Introduction
Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and ...total‐tau (t‐tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders.
Methods
Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt‐Jakob registry (Creutzfeldt‐Jakob disease CJD and rapidly progressive dementias/atypically rapid variants of common ND, RapidND).
Results
A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t‐tau in most real‐life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND.
Discussion
We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
Background
Accurate, timely diagnosis of neuropsychiatric symptoms, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. ...Neurofilament light (NfL) and other blood biomarkers have shown promise to reduce the diagnostic odyssey and improve outcomes. The MiND Study in investigating the diagnostic utility of NfL and other markers, to distinguish neurological/neurodegenerative from psychiatric disorders, to lead to a widely available, routine screening blood test.
Methods
We assessed NfL, p‐tau181 and GFAP in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, functional neurological disorders, Niemann‐Pick Type C, epilepsy.
Results
Updates on the The MiND Study progress and findings that NfL differentiated diverse neurodegenerative from psychiatric disorders, with 90+% accuracy, from over 500 patients/participants, will be presented, with real patient and family stories to demonstrate the challenges and potential clinical impact of The MiND Study. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), from non‐Alzheimer. As recruitment, sample analysis, data collection is ongoing, the most up to date results including GFAP, cognitive and neuroimaging markers, will be presented.
Conclusions
NfL shows great promise as a diagnostic screening blood test, akin to a “CRP for the brain”. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials, facilitating precision medicine algorithmic diagnostics incorporating other biomarkers and clinical/cognitive markers, for real‐world clinical settings.
Objective:
Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a ...subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias.
Methods:
This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59).
Results:
We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: 5.5, 7.2), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: 5.2, 8.2; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: 4.7, 8.8), controls (M = 5.8 pg/mL, 95% confidence interval: 5.3, 6.3) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: 4.0, 5.8). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman’s r = 0.258, 95% confidence interval: 0.034, 0.457), dyslipidaemia (r = 0.280, 95% confidence interval: 0.064, 0.470) and a negative correlation with weight (r = −0.305, 95% confidence interval: −0.504, −0.076).
Conclusion:
Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.
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