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INTRODUCTION: People with neurodegenerative disorders (ND) frequently face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (PPD), a common challenge in clinical settings. METHODS: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight. RESULTS: A total of 337 participants were included: 136 ND, 77 PPD, and 124 Controls. Plasma NfL was 2.5‐fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, [AUC]: 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2‐fold elevated, AUC: 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40– < 60 years). Additional findings were cutoffs optimized for sensitivity and specificity, and issues important for future clinical translation. CONCLUSIONS: This study adds important evidence for a simple blood‐based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings. Highlights: NfL levels were significantly higher in ND versus PPD.Plasma NfL showed strong diagnostic performance, comparable to CSF NfL, to distinguish ND from PPD.Diagnostic performance was higher in younger people, where diagnostic challenges are greater.Further research is needed on analytical and reference range factors, for clinical translation.These findings support a simple screening blood test for neurodegeneration. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim of this pragmatic stepped‐wedge cluster RCT was to determine the efficacy of a co‐designed dementia specialist training program (the PITCH program) for home care workers (HCWs) to improve their confidence and knowledge when providing care for clients living with dementia. Methods: HCWs who provided care to clients with dementia were recruited from seven home care service provider organisations in Australia between July 2019 and May 2022, and randomised into one of 18 clusters. The primary outcome was HCW's sense of self‐competence in providing care services to people living with dementia at 6 months post PITCH training measured by the Sense of Competence in Dementia Care Staff (SCIDS) Scale. Results: Two hundred and thirteen HCWS completed baseline assessment and almost half (48.4%) completed all three study assessments. HCWs in clusters that received PITCH training had significantly higher sense of competence (measured by SCIDS) than those who had not received PITCH training. Post hoc analysis revealed that face‐to‐face PITCH training consistently resulted in improvements in the HCWs sense of competence, dementia attitudes and knowledge when compared to online training and when compared to no training. PITCH training had no effect on the sense of strain HCWs felt in delivering dementia care. Conclusions: Given the majority of care for people living with dementia is provided at home by family carers supported by HCWs, it is essential that HCWs receive training that improves their skills in dementia care. This study is an important step towards better care at home for people living with dementia. [ABSTRACT FROM AUTHOR]

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 > 582 pg/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. [ABSTRACT FROM AUTHOR]

Objective: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Methods: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Results: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. Conclusions: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings. [ABSTRACT FROM AUTHOR]

Background: People living with dementia increasingly prefer to live in their own home as their care needs progress. Home care workers (HCWs) are essential for supporting independent living, and need training and support on how to deliver evidence‐based and best‐practice dementia care. The home care workforce is diverse, and in Australia, the number of workers who identify as culturally and linguistically diverse (CALD) in 2020 represented 21% of the total direct‐care workforce. The Promoting Independence Through quality Care at Home (PITCH) project aims to improve outcomes for people living with dementia and their paid and family carers by co‐designing and testing an evidence‐based specialist training program for dementia care. A pragmatic stepped‐wedge cluster RCT is being conducted to evaluate the program. To date, 227 HCWs from seven home care providers across Australia have completed baseline measures. Method: HCWs completed the Strain in Dementia Care Scale (SDCS), Sense of Competence In Dementia Care – Staff (SCIDS), Dementia Attitudes Scale (DAS) and Dementia Knowledge Assessment Scale (DKAS). Associations between these measures was assessed using Pearson correlations. HCWs were grouped into CALD/non‐CALD groups based on self‐reported cultural background. ANOVAs examined group differences by CALD status. Result: For the whole sample, SCIDS was correlated with DAS (r = 0.599, p<0.005) and DKAS (r = 0.257, p<0.005). DAS and DKAS were moderately correlated (r = 0.334, p<0.005). Nearly 30% of HCWs in our sample identified as CALD. The CALD group showed lower DAS, DKAS and SCIDS compared to the non‐CALD group (p's<0.001). No differences were observed on SDCS (p = 0.58). Conclusion: HCWs who were more knowledgeable about dementia had more positive attitudes toward dementia and a higher sense of competence in dementia care. HCWs who did not identify as CALD showed greater dementia knowledge, more positive dementia attitudes, and higher sense of competence in dementia care. Findings suggest that better dementia literacy supports more positive attitudes to dementia and sense of competence, and highlights that more targeted and specialized support may be beneficial for staff from CALD backgrounds (who comprise a high proportion of the Australian aged care workforce). Findings have implications for clinicians, researchers, policy‐makers, educators, and providers of dementia services. [ABSTRACT FROM AUTHOR]

Objective: Timely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP., Methods: We investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD., Results: Plasma GFAP levels were significantly (all p < 0.001) elevated in bvFTD (n = 22, mean (M) = 273 pg/mL) compared to BPAD (n = 121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95 % confidence interval [0.76, 0.95]. The optimal cut-off of 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (p = 0.02863) and combination of GFAP and NfL (p = 0.04726)., Conclusions: This study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD., Competing Interests: Declaration of competing interest All the authors have nothing to disclose. AB serves on the editorial boards of Neurology, Stroke and International Journal of Stroke and Scientific Advisory Boards for Eisai, Eli Lilly, Biogen and Novo Nordisk. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: People with neurodegenerative disorders (ND) frequently face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (PPD), a common challenge in clinical settings., Methods: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight., Results: A total of 337 participants were included: 136 ND, 77 PPD, and 124 Controls. Plasma NfL was 2.5-fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, [AUC]: 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2-fold elevated, AUC: 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40- < 60 years). Additional findings were cutoffs optimized for sensitivity and specificity, and issues important for future clinical translation., Conclusions: This study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings., Highlights: NfL levels were significantly higher in ND versus PPD. Plasma NfL showed strong diagnostic performance, comparable to CSF NfL, to distinguish ND from PPD. Diagnostic performance was higher in younger people, where diagnostic challenges are greater. Further research is needed on analytical and reference range factors, for clinical translation. These findings support a simple screening blood test for neurodegeneration., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)