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

  • Author Footnotes
    1 First equal authors.
    Dhamidhu Eratne
    Correspondence
    Corresponding author at: Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC 3050, Australia.
    Footnotes
    1 First equal authors.
    Affiliations
    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
    Search for articles by this author
  • Author Footnotes
    1 First equal authors.
    Michael Keem
    Footnotes
    1 First equal authors.
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
    Search for articles by this author
  • Courtney Lewis
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
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  • Matthew Kang
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
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  • Mark Walterfang
    Affiliations
    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
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  • Sarah Farrand
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
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  • Samantha Loi
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
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  • Wendy Kelso
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia
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  • Claire Cadwallader
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia
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  • Samuel F. Berkovic
    Affiliations
    Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia
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  • Qiao-Xin Li
    Affiliations
    National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
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  • Colin L. Masters
    Affiliations
    National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
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  • Steven Collins
    Affiliations
    National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
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  • Alexander Santillo
    Affiliations
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sölvegatan 18, Sweden
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  • Dennis Velakoulis
    Affiliations
    Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia

    Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
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  • The MiND Study Group
    Author Footnotes
    2 The MiND Study Group Collaborators listed in Appendix A
  • Author Footnotes
    1 First equal authors.
    2 The MiND Study Group Collaborators listed in Appendix A
Published:September 30, 2022DOI:https://doi.org/10.1016/j.jns.2022.120439

      Highlights

      • Accurate diagnosis of behavioural variant frontotemporal dementia is challenging.
      • bvFTD is commonly misdiagnosed, and distinguishing from non-progressor mimics is challenging.
      • The biomarker of neuronal injury, neurofilament light, improves diagnostic confidence in bvFTD.

      Abstract

      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.

      Keywords

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