Professor EmeritusJames Vickers

Project Total: $65,120; This NHMRC CRE brings together a range of researchers from across Australia with expertise in biomedical studies of Alzheimer's disease to work collaboratively towards new insights and therapeutic approaches for this neurodegenerative condition. Subproject: Multi-omic approaches have greatly improved our understanding of the molecular landscape of the nervous system, helping us understand how neurons have different vulnerabilities in neurodegenerative disease. However, significantly less research has sought to understand neurodegeneration in different subcellular compartments, in part due to the technical challenge of isolating RNA from the neuronal axon, a structure that in vivo can be meters long. The development of compartmented microfluid chambers has enabled the unbiassed profiling of the axonal transcriptome from cultured neurons. By combining these techniques with induced pluripotent stem cells (iPSC), we have developed a microfluidic model of acute neurodegeneration that recapitulates many of the morphological traits that are seen in axons in neurodegenerative disease. Using this model with unaffected donor-specific iPSCs, we have performed the first transcriptomic and proteomic screen of isolated human axons over a time course of degeneration, identifying key pathways such as mitochondria, GTPases, and exocytosis. Here we will advance this technique further using chronic and less aggressive models of neurodegeneration related to dementia, such as familial gene variants (and corrected controls) available in our laboratory, to build a pipeline for analysis of proteomic and transcriptomic alterations. It is our goal that future technique development will include a third omic analysis using high-content imaging (cell painting) techniques to quantify alterations in axonal organelles and other structural features. Funded by: National Health & Medical Research CouncilNational Health & Medical Research Council - MIND-AD CRE Grant; University of Queensland; University of Tasmania.

Project Total: $85,000; Every Australian deserves to age well. Dementia is a considerable threat to quality of life and is set to become the leading cause of death in Australia, yet we are not harnessing existing evidence for dementia risk reduction effectively. We know around 40% of dementia cases can be prevented by addressing modifiable risk factors and we know that individuals respond stronger to personal information than aggregated evidence. We know that individuals in longitudinal research projects benefit from receiving personal information, such as digital and biological markers that are indicators of dementia risk, yet we still dont know the best method of presenting this information. This project aims to bridge the gap between knowledge and practice by understanding how people respond to their digital and biological markers of dementia. We will co-design an online dashboard in which to present personal information, alongside personalized evidence-based information to empower individuals to take steps toward positive behavior change. We will engage qualitative (focus groups with community stakeholders, clinicians, participants, researchers, people living with dementia and their caregivers) and quantitative methods (A/B and feasibility testing) to ensure the messaging is presented in a safe, user-friendly and ergonomic fashion. We will then test the impact of revealing this information on wellbeing, self-efficacy and adherence to known modifiable risk factors for dementia. By harnessing personal resonance, we can enact positive behaviour change, improve quality of life and ultimately reduce dementia risk, ensuring Australians can live better for longer. Funded by: Dementia Australia Research Foundation Ltd - Grant-Project ($84,815); University of Tasmania.

Project Total: $14,974; The travel activities proposed for this project are essential to enhance the Hindi, Farsi, and Dari versions of the Preventing Dementia Massive Open Online Course (PD MOOC) tailored for migrants aged 45 and above from India, Iran, and Afghanistan in Australia. Methods include international workshops aimed at refining the PD MOOC through iterative feedback from migrants and health experts, supplemented by pilot testing. Collaboration with the National Brain Research Centre in India and the University of Tehran will focus on refining and culturally adapting the PD MOOC. Participation in relevant conferences will allow us to share findings and address knowledge gaps on dementia risks and prevention strategies among migrant populations. Workshops will be conducted to improve the quality and cultural appropriateness of the PD MOOC, while networking with project stakeholders and collaborators will facilitate effective partnerships. Migrants from these regions often face challenges like lower health literacy due to limited access to education, information, and language barriers, increasing their dementia risk. The PD MOOC, designed to be culturally sensitive, aims to mitigate these challenges by enhancing knowledge and managing modifiable dementia risk factors. Travel to India and Iran is crucial for conducting collaborative workshops necessary to refine the PD MOOC and ensure it meets cultural and linguistic needs. In-person engagement with local experts and migrant communities is essential for enhancing research impact. By prioritizing culturally sensitive approaches, this initiative aims to help public health professionals effectively address dementia risk factors and promote healthier lifestyles among these populations. Funded by: Dementia Australia Research Foundation Ltd - Grant-Travel ($14,974); University of Tasmania.

