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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

Eratne, Dhamidhu ; Loi, Samantha M ; Li, Qiao-Xin ; Stehmann, Christiane ; Malpas, Charles B ; Santillo, Alexander LU orcid ; Janelidze, Shorena LU ; Cadwallader, Claire ; Walia, Nirbaanjot and Ney, Blair , et al. (2022) In Alzheimer's & Dementia 18(11). p.2218-2233
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... (More)

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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Alzheimer's & Dementia
volume
18
issue
11
pages
2218 - 2233
publisher
Wiley
external identifiers
  • scopus:85126010374
  • pmid:35102694
ISSN
1552-5279
DOI
10.1002/alz.12549
language
English
LU publication?
yes
additional info
© 2022 the Alzheimer's Association.
id
a48825c4-ab3d-477b-b8dd-ae8b32a7d7c9
date added to LUP
2022-03-04 13:22:46
date last changed
2024-06-13 16:50:16
@article{a48825c4-ab3d-477b-b8dd-ae8b32a7d7c9,
  abstract     = {{<p>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.</p><p>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).</p><p>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.</p><p>DISCUSSION: We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.</p>}},
  author       = {{Eratne, Dhamidhu and Loi, Samantha M and Li, Qiao-Xin and Stehmann, Christiane and Malpas, Charles B and Santillo, Alexander and Janelidze, Shorena and Cadwallader, Claire and Walia, Nirbaanjot and Ney, Blair and Lewis, Victoria and Senesi, Matteo and Fowler, Christopher and McGlade, Amelia and Varghese, Shiji and Ravanfar, Parsa and Kelso, Wendy and Farrand, Sarah and Keem, Michael and Kang, Matthew and Goh, Anita M Y and Dhiman, Kunal and Gupta, Veer and Watson, Rosie and Yassi, Nawaf and Kaylor-Hughes, Cath and Kanaan, Richard and Perucca, Piero and Dobson, Hannah and Vivash, Lucy and Ali, Rashida and O'Brien, Terence J and Hansson, Oskar and Zetterberg, Henrik and Blennow, Kaj and Walterfang, Mark and Masters, Colin L and Berkovic, Samuel F and Collins, Steven and Velakoulis, Dennis}},
  issn         = {{1552-5279}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2218--2233}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's & Dementia}},
  title        = {{Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings}},
  url          = {{http://dx.doi.org/10.1002/alz.12549}},
  doi          = {{10.1002/alz.12549}},
  volume       = {{18}},
  year         = {{2022}},
}