Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent

Victoria Light; Sherri Lee Jones; Elham Rahme; Katerine Rousseau; Sterre de Boer; Lisa Vermunt; Mahdie Soltaninejad; Charlotte Teunissen; Yolande Pijnenburg; Simon Ducharme; For Signature Consortium and CCNA

doi:10.1016/j.jagp.2024.03.008

Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent

Am J Geriatr Psychiatry. 2024 Mar 24:S1064-7481(24)00290-2. doi: 10.1016/j.jagp.2024.03.008. Online ahead of print.

Affiliations

¹ Department of Psychiatry, McGill University (VL, SD), Douglas Mental Health University Institute, Montreal, QC, Canada; Integrated Program of Neuroscience (VL), McGill University, Montreal, QC, Canada.
² Douglas Research Centre (SLJ), Montreal, QC, Canada.
³ Research Institute of the McGill University Health Centre (RI-MUHC) (ER), Montreal, QC, Canada.
⁴ Institut Universitaire en Santé Mentale de Montréal, Département de Psychiatrie (KR), Université de Montréal, Montreal, QC, Canada.
⁵ Alzheimer Center Amsterdam, Department of Neurology (SB, YP), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands; School of Psychology (SB), The University of Sydney, Sydney, NSW, Australia.
⁶ Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Neurodegeneration, Amsterdam UMC (LV, CT), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
⁷ McConnell Brain Imaging Centre, Montreal Neurological Institute, Department of Neurology & Neurosurgery (MS, SD), McGill University, Montreal, QC, Canada.
⁸ Alzheimer Center Amsterdam, Department of Neurology (SB, YP), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
⁹ Department of Psychiatry, McGill University (VL, SD), Douglas Mental Health University Institute, Montreal, QC, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Department of Neurology & Neurosurgery (MS, SD), McGill University, Montreal, QC, Canada. Electronic address: simon.ducharme@mcgill.ca.
¹⁰ Centre de Recherche de l'institut universitaire en santé mentale de Montréal (SC, CCNA), Montreal, QC, Canada.

PMID: 38609836
DOI: 10.1016/j.jagp.2024.03.008

Abstract

Background: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking.

Objective: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy.

Design, settings, subjects, measurements: Clinical data of people aged 40-81 were obtained from healthy subjects (n = 69), and patients with PPD (n = 848) or bvFTD (n = 82). sNfL was measured using Simoa technology on an HD-X instrument. Data were analyzed using general linear models, and Receiver Operating Characteristic (ROC) curve analyses to determine global and age-specific sNfL cutoffs to distinguish bvFTD from PPD, using the Youden Index.

Results: sNfL increased with age, while sex, BMI and diabetes status were modestly associated with sNfL. sNfL was slightly higher in PPD than healthy subjects (14.1 versus 11.7 pg/mL), when controlling for covariates. sNfL was markedly lower in PPD than bvFTD (14.1 versus 44.1 pg/mL). sNfL could differentiate PPD from bvFTD with an AUC = 0.868, but the effect was driven by the younger subjects between age 40-60 years at a cutoff of 16.0 pg/mL. No valid cutoff was detected over age 60, however, values of sNfL above 38.5 pg/mL, or below 13.9 pg/mL, provided 90% diagnostic certainty of bvFTD or PPD, respectively.

Conclusion: PPD have mildly elevated sNfL compared to healthy subjects but much lower than bvFTD. Results support the use of sNfL as a biomarker to differentiate PPD from bvFTD at age 60 or below, but accuracy decreases in older ages.

Keywords: Behavioral variant of frontotemporal dementia (bvFTD); biomarker; dementia; diagnosis; primary psychiatric disorders (PPD); serum neurofilament light (NfL).