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Full-Text Articles in Medical Sciences

The Associations Between Sleep Environment Factors And Sleep Health In Individuals Living With Neurological Conditions, Mitchell Turner, Laws, Madeline Griffiths, Travis Cruickshank Jan 2026

The Associations Between Sleep Environment Factors And Sleep Health In Individuals Living With Neurological Conditions, Mitchell Turner, Laws, Madeline Griffiths, Travis Cruickshank

Research outputs 2022 to 2026

Objectives: To explore associations between air temperature and light in the sleeping environment and sleep health in individuals with neurological conditions. Methods: The sleep health of 46 individuals with neurological conditions (mean age 51.37 ± 14.24 years; 20 males, 26 females) was measured using the Sleep Health Index (SHI). Air temperature and light data were captured across seven days using a light/temperature data logger positioned next to the participant’s bed. Data recorded during the participants’ sleeping periods (determined using a sleep diary) were analyzed. Linear regression models were used to assess the associations between air temperature and light and sleep …


Deep Reinforcement Learning–Driven Multi-Omics Integration For Constructing Gtage: A Novel Aging Clock From Igg N-Glycome And Blood Transcriptome, Yao Xia, Syed Mohammed Shamsul Islam, Xingang Li, Abdul Baten, Xuerui Tan, Wei Wang Jan 2026

Deep Reinforcement Learning–Driven Multi-Omics Integration For Constructing Gtage: A Novel Aging Clock From Igg N-Glycome And Blood Transcriptome, Yao Xia, Syed Mohammed Shamsul Islam, Xingang Li, Abdul Baten, Xuerui Tan, Wei Wang

Research outputs 2022 to 2026

Previous studies have demonstrated that the immunoglobulin G (IgG) N-glycome and transcriptome are potential biochemical signatures of chronological and biological ages, and several aging clocks have been developed. By integrating the IgG N-glycome and transcriptome, we propose a novel aging clock, gtAge. We developed a deep reinforcement learning-based multiomics integration method called AlphaSnake. The results showed that AlphaSnake achieved a predicted coefficient of determination (R2) value of 0.853, outperforming the concatenation-based integration method (R2 = 0.820). The gtAge estimated by AlphaSnake explained up to 85.3% of the variance in chronological age, which was higher than that in …


Multiparametric Flow Cytometry Immune Profiling Of Pulmonary And Extra-Pulmonary Tuberculosis Reveals Distinct Blood-Based Biomarker Signatures, Kalaiarasan Ellappan, Prakash Babu Narasimhan, Harriet N. Garlant, Seshadri Vasan, Komal Jain, Saka Vinod Kumar, Vishnukanth Govindaraj, Vir Singh Negi, Karen E. Kempsell Jan 2026

Multiparametric Flow Cytometry Immune Profiling Of Pulmonary And Extra-Pulmonary Tuberculosis Reveals Distinct Blood-Based Biomarker Signatures, Kalaiarasan Ellappan, Prakash Babu Narasimhan, Harriet N. Garlant, Seshadri Vasan, Komal Jain, Saka Vinod Kumar, Vishnukanth Govindaraj, Vir Singh Negi, Karen E. Kempsell

Research outputs 2022 to 2026

This study investigated immune cell distributions, cell-specific immune markers, and selected biomarker targets in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) using multiparametric flow cytometry (MFC). Whole blood was collected from 45 individuals, including healthy controls (HC), EPTB, and PTB patients (n = 15/group). Peripheral blood leukocytes were analysed by MFC to characterize CD4+ and CD8+ T cells, natural killer (NK), invariant NKT (iNKT) and NKT cells, classical (CM), intermediate (IM) and non-classical monocytes (NCM), and activated monocytes (AM). Expression of GBP1, CALCOCO2, IFIT3, SNX10, ARG1, PD-1, and PD-L1 was assessed across these immune subsets. Increased frequencies of NK, NKT, …


Meta-Analysis Of Dna Methylation Aging Signatures In 17 Human Tissues, Macsue Jacques, Kirsten Seale, Sarah Voisin, Anna Lysenko, Robin Grolaux, Bernadette Jones-Freeman, Severine Lamon, Mandhri Abeysooriya, Itamar Levinger, Carlie Bauer, Adam P. Sharples, Aino Heikkinen, Elina Sillanpaa, Miina Ollikainen, Cassandra Smith, James R. Broatch, Navabeh Zarekookandeh, Linn Gillberg, Ida Blom, Jesse R. Poganik, Mahdi Moqri, Vadim N. Gladyshev, Matthew Taper, Cassandra Malecki, Sean Lal, Nathalie Saurat, Steve Horvath, Andrew Teschendorff, Nir Eynon Jan 2026

