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Title: Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors.
Austin Authors: 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;Velakoulis, Dennis
Affiliation: Epilepsy Research Centre
Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia
Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
The Florey Institute of Neuroscience and Mental Health
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sölvegatan 18, Sweden..
Issue Date: 30-Sep-2022
Date: 2022
Publication information: Journal of the Neurological Sciences 2022; 442: 120439
Abstract: 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. 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). 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. 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.
DOI: 10.1016/j.jns.2022.120439
Journal: Journal of the Neurological Sciences
PubMed URL: 36201960
Type: Journal Article
Subjects: Behavioural variant frontotemporal dementia
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