Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Dhamidhu Eratne^{1

2

3}, Samantha M Loi^{1

2

3}, Qiao-Xin Li³, Christiane Stehmann^{3

4}, Charles B Malpas⁵, Alexander Santillo^{6

7}, Shorena Janelidze^{6

7}, Claire Cadwallader¹, Nirbaanjot Walia¹, Blair Ney^{8

9}, Victoria Lewis⁴, Matteo Senesi⁴, Christopher Fowler⁸, Amelia McGlade³, Shiji Varghese³, Parsa Ravanfar^{1

2}, Wendy Kelso¹, Sarah Farrand^{1

2}, Michael Keem¹, Matthew Kang¹, Anita M Y Goh^{1

2}, Kunal Dhiman^{10

11}, Veer Gupta^{10

11}, Rosie Watson¹², Nawaf Yassi^{12

13}, Cath Kaylor-Hughes¹⁴, Richard Kanaan¹⁵, Piero Perucca^{16

17

18}, Hannah Dobson^{1

19}, Lucy Vivash¹⁸, Rashida Ali¹⁸, Terence J O'Brien¹⁸, Oskar Hansson^{6

7}, Henrik Zetterberg^{20

21

22

23}, Kaj Blennow^{20

21}, Mark Walterfang^{1

2

8}, Colin L Masters³, Samuel F Berkovic²⁴, Steven Collins⁴, Dennis Velakoulis^{1

2}; MiND Study Group

Affiliations

¹ Neuropsychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia.
² Department of Psychiatry & Melbourne Neuropsychiatry Centre, University of Melbourne, Parkville, Victoria, Australia.
³ National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁴ Australian National Creutzfeldt-Jakob Disease Registry, Florey Institute of Neuroscience and Mental Health and Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Department of Medicine, Department of Neurology, Clinical Outcomes Research Unit (CORe), Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁶ Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
⁷ Memory Clinic, Skåne University Hospital, Malmo, Sweden.
⁸ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁹ St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
¹⁰ School of Medicine, Deakin University, Geelong, Victoria, Australia.
¹¹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
¹² Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
¹³ Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
¹⁴ Department of General Practice, Integrated Mental Health Team, University of Melbourne, Parkville, Victoria, Australia.
¹⁵ Department of Psychiatry, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
¹⁶ Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁷ Comprehensive Epilepsy Program, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁸ Department of Neuroscience, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
¹⁹ Department of Psychiatry, Alfred Health, Melbourne, Victoria, Australia.
²⁰ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
²² Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
²³ UK Dementia Research Institute at UCL, London, UK.
²⁴ Department of Medicine, Austin Health, Epilepsy Research Centre, The University of Melbourne, Heidelberg, Victoria, Australia.

PMID: 35102694
DOI: 10.1002/alz.12549

Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Dhamidhu Eratne et al. Alzheimers Dement. 2022 Nov.

. 2022 Nov;18(11):2218-2233.

doi: 10.1002/alz.12549. Epub 2022 Feb 1.

Authors

Affiliations

¹ Neuropsychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia.
² Department of Psychiatry & Melbourne Neuropsychiatry Centre, University of Melbourne, Parkville, Victoria, Australia.
³ National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁴ Australian National Creutzfeldt-Jakob Disease Registry, Florey Institute of Neuroscience and Mental Health and Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Department of Medicine, Department of Neurology, Clinical Outcomes Research Unit (CORe), Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁶ Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
⁷ Memory Clinic, Skåne University Hospital, Malmo, Sweden.
⁸ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁹ St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
¹⁰ School of Medicine, Deakin University, Geelong, Victoria, Australia.
¹¹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
¹² Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
¹³ Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
¹⁴ Department of General Practice, Integrated Mental Health Team, University of Melbourne, Parkville, Victoria, Australia.
¹⁵ Department of Psychiatry, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
¹⁶ Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁷ Comprehensive Epilepsy Program, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁸ Department of Neuroscience, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
¹⁹ Department of Psychiatry, Alfred Health, Melbourne, Victoria, Australia.
²⁰ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
²² Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
²³ UK Dementia Research Institute at UCL, London, UK.
²⁴ Department of Medicine, Austin Health, Epilepsy Research Centre, The University of Melbourne, Heidelberg, Victoria, Australia.

PMID: 35102694
DOI: 10.1002/alz.12549

Abstract

Introduction: Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders.

Methods: Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND).

Results: A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND.

Discussion: We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.

Keywords: biomarker; dementia; diagnosis; neurofilament; neurology; psychiatric disorders; psychiatry.

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References

REFERENCES

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1. Draper B, Cations M, White F, et al. Time to diagnosis in young-onset dementia and its determinants: the INSPIRED study. Int J Geriatr Psychiatry. 2016;31:1217-1224.
1. Eratne D, Loi SM, Farrand S, Kelso W, Velakoulis D, Looi JC. Alzheimer's disease: clinical update on epidemiology, pathophysiology and diagnosis. Australas Psychiatry. 2018;26:347-357.
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Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Affiliations

Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

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Substances

LinkOut - more resources

Full Text Sources

Medical