Meta-Analysis Of Dna Methylation Aging Signatures In 17 Human Tissues, Macsue Jacques, Kirsten Seale, Sarah Voisin, Anna Lysenko, Robin Grolaux, Bernadette Jones-Freeman, Severine Lamon, Mandhri Abeysooriya, Itamar Levinger, Carlie Bauer, Adam P. Sharples, Aino Heikkinen, Elina Sillanpaa, Miina Ollikainen, Cassandra Smith, James R. Broatch, Navabeh Zarekookandeh, Linn Gillberg, Ida Blom, Jesse R. Poganik, Mahdi Moqri, Vadim N. Gladyshev, Matthew Taper, Cassandra Malecki, Sean Lal, Nathalie Saurat, Steve Horvath, Andrew Teschendorff, Nir Eynon

Research outputs 2022 to 2026

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD+ metabolism, supporting NAD+ as a potential therapeutic target in …


Insulin Resistance As A Mediator Of Physical Activity's Effects On Beta-Amyloid Accumulation And Tau Phosphorylation: A Scoping Review, Michael G. Slee, Joanne Scotney, Stephanie R. Rainey-Smith, Kirk I. Erickson, Hamid R. Sohrabi, Giuseppe Verdile, Belinda M. Brown Jan 2026

Insulin Resistance As A Mediator Of Physical Activity's Effects On Beta-Amyloid Accumulation And Tau Phosphorylation: A Scoping Review, Michael G. Slee, Joanne Scotney, Stephanie R. Rainey-Smith, Kirk I. Erickson, Hamid R. Sohrabi, Giuseppe Verdile, Belinda M. Brown

Research outputs 2022 to 2026

Background Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective …


Plasma Aβ42/40 Predicts Progression From Aβ-Amyloid Negative To Positive Pet Scans, Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Canovas, Simon M. Laws, Tenielle Porter, Kun Huang, Christopher Fowler, Ralph N. Martins, Paul Maruff, Hamid R. Sohrabi, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Randall J. Bateman, Yan Li, Ovod Vitaliy, Larry Ward, Jurgen Mejan-Fripp, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe Jan 2026

Plasma Aβ42/40 Predicts Progression From Aβ-Amyloid Negative To Positive Pet Scans, Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Canovas, Simon M. Laws, Tenielle Porter, Kun Huang, Christopher Fowler, Ralph N. Martins, Paul Maruff, Hamid R. Sohrabi, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Randall J. Bateman, Yan Li, Ovod Vitaliy, Larry Ward, Jurgen Mejan-Fripp, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Background The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether this reflects Aβ changes in plasma before PET-detectable. Objectives To assess the influence of Aβ42/40 positivity on risk of progression to Aβ PET positivity, and feasibility of using plasma Aβ42/40 tests to enrich a primary prevention trial. Design A prospective longitudinal cohort study. Setting Participants of Australian Imaging, Biomarkers and Lifestyle study (AIBL), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and Open Access Series of Imaging Studies 3 (OASIS3). …


Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando Jan 2026

Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer’s disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial–SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most …


Prevalence Of Dementia In Selected Middle East And North Africa (Mena) Countries: A Systematic Review And Meta-Analysis, Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C.M. Stephan, Ali Chaari, Hamid R. Sohrabi Jan 2026

Prevalence Of Dementia In Selected Middle East And North Africa (Mena) Countries: A Systematic Review And Meta-Analysis, Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C.M. Stephan, Ali Chaari, Hamid R. Sohrabi

Research outputs 2022 to 2026

Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta-analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI). Fifty-two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia …


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 Jan 2026

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 …


Unraveling The Significance Of Fecal Microrna Profile In Alzheimer’S Disease, Kavisha Katuwawala, Prashant Bharadwaj, Ian Martins, B. G.D.N.K. De Silva, Vincent Ho, Asiri Dissanayake, Ralph N. Martins, W. M.A.D.Binosha Fernando Jan 2026

Unraveling The Significance Of Fecal Microrna Profile In Alzheimer’S Disease, Kavisha Katuwawala, Prashant Bharadwaj, Ian Martins, B. G.D.N.K. De Silva, Vincent Ho, Asiri Dissanayake, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), a complex neurodegenerative disorder characterised by progressive cognitive decline, affects millions globally. With no current cure, treatment focuses on symptom management and slowing disease progression. Early identification is therefore crucial. Fecal microRNA (miRNA) analysis is emerging as a promising non-invasive diagnostic tool. Evidence suggests that miRNAs present in fecal samples may regulate gene expression linked to AD pathology, impacting cellular functions and disease progression. Dietary factors critically influence gut microbiota composition and diversity, affecting brain health via the gut brain axis. Macronutrients such as carbohydrates, proteins, and fats modulate miRNA expression and gut microbiota, influencing AD risk. …


