Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

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.

Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort

“…Patients were recruited from the Neuropsychiatry Centre, The Royal Melbourne Hospital, Australia. As previously described [12,13,17], The Neuropsychiatry Centre is a tertiary clinical service providing diagnostic input to people with a range of neuropsychiatric presentations, particularly young-onset dementia. Patients are referred for diagnostic assessment and management of possible young-onset dementia and undergo comprehensive multidisciplinary and multimodal assessments and investigations, including CSF AD proteins.…”

“…Other promising biomarkers include glial fibrillary acidic protein (GFAP) in AD and other disorders, [6,10] and neurofilament light chain (NfL) in neurodegenerative disorders broadly and in distinguishing neurodegenerative from non-neurodegenerative and neuroinflammatory disorders. [11,12,12,13].…”

“…There has been limited literature on plasma ptau217 and other AD biomarkers in clinically heterogeneous cohorts (including AD as well as non-AD neurodegenerative disorders and primary psychiatric conditions), and limited research in younger people with dementia (traditionally defined in dementia care and research as symptom onset under 65 years of age). However, real-world clinical practice and research in younger onset dementia services and settings has consistently demonstrated the significant diagnostic challenges, broader range of diagnoses encountered (including non-AD neurodegenerative disorders such as frontotemporal dementia, and primary psychiatric disorders), uncertainty, misdiagnosis and diagnostic delay in younger people, despite access to current gold standard assessments [13][14][15][16][17][18]. Furthermore, most studies in research settings have excluded participants with significant psychiatric and other comorbidities, limiting generalisability.…”

Plasma neurofilament light chain is elevated in Niemann-Pick Type C but glial fibrillary acidic protein is not

“…Elevated NfL and GFAP levels have been identified in neurodegenerative conditions such as Alzheimer disease and frontotemporal dementia, 4–6 and NfL has been shown to distinguish neurodegenerative from primary psychiatric and non-neurodegenerative conditions, and potentially reduce misdiagnosis. 6–10…”