Basic Science and Pathogenesis.

Background: The glymphatic system has been suggested as an important clearance mechanism for amyloid-β (Aβ) during sleep. Animal and cellular models have suggested this clearance mechanism involves the water-channel protein, Aquaporin-4 (encoded by the AQP4 gene), located primarily in the astrocytic end-feet. We have previously reported on the interaction between genetic variants within AQP4, sleep and cross-sectional cortical amyloid-β (Aβ) burden.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer's disease (AD) risk, but genetic variation in the onset and progression of AD pathology is less understood. Accumulation of amyloid-β (Aβ) in the brain is a key pathological hallmark of AD beginning 10 - 20 years prior to cognitive symptoms. We investigated the genetic basis of variation in age at onset (AAO) of brain Aβ by comparing the performance of polygenic scores (PGSs) based on AD risk and resilience with a Aβ-AAO trait-specific PGS.

Clinical Manifestations.

Background: Cognitive dysfunction is central to clinicopathological models of Alzheimer's disease (AD). While AD prospective studies assess similar cognitive domains, the neuropsychological tests used vary between studies, limiting potential for aggregation. We examined a machine learning (ML) data harmonisation method for neuropsychological test data to develop a harmonised PACC score for the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) consortium.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) individuals, the PACC is widely used as a cognitive outcome measure and endpoint in observational studies and clinical trials. However, it has drawn criticism for being heavily weighted towards memory. Increasing evidence indicates a decline spanning multiple cognitive domains in CU individuals.

Clinical Manifestations.

Background: The success of therapeutic options for treatment of Alzheimer's disease (AD) and the growing emphasis for such treatment to commence in the pre-clinical phase makes it necessary to have robust empirical models of clinical disease progression to understand findings from clinical trials, allow clinicians to evaluate effects of new drugs, and to select individuals for future trials. Such models have been developed from relatively small samples, with incomplete data/substantial loss to follow-up. The ADOPIC consortium provides the largest complete AD natural history sample to date.

Diagnostic accuracy of early neonatal MRI in predicting adverse motor outcomes in children born preterm: Systematic review and meta-analysis.

Aim: To examine the diagnostic accuracy of Early structural and diffusion-weighted magnetic resonance imaging (MRI) (acquired at < 36 weeks postmenstrual age) to detect cerebral palsy (CP) or other adverse motor outcomes at or beyond 3 years corrected age in infants born preterm.

Method: In this systematic review and meta-analysis, we searched the CINAHL, Embase, PubMed, and Web of Science databases for studies without language restrictions and a prospectively registered protocol up to October 2023. We extracted the study details, associations presented, and meta-analyses conducted with pooled sensitivity and specificity.

Diagnostic accuracy of neonatal structural MRI scores to predict 6-year motor outcomes of children born very preterm.

Aims: This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA.

Methods: Infants born < 31-weeks gestational age (GA) returning for 6-year follow-up were included. Early and Term sMRI were scored using a validated method, deriving white matter, cortical grey matter, deep grey matter, cerebellar and global brain abnormality scores (GBAS).

A Machine Learning Model to Harmonize Volumetric Brain MRI Data for Quantitative Neuroradiological Assessment of Alzheimer Disease.

Purpose To extend a previously developed machine learning algorithm for harmonizing brain volumetric data of individuals undergoing neuroradiological assessment of Alzheimer disease not encountered during model training. Materials and Methods Neuroharmony is a recently developed method that uses image quality metrics (IQM) as predictors to remove scanner-related effects in brain-volumetric data using random forest regression. To account for the interactions between Alzheimer disease pathology and IQM during harmonization, the authors developed a multiclass extension of Neuroharmony for individuals with and without cognitive impairment.

A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship.

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD).

Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS.

Standardizing MRI orientation improves reliability of entorhinal and transentorhinal cortical volume measurement.

The current study compared the reliability of manual collateral sulcus depth and entorhinal and transentorhinal cortical volume measurements between native oriented MRI scans versus MRI scans realigned to the hippocampal long axis. Data included 10 participants with two serial 3.0T MRI scans from the Alzheimer's Disease Neuroimaging Initiative.

Autoantibodies to BACE1 promote Aβ accumulation and neurodegeneration in Alzheimer's disease.

The profile of autoantibodies is dysregulated in patients with Alzheimer's disease (AD). Autoantibodies to beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) are present in human blood. This study aims to investigate the clinical relevance and pathophysiological roles of autoantibodies to BACE1 in AD.

Promoting the Secondary Use of Clinical Research Data in Australia.

The research community in Australia is building a national infrastructure to facilitate access to and sharing of data from health studies. A federation of nine nodes representing 72 health research organisations provides coordination across their partners to establish systems, processes and relationships promoting FAIR approaches to clinical trial data. This paper describes this initiative.

Prediction of Antibiotic Susceptibility in E. coli Isolates Using Machine Learning.

Antimicrobial resistance (AMR) poses a significant global health threat, resulting in 4.96 million deaths in 2019, with projections reaching 10 million by 2050. This resistance, primarily due to the overuse of antibiotics, complicates the treatment of infections caused by various microorganisms, including the gram-negative bacterium Escherichia coli.

Is eHealth Research with or on Our People?: Lessons Learned Using the Aboriginal and Torres Strait Islander Quality Appraisal Tool.

There is growing evidence for the benefits of eHealth interventions with Aboriginal and Torres Strait Islander people. Yet, there is a lack of guidance for culturally safe, relevant, and sustainable initiatives with Aboriginal and Torres Strait Islander peoples and organisations. To this end a research program was established to develop a roadmap for eHealth with Aboriginal and Torres Strait Islander peoples.

Building a Natural Language Interface for FHIR Clinical Terminology Server.

While Fast Healthcare Interoperability Resources (FHIR) clinical terminology server enables quick and easy search and retrieval of coded medical data, it still has some drawbacks. When searching, any typographical errors, variations in word forms, or deviations in word sequence might lead to incorrect search outcomes. For retrieval, queries to the server must strictly follow the FHIR application programming interface format, which requires users to know the syntax and remember the attribute codes they wish to retrieve.

The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses.

Purpose: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet many remain without a molecular diagnosis. The Australian Genomics Mitochondrial Flagship, comprising clinicians, diagnostic, and research scientists, conducted a prospective national study to identify the diagnostic utility of singleton genomic sequencing using blood samples.

Methods: A total of 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mitochondrial DNA (mtDNA) sequencing or genome sequencing.

Leveraging existing data to improve antimicrobial resistance-related mortality estimates for Australia.

Antimicrobial resistance (AMR) is a global pandemic, however, estimating its burden is a complex process. As a result, many countries rely on global estimates to infer burden within their own setting. With a growing number of recent publications quantifying AMR burden in Australia, and an expansion of surveillance programs, enumerating AMR mortality for Australia is feasible.

The experiences of individuals who have had gestational diabetes: A qualitative exploration.

Aim: To qualitatively explore the experiences of individuals with Gestational Diabetes Mellitus (GDM) in Australia, and to recognise opportunities for leveraging digital health to enhance the support of GDM management.

Method: A cross sectional online survey assessed the experiences of individuals with GDM, the healthcare system and their digital health usage. Respondents (recruited via a national diabetes registry or social media) were adults receiving GDM care within Australia in the last 5 years, who responded to any of three open-ended questions (n = 815) exploring positive, negative and other GDM experiences.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.

Objective: A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.