Project Total: $15,000; Currently, social activity is recommended to reduce dementia risk. However, experiences of socialising are different for people with different personalities, particularly for introverts and extroverts. This makes well-intentioned recommendations to pursue social activity jarring for some people. Feeling lonely increases dementia risk, and so does social isolation, but differences in the impacts of loneliness and social isolation between introverts and extroverts arent yet understood. Loneliness is also yet to be differentiated from social engagement in many contemporary cohort studies investigating dementia risk reduction, including the Wicking Centres large longitudinal Island Project Linking Aging and Neurodegenerative disease (ISLAND). Socialising may also impact dementia risk by influencing health and lifestyle behaviour. For example, friends may encourage each other to go for a run, or instead encourage each other to drink large amounts of alcohol. Physical activity and avoiding excessive alcohol consumption are two behaviours that reduce dementia risk, with others including refraining from cigarette use, undertaking regular GP checkups, and adhering to chronic disease management plans. Social networks could have a positive or negative impact on other dementia risk, depending on the behaviour that is promoted within the network. This phenomenon is referred to as social contagion, and has not yet been investigated in the context of dementia risk reduction. We therefore plan to undertake travel that aims to: Explore personality and perceptions: characterise the impact of personality and loneliness on cognition in the ISLAND project, expanding on the established link between social engagement and cognition Prepare to study propagation: expand our skills and collaborations, building the foundation for project funding to study social contagion of dementia risk factors These travel outcomes will be obtained through three interrelated travel elements: Interstate travel to attend a 1-week in-person social network analysis course: propagation - skills, propagation - collaborations (social network researchers)Intrastate travel to meet in-person with ISLAND project participants to collaboratively design and implement research on personality and loneliness: personality and perceptions design and data, propagation - collaborations (ISLAND participants)Interstate travel to attend, and present at, the Australian Dementia Research Forum: personality and perceptions disseminate findings, propagation collaborations (dementia researchers) Ultimately, we aim to create accurate, sensitive, and individualised recommendations around social engagement for dementia risk reduction. Funded by: Dementia Australia Research Foundation Ltd - Grant-Travel ($15,000); University of Tasmania.

Project Total: $22,943; Dementia is the leading cause of death in Australian women. Intervention and treatment when provided in early dementia can improve the disease trajectory and prolong quality of life. However, early symptoms can vary, posing substantial challenges for clinicians. Symptoms are believed to result from neurological breakdown. This project investigates neuroanatomical differences in previously-collected MRI scans of a large group of Tasmanians either with, or at risk of, dementia, By identifying MRI biomarkers and linking them to specific clinical behaviours or symptoms, the project will optimise MRI scanning and analysis techniques to inform earlier diagnosis and more accurate dementia risk stratification. Funded by: Royal Hobart Hospital Research Foundation - Grant-Project ($22,943); University of Tasmania.

Project Total: $3,000,000; Our mission is to capitalise on our interdisciplinary expertise and access to human brain tissue and a host of experimental systems including worms, mice and human induced pluripotent stem cell (hiPSC)-derived neurons to determine (i) how mitochondria modulate protein aggregation and vice versa, (ii) how they can be manipulated for therapeutic intervention, (iii) how this is best combined with strategies targeting aggregates, and (iv) what feedback mechanisms between mitochondria-de- pendent processes and protein aggregation are at play, using innovative animal experimentation, de-livery methods and computational modelling strategies. Funded by: National Health & Medical Research CouncilNational Health & Medical Research Council - Grant-Centre of Research Excellence; University of Tasmania.

