Neurosciences Commons^™

Discriminative Performance Of Externally Validated Dementia Risk Prediction Models: A Systematic Review And Meta-Analysis, Blossom C.M. Stephan, Jacob Brain, Kaarin J. Anstey, Tanya Buchanan, Claire V. Burley, Elissa Burton, Jennifer Dunne, Linda Errington, Matthew Gorringe, Zhongyang Guan, Bronwyn Myers, Serena Sabatini, Marc Sim, William Stephan, Eugene Yee Hing Tang, Narelle Warren, Mario Siervo

Research outputs 2022 to 2026

Background: Data on the external validation of current dementia risk prediction models has not yet been systematically synthesised. This systematic review and meta-analysis collated results from three previous reviews to evaluate the predictive discriminative performance of dementia risk models when validated in population-based settings. Methods: Embase (via Ovid), Medline (via Ovid), Scopus, and Web of Science were searched from inception to June 2022 with an updated search conducted up to November 2024. Included studies (1) had a population-based cohort design; (2) assessed incident late-life (i.e. ≥ 60 years) dementia; and (3) reported predictive performance of at least one dementia risk …

The Relationship Between Dietary Sodium Intake And Cognitive Function: A Narrative Review, Samantha L. Gardener, M. Fu, L. Morini, T. Schwartzkopff, G. Savage, R. N. Martins, S. R. Rainey-Smith

Research outputs 2022 to 2026

Purpose of Review: This narrative review provides discussion on current evidence regarding the relationship between sodium intake and cognitive function in animal and human studies, as well as potential mechanisms underlying this relationship. Recent Findings: Recent evidence suggests high sodium intake is associated with development of cognitive impairment and neural dysfunction. Additionally, studies have proposed that high sodium intake is associated with increased aggregation of Aβ-amyloid and that hypertension (for which high sodium intake is a risk factor) modulates the relationship between Aβ-amyloid and development of cognitive impairment and Alzheimer’s disease. However, while animal studies demonstrate a consistent relationship between …

Neurochemical Impact Of Psychostimulants: Longitudinal Mri Analysis Of Brain Iron Content In Children With Adhd, Hugo A.E. Morandini, Sjoerd B. Vos, Paola Chivers, Tim J. Silk, Pradeep Rao

Research outputs 2022 to 2026

Background: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in school-aged children and has been associated with impaired brain iron homeostasis. Evidence has shown that psychostimulant treatment may affect brain iron content in children with ADHD, however, longitudinal evidence remains limited. The present longitudinal study investigated the effect of psychostimulant treatment duration and age at treatment onset on brain iron content in children with ADHD. Methods: Neuroimaging and phenotypical data were collected from the publicly available Oregon ADHD-1000 dataset. After screening, data from 29 psychostimulant-medicated children with ADHD and 38 neurotypical children were included. Individual General Estimating Equation (GEE) …

Characterising Manual Dexterity, Motor Cortex Neuroplasticity, And Intracortical Inhibition Long After Burn Injury, Grant S. Rowe, Alecia Wood, Mark Fear, Dale W. Edgar, Aleksandra Miljevic, Tyler Osborne, Natalie Morellini, Merrilee Needham, Ann Maree Vallence, Fiona Wood

Research outputs 2022 to 2026

Purpose: Persistent motor dysfunction after burn injury may be due to altered motor cortex and corticospinal tract function. This study examined manual dexterity, motor cortex neuroplasticity, and intracortical inhibition in former burn patients 1–3 years after minor injury (<10% TBSA). Method: Thirty former burn patients (TBSA: 0.78 ± 1.08%) and 30 non-injured controls participated. Manual dexterity was assessed using the Purdue Pegboard. Transcranial magnetic stimulation (TMS) was used to measure motor cortex excitability (motor evoked potential [MEP] amplitude) and short- and long-interval intracortical inhibition (SICI, LICI) before and after paired-associative stimulation (PAS) to induce neuroplasticity. Results: Former burn patients performed worse than controls on the bimanual assembly subtest of the Purdue Pegboard. PAS did not induce changes in MEP amplitude but increased LICI in both burn patients and control participants. In burn patients, baseline LICI was related to bimanual performance differently than controls. Conclusions: These findings suggest poorer bimanual motor function persists after minor burns, and differences in the association between inhibition and bimanual dexterity between burn and control groups. Further research should explore whether targeting motor cortex inhibitory circuits can improve motor performance following burn injury

