farrand (S)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

Samantha Loi (S)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

Wendy Kelso (W)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.

Claire Cadwallader (C)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.

Samuel F Berkovic (SF)

Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.

Qiao-Xin Li (QX)

National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.

Colin L Masters (CL)

National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.

Steven Collins (S)

National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.

Alexander Santillo (A)

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sölvegatan 18, Sweden.

Dennis Velakoulis (D)

Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia; Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Dégénérescence lobaire frontotemporale › Démence frontotemporale › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Cytosquelette › Filaments intermédiaires › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines neurofilamenteuses › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Cerebrospinal fluid neurofilament light chain...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Cerebrospinal fluid neurofilament light chain...