Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer\u27s disease

Introduction This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer\u27s disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation. Methods CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL). Results CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P \u3c .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P\u3c .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition. Discussion CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders

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

Factors associated with burden of caring in Huntington’s disease

Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder which affects motor function, cognition and the psychological state of HD patients. Its triad of unique symptoms compared to other neurodegenerative disorders might give rise to a higher level of burden for their carers. Aims: The aim of this study was to explore factors associated with the burden of caring in patients with HD. Methods: Eighty-one HD patients and their carers participated in this study. Motor disturbances was assessed using the Unified Huntington’s Disease Rating Scale (UHDRS) motor scale, cognitive impairment was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), psychological status of both patient and carer were assessed using the Depression Anxiety Stress scale (DASS21), behavior of the patient was assessed with Revised Cambridge Behavioural Inventory (CBI-r) and carer burden was assessed with Zarit Burden Interview (ZBI). Results: Motor disturbances, attention and executive domains of cognition, psychological state of carers and patient’s behavior disturbances were found to affect burden of care in this study. Conclusion: HD has a major impact on carers. These findings highlight the needs for these factors to be targeted in order to reduce the burden among carer in HD

Factors associated with quality of life (QOL) in Huntington’s disease (HD).

Background: Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder which affects motor function, cognition and the psychological state of HD patients. Its triad of unique symptoms compared to other neurodegenerative disorders might give rise to a higher level of burden for their carers. Aims: The aim of this study was to explore factors associated with the quality of life in patients with HD. Methods: Sixty-three HD patients and their carers participated in this study. Cognitive impairment was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), motor disturbances was scored using the Unified Huntington’s Disease Rating Scale (UHDRS) motor scale, psychological status of both patient and carer were assessed using the Depression Anxiety Stress scale (DASS21), behavior of the patient was assessed using Revised Cambridge Behavioural Inventory (CBI-r) and patient’s quality of life was assessed with WHOQOL-BREF questionnaire. Results: Patients’ psychological conditions, motor disturbances and behavior of the patient are correlated with low QOL in HD patient. Conclusion: Patients’ factors are more likely to affect QOL in HD patient compared to carers’ factors; motor and psychological symptoms are key

APY766123_Appendix – Supplemental material for Alzheimer Disease: Non-pharmacological and pharmacological management of cognition and neuropsychiatric symptoms

<p>Supplemental material, APY766123_Appendix for Alzheimer Disease: Non-pharmacological and pharmacological management of cognition and neuropsychiatric symptoms by Samantha M Loi, Dhamidhu Eratne, Wendy Kelso, Dennis Velakoulis and Jeffrey CL Looi in Australasian Psychiatry</p

The Three Glycotypes in the London Classification System of Sporadic Creutzfeldt-Jakob Disease Differ in Disease Duration

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of CJD and is believed to be caused by the misfolding and aggregation of endogenous prion protein. Several classification systems have been developed to correlate the molecular characteristics of these misfolded prions (PrPSc) to the heterogeneous clinical presentations of sCJD. A central component of these systems is glycotyping, which involves the interpretation of the results of western immunoblotting of the protease-resistant fragment of the misfolded prion protein (PrPres). The two main classification systems differ in their recognition of a unique banding pattern on electrophoretic gels correlating to a putative clinical subtype. The perpetuation of both classification systems within scientific literature is, in part, due to a paucity of high-level evidence that conclusively addresses the merit of recognising each unique banding pattern. Here, 110 post-mortem confirmed cases of sCJD collected at the Australian Creutzfeldt-Jakob Disease Registry (ANCJDR) between 1993 and 2018 were analysed and classified as per the London classification system. The data presented here demonstrated that sCJD cases with ‘type 1′ and ‘type 2′ PrPSc as defined by the London classification system differ in their disease duration. No other differences in clinical phenotype or biological characteristics were found to be statistically significant. These findings highlight the importance of sample size and replicability in analyses of this rare disease process. Recognising these glycotypes as phenotypically distinct may represent ‘best practice’ in the collection and processing of sCJD samples within international registries for research purposes.</p

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?

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\u27s 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