Musical Training Increases Anticipatory Responding And Predictive Control In Sequence Learning, Li Ann Leow, Jarrad Lum, Sara Johnson, Emily Corti, Welber Marinovic

Research outputs 2022 to 2026

Musicians demonstrate advantages in acquiring motor sequences, showing faster learning and better explicit sequence knowledge than non-musicians. However, it is unclear whether this advantage extends beyond acquisition to the consolidation phase, which is when newly learned skills stabilize and become resistant to interference. Additionally, while interference from executing competing motor tasks is well-established, less is known about whether purely sensory information presented after learning can disrupt consolidation of a bimodal motor sequence. We investigated how post-acquisition sensory interference affects performance of a learned audio-visual sequence, and whether musical training moderates this vulnerability. Participants first learned an explicit sequence in a …

Sarcopenic Obesity And Dementia Risk: Primary Associations And Landmark Analyses Of Muscle Strength And Body Composition Trajectories, Zhongyang Guan, Blossom C.M. Stephan, Lorenzo M. Donini, Justyna Godos, Giuseppe Grosso, Leticia Radin Pereira, Carla M. Prado, Carlos J. Toro-Huamanchumo, Jonathan C.K. Wells, Marc Sim, Mario Siervo

Research outputs 2022 to 2026

Background and aims: Sarcopenic obesity (SO) has been proposed as a risk factor for cognitive impairment. Yet evidence is inconsistent and often limited by heterogeneous definitions and lack of longitudinal assessments. This study aimed to examine associations of SO with all-cause and subtype-specific dementia, and to assess dose–response patterns and how longitudinal changes in body composition and muscle strength relate to dementia risk. Methods: We included 489,972 adults (mean age 56.5 ± 8.1 years) followed for a median of 13.6 years. SO was defined using the Sarcopenic Obesity Global Leadership Initiative (SOGLI) criteria. Cox models estimated hazard ratios (HRs) for …

Gut Microbiome Changes In Preclinical Alzheimer’S Disease, D. M. Sithara Dissanayaka, Stephanie R. Rainey-Smith, Hamid R. Sohrabi, Thilini N. Jayasinghe, Vincent Ho, Vijay Jayasena, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops many years before clinical symptoms appear. The biological changes involved in the earliest stages remain poorly understood, particularly during the preclinical stage. Our previous work has identified gradual gut microbial and metabolic changes during this stage, suggesting these may represent early biological shifts that precede disease progression. Recent studies suggest that the gut microbiome may contribute to early AD processes through its effects on immune regulation, metabolism, and gut–brain communication. Changes in gut microbial composition, including reduced levels of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium, Roseburia, and Eubacterium, …

Peripheral Nerve Sensory Fibers Are Recruited With Less Current And Greater Selectivity By Conventional Waveforms Compared With High-Frequency Waveforms, Janie Provencher, Harrison T. Finn, Janet L. Taylor, Simon C. Gandevia, Jane E. Butler, Martin E. Héroux

Research outputs 2022 to 2026

Transcutaneous spinal stimulation aims to target dorsal spinal roots, which deliver sensory information to the spinal cord. However, the stimulation waveform that most effectively recruits sensory fibers at the lowest intensity has not been identified. The purpose of this study was to compare conventional and high-frequency burst-modulated stimulation waveforms in their ability to recruit sensory fibers, as assessed by H-reflex threshold, recruitment characteristics, and motor fiber activation. In participants with intact neurological function (n ¼ 12), soleus H-reflex recruitment curves were recorded for 10 stimulation waveforms: a conventional waveform (400 μs), serving as the reference condition, high-frequency burst-modulated waveforms (2, …