Exploring The Mechanisms Of Tanshinone Iia In The Treatment Of Intracranial Aneurysm Based On Network Pharmacology And Machine Learning, Wanqi Wang, Lois Balmer, Shaotao Weng Jan 2026

Exploring The Mechanisms Of Tanshinone Iia In The Treatment Of Intracranial Aneurysm Based On Network Pharmacology And Machine Learning, Wanqi Wang, Lois Balmer, Shaotao Weng

Research outputs 2022 to 2026

Background Intracranial aneurysm (IA) is a cerebrovascular disease with high mortality and limited treatment options. Tanshinone IIA (Tan IIA), a bioactive compound from Salvia miltiorrhiza , has shown vascular protective effects, but its mechanism in the treatment of IA remains unclear. Methods The GSE75436 dataset was used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-related modules. IA targets were obtained from GeneCards and the Comparative Toxicogenomics Database (CTD). Potential targets of Tan IIA were predicted using TCMSP, SwissTargetPrediction, and SymMap. KEGG enrichment analysis was conducted for DEGs, WGCNA modules, disease-related genes, …


Caveolin 1 And 2 Enhance The Proliferative Capacity Of Bcam-Positive Corneal Progenitors, Yuzuru Sasamoto, Shoko Kiritoshi, Catherine A.A. Lee, Yoshiko Fukuda, Gabrielle Martin, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank Dec 2025

Caveolin 1 And 2 Enhance The Proliferative Capacity Of Bcam-Positive Corneal Progenitors, Yuzuru Sasamoto, Shoko Kiritoshi, Catherine A.A. Lee, Yoshiko Fukuda, Gabrielle Martin, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank

Research outputs 2022 to 2026

Caveolin (CAV) 1 and 2 are integral membrane proteins that constitute major components of small membrane pouches termed caveolae. While several functions have been described in other tissues, the roles of CAV1 and CAV2 in the ocular surface have remained unknown. In the current study, we investigated the expression and function of CAV1 and CAV2 in the human cornea. We found CAV1 and CAV2 to be preferentially expressed by proliferative Basal Cell Adhesion Molecule (BCAM)-positive progenitor cells along the entire limbal and corneal basal epithelial layer. Functional gene knockdown studies reveal that BCAM, BCAM co-expressed Laminin α5 (LAMA5) and Laminin …


Profiling Of Igg N-Glycosylation For Axial Spondyloarthritis And Other Rheumatic Diseases, Xiaojia Xu, Zhixian Chen, Manshu Song, Zhiduo Hou, Lois Balmer, Chunbin Zhou, Yayi Huang, Haifeng Hou, Wei Wang, Ling Lin Dec 2025

Profiling Of Igg N-Glycosylation For Axial Spondyloarthritis And Other Rheumatic Diseases, Xiaojia Xu, Zhixian Chen, Manshu Song, Zhiduo Hou, Lois Balmer, Chunbin Zhou, Yayi Huang, Haifeng Hou, Wei Wang, Ling Lin

Research outputs 2022 to 2026

Background: Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease with challenges in diagnosis and disease activity assessment. While alterations in immunoglobulin G (IgG) N-glycosylation have been observed in varied rheumatic diseases, those in axSpA remains unclear. This study aims to explore the role of IgG N-glycan profiles in diagnosis and disease activity of axSpA. Methods: A clinical case-control study was conducted involving patients with axSpA (n = 138), systemic lupus erythematosus (n = 102), rheumatoid arthritis (n = 106), osteoarthritis (n = 33), gout (n = 41) and healthy controls (n = 117). Ultra-performance liquid chromatography was employed to analyze …


Alzheimer’S Disease Biological Pet Staging Using Plasma P217+Tau, Azadeh Feizpour, Vincent Doré, Natasha Krishnadas, Pierrick Bourgeat, James D. Doecke, Ziad S. Saad, Gallen Triana-Baltzer, Simon M. Laws, Rosita Shishegar, Kun Huang, Christopher Fowler, Larry Ward, Colin Masters, Jurgen Fripp, Hartmuth Kolb, Victor Villemagne, Christopher Rowe Dec 2025

