Cerebrospinal fluid neurofilament light improves accurate distinction between neurodegenerative and psychiatric disorders at a cognitive neuropsychiatry service

Abstract

Objective: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods: We collected longitudinal diagnostic information (mean=36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other), and PSY. We pre-specified NfL>582pg/mL as indicative of ND/MCI/other. Results: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders

“…This is of high relevance to a diverse range of clinicians and clinical settings. While this study was not focused only on patients presenting to clinical settings for assessment of possible neurodegenerative disorders, unlike our previous studies (Eratne et al, 2020(Eratne et al, , 2022cKang et al, 2023), studies investigating generalisability to diverse clinical settings are underway.…”

“…One of the most challenging clinical distinctions, associated with some of the highest diagnostic uncertainty/instability and misdiagnoses, is distinguishing PPD from behavioural variant frontotemporal dementia (bvFTD), a neurodegenerative condition associated with personality, behavioural and psychiatric changes (Ducharme et al, 2020;Eratne et al, 2022b;Kang et al, 2023;Tsoukra et al, 2022). Previous studies have investigated blood and cerebrospinal fluid (CSF) NfL in bvFTD compared to PPD (Al Shweiki et al, 2019;Ashton et al, 2021;Katisko et al, 2020;Vijverberg et al, 2017), and in bvFTD and range of other neurodegenerative conditions compared to PPD and non-progressive/phenocopy syndromes (Eratne et al, 2020(Eratne et al, , 2022b(Eratne et al, , 2022cLoi et al, 2022), finding significantly elevated levels in neurodegenerative disorders including bvFTD, compared to PPD.…”

“…NfL is of particular interest as a diagnostic biomarker, as it may help distinguish disorders with significant neuronal degeneration, from those without. Distinguishing neurodegenerative dementias from primary psychiatric disorders (PPD) is a frequent clinical diagnostic dilemma and one associated with uncertainty, misdiagnosis, and negative impacts for patients and healthcare systems (Kang et al, 2023; Loi et al, 2022; Tsoukra et al, 2022; Woolley et al, 2011).…”

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders

“…One of the most challenging clinical distinctions, associated with some of the highest diagnostic uncertainty/instability and misdiagnoses, is distinguishing primary psychiatric disorders (PPD) from behavioural variant frontotemporal dementia (bvFTD), a neurodegenerative condition associated with variable personality, behavioural and psychiatric changes (Ducharme et al, 2020;Eratne, Keem, et al, 2022;Kang et al, 2022;Tsoukra et al, 2021). Previous studies have investigated blood and cerebrospinal fluid (CSF) NfL in bvFTD compared to PPD (Al Shweiki et al, 2019;Ashton et al, 2021;Katisko et al, 2020;Vijverberg et al, 2017), and in bvFTD and range of other neurodegenerative conditions compared to PPD and non-progressive/phenocopy syndromes (Eratne et al, 2020;Eratne, Keem, et al, 2022;Eratne, Loi, et al, 2022;Fourier et al, 2020), finding significantly elevated levels in neurodegenerative disorders including bvFTD compared to PPDs.…”

“…NfL is of particular interest as a potential diagnostic biomarker, as it may help distinguish disorders with significant neuronal degeneration, from those without. Distinguishing neurodegenerative dementias from primary psychiatric disorders (PPD) is a frequent clinical diagnostic dilemma and one associated with uncertainty, misdiagnosis, and negative impacts for patients and healthcare systems (Kang et al, 2022; Loi et al, 2020; Tsoukra et al, 2021; Woolley et al, 2011).…”