Project Total: $2,035,000; This document outlines how the Wicking Dementia Research and Education Centre (Wicking Centre) as part of the University of Tasmania will continue to develop, deliver and maintain the Equip Aged Care Training Packages currently hosted by the University of Tasmania until June 30th 2027. The Wicking Centre will lead the continuation of the project, with close collaboration from other academic units including the School of Nursing, professional and peak bodies, and the Department of Health and Aged Care. The primary audience will continue to be carers, nurses, and allied health professionals. This tender includes reviewing, updating, developing, delivering and hosting the training modules, as well as supporting the uptake of modules through promotion and marketing. Funded by: Department of Health and Aged Care - Tender ($2,034,998); University of Tasmania.

Project Total: $1,006,412; Alzheimers disease (AD) and Parkinsons disease (PD) start damaging the brain 15-20 years before symptoms begin. At the time of diagnosis, AD and PD are hard to treat because the damage is so severe. We need a way to detect AD and PD much earlier. We will develop a simple new computer test to detect early signs of AD and PD by analysing face and eye movements. Then people can start prevention earlier and scientists can research better treatments to improve peoples quality of life. Funded by: National Health & Medical Research CouncilNational Health & Medical Research Council - Grant-Ideas ($2,012,824); University of Tasmania.

Project Total: $75,000; This funding will support the appointment of a project officer to assist in engagement and outreach components of the ISLAND Project. Funded by: Masonic Medical Research Foundation Limited - Grant-Neurological Diseases Research Program ($75,000); University of Tasmania.

Project Total: $13,660,425; Dementia respite care training: delivering education and training to improve aged care provider capability to deliver quality respite care for people living with dementia, including successful transitions in and out of their respite services, and evaluation of program. Funded by: Department of Health, Disability and Ageing (Cth) - Grant-Improving respite care for people with demen ($13,660,426); University of Tasmania.

Project Total: $75,000; Around 40% of dementia cases are attributable to modifiable risk factors. Lower utilisation of health services and higher rates of chronic health conditions among migrants, factors that are also related to dementia risk, pose a continuing challenge for the health care system in Australia. We will examine the prevalence and correlates of modifiable risk factors for dementia among migrants aged 50 or over from four South Asian countries. Funded by: Dementia Australia Research Foundation Ltd - Grant-Project Grants ($75,000); University of Tasmania ($17,768).

Project Total: $956,328; Probucol, a historic and safe cholesterol-lowering drug, has been shown to supress neurovascular inflammation and support cognitive function. The pleiotropic properties of probucol and significant clinical use experience justifies considering repurposing probucol to test efficacy in supporting cognitive function in patients with Alzheimers Disease (AD). This study is a phase II, randomised, placebo-controlled, double-blind multi-site clinical trial held in Perth, Brisbane, and Hobart. The target sample is 314 adult male and female participants (15-45 from Hobart), aged 18-84 with mild-to-moderate Alzheimers Disease. They will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo for 2 weeks followed by 102weeks of probucol (Lorelco) or placebo. The primary outcome is change in cognitive performance, determined via standardised tests, between baseline and 104-weeks. Secondary outcome measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104-week intervention. Funded by: Medical Research Future Fund; Curtin University ($956,328); University of Tasmania.

Project Total: $446,957; Alzheimer's disease (AD) starts damaging the brain >10 years before memory problems begin. To reduce dementia incidence, we must detect AD earlier so we can target prevention through early clinical trial recruitment and risk reduction (that could prevent 40% cases). With 10,000 available UTAS research participants and 200 patients from RHH and the community, we aim to develop a test to detect early signs of AD by analysing hand- AND speech- movements using a smartphone and machine learning algorithms. Funded by: Royal Hobart Hospital Research Foundation - Grant-Major Project ($446,957); University of Tasmania.