Alzheimer’S Disease Biological Pet Staging Using Plasma P217+Tau, Azadeh Feizpour, Vincent Doré, Natasha Krishnadas, Pierrick Bourgeat, James D. Doecke, Ziad S. Saad, Gallen Triana-Baltzer, Simon M. Laws, Rosita Shishegar, Kun Huang, Christopher Fowler, Larry Ward, Colin Masters, Jurgen Fripp, Hartmuth Kolb, Victor Villemagne, Christopher Rowe

Research outputs 2022 to 2026

Background: Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s disease (AD) neuropathology. However, their ability to substitute for tau PET to identify AD biological stage is unclear. Methods: Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, 18F-NAV4694 Aβ-PET (A) and 18F-MK6240 tau-PET (T) data. Biological PET stages were defined according to the Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease (2024): Initial (A + T-), Early (A + TMTL +), Intermediate (A + TMOD +), and Advanced (A + THIGH +). The threshold for A+ was 25 …


Summarizing Attributable Factors And Evaluating Risk Of Bias Of Mendelian Randomization Studies For Alzheimer’S Dementia And Cognitive Status: A Systematic Review And Meta-Analysis, Xiaoni Meng, Xiaochun Li, Meiling Cao, Jing Dong, Haotian Wang, Weijie Cao, Di Liu, Youxin Wang Dec 2025

Summarizing Attributable Factors And Evaluating Risk Of Bias Of Mendelian Randomization Studies For Alzheimer’S Dementia And Cognitive Status: A Systematic Review And Meta-Analysis, Xiaoni Meng, Xiaochun Li, Meiling Cao, Jing Dong, Haotian Wang, Weijie Cao, Di Liu, Youxin Wang

Research outputs 2022 to 2026

Background: No effective treatment is available to delay or reverse the onset and progression of Alzheimer’s dementia (AD). Mild cognitive impairment, a clinical state between normal aging and AD, may offer the proper window for AD intervention and treatment. This systematic review aimed to summarize evidence from Mendelian randomization (MR) studies exploring factors attributable to AD and related cognitive status and to assess its credibility. Methods: We searched PubMed, Embase, MEDLINE, and the Cochrane Library to identify MR studies investigating the associations between any factor and AD and related cognitive status. The risk of bias in MR studies was evaluated …


Development And Validation Of An Interpretable Risk Prediction Model For The Early Classification Of Thalassemia, Jin Xin Lai, Jia Wei Tang, Shan Shan Gong, Ming Xiong Qin, Yu Lu Zhang, Quan Fa Liang, Li Yan Li, Zhen Cai, Liang Wang Dec 2025

Development And Validation Of An Interpretable Risk Prediction Model For The Early Classification Of Thalassemia, Jin Xin Lai, Jia Wei Tang, Shan Shan Gong, Ming Xiong Qin, Yu Lu Zhang, Quan Fa Liang, Li Yan Li, Zhen Cai, Liang Wang

Research outputs 2022 to 2026

Thalassemia is an inherited blood disorder. Current diagnostic methods mainly rely on sophisticated equipment and specifically trained technicians. This study aims to identify and genotype thalassemia by applying machine learning (ML) algorithms to routine blood parameters. This study recruited a derivation cohort of 31,311 individuals from four independent hospitals and developed eight machine learning (ML) models for the purpose. The performance of these models was compared using a set of evaluation metrics. An additional cohort of 2000 patients was recruited for external validation to assess the generalization of the models. The results demonstrated that the categorical boosting (CatBoost) model exhibited …


Relationship Between Cytomegalovirus Antibody Levels And Cognitive Performance Is Dependent On Age And Genetic Risk, Michael Vacher, Silvia Lee, Patricia Price, Phuongnhi Ha, Shelley Waters, Simon M. Laws Dec 2025

Relationship Between Cytomegalovirus Antibody Levels And Cognitive Performance Is Dependent On Age And Genetic Risk, Michael Vacher, Silvia Lee, Patricia Price, Phuongnhi Ha, Shelley Waters, Simon M. Laws

Research outputs 2022 to 2026

Human cytomegalovirus (CMV) is endemic worldwide. It is often acquired in childhood and persists throughout adult life. CMV is linked with several diseases of aging, but associations with cognitive performance are not consistent. Here we address whether this may reflect a dependence on putative genetic determinants, Apolipoprotein E (APOE) ε4 and Tumour Necrosis Factor (TNF), and/or the age of the subjects tested. CMV-reactive antibodies were quantitated in 419 individuals aged 71.7 [53.2—89.1] years, drawn from the Australian Imaging, Biomarker & Lifestyle (AIBL) study. Cognitive composite scores, covering five domains, a global score of cognitive performance, brain amyloid-β (Aβ) burden and …


