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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]

Memory deficits in aging are characterized by impaired hippocampus‐mediated relational binding—the formation of links between items in memory. By reducing reliance on relational binding, unitization of two items into one concept enhances associative recognition among older adults. Can a similar enhancement be obtained when probing memory with recall? This question has yet to be examined, because recall has been assumed to rely predominantly on relational binding. Inspired by recent evidence challenging this assumption, we investigated individual differences in older adults' recall of unitized and nonunitized associations. Compared with successfully aging individuals, older adults with mild memory deficits, typically mediated by the hippocampus, were impaired in recall of paired‐associates in a task which relies on relational binding (study: "PLAY–TUNNEL"; test: PLAY–T?). In stark contrast, the two groups showed similar performance when items were unitized into a novel compound word (study: "LOVEGIGGLE"; test: LOVEG?). Thus, boosting nonrelational aspects of recall enhances associative memory among aging individuals with subtle memory impairments to comparable levels as successfully aging older adults. [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]

Cognitive decline is considered an inevitable consequence of aging; however, estimates of cognitive aging may be influenced negatively by undetected preclinical Alzheimer's disease (AD). This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from positron emission tomography neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72 months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models. The presence of preclinical AD and clinical progression to mild cognitive impairment or dementia during the study were then added to these models as covariates. Initially, age was associated with decline across all 4 cognitive domains. With the effects of elevated amyloid-β and clinical progression controlled, age was no longer associated with decline in verbal or working memory. However, the magnitude of decline was reduced only slightly for executive function and was unchanged for processing speed. Thus, considered together, the results of the study indicate that undetected preclinical AD negatively biases estimates of age-related cognitive decline for verbal and working memory. [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.)

Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid β (Aβ) deposition (Aβ+) has been associated with increased cortical atrophy, it remains unknown whether "SuperAgers" may be protected from Aβ-associated neurodegeneration., Methods: Neuropsychologically defined SuperAgers (n = 172) and cognitively normal for age (n = 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Aβ status., Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Aβ+. Rates of age- and Aβ-associated atrophy did not differ between the groups on any measure. Aβ- individuals displayed the slowest rates of atrophy., Discussion: Maintenance of superior memory in late life does not reflect resistance to age- or Aβ-associated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Aβ deposition (i.e. Aβ-) displayed reduced rates of cortical atrophy., (© 2019 The Authors.)

Objective: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition., Method: Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30-44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time., Results: Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%-73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27-0.31, 95% CI: 0.11-0.73, p < .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA., Conclusions: SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer's disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults., Objective: To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study., Methods: Fine-Gray subdistribution modeling was used to examine the risk of progression from CN to MCI/dementia due to Aβ+, APOEɛ4 carriage, and their interaction in the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging CN cohort (n = 599) over 8 years., Results: 17.7% Aβ+ and 8.1% Aβ-progressed over 8 years (OR: 2.43). Risk of progression for Aβ+ was 65-104% greater than Aβ-. Aβ+ APOEɛ4 carriers were at 348% greater risk than all other participants. Significant risk factors of progression in Aβ+ were age (HR: 1.05), PET SUVR (HR: 2.49) and APOE ɛ4 carriage (HR: 2.63); only age was a significant risk factor in Aβ-(HR: 1.09). Aβ-progressors were not near the threshold for Aβ+. These relationships were not moderated by hypertension, diabetes, obesity, or stroke/TIA., Conclusion: Aβ+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOEɛ4 carriage provides further predictive value in the presence of Aβ+. These data suggest that Aβ-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated Aβ deposition may be the result of neuropathological processes other than AD that accumulate with age.