Project Total: $999,998; The proposal has outstanding levels of community engagement. The team has allocated time (milestone indicators) and resources (budget) for extended community engagement at all stages of the project making the proposal highly feasible. Additionally, we have already established relationships with Aboriginal and Torres Strait Islander communities. Tasmanian Aboriginal Centre (TAC) and CI Schramm have assisted with the design of the project and TAC have agreed to host at least one Aboriginal health worker for the duration of this project. In addition, TAC has confirmed the transferability of the skills (e.g. communication, analysis, education design) gained from working on this project are highly desirable for future research and education programs. The incidence of TBI in the Aboriginal and Torres Strait Islander communities is almost twice the national average this means urgent attention is needed to increase awareness and educate. Tasmanian Aboriginal Centre (TAC) has indicated to the research team that brain injury awareness and education are a priority for their communities. Our research proposal aims to not only establish awareness of TBI but also the lived experience of those who have sustained a TBI. Accounts can be captured in their language making the applicability to others in the community stronger. These personal accounts may also identify areas of need for specific educational programs, which are culturally appropriate and can be developed in consultation with the local communities. Funded by: Medical Research Future Fund - Grant - Traumatic Brain Injury Mission ($999,998); University of Tasmania.

Project Total: $25,000; Older Tasmanians undergoing emergency surgery are at high risk of complications and of subsequently needing rehabilitation or nursing home placement following discharge. We will investigate the need for a novel model of shared Geriatric/General Surgery care for older RHH patients, and measure its effect on return to pre-admission residence and in-hospital complications. Funded by: Royal Hobart Hospital Research Foundation - Grant-Project; University of Tasmania.

Project Total: $899,782; Global dementia prevalence is rising. Alzheimer's disease (AD), the most common cause, has devastating effects on people's quality of life. AD has a preclinical (pre-AD) period of 10-20 years when brain pathology silently progresses before any cognitive symptoms appear. Current tests for pre-AD are invasive, costly and unsuitable for screening at population level. If we can't identify people with pre-AD, we can't offer them early interventions. This hinders our strategies to reduce AD prevalence. We will develop a new scalable test (HandTest) by combining two innovative ideas: hand-movement tests to detect pre-AD >10 years before cognitive symptoms begin; and computer vision so people can self-test? online at home. This unique approach builds on the recent discoveries that the posterior cingulate cortex (the first brain region to show abnormalities in pre-AD) is involved in hand-movement control, and that hand-movement patterns change in pre-AD. We will use exquisitely precise computer vision methods to automatically analyse movement data from thousands of participants, who complete the online test by simply opening and closing their hands repeatedly for 5 minutes in front of a standard computer, tablet or smartphone camera. The CI/AI team of experts in hand-movement analysis, pre-AD, computer vision, AD biomarkers and biostatistics has access to 3 well-phenotyped cohorts, >10,000 existing participants and a cutting-edge assay for a blood AD biomarker, ptau181. We will develop a HandTest algorithm to classify hand-movement data for pre-AD risk. In a longitudinal cohort we will determine HandTest's precision to prospectively predict 5-year risks of cognitive decline and AD. This is the critical first step for up-scaling HandTest nationwide via memory clinics of the Australian Dementia Network. With worldwide access to computers, tablets and smartphones increasing, HandTest is scalable globally, potentially transforming dementia prevention and management. Funded by: National Health & Medical Research CouncilNational Health & Medical Research Council - Grant-Ideas ($1,799,564); University of Tasmania.