The Effects Of Anti-Parkinsonian Medications On Bone Mineral Density: A Systematic Review, Mícheál Ó Breasail, Motaz B. El-Leissy, Karan P. Singh, Matthew Smith, Jakub Mesinovic, Marc Sim, Andrew Evans, David Blacker, Saman Heshmat, Neil Mahant, Christian Girgis, Peter R. Ebeling, Ayse Zengin

Research outputs 2022 to 2026

IntroductionParkinson's disease (PD) is associated with elevated fracture risk, particularly at the hip. Antiparkinsonian medications have also been associated with increased fracture risk; although their direct effects on bone mineral density (BMD) remains unclear.ObjectiveInvestigate whether antiparkinsonian medications influence BMD.MethodsA systematic search of four databases (Embase, MEDLINE, APA PsycINFO, Web of Science) was conducted up to 24/11/2025 using terms related to PD, antiparkinsonian medications and bone.ResultsA total of 748 records were identified, with 543 screened following deduplication. Fourteen studies underwent full-text review, of which seven met inclusion criteria. Three studies assessed bone mineral content or surrogate measures at non-standard sites (hand …

Neuroprotective Effects Of Sorghum Polyphenol In Alzheimer’S Disease: In Vitro And In Silico Analyses, Rasheed A. Abdulraheem, Ralph N. Martins, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Vijay Jayasena, Stuart K. Johnson, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Background/Objective: Accumulation of amyloid-beta (Aβ) senile plaques in the human brain is a major hallmark of Alzheimer’s disease (AD), which manifests as progressive decline in memory and cognitive functions and currently lacks effective disease-modifying therapies. Emerging evidence demonstrates that polyphenol-rich plant foods are potential complementary therapies for AD. Methods: In this study, we investigated crude polyphenol extracts (CPEs) and purified polyphenol extracts (PPEs) from three sorghum genotypes for their ability to inhibit Aβ42-induced toxicity in MC-65 cells. Thioflavin T fluorescence, cell viability, mitochondrial function, oxidative stress assays, and Western blotting, along with RNA sequencing and computational analyses, were used to …

Predicting Accumulation And Age At Onset Of Amyloid-Β From Genetic Risk And Resilience For Alzheimer's Disease, Eleanor K. O'Brien, Timothy Cox, Shane Fernandez, Pierrick Bourgeat, Tenielle Porter, Ben Goudey, James D. Doecke, Colin L. Masters, Jurgen Fripp, Kwangsik Nho, Victor L. Villemagne, Carlos Cruchaga, Christopher C. Rowe, Andrew J. Saykin, Vincent Doré, Simon M. Laws

Research outputs 2022 to 2026

Background: Accumulation of brain amyloid beta (Aβ), a key pathological hallmark of Alzheimer's disease (AD), begins decades before cognitive symptoms. Being able to predict the risk of Aβ accumulation, or the age at which Aβ exceeds a critical threshold, may enable intervention to delay or prevent onset of AD. Methods: Using published genome-wide association studies (GWASs), we developed polygenic scores (PGS) for AD risk (PGSrisk) and resilience (PGSresilience), and tested whether these predicted (i) if an individual is an Aβ accumulator (‘Accumulator Status’), and (ii) in accumulators, the age at which brain Aβ exceeds a 20 centiloid (CL) threshold (‘Age …

Cognitive Decline In Dutch-Type Hereditary And Sporadic Cerebral Amyloid Angiopathy: A 5-Year Follow-Up Study, Rosemarie Van Dort, Vera C.J. Van Stek-Smits, Sanne E. Schriemer, Reinier G.J. Van Der Zwet, Manon R. Schipper, Sabine Voigt, Ellen P. Hart, Vandhana Easwaran, Hamid R. Sohrabi, Kevin Taddei, Samantha L. Gardener, Ralph N. Martins, Steven M. Greenberg, Matthias J.P. Van Osch, Marianne A.A. Van Walderveen, Marieke J.H. Wermer, Ellis S. Van Etten

