Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors
(2022) In Journal of the Neurological Sciences 442.- 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... (More)
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.
(Less)
- author
- Eratne, Dhamidhu
; Keem, Michael
; Lewis, Courtney
; Kang, Matthew
; Walterfang, Mark
; Farrand, Sarah
; Loi, Samantha
; Kelso, Wendy
; Cadwallader, Claire
; Berkovic, Samuel F.
; Li, Qiao Xin
; Masters, Colin L.
; Collins, Steven
; Santillo, Alexander
LU
and Velakoulis, Dennis
(Less) - author collaboration
- organization
- publishing date
- 2022-11-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Behavioural variant frontotemporal dementia, Diagnosis, Neurofilament, Non-progressor, Phenocopy, Psychiatric
- in
- Journal of the Neurological Sciences
- volume
- 442
- article number
- 120439
- publisher
- Elsevier
- external identifiers
-
- pmid:36201960
- scopus:85139344317
- ISSN
- 0022-510X
- DOI
- 10.1016/j.jns.2022.120439
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: We are grateful for funding that supported this work: the Trisno Family Research Grant in Old Age Psychiatry, three NorthWestern Mental Health Research Seed Grants , MACH MRFF RART 2.1, and NHMRC ( 1185180 ). Finally, the authors would like to thank all the patients and their families for their participation. Publisher Copyright: © 2022 Elsevier B.V.
- id
- 70da2537-9e8b-4207-b633-70cf614c4533
- date added to LUP
- 2022-10-21 08:09:00
- date last changed
- 2024-04-18 15:55:54
@article{70da2537-9e8b-4207-b633-70cf614c4533,
abstract = {{<p>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.</p>}},
author = {{Eratne, Dhamidhu and Keem, Michael and Lewis, Courtney and Kang, Matthew and Walterfang, Mark and Farrand, Sarah and Loi, Samantha and Kelso, Wendy and Cadwallader, Claire and Berkovic, Samuel F. and Li, Qiao Xin and Masters, Colin L. and Collins, Steven and Santillo, Alexander and Velakoulis, Dennis}},
issn = {{0022-510X}},
keywords = {{Behavioural variant frontotemporal dementia; Diagnosis; Neurofilament; Non-progressor; Phenocopy; Psychiatric}},
language = {{eng}},
month = {{11}},
publisher = {{Elsevier}},
series = {{Journal of the Neurological Sciences}},
title = {{Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors}},
url = {{http://dx.doi.org/10.1016/j.jns.2022.120439}},
doi = {{10.1016/j.jns.2022.120439}},
volume = {{442}},
year = {{2022}},
}