What Are The Optimal Transcranial Direct Current Stimulation Parameters And Design Elements To Modulate Corticospinal Excitability? A Systematic Review And Longitudinal Meta-Analysis, Liam C. Tapsell, Matheus D. Pinto, Ann Maree Vallence, Casey Whife, Maria Luciana Perez Armendariz, Shaswat Senger, Jack Andringa-Bate, Dana Hince, Myles C. Murphy Dec 2025

What Are The Optimal Transcranial Direct Current Stimulation Parameters And Design Elements To Modulate Corticospinal Excitability? A Systematic Review And Longitudinal Meta-Analysis, Liam C. Tapsell, Matheus D. Pinto, Ann Maree Vallence, Casey Whife, Maria Luciana Perez Armendariz, Shaswat Senger, Jack Andringa-Bate, Dana Hince, Myles C. Murphy

Research outputs 2022 to 2026

Background: Corticospinal excitability, measured by motor-evoked potentials (MEPs), is often impaired in neurological and musculoskeletal conditions. Transcranial direct current stimulation (tDCS) can modulate cortical excitability and improve clinical outcomes, yet inconsistencies in parameter settings complicate identification of optimal protocols. Objective: Our primary objective was to examine the effects of: (i) stimulation polarity, (ii) duration, (iii) intensity, (iv) frequency, (v) electrode montage, and (vi) electrode design (size/shape) on MEP size. Methods: Nine databases were searched from inception to 24th November 2023. We identified 84 individual cohorts (1,709 participants) and assessed time-dependent effects of each parameter on M1 MEP-to-baseline ratio in healthy …


Mitochondrial Methylcytosines As Blood-Based Biomarkers For Alzheimer's Disease Dementia Prognosis, Jordi Gascón-Bayarri, Jose Luis Mosquera, Marta Blanch, Pau Martí, Beatriz Fontal, Carla Trapero, Nuria Rojo, Inma Rico, Jaume Campdelacreu, Cristopher Fowler, Simon M. Laws, Adrià Tort-Merino, Raquel Sanchez-Valle, Joan Bello, Juan Fortea, Alberto Lleó, Courosh Mehanian, Russell H. Swerdlow, Ramón Reñé-Ramírez, Marta Barrachina Sep 2025

Mitochondrial Methylcytosines As Blood-Based Biomarkers For Alzheimer's Disease Dementia Prognosis, Jordi Gascón-Bayarri, Jose Luis Mosquera, Marta Blanch, Pau Martí, Beatriz Fontal, Carla Trapero, Nuria Rojo, Inma Rico, Jaume Campdelacreu, Cristopher Fowler, Simon M. Laws, Adrià Tort-Merino, Raquel Sanchez-Valle, Joan Bello, Juan Fortea, Alberto Lleó, Courosh Mehanian, Russell H. Swerdlow, Ramón Reñé-Ramírez, Marta Barrachina

Research outputs 2022 to 2026

Alzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to ADD (P), MCI remained stable (NP), and Cognitively Normal (CN) individuals. Differentially methylated sites were identified in the D-loop region in both CN vs. NP and NP vs. P comparisons, even before β-amyloid positivity. A Random Forest model was developed using mtDNA methylation data combined with cognitive and risk factor features. Model's performance was assessed by cross-validation and tested on …


Moderate Coffee And Tea Consumption Is Associated With Slower Cognitive Decline, Stephanie R. Rainey-Smith, Kelsey R. Sewell, Belinda M. Brown, Hamid R. Sohrabi, Ralph N. Martins, Samantha L. Gardener Sep 2025