Research outputs 2022 to 2026

Introduction: Cerebral amyloid angiopathy (CAA) is associated with cognitive impairment, but its longitudinal course of cognitive decline remains unclear. We investigated domain-specific cognitive trajectories in Dutch-type hereditary (D-CAA) and sporadic CAA (sCAA) to compare patterns and rates of decline. Methods: We included 181 participants – 93 D-CAA mutation carriers (59 without, 34 with prior intracerebral hemorrhage [ICH]) and 88 with sCAA (57 without, 31 with ICH) – who underwent annual neuropsychological assessment. Longitudinal change in global cognition, memory, processing speed, and executive function was analyzed using linear mixed models. Results: Over 5 years, cognitive decline was subtle but measurable. Memory …

The Poly-Arginine Peptide R18d Inhibits Amyloid-Beta (Aβ) Aggregation And Aβ-Induced Cytotoxicity, Reduces Intracellular Tau Aggregation, And Exhibits Oral Bioavailability, Vaishali Bagda, Zainab H. Farooz, Neville W. Knuckey, Samantha M. South, Stuart K. Gribble, Maitri Tomar, Prashant Bharadwaj, Ajish Ariyath, Kevin Taddei, Ralph N. Martins, Bruno P. Meloni

Research outputs 2022 to 2026

Background/Objectives: Effective disease-modifying therapies targeting pathogenic proteins associated with Alzheimer’s disease (AD) remain limited. This study investigated the therapeutic potential of the neuroprotective, cationic arginine-rich peptide R18D to mitigate the pathogenic effects of amyloid-beta (Aβ) and tau associated with AD.

Methods: R18D was examined for its ability to inhibit Aβ aggregation in a cell-free assay, attenuate Aβ-induced cytotoxicity in MC65 cells, and suppress intracellular tau aggregation in two neural cell models. Intracellular tau aggregation was quantified using a homogeneous time-resolved fluorescence assay. Additionally, a pilot pharmacokinetic study of R18D was conducted in mice following oral gavage administration.

Results: In the …

Patterns Of Language And Visuospatial Lateralisation In Three-Year-Old Children, Josephine E. Quin-Conroy, Donna M. Bayliss, Stephanie J. Bovell, Debra Eamer, Georgina H.M. Earl, Simon E. Fisher, Clyde Francks, Murray T. Maybery, Sarah Pillar, Desiree Silva, Andrew J.O. Whitehouse, Nicholas A. Badcock

Research outputs 2022 to 2026

Little is known about how or when language and visuospatial processing lateralise in the brain, and if individual differences in lateralisation are related to early language or visuospatial abilities. We explored if patterns of language and visuospatial lateralisation are related to cognitive skills in young children. A large sample of 3-year-olds (n = 136) attempted two functional transcranial Doppler ultrasound (fTCD) tasks to estimate language and visuospatial lateralisation. At the group level, language was lateralised to the left hemisphere, but visuospatial processing was weakly lateralised to the right hemisphere. The relationship between patterns of lateralisation and cognitive skills was investigated …

Assessing Shifts In Research Priority Areas From The Neurological Community Before And After The Covid-19 Pandemic, Leah Dempsey, Travis Cruickshank, Mitchell Turner, Manja Laws, Danielle Bartlett, Barby Singer, Onno Van Der Groen, Moira Sim, Mandy Stanley

Research outputs 2022 to 2026

Introduction: People living with a neurological condition face many difficulties in daily life, impacting their function and quality of life (QoL). There is currently no cure to many neurological conditions, therefore identifying interventions to improve QoL is of high importance. COVID-19 changed society in many ways and understanding the research priorities from the neurological community post pandemic is urgently needed to ensure resources are used efficiently and aligned with the needs and priorities of the community. To better understand the priority areas, it is essential for individuals with lived experience to have input into priority areas for research. Therefore, the …

