Longitudinal trajectories of digital upper limb biomarkers for multiple sclerosis.

Background: Upper limb dysfunction is a common debilitating feature of relapsing-remitting multiple sclerosis (RRMS). We aimed to examine the longitudinal trajectory of the iPad®-based Manual Dexterity Test (MDT) and predictors of change over time.

Methods: We prospectively enrolled RRMS patients (limited to Expanded Disability Status Scale (EDSS) < 4).

Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders.

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.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.

Cognitive assessment during the phases of a spontaneous migraine: a prospective cohort study.

Introduction: Cognitive symptoms are reported commonly throughout all phases of a migraine; however, there is a paucity of objective cognitive profiling. Previous studies have been limited by practice effect, and variable populations.

Methods: Participants completed 1 month of daily testing with a computerised cognitive battery involving a simple reaction (SRT), choice reaction (CRT) and a working memory test (WM).

Deep phenotyping of socio-emotional skills in children with typical development, neurodevelopmental disorders, and mental health conditions: Evidence from the PEERS.

Objective: Socio-emotional skills, including social competence and social cognition, form the basis for robust relationships and wellbeing. Despite their importance, these skills are poorly defined and measured, particularly in children with developmental vulnerabilities. As a consequence, targets for effective management and treatment remain unclear.

Managing cognitive impairment and its impact in multiple sclerosis: An Australian multidisciplinary perspective.

Cognitive impairment in multiple sclerosis (MS) affects approximately 40-70% of patients and can have varying degrees of severity. Even mild cognitive impairment can impact on quality of life and productivity. Despite this, patients are not routinely screened or monitored for cognitive impairment in Australia due to a range of issues, with time and space being the main limiting factors.

The Patient-Determined Disease Steps scale is not interchangeable with the Expanded Disease Status Scale in mild to moderate multiple sclerosis.

Background And Purpose: The validity, reliability, and longitudinal performance of the Patient-Determined Disease Steps (PDDS) scale is unknown in people with multiple sclerosis (MS) with mild to moderate disability. We aimed to examine the psychometric properties and longitudinal performance of the PDDS.

Methods: We included relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of less than 4.

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, = 42), bipolar affective disorder (BPAD, = 121), treatment-resistant schizophrenia (TRS, = 82), bvFTD ( = 22), and compared to the reference cohort (Control Group 2, = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, = 96, using general linear models).

Plasma Neurofilament Light Chain and Clinical Diagnosis in Frontotemporal Dementia Syndromes.

Background: Frontotemporal dementia (FTD) syndromes, mimics, phenocopy (phFTD), and slowly progressive behavioral variant FTD (bvFTD) can be difficult to distinguish clinically. Biomarkers such as neurofilament light chain (NfL) may be helpful.

Objective: To study plasma NfL levels in people with FTD syndromes and determine if plasma NfL can distinguish between FTD syndromes and phFTD.

Clinical impact of whole-genome sequencing in patients with early-onset dementia.

Background: In the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation.

Methods: WGS analysis was performed in 50 patients with EOD.

A phase 1b open-label study of sodium selenate as a disease-modifying treatment for possible behavioral variant frontotemporal dementia.

Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD).

Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks.

Subjective versus objective performance in people with multiple sclerosis using the MSReactor computerised cognitive tests.

Background: Perceived cognitive impairment in MS is associated with adverse changes in employment capacity, sexual function, and aspects of daily living. Studies have shown relationships between perceived cognitive impairment and objective neuropsychological functioning and mood. Subjective cognitive performance in people with MS has not previously been compared to their objective performance on a computerised cognitive battery.

Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial.

Introduction: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder for which there are currently no disease-modifying therapies. The neuropathology of PSP is associated with the accumulation of hyperphosphorylated tau in the brain. We have previously shown that protein phosphatase 2 activity in the brain is upregulated by sodium selenate, which enhances dephosphorylation.

Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study.

Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls.

Association Between Cognitive Trajectories and Disability Progression in Patients With Relapsing-Remitting Multiple Sclerosis.

Background And Objectives: Longitudinal cognitive trajectories in multiple sclerosis are heterogeneous and difficult to measure. We aimed to identify discrete longitudinal reaction time trajectories in relapsing-remitting multiple sclerosis using a computerized cognitive battery and to assess the association between trajectories of reaction time and disability progression.

Methods: All participants serially completed computerized reaction time tasks measuring psychomotor speed, visual attention, and working memory.

A study protocol for a phase II randomised, double-blind, placebo-controlled trial of sodium selenate as a disease-modifying treatment for behavioural variant frontotemporal dementia.

Introduction: Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder often neuropathologically associated with the accumulation of abnormally hyperphosphorylated tau, for which there is currently no disease-modifying treatment. Previous work by our group has shown sodium selenate upregulates the activity of protein phosphatase 2 in the brain, increasing the rate of tau dephosphorylation. The objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying treatment for bvFTD.

Aggregation of Abnormal Memory Scores and Risk of Incident Alzheimer's Disease Dementia: A Measure of Objective Memory Impairment in Amnestic Mild Cognitive Impairment.

Objectives: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer's disease (AD) dementia.

Methods: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory.

The MSReactor computerized cognitive battery correlates with the processing speed test in relapsing-remitting multiple sclerosis.

Background: Monitoring and screening of cognitive function in the ambulatory setting requires simple, brief cognitive tests that are reproducible. MSReactor (MSR) is a web-based platform that screens psychomotor (processing) speed, attention and working memory using a game-like interface. The Processing Speed Test (PST) is a validated computerized version of the Symbol Digit Modalities test (SDMT) and component of the Multiple Sclerosis Performance Test (MSPT).

Cognitive effects of onabotulinumtoxinA in chronic migraine.

Background: Chronic migraine is a disabling condition, often associated with comorbidities including cognitive dysfunction, anxiety and depression. It is unclear whether cognitive complaints are associated with the underlying migraine pathophysiological process or related to drugs or comorbidities of depression and anxiety.

Objective: To evaluate cognitive changes in chronic migraine and assess reversibility of cognitive dysfunction following effective migraine treatment using onabotulinumtoxinA.

The feasibility, reliability and concurrent validity of the MSReactor computerized cognitive screening tool in multiple sclerosis.

Background: Multiple sclerosis (MS) cognitive tests are resource intensive and limited by practice effects that prevent frequent retesting. Brief, reliable and valid monitoring tools are urgently needed to detect subtle, subclinical cognitive changes in people with MS. Cognitive monitoring over time could contribute to a new definition of disease progression, supplementing routine clinical monitoring.