A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: A ‘C-reactive protein’ for psychiatrists and neurologists?

Abstract

Objective: Neurofilament light has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of neurological and neurodegenerative disorders. This study explored the utility of cerebrospinal fluid neurofilament light in distinguishing primary psychiatric disorders from neurodegenerative and neurological disorders, a common diagnostic dilemma for psychiatrists and neurologists. Methods: This cross-sectional retrospective pilot study assessed cerebrospinal fluid neurofilament light on patients referred to a tertiary neuropsychiatry service from 2009 to 2017 for diagnostic assessment of neuropsychiatric and neurocognitive symptoms, where a neurodegenerative disorder was a differential diagnosis, who received lumbar punctures as part of a comprehensive workup. The most recent gold-standard clinical consensus diagnosis was categorised into psychiatric disorder or neurodegenerative or neurological disorder. Data from healthy controls were available for comparison. Data extraction and diagnostic categorisation was blinded to neurofilament light results. Results: A total of 129 participants were included: 77 neurodegenerative or neurological disorder (mean age 57 years, including Alzheimer’s dementia, frontotemporal dementia), 31 psychiatric disorder (mean age 51 years, including schizophrenia, major depressive disorder) and 21 healthy controls (mean age 66 years). Neurofilament light was significantly higher in neurodegenerative or neurological disorder (M = 3560 pg/mL, 95% confidence intervals = [2918, 4601]) compared to psychiatric disorder (M = 949 pg/mL, 95% confidence intervals = [830, 1108]) and controls (M = 1036 pg/mL, 95% confidence intervals = [908, 1165]). Neurofilament light distinguished neurodegenerative or neurological disorder from psychiatric disorder with an area under the curve of 0.94 (95% confidence intervals = [0.89, 0.98]); a cut-off of 1332 pg/mL was associated with 87% sensitivity and 90% specificity. Conclusion: Cerebrospinal fluid neurofilament light shows promise as a diagnostic test to assist with the often challenging diagnostic dilemma of distinguishing psychiatric disorders from neurodegenerative and neurological disorders. Further studies are warranted to replicate and expand on these findings, including on plasma neurofilament light.

Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia

“…NfL is the most promising fluid biomarker for diagnostics and monitoring degeneration in FTD both in the context of clinical practice as well as in clinical trials [ 33 ] In the diagnostic process, NfL is the only fluid biomarker with potential to separate bvFTD from psychiatric disorders [ 34 , 35 ], which constitute the main differential diagnosis for bvFTD [ 36 ]. Plasma is arguably preferable to CSF for NfL measurements due to the minimally invasive procedure required to sample it.…”

A 10 year retrospective cohort study of inpatients with younger‐onset dementia

“…This will yield much more rich data about YOD in order to more easily, timely and accurately diagnose YOD and to monitor epidemiology in order to facilitate best practice guidelines. The utility of new investigative processes such as amyloid PET and neurofilament light chain is likely to assist in more definitive diagnoses of YOD and accurately distinguishing YOD from non‐neurodegenerative and psychiatric disorders 25 . Following these patients over time may also provide information regarding mortality rates in the different types of YOD.…”

Cerebrospinal fluid neurofilament light chain is elevated in Niemann–Pick type C compared to psychiatric disorders and healthy controls and may be a marker of treatment response

“…As for many psychiatric and neurological dis orders, there is a need for biomarkers for early diagnosis and to aid in differential diagnosis, pro gnostica tion and treat ment response. Neurofilament light chain (NfL), as a biomarker of neuronal injury that can be measured in cerebrospinal fluid (CSF) and blood, has shown great promise in diagnosis and differential diagnosis of a range of psychiatric and neurological disorders (Eratne et al, 2019). To our knowledge, NfL has not been explored in NPC.…”