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

Dhamidhu Eratne; Samantha M Loi; Qiao-Xin Li; Christiane Stehmann; Charles B Malpas; Alexander Santillo; Shorena Janelidze; Claire Cadwallader; Nirbaanjot Walia; Blair Ney; Victoria Lewis; Matteo Senesi; Christopher Fowler; Amelia McGlade; Shiji Varghese; Parsa Ravanfar; Wendy Kelso; Sarah Farrand; Michael Keem; Matthew Kang; Anita M Y Goh; Kunal Dhiman; Veer Gupta; Rosie Watson; Nawaf Yassi; Cath Kaylor-Hughes; Richard Kanaan; Piero Perucca; Hannah Dobson; Lucy Vivash; Rashida Ali; Terence J O'Brien; Oskar Hansson; Henrik Zetterberg; Kaj Blennow; Mark Walterfang; Colin L Masters; Samuel F Berkovic; Steven Collins; Dennis Velakoulis; MiND Study Group

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, Samantha M Loi, Qiao-Xin Li, Christiane Stehmann, Charles B Malpas, Alexander Santillo, Shorena Janelidze, Claire Cadwallader, Nirbaanjot Walia, Blair Ney, Victoria Lewis, Matteo Senesi, Christopher Fowler, Amelia McGlade, Shiji Varghese, Parsa Ravanfar, Wendy Kelso, Sarah Farrand, Michael Keem, Matthew KangAnita M Y Goh, Kunal Dhiman, Veer Gupta, Rosie Watson, Nawaf Yassi, Cath Kaylor-Hughes, Richard Kanaan, Piero Perucca, Hannah Dobson, Lucy Vivash, Rashida Ali, Terence J O'Brien, Oskar Hansson, Henrik Zetterberg, Kaj Blennow, Mark Walterfang, Colin L Masters, Samuel F Berkovic, Steven Collins, Dennis Velakoulis, MiND Study Group

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	2218-2233
Tidskrift	Alzheimer's & Dementia
Volym	18
Nummer	11
DOI	https://doi.org/10.1002/alz.12549
Status	Published - 2022

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Neurologi

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10.1002/alz.12549

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Eratne, D., Loi, S. M., Li, Q-X., Stehmann, C., Malpas, C. B., Santillo, A., Janelidze, S., Cadwallader, C., Walia, N., Ney, B., Lewis, V., Senesi, M., Fowler, C., McGlade, A., Varghese, S., Ravanfar, P., Kelso, W., Farrand, S., Keem, M., ... MiND Study Group (2022). Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings. Alzheimer's & Dementia, 18(11 ), 2218-2233. https://doi.org/10.1002/alz.12549

@article{a48825c4ab3d477bb8ddae8b32a7d7c9,

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

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.",

author = "Dhamidhu Eratne and Loi, {Samantha M} and Qiao-Xin Li and Christiane Stehmann and Malpas, {Charles B} and Alexander Santillo and Shorena Janelidze and Claire Cadwallader and Nirbaanjot Walia and Blair Ney and Victoria Lewis and Matteo Senesi and Christopher Fowler and Amelia McGlade and Shiji Varghese and Parsa Ravanfar and Wendy Kelso and Sarah Farrand and Michael Keem and Matthew Kang and Goh, {Anita M Y} and Kunal Dhiman and Veer Gupta and Rosie Watson and Nawaf Yassi and Cath Kaylor-Hughes and Richard Kanaan and Piero Perucca and Hannah Dobson and Lucy Vivash and Rashida Ali and O'Brien, {Terence J} and Oskar Hansson and Henrik Zetterberg and Kaj Blennow and Mark Walterfang and Masters, {Colin L} and Berkovic, {Samuel F} and Steven Collins and Dennis Velakoulis and {MiND Study Group}",

note = "{\textcopyright} 2022 the Alzheimer's Association.",

year = "2022",

doi = "10.1002/alz.12549",

language = "English",

volume = "18",

pages = "2218--2233",

journal = "Alzheimer's & Dementia",

issn = "1552-5279",

publisher = "Wiley",

number = "11 ",

}

Eratne, D, Loi, SM, Li, Q-X, Stehmann, C, Malpas, CB, Santillo, A , Janelidze, S, Cadwallader, C, Walia, N, Ney, B, Lewis, V, Senesi, M, Fowler, C, McGlade, A, Varghese, S, Ravanfar, P, Kelso, W, Farrand, S, Keem, M, Kang, M, Goh, AMY, Dhiman, K, Gupta, V, Watson, R, Yassi, N, Kaylor-Hughes, C, Kanaan, R, Perucca, P, Dobson, H, Vivash, L, Ali, R, O'Brien, TJ, Hansson, O, Zetterberg, H, Blennow, K, Walterfang, M, Masters, CL, Berkovic, SF, Collins, S, Velakoulis, D & MiND Study Group 2022, 'Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings', Alzheimer's & Dementia, vol. 18, nr. 11 , s. 2218-2233. https://doi.org/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. / Eratne, Dhamidhu; Loi, Samantha M; Li, Qiao-Xin et al.

I: Alzheimer's & Dementia, Vol. 18, Nr. 11 , 2022, s. 2218-2233.

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

TY - JOUR

T1 - Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

AU - Eratne, Dhamidhu

AU - Loi, Samantha M

AU - Li, Qiao-Xin

AU - Stehmann, Christiane

AU - Malpas, Charles B

AU - Santillo, Alexander

AU - Janelidze, Shorena

AU - Cadwallader, Claire

AU - Walia, Nirbaanjot

AU - Ney, Blair

AU - Lewis, Victoria

AU - Senesi, Matteo

AU - Fowler, Christopher

AU - McGlade, Amelia

AU - Varghese, Shiji

AU - Ravanfar, Parsa

AU - Kelso, Wendy

AU - Farrand, Sarah

AU - Keem, Michael

AU - Kang, Matthew

AU - Goh, Anita M Y

AU - Dhiman, Kunal

AU - Gupta, Veer

AU - Watson, Rosie

AU - Yassi, Nawaf

AU - Kaylor-Hughes, Cath

AU - Kanaan, Richard

AU - Perucca, Piero

AU - Dobson, Hannah

AU - Vivash, Lucy

AU - Ali, Rashida

AU - O'Brien, Terence J

AU - Hansson, Oskar

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Walterfang, Mark

AU - Masters, Colin L

AU - Berkovic, Samuel F

AU - Collins, Steven

AU - Velakoulis, Dennis

AU - MiND Study Group

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1002/alz.12549

DO - 10.1002/alz.12549

M3 - Article

C2 - 35102694

VL - 18

SP - 2218

EP - 2233

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5279

IS - 11

ER -

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

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