Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.

Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.

Trajectory of Depressive Symptoms in a Longitudinal Stroke Cohort.

Objectives: Knowledge of the trajectory of post-stroke depression is important to identify high-risk patients, develop precise management programs and enhance prognosis. We aimed to characterise the course of depressive symptoms within the first year post-stroke and to evaluate associations with time.

Materials And Methods: Depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) within the first week, and at 3- and 12-months post-stroke.

Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

The Prominent Subarachnoid Space in Children: How has a Normal Variant Become Medicolegally Life-Threatening Pathology?

A prominent subarachnoid space (SAS) in infants under 24 months is a very common finding and is a normal variant that can be associated with macrocephaly. This must be differentiated from various pathological conditions that also cause a prominent SAS, including a reduction in brain volume, obstruction to the cerebrospinal fluid (CSF) or malformations of the skull. The inappropriate labelling of normal SAS prominence as enlargement due to pathology and misrepresentation of published literature by some author groups has created confusion medicolegally, contributing to inappropriate conclusions that a normal prominent SAS may cause subdural haemorrhage (SDH) and brain injury.

Randomised trial of same vs opposite arm co-administration of inactivated influenza and SARS-CoV-2 mRNA vaccines.

Background: The immunogenicity of current influenza vaccines need improvement. Inactivated influenza and COVID-19 mRNA vaccines can be co-administered but randomized controlled trial data is lacking on whether the two vaccines are more immunogenic if given in the same or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when co-formulated and delivered together.

Biomarkers.

Background: Dual decline in gait and cognition is associated with an increased risk of dementia, with combined gait and memory decline exhibiting the strongest association. However, little is known about the underlying brain correlates. Therefore, we aimed to examine the associations between measures of brain structure and dual decline in gait and cognition across several cognitive domains.

Biomarkers.

Background: Finding low-cost, accessible methods to detect people with early-stage Alzheimer's disease is a research priority for neuroprotective drug development. Subtle motor impairment of gait occurs years before episodic memory decline but there has been little investigation of whether self-administered hand motor tests can detect this pre-symptomatic period. This study evaluated how home-based unsupervised keyboard tapping tests from the TAS Test protocol predict episodic memory performance in a sample of older adults without overt cognitive impairment, as a potential indicative measure of early Alzheimer's disease.

Biomarkers.

Background: Younger-onset neurocognitive symptoms result from a heterogenous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the BeYOND (Biomarkers in Younger-Onset Neurocognitive Disorders) cohort, a study of individuals less than 65 years old presenting with neurocognitive symptoms for a clinical diagnosis and who have undergone cognitive and biomarker analyses.

Method: 65 participants were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia.

Biomarkers.

Background: Young-onset dementia (YOD) refers to the occurrence of dementia symptoms in people under the age of 65. Neuropsychiatric symptoms (NPS) are increasingly considered as the preclinical manifestations of YOD, posing a challenge to differentiate from psychiatric conditions with overlapping symptoms. The aim of this study is to investigate the AT(N), neuronal and glial pathologies underlying NPS and cognition in YOD.

Biomarkers.

Background: We performed a systematic review and meta-analysis of blood astrocyte biomarkers in Alzheimer's disease (AD).

Method: MEDLINE and Web of Science were searched without any restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, and S100B in AD patients. Pooled effect sizes were determined using Hedge's g method with a random effects model.

Public Health.

Background: Population dementia prevalence is traditionally estimated using cohort studies, surveys, routinely-collected administrative data, and registries. Hospital Electronic Health Records (EHRs) are comprised of rich structured and unstructured (text) clinical data that are underutilised for this purpose. We aimed to develop a suite of algorithms using routinely-collected EHR data to reliably identify cases of dementia, as a key step towards incorporating such data in prevalence estimation.

Public Health.

Background: The BetterBrains Trial is a prospective behavior-modification blinded endpoint randomized controlled trial to delay cognitive decline in middle-aged adults (aged 40-70) with a family history of dementia. The primary outcome is absence of decline on at-least one out of four cognitive tests at 24-months. We present trial recruitment and current participant completion statistics and baseline demographic, modifiable dementia risk factor (MDRF) and cognitive characteristics of the randomized sample, blinded to intervention arm.

Biomarkers.

Background: The Markers in Neuropsychiatric Disorders Study (The MiND Study) is investigating the diagnostic and wider utility of blood based biomarkers such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau), as well as other markers, to improve timely and accurate diagnosis of dementia and distinction from non-neurodegenerative and primary psychiatric disorder (PPD). This in-progress study has expanded significantly, becoming a robust platform for Australian and international collaborations.

Methods: Participants have been recruited and blood samples collected across Australia.

Biomarkers.

Background: Identifying biomarkers for primary tau pathologies like Progressive Supranuclear Palsy (PSP) is crucial for diagnosis and treatment development. The novel positron emission tomography (PET) radiotracer F-PI-2620 shows promise in detecting tau protein in PSP and this study investigates its correlation with clinical markers.

Methods: We conducted a cross-sectional analysis on 20 patients with clinically diagnosed probable PSP (Richardson's Syndrome), who underwent T1-weighted MRI, lumbar puncture, blood testing, and 0-60 min dynamic F-PI-2620 PET scanning.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Biomarkers.

Background: The Motoric Cognitive Risk Syndrome (MCR) is a predementia stage characterized by slow gait speed and subjective cognitive complaints. Defining the heterogeneity of brain volumetrics in individuals with MCR will improve current dementia risk assessments.

Method: We used data from 6 cohorts from the MCR consortium (N=2,007).

Biomarkers.

Background: It is clinically a challenging task to accurately differentiate complex young-onset neurodegenerative disorders from psychiatric disorders which often present with similar neuropsychiatric symptoms (NPS) in their early stages. The aim of this study is to provide a more nuanced understanding of the interplay between NPS, cognition and multiple pathologies that may drive these disorders.

Method: This study was conducted at the Neuropsychiatry Centre, the Royal Melbourne Hospital, Melbourne, Australia, as part of a large, multi-site research study, the Markers in Neuropsychiatric Disorders Study.

Alzheimer's Imaging Consortium.

Background: Identifying biomarkers for primary tau pathologies like Progressive Supranuclear Palsy (PSP) is crucial for diagnosis and treatment development. The novel positron emission tomography (PET) radiotracer 18F-PI-2620 shows promise in detecting tau protein in PSP and this study investigates its correlation with clinical markers.

Methods: We conducted a cross-sectional analysis on 20 patients with clinically diagnosed probable PSP (Richardson's Syndrome), who underwent T1-weighted MRI, lumbar puncture, blood testing, and 0-60 min dynamic 18F-PI-2620 PET scanning.

Dementia Care Research and Psychosocial Factors.

Background: The Promoting Independence Through quality Care at Home (PITCH) project aimed to improve outcomes for people with dementia and their carers via a co-designed training intervention for home care workers (HCWs). The results of the primary efficacy analysis of the successful stepped-wedge cluster RCT (n = 172 HCWs in 18 clusters in 7 Australian service providers) were presented at AAIC 2023.

Method: This presentation goes beyond efficacy and discusses the implementation science (process evaluation and behavioural change) and health economic analysis of the intervention.

Dementia Care Research and Psychosocial Factors.

Background: Australia has a rich migration history, with one in three older people coming from a culturally and linguistically diverse (CALD) background. Patients from CALD backgrounds tend to present at later stages of their diseases but face difficulties accessing appropriate dementia care compared to English-speaking patients. Limited literature exists on the clinical experience among CALD patients who have been historically underrepresented in dementia research.