Higher Sodium Intake Is Associated With Episodic Memory Decline In Cognitively Unimpaired Older Males: A 6-Year Longitudinal Study, Francisca Chuwa, Stephanie R. Rainey-Smith, Hilal Salim Said Al Shamsi, Hamid Sohrabi, Kevin Taddei, Colin L. Masters, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Recent evidence has suggested an association between high sodium intake and development of cognitive impairment. However, while animal studies demonstrate consistent relationships between sodium intake and cognitive impairment, this relationship remains less clear in humans. Our aim was to investigate the relationship between self-reported baseline sodium intake and cognitive decline over 72 months. Cognitively unimpaired participants (n = 1208) from the Australian Imaging, Biomarkers and Lifestyle study were included (70.87 years of age; 41 % male). Participants completed a food frequency questionnaire to quantify sodium intake and underwent comprehensive neuropsychological assessment at baseline and four additional timepoints, 18 months apart. …

Age-Related Increase In Plasma P-Tau217 In Amyloid-Beta–Negative Cognitively Unimpaired Individuals Affects Diagnostic Interpretation, Anna E. Mammel, Fernando Gonzalez-Ortiz, Ali Mousavi, Kelsey Hallett, Mary Encarnacion, Don Biehl, Pradip Gill, Sazan Ismael, Christopher Fowler, James D. Doecke, Larry Ward, Hans Frykman

Research outputs 2022 to 2026

Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = …

Evidence For Direct And Sleep-Moderated Relationships Between Aquaporin-4 Genetic Variants And Alzheimer's Disease Phenotypes, Tenielle Porter, Ayeisha Milligan Armstrong, Eleanor K. O'Brien, Vincent Doré, Pierrick Bourgeat, Mitchell Turner, Paul Maruff, Christopher C. Rowe, Belinda M. Brown, Victor L. Villemagne, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Introduction: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association with other AD-related phenotypes/disease progression remain largely unknown. Methods: Associations between AQP4 variants, self-reported sleep measures, and AD-related phenotypes in cognitively unimpaired individuals with evidence of Aβ accumulation were examined using data from the Australian Imaging, Biomarkers and Lifestyle study. Results: AQP4 variants were directly associated with regional brain volumes, atrophy, and cognition. They were also associated with differences in regional brain volumes and atrophy in interaction with sleep …

Maximal Motor Unit Firing Rates Decline With Amyotrophic Lateral Sclerosis Progression, Gabriel L. Fernandes, Lucas B.R. Orssatto, Matheus D. Pinto, Joao S. Henkin, Ehsan Shandiz, Pamela A. Mccombe, Robert D. Henderson, Gabriel S. Trajano

Research outputs 2022 to 2026

Objective: Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of upper and lower motor neurons and their motor units (MUs). MU loss is compensated by collateral sprouting and reinnervation of muscle fibres. There is limited information about the properties of these surviving MUs as these processes take place. High-density surface electromyography (HD-sEMG) decomposition enables non-invasive analysis of individual MU firing behaviour during maximal voluntary contractions and assess their changes with ALS progression. Methods: Thirty-nine individuals with ALS (24 men; mean age 63 ± 16 years) completed up to five visits (interval 20.0 ± 7.9 weeks). Tibialis anterior HD-sEMG recordings …

A High-Throughput Assay For Monitoring And Quantifying Amyloid-Β Accumulation And Clearance In Alzheimer's Disease Cell Models, Ajish Ariyath, Fraulein Denise Arigo, Anna Fyfe, W. M.A.D.Binosha Fernando, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Amyloidogenic proteins, such as amyloid-β (Aβ), self-assemble into cross-β fibrils whose accumulation is central to Alzheimer's disease (AD). Measuring Aβ aggregation and clearance in living cells remains challenging using current cell-based assays, which are often low-throughput or not suited for real-time monitoring. This study aimed to (1) develop a robust, quantitative, and scalable fluorescence-based assay using Amytracker to monitor Aβ accumulation and clearance in an Aβ-producing neuronal cell model, and (2) validate its utility for mechanistic studies and therapeutic screening. We established a plate-based fluorescence assay using Amytracker in MC65 neuronal AD model expressing the Amyloid precursor protein C-terminal fragment …