Moderate Coffee And Tea Consumption Is Associated With Slower Cognitive Decline, Stephanie R. Rainey-Smith, Kelsey R. Sewell, Belinda M. Brown, Hamid R. Sohrabi, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Background: Globally, coffee and tea are consumed extensively, potentially providing neuroprotection through anti-inflammatory and antioxidative stress effects. Objective: This study aimed to investigate associations between coffee and tea intake and cognitive function. Methods: In a longitudinal prospective cohort study, dementia-free (n = 8715; age range 60.0–85.2 years) older adults from the UK Biobank self-reported coffee and tea intake over the previous year; ‘never’, ‘moderate’ (1–3 cups/day), or ‘high’ (≥4 cups/day). Participants completed cognitive assessments at ≥2 timepoints (mean of 9.11 years). Results: Those ‘never’ consuming coffee and ‘moderate’ coffee consumers (β = 0.06, p = 0.005; β = 0.07, p <  0.001, respectively), as well as ‘moderate’ tea consumers and ‘high’ tea consumers (β = 0.06, p = 0.009; β = 0.06, p = 0.003, respectively) had slower fluid intelligence decline. Additionally, those ‘never’ consuming coffee and ‘moderate’ coffee consumers had a slower increase in pairs matching errors (β = −0.05, p = 0.022; β = 0.05, p = 0.013) compared to ‘high’ consumers. Conclusions: ‘Moderate’ coffee, and ‘moderate’ and ‘high’ tea intake may be a protective factor against cognitive decline. Randomized controlled trials are required to establish causal relationships leading to evidence-based recommendations regarding benefits of coffee and tea intake.


Combining Lumipulse P-Tau217 And Aβ42/40 As Confirmatory Tests For Aβ Positivity Prior To Disease-Modifying Therapy, James D. Doecke, Ahmed Chenna, Mintzu Lo, Youssouf Badal, Brandon Yee, Robert Martone, Christos Petropoulos, Christopher J. Fowler, Simon Laws, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, John Winslow Sep 2025

Combining Lumipulse P-Tau217 And Aβ42/40 As Confirmatory Tests For Aβ Positivity Prior To Disease-Modifying Therapy, James D. Doecke, Ahmed Chenna, Mintzu Lo, Youssouf Badal, Brandon Yee, Robert Martone, Christos Petropoulos, Christopher J. Fowler, Simon Laws, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher C. Rowe, Colin L. Masters, John Winslow

Research outputs 2022 to 2026

Introduction: For a blood-based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (Aβ) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests. Methods: In the current study we assessed the ability of phosphorylated tau (p-tau)217 and Aβ42/40 from the Lumipulse G p-tau217 and β-amyloid ratio (1-42/1-40) tests, individually and combined, to predict Aβ positron emission tomography status in two sub-cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Results: Testing an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for …


A Large-Scale Multi-Centre Study Characterising Atrophy Heterogeneity In Alzheimer's Disease, Vikram Venkatraghavan, Damiano Archetti, Pierrick Bourgeat, Chenyang Jiang, Mara Ten Kate, Anna C. Van Loenhoud, Rik Ossenkoppele, Charlotte E. Teunissen, Elsmarieke Van De Giessen, Yolande A.L. Pijnenburg, Giovanni B. Frisoni, Béla Weiss, Zoltán Vidnyánszky, Tibor Auer, Stanley Durrleman, Alberto Redolfi, Simon M. Laws, Paul Maruff, Neil P. Oxtoby, Andre Altmann, Daniel C. Alexander, Wiesje M. Van Der Flier, Frederik Barkhof, Betty M. Tijms Sep 2025

A Large-Scale Multi-Centre Study Characterising Atrophy Heterogeneity In Alzheimer's Disease, Vikram Venkatraghavan, Damiano Archetti, Pierrick Bourgeat, Chenyang Jiang, Mara Ten Kate, Anna C. Van Loenhoud, Rik Ossenkoppele, Charlotte E. Teunissen, Elsmarieke Van De Giessen, Yolande A.L. Pijnenburg, Giovanni B. Frisoni, Béla Weiss, Zoltán Vidnyánszky, Tibor Auer, Stanley Durrleman, Alberto Redolfi, Simon M. Laws, Paul Maruff, Neil P. Oxtoby, Andre Altmann, Daniel C. Alexander, Wiesje M. Van Der Flier, Frederik Barkhof, Betty M. Tijms

Research outputs 2022 to 2026

Previous studies identified atrophy-based Alzheimer's disease(AD) subtypes linked to distinct clinical symptoms, but their consistency across subtyping approaches remains unclear. This large-scale study evaluates subtype concordance using two data-driven approaches. In this work, we analyzed data from n=10,011 patients across 10 AD cohorts spanning Europe, the US, and Australia, extracting regional volumes using Freesurfer. To characterize atrophy heterogeneity in the AD continuum, we developed a two-step approach, Snowphlake (Staging NeurOdegeneration With PHenotype informed progression timeLine of biomarKErs), to identify subtypes and atrophy-event sequences within each subtype. Results were compared with SuStaIn (Subtype and Stage Inference), which jointly estimates subtypes and …


Blood Biomarkers Of Alzheimer's Disease In Australians Habitually Consuming Various Plant-Based Diets, Shaun Eslick, Grace Austin, Jessica J.A. Ferguson, Manohar L. Garg, Christopher Oldmeadow, Ralph N. Martins Aug 2025

