Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

Matthew J Y Kang^{1

2

3}, Dhamidhu Eratne^{1

2}, Hannah Dobson^{1

3}, Charles B Malpas^{4

5}, Michael Keem^{1

2}, Courtney Lewis¹, Jasleen Grewal³, Vivian Tsoukra⁶, Christa Dang⁷, Ramon Mocellin⁸, Tomas Kalincik^{4

9}, Alexander F Santillo^{10

11}, Henrik Zetterberg^{12

13

14

15}, Kaj Blennow^{12

13}, Christiane Stehmann¹⁶, Shiji Varghese¹⁷, Qiao-Xin Li^{17

18}, Colin L Masters^{18

19}, Steven Collins^{4

17}, Samuel F Berkovic²⁰, Andrew Evans^{1

9}, Wendy Kelso¹, Sarah Farrand^{1

2}, Samantha M Loi^{1

2}, Mark Walterfang^{1

2

19}, Dennis Velakoulis^{1

2}

Affiliations

¹ Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.
² Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
³ Alfred Mental and Addiction Health, Alfred Health, Melbourne, VIC, Australia.
⁴ Department of Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁵ Melbourne School of Psychological Sciences, University of Melbourne, Parkville, VIC, Australia.
⁶ Department of Neurology, Evangelismos Hospital, Athens, Greece.
⁷ National Ageing Research Institute, University of Melbourne, Parkville, VIC, Australia.
⁸ Delmont Private Hospital, Glen Iris, VIC, Australia.
⁹ Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁰ Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
¹¹ Memory Clinic, Skåne University Hospital, Malmo, Sweden.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁵ UK Dementia Research Institute at UCL, London, UK.
¹⁶ The Australian National CJD Registry, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
¹⁷ National Dementia Diagnostic Laboratory, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
¹⁸ Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
¹⁹ The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
²⁰ Department of Medicine, Austin Health, Epilepsy Research Centre, The University of Melbourne, Heidelberg, VIC, Australia.

PMID: 37114460
DOI: 10.1017/neu.2023.25

Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

Matthew J Y Kang et al. Acta Neuropsychiatr. 2024 Feb.

. 2024 Feb;36(1):17-28.

doi: 10.1017/neu.2023.25. Epub 2023 Apr 28.

Authors

Affiliations

¹ Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.
² Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
³ Alfred Mental and Addiction Health, Alfred Health, Melbourne, VIC, Australia.
⁴ Department of Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁵ Melbourne School of Psychological Sciences, University of Melbourne, Parkville, VIC, Australia.
⁶ Department of Neurology, Evangelismos Hospital, Athens, Greece.
⁷ National Ageing Research Institute, University of Melbourne, Parkville, VIC, Australia.
⁸ Delmont Private Hospital, Glen Iris, VIC, Australia.
⁹ Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia.
¹⁰ Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
¹¹ Memory Clinic, Skåne University Hospital, Malmo, Sweden.
¹² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁵ UK Dementia Research Institute at UCL, London, UK.
¹⁶ The Australian National CJD Registry, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
¹⁷ National Dementia Diagnostic Laboratory, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
¹⁸ Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
¹⁹ The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
²⁰ Department of Medicine, Austin Health, Epilepsy Research Centre, The University of Melbourne, Heidelberg, VIC, Australia.

PMID: 37114460
DOI: 10.1017/neu.2023.25

Abstract

Objective: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.

Methods: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.

Results: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.

Conclusions: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Keywords: biomarker; dementia; diagnosis; diagnostic delay; neurofilament; neuropsychiatry; psychiatric disorders.

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Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

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Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

Authors

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Abstract

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LinkOut - more resources

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Medical