Circulating Sphingomyelins Correlate With Plasma T-Tau In Cognitively Unimpaired Older Adults At Risk Of Developing Alzheimer's Disease, Tahmida Sharmin, James D. Doecke, Pratishtha Chatterjee, Steve Pedrini, Hamid R. Sohrabi, Nicholas J. Ashton, Henrik Zetterberg, Manohar L. Garg, Kaj Blennow, Ralph N. Martins

Research outputs 2022 to 2026

Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total-tau (T-tau) remain valuable in indicating AD-related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non-invasive detection and treatment approaches. This cross-sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid-β (Aβ) status through positron …

3-Deoxyanthocyanidins Inhibit Β-Amyloid Aggregation, Toxicity, And Mitochondrial Dysfunction: Evidence From Mc-65 Cells And Molecular Dynamics Simulations, Rasheed A. Abdulraheem, Ammar U. Danazumi, Philipp Nitschke, Luke Gray Whiley, Abdulrahman Ibrahim Tudu, Ranil Coorey, Zhoyu Li, Prashant Bharadwaj, Vijay Jayasena, Stuart K. Johnson, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Accumulation of amyloid-beta (Aβ42) senile plaques in the brain is a hallmark of Alzheimer's disease (AD). Although some drug have been approvaled recently, none has demonstrated robust disease-modifying outcome. The 3-deoxyanthocyanidins (3-DXA) and their derivatives represent a more stable class of polyphenols, present at uniquely high concentrations in sorghum grains. Although 3-DXA exhibit strong potential to modulate protein aggregation processes, their effects on AD pathology remain unexplored. In this study, we investigated the inhibitory effects of three 3-DXA derivatives, apigeninidin chloride (AC), luteolinidin chloride (LC), and 7-methoxy apigeninidin (7-MAC), on Aβ42 aggregation and associated neurotoxicity. Thioflavin T fluorescence assay was …

The Association Of Apolipoprotein E Ε4 With Symptomatic Intracerebral Hemorrhage, Mri Markers And Cognition In Dutch-Type Hereditary Cerebral Amyloid Angiopathy, Maaike C. Van Der Plas, Rosemarie Van Dort, Ingeborg Rasing, Yongxi Long, Erik W. Van Zwet, Matthias J.P. Van Osch, Hamid R. Sohrabi, Kevin Taddei, Samantha L. Gardener, Ralph N. Martins, Steven M. Greenberg, Gisela M. Terwindt, Marianne A.A. Van Walderveen, Marieke J.H. Wermer

Research outputs 2022 to 2026

Background: Apolipoprotein E (APOE) genotype influences the presence, course and severity of sporadic cerebral amyloid angiopathy (sCAA). We investigated the effect of the APOE ε4-allele on clinical and neuroradiological outcomes in mutation-carriers with Dutch-type hereditary (D-)CAA. Methods: Participants with D-CAA from a prospective cohort study, with data collected on history of symptomatic intracerebral hemorrhages (sICH) and vascular risk factors, underwent 3 Tesla magnetic resonance imaging (MRI) scans to assess macrobleeds, cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH) volume and WMH multispot lesions. Global cognition was measured using Montreal Cognitive Assessment (MoCA) and …

Impact Of Plasma Ptau181 Levels On Clinician Diagnostic Confidence And Management In Memory And Cognition Clinics: A Multi-Site Before-And-After Study, Johannes C. Michaelian, Azadeh Feizpour, James C. Vickers, Jane E. Alty, Jessica M. Collins, Vincent Doré, Catriona Ireland, Anna E. King, Ralph N. Martins, Michael Woodward, Sharon L. Naismith, Christopher C. Rowe