Blood Biomarkers Of Alzheimer's Disease In Australians Habitually Consuming Various Plant-Based Diets, Shaun Eslick, Grace Austin, Jessica J.A. Ferguson, Manohar L. Garg, Christopher Oldmeadow, Ralph N. Martins

Research outputs 2022 to 2026

Background: Evidence suggests that plant-based diets (PBDs) may be protective against neurodegenerative diseases such as Alzheimer's disease (AD). Objective: This study examined associations between blood-based AD biomarkers in individuals 30–75 years without current or diagnosed cardiovascular disease following different PBDs versus regular meat-eating diets (RMEs). Methods: This secondary analysis of the Plant-based Diets study measured Aβ1–42/Aβ1–40, p-tau181, NFL, and GFAP in 237 plasma samples using SIMOA from individuals following vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or RME diets. Multivariable regression adjusted for age and sex. Results: Following adjustments for age and sex, plasma Aβ1–42/Aβ1–40ratio was significantly higher in …


Ocular Changes As Potential Biomarkers For Early Diagnosis Of Alzheimer's Disease, Purna Chandra Poudel, Shaun M. Frost, Shaun Eslick, Hamid R. Sohrabi, Kevin Taddei, Eugene Hone, Ralph N. Martins Aug 2025

Ocular Changes As Potential Biomarkers For Early Diagnosis Of Alzheimer's Disease, Purna Chandra Poudel, Shaun M. Frost, Shaun Eslick, Hamid R. Sohrabi, Kevin Taddei, Eugene Hone, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. AD diagnosis often involves a thorough assessment, including clinical evaluation, cognitive testing, medical history examination, genetic testing, and biomarker analysis. Currently, the invasive nature and high costs of biomarker testing, such as cerebrospinal fluid analysis and neuroimaging, have limited the early detection and intervention of the disease. Therefore, researchers have explored cheaper and less invasive options, such as ocular imaging. This review discusses the close relationship between the eye and the central nervous system and ocular changes as a potential non-invasive AD biomarker. Ocular changes …


The Role Of Diet In Moderating The Relationship Between Symptoms Of Depression And Brain Amyloid Load, Hilal Salim Said J. Al Shamsi, Samantha L. Gardener, Stephanie R. Rainey-Smith, Hamid R. Sohrabi, Kevin C.M. Taddei, Colin L. Masters, Vincent M. Doré, Christopher L. Rowe, W. M.A.D.Binosha Fernando, Ralph N. Martins Aug 2025

The Role Of Diet In Moderating The Relationship Between Symptoms Of Depression And Brain Amyloid Load, Hilal Salim Said J. Al Shamsi, Samantha L. Gardener, Stephanie R. Rainey-Smith, Hamid R. Sohrabi, Kevin C.M. Taddei, Colin L. Masters, Vincent M. Doré, Christopher L. Rowe, W. M.A.D.Binosha Fernando, Ralph N. Martins

Research outputs 2022 to 2026

Background: Healthy lifestyle factors, including diet, may affect brain amyloid beta (Aβ) load. This study examines dietary patterns as moderators of the relationships among symptoms of depression, anxiety, and brain Aβ load. Method: A cross-sectional study of cognitively unimpaired older adults (n = 524) from the Australian Imaging, Biomarkers, and Lifestyle study assessed dietary patterns, depressive and anxiety symptoms, and brain Aβ load. Moderation and simple slope analyses were conducted. Results: The Dietary Approaches to Stop Hypertension (DASH) diet moderated the relationship between depressive and anxiety symptoms and brain Aβ load. Higher symptoms were associated with greater Aβ load in …


Atopy-Related Immune Profiles Are Subject To Genetic Influence As Evaluated Using School-Aged Twin Pairs, Jonatan Leffler, James F. Read, Danny Mok, Michael Serralha, Anthony Bosco, Patrick G. Holt, Richard Saffery, Deborah H. Strickland Jul 2025

Atopy-Related Immune Profiles Are Subject To Genetic Influence As Evaluated Using School-Aged Twin Pairs, Jonatan Leffler, James F. Read, Danny Mok, Michael Serralha, Anthony Bosco, Patrick G. Holt, Richard Saffery, Deborah H. Strickland