Project Total: $2,400,000; An ageing Australia will increasingly impact social, health and economic activity, as exemplified in complex disorders such as dementia. Obesity is also increasing at a rapid rate and is a major antecedent risk factor for a range of chronic illnesses. Both conditions will be a particular challenge for rural and regional communities as they have the highest rates of related risk factors and chronic illness, and also relatively reduced access to specialist medical services and preventative health programs. This proposal focusses on dementia and obesity in north-west Tasmania, developing innovative initiatives to manage and reduce risk of these conditions, which will reduce medical procedures overall including presentations to hospital. The program involves two major projects: the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) and the Critical Age Periods for Impacting Obesogenic Lifestyles (CAPITOL) study. The ISLAND study will involve a pragmatic clustered randomised controlled on interventions for major potentially modifiable risk factors for dementia, including obesity, physical activity, diabetes, smoking, hypertension, depression and cognitive stimulation/education, most of which are antecedents to chronic illness. The CAPITOL study will facilitate a transdisciplinary professional network to build a community-specific, sustainable approach to supporting children and families in relation to physical health and wellbeing. This project will identify enabling contextual factors which influence engagement in healthy physical play practices; foster buy-in from families (at multiple entry points); improve school readiness (through enhancing outcomes for children (0-8 years) in the AEDC domain of physical health and wellbeing), and generate sustainable communities of practice. North-west Tasmania is an ideal 'test-bed' to develop preventative health strategies that are relevant and scalable to other Australian rural and regional communities. Funded by: Medical Research Future Fund - Grant - Keeping Australians Out of Hospital ($2,400,000); University of Tasmania.

Project Total: $5,000; This project focuses on the development of collaborative links between Australian and Indonesian researchers in the broad area of dementia research. Funded by: Department of Education ACT - Travel Grant - PhillipsKPA - SEA ($5,000); University of Tasmania.

Project Total: $449,386; This project will characterise a blood biomarker of neurodegeneration for prognostic and diagnostic value to predict cognitive decline and dementia. Funded by: Royal Hobart Hospital Research Foundation - Grant-Major Project ($449,386); University of Tasmania.

Project Total: $150,000; Funding to support a Project Officer working on the Island Project. Funded by: Masonic Medical Research Foundation Limited ($150,000); University of Tasmania.

Project Total: $400,000; The ISLAND Project has three overall objectives: 1. Establish the incidence of dementia across our community. 2. Build awareness of dementia and its risk factors within the Tasmanian population. 3. Undertake a community-engaged public health program as a partnership to reduce dementia risk, and hence the age specific incidence of dementia across Tasmania. Funded by: Terry and Maureen Hopkins Foundation - Donation ($400,000); University of Tasmania.

Project Total: $597,651; Loss of axonal connections between nerve cells results in reduced cognitive function and memory loss. Axons, like cells, can orchestrate their own death mechanisms and the SARM1 protein mediates Wallerian degeneration the best known axon death pathway. It is not yet understood, why neurons have evolved to have this axon degeneration pathway; whether it is aberrantly activate in neurodegenerative disease or whether it protects the nervous system from adverse nerve cell connections. By using a combination of methods, including axon injury and neurodegeneration mouse models, and human stem cell research, we will identify the exact role of SARM1 in the response to injury and neurodegeneration and determine whether blocking axons from this protein is beneficial or harmful. Our team is comprised of world leaders in investigating axon pathology, degeneration and regeneration in neurodegenerative disease and injury, and outcomes of this research will advance treatment of diseases such as dementia and motor-neuron disease. Funded by: National Health & Medical Research CouncilNational Health & Medical Research Council - Grant-Ideas ($1,195,302); University of Tasmania.

Project Total: $997,046; We will test an HDAC6 inhibitor in models of ALS. We will investigate the HDA6 inhibitor activity of novel compounds Funded by: FightMND - Grant - Drug Development Grant ($997,046); University of Tasmania.

Project Total: $222,212; This project looks at the effect of leptin resistance induced by high path diet on the neurodegenerative pathways induced by TDP-43. Funded by: Fundacion Hospital Nacional de Paraplejicos - Consortium Agreement; University of Tasmania.

Project Total: $175; Funded by: The Trustee for THE MERRIDEW FOUNDATION - Donation ($175,000); University of Tasmania.