Research outputs 2022 to 2026

Introduction: Recent advances allow blood tests to detect key proteins linked to Alzheimer's disease (AD). Methods: In this before-and-after study across three Australian memory and cognition clinics, we evaluated the impact on clinicians' diagnostic confidence and management following disclosure of routine patients' AD probability, using predefined plasma phosphorylated tau 181 (pTau181) thresholds set at 90% sensitivity and 90% specificity for amyloid-beta (Aβ) positron emission tomography (PET) positivity. Results: One hundred thirteen participants (mean age: 71.2 ± 8.4; mean Mini-Mental State Examination score: 27.7 ± 2.5) with dementia (n = 17, 15.0%), mild cognitive impairment (n = 48, 42.5%), and subjective …

The Relationships Between Social Network Size, Loneliness And Personality In Individuals Living With A Neurological Condition: An Exploratory Study, Isabella Branson, Kate Turner, Mitchell Turner, Manja Laws, Leah Dempsey, Simon Laws, Mandy Stanley, Johnny Lo, Travis Cruickshank

Research outputs 2022 to 2026

Background: People living with a neurological condition often report having smaller social networks and less frequent social contact, leading to greater loneliness and worse quality of life. This study explored the relationships between personality traits, social network size (SNS) and perceived loneliness in this population. Methods: Sixty-eight individuals diagnosed with a neurological condition participated in this study. Perceived loneliness was assessed using the UCLA Loneliness Scale – Version 3, SNS was evaluated by the Social Network Index and personality traits were examined using the NEO Factor Five Inventory. Path analysis was conducted to determine if loneliness was negatively associated with …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

Plasma Biomarker Progression Across The Alzheimer's Disease Amyloid Beta And Tau Positron Emission Tomography Trajectories, Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Introduction: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations. Methods: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden. RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants …

Regulation Of Autophagy-Mediated Pathways By Diet, Physical Activity, And Sleep In Alzheimer's Disease, Ajish Ariyath, Zoe Mputhia, Christopher Dougherty, Bushra Kaleelur Rahuman, W. M.A.D.Binosha Fernando, Belinda Brown, Samantha L. Gardener, Stephanie R. Rainey-Smith, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and …

Novel Small-Molecule Analogues Of Iu1 Ameliorate Amyloid-Β Mediated Toxicity In Alzheimer’S Disease Cell And Worm Models, Ajish Ariyath, Fraulein Denise Arigo, Izhar Wallach, W. M.A.D.Binosha Fernando, Ralph N. Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Dysregulation of the deubiquitinating enzyme Ubiquitin-specific peptidase 14 (USP14) is implicated in several neurodegenerative diseases, and IU1, an allosteric inhibitor, has shown neuroprotective effects by reducing protein aggregate toxicity. This study aimed to develop new IU1 analogues and evaluate their ability to mitigate amyloid-β (Aβ) accumulation and toxicity in Alzheimer’s disease (AD) cell and Caenorhabditis elegans worm models. IU1 and 71 newly designed analogues identified using the AtomNet^® virtual screening platform were assessed in an amyloid precursor protein-C terminal fragment/amyloid-β (APP-C99/Aβ)-producing AD cell model using a high-throughput toxicity assay. Lead compounds were further evaluated for their effects on neurodegeneration, …

Beta-Band Modulation Reveals The Cortical Dynamics Of Auditory Statistical Learning In Children, Jarrad A.G Lum, Christine N. Moreau, Li Ann Leow, Welber Marinovic, Sarah J. Lum, Marc F. Joanisse, Laura J. Batterink

Research outputs 2022 to 2026

Children's ability to extract statistical regularities from speech is considered fundamental to lexical, syntactic, and grammatical development. However, the neural oscillatory mechanisms supporting this process in childhood remains poorly understood. While beta-band oscillations have been linked to statistical learning in visual and motor domains, it is unclear whether similar dynamics support auditory statistical learning in children. In this study, we recorded electroencephalography (EEG) from children aged 8–12 years as they listened to a continuous stream of trisyllabic nonwords (e.g., dapiku), where syllable order within each nonword was fixed (high predictability), but transitions between nonwords were variable (low predictability). Beta power …