Research outputs 2022 to 2026

The interaction of genetic and environmental contributions to immunological traits and their association with atopic disease remain unclear. Flow cytometry and in vitro cytokine responses were used to characterize immune profiles from 93 school-aged twin pairs. Using an established twin pair analytical strategy, the genetic and environmental influences on immunological traits were evaluated, along with their association with atopy. Our findings suggest strong genetic influence on several traits, particularly B cell abundance. In contrast, cytokine responses from in vitro stimulations appeared mainly shaped by environmental exposures. Regarding associations with atopy, greater abundance of both B cells and basophils were observed …


The Therapeutic Potential Of Butyrate And Lauric Acid In Modulating Glial And Neuronal Activity In Alzheimer’S Disease, Rathnayaka Mudiyanselage Uththara Sachinthanie Senarath, Lotta E. Oikari, Prashant Bharadwaj, Vijay Jayasena, Ralph N. Martins, Wanakulasuriya Mary Ann Dipika Binosha Fernando Jul 2025

The Therapeutic Potential Of Butyrate And Lauric Acid In Modulating Glial And Neuronal Activity In Alzheimer’S Disease, Rathnayaka Mudiyanselage Uththara Sachinthanie Senarath, Lotta E. Oikari, Prashant Bharadwaj, Vijay Jayasena, Ralph N. Martins, Wanakulasuriya Mary Ann Dipika Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim …


Amyloid Accumulation, Brain Atrophy, And Cognitive Decline In Emergent Alzheimer's Disease, Ying Xia, Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, Yen Ying Lim, Simon M. Laws, Christopher Fowler, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff Jul 2025

Amyloid Accumulation, Brain Atrophy, And Cognitive Decline In Emergent Alzheimer's Disease, Ying Xia, Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, Yen Ying Lim, Simon M. Laws, Christopher Fowler, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff

Research outputs 2022 to 2026

Introduction : Emergent Alzheimer's disease (AD) represents a transitional stage where cognitively unimpaired (CU) individuals exhibit subthreshold but increasing amyloid-β (Aβ) levels. The impact of Aβ accumulation on brain volume loss and cognition during this early stage remains unclear. Methods: This retrospective cohort study analyzed data from 408 CU participants who were initially Aβ− (< 15 Centiloids) and followed for up to 15 years. Changes in basal forebrain and hippocampal volume, along with domain-specific cognitive performance, were compared between those who progressed to Aβ+ (≥20 Centiloids) and those who remained Aβ−. Results: Sixty-five CU participants progressed to Aβ+, indicating emergent AD, and showed faster Aβ accumulation and subtle memory decline. However, no significant differences in rate of BF and hippocampal atrophy were observed between groups. Discussion: The results suggest that during this emergent phase of AD, Aβ accumulation is associated with episodic memory loss, in the absence of detectable accelerated brain atrophy. Highlights: Identified cognitively unimpaired individuals in the emergent stage of Alzheimer's disease (AD). Emergent AD exhibits a greater rate of amyloid-β (Aβ) accumulation. No accelerated volume loss detected in the basal forebrain or hippocampus. Emergent AD is also associated with a subtle decline in memory. Early Aβ accumulation may impair cognitive function before structural atrophy.


Longitudinal Associations Between Self-Reported Exercise Levels And Cognition In Adad, Kelsey R. Sewell, James D. Doecke, Ralph N. Martins, Stephanie R. Rainey-Smith, Jeremiah Peiffer, Samantha L. Gardener, Hamid R. Sohrabi, Kirk I. Erickson, Belinda M. Brown Jun 2025

Longitudinal Associations Between Self-Reported Exercise Levels And Cognition In Adad, Kelsey R. Sewell, James D. Doecke, Ralph N. Martins, Stephanie R. Rainey-Smith, Jeremiah Peiffer, Samantha L. Gardener, Hamid R. Sohrabi, Kirk I. Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Introduction: This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset. Methods: Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months. Results: Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not …


Baseline Habitual Dietary Nitrate Intake And Alzheimer's Disease Related Neuroimaging Biomarkers In The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Anjana Rajendra, Nicola P. Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Vincent Doré, Victor L. Villemagne, Simon M. Laws, Belinda M. Brown, Kevin Taddei, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Jonathan M. Hodgson, Catherine P. Bondonno Jun 2025

Baseline Habitual Dietary Nitrate Intake And Alzheimer's Disease Related Neuroimaging Biomarkers In The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Anjana Rajendra, Nicola P. Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Vincent Doré, Victor L. Villemagne, Simon M. Laws, Belinda M. Brown, Kevin Taddei, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Jonathan M. Hodgson, Catherine P. Bondonno

Research outputs 2022 to 2026

Background: Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia. Objective: Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD). Participants: Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline. Methods: Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates …