Our researchers

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Anna Konopka

Understanding the causes of DNA damage in dementia associated with abnormal TDP-43

DNA carries genes that define any living being. The genes are essential for function of the whole organism, but they are damaged everyday due to normal cellular processes and exposition to toxic agents. Therefore, efficient DNA repair mechanisms are crucial for the proper functioning of genes and the maintenance of healthy cells. Abnormal accumulation of DNA damage actively contributes to neurodegeneration in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), the two most common causes of dementia. However, precise mechanism underlining this phenomenon is unknown. In both, AD and FTLD, abnormal protein called TDP-43 is present. Interestingly, recently it was discovered that TDP-43 repairs DNA. Given that DNA is damaged in dementia and TDP-43 does not work properly, defective DNA repair may be a potential cause of the disease. In this project I investigate how abnormal TDP-43 damages DNA in dementia to be able to repair this mechanism and therefore treat dementia. Because damage to DNA targets genes, I also aim to identify these genes. This information will provide better understanding of the causes of dementia and will also pave way for the establishing new therapeutic strategies for dementia.

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Claire O'Connor

Bridging the implementation gap: maximising everyday function for people with dementia

One in 10 Australians aged 65 or over have dementia, a leading cause of progressive disability. The Royal Commission into Aged Care recommends enabling interventions such as occupational therapy and exercise to support ability to do everyday activities, and people living with dementia want access, but these interventions are not being offered in usual dementia care. This research seeks to understand how to overcome barriers to successfully delivering enabling interventions within the real-world setting of existing community aged care service providers using available Commonwealth funding sources. In parallel, the project aims to explore whether meaningful outcomes can be achieved for people living with dementia participating in enabling interventions. In partnership with an advisory group (people impacted by dementia and industry stakeholders), we will: (1) explore current practice (clinical audit); (2) seek national input on strategies for how to deliver enabling interventions within community aged care services; (3) test these strategies and explore program outcomes for people with dementia; (4) develop a national guide on how to deliver enabling programs to support everyday abilities in people living with dementia accessing community aged care services. Outcomes have potential to improve the national landscape of services offered to Australians living with dementia.

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Deborah Brooks

Towards better mental health of people living with dementia in residential aged care: Co-design of a performance measurement tool to aid organisational governance

Mental health practices for people living with dementia in residential care are often poor, with an increased risk of prescribing medication for those who experience psychological symptoms and changed behaviours such as agitation. Additionally, psychological, social and person-centred care can be poorly implemented. The COVID pandemic has exacerbated existing concerns about the mental health of residents. However, there is currently no measure to monitor and promote mental health for people living with dementia in residential care.

This study aims to improve current practices and outcomes for people living with dementia in residential care by co-designing a performance measurement tool for use in care facilities. We will ask residents both with and without a diagnosis of dementia, family/care partners and residential care staff, about the key areas that need to be addressed and measured to improve mental health practices and outcomes. We will also seek to gain the consensus of aged care industry, consumer organisations, academics, and clinicians on the quality indicators to be included. We aim to co-design a Mental Health Tool for Residential Aged Care (MHICare Tool) that can eventually be rolled out across residential aged care facilities in Australia to improve mental health practices and outcomes for residents.

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Grace Lidgerwood

Modelling Alzheimer’s Disease using a novel stem cell model of the human retina

Alzheimer’s disease is a neurodegenerative disease with no definitive cause or cure. A common feature of the disease are plaques of protein in the brain called beta amyloid (Aβ) which can appear decades before the first symptoms of dementia are observed. The retina, which is the light sensing tissue of the eye, is an extension of the brain and thus a “window” into the health of the brain. Recent research has found that the Aβ load in Alzheimer’s patient brains correlates with levels detected in the retina, heralding an exciting avenue of clinical research for non-invasive detection of the disease. It is now possible to study the molecular events that underpin Alzheimer’s disease in the laboratory using a patient’s very own stem cells (called induced pluripotent stem cells or iPSCs). Using iPSCs from patients with clinically diagnosed AD, our study aims to create the first lab-based retinal model of Alzheimer’s disease. Using a range of cutting-edge technologies, we aim to develop a robust model that can ultimately be used for drug screening, to identify therapeutics that inhibit or reverse Aβ-mediated damage in the retina. Findings from this study may provide new avenues for Alzheimer’s research and therapeutic discovery.

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Helen English

Designing evidence-based creative arts programs to maintain healthy minds in older adults

Keeping active in later life is important for maintaining social, cognitive and emotional wellbeing, and delaying or preventing the onset of dementia. While physical activity can promote wellbeing in older adulthood, not everyone can participate in sports or exercise. Creative arts activities offer a promising, complementary approach to engage our thinking, emotions, creativity and imagination. While engagement in creative activities is linked to beneficial effects on wellbeing, research into the specific effects of creative arts engagement on brain and cognitive health is lacking. This project uses a cluster randomised control trial design to compare the effects of artmaking and songwriting courses on brain, cognitive and emotional processes in healthy older adults. We aim to identify the important ‘ingredients’ of creative activity programs that drive benefits in wellbeing. Findings from this project will inform the development of evidence-based creative arts programs with protective effects on cognitive functioning, emotional wellbeing and quality of life for adults at all stages of ageing.

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Janet van Eersel

Pre-clinical development of next-generation tau aggregation-inhibitors for the treatment of dementia

Alzheimer's disease and Frontotemporal dementia are two common causes of dementia, for which there is no effective treatment or cure. In the brains of people with these disorders, abnormal clumping of a protein known as tau is observed. These tau clumps start off small, but over time mature, grow and form large tau tangles. Historically, it was thought that tau tangles cause cells within the brain to die. However, new research suggests that it is the smaller, initial tau clumps which are responsible for this. This has major implications, as current drugs in clinical trials are known to target tau tangles and, by causing them to disassemble, these drugs may in fact cause the release of smaller toxic tau clumps that were safely trapped away.

This project aims to develop the next-generation of tau-targeting drugs which act specifically on the smaller, toxic tau clumps but NOT on tau tangles. We believe this will lead to greater clinical benefits. We will use several newly-developed, cutting-edge technologies that can detect tau clumps with better sensitivity. Promising candidates will then be tested in various models to determine their potential. This will lay the groundwork for, hopefully, future clinical trial testing in patients.

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Leah Bauchamp

Protein phosphatase 2A methylation as a therapeutic target in Alzheimer’s disease

The impact Alzheimer’s has on our minds and lives is evident to all of us, and we are in desperate need of drugs that are safer and more effective. There are failures in biochemical processes in the Alzheimer’s disease brain, and as this disease progresses there is an accumulation of a protein called tau that becomes toxic. Tau is a protein that we need throughout life, however, in Alzheimer’s disease it changes and becomes ‘sticky’, causing the protein to aggregate in our brain cells. Over time these protein aggregates give way to a range of toxic pathways that build up over time resulting in what we know as dementia.

This research will develop strategies that correct this biochemical failure leading to toxic tau aggregates. Firstly, we have designed several new drugs that will promote the stability of ‘good tau’, and we have designed a compound that can reduce the dynamic process that turns ‘good tau’ into ‘bad tau’. This work aims to create new therapies that specifically target tau and help to reduce the burden of these protein aggregates in the brain leading to better brain health as we age.  

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Lidia Engel

The COCOON research project: incorporating Carer Outcomes in COst-effectiveness analyses Of dementia iNterventions

Providing informal care to a person living with dementia is not only associated with significant costs but there can also be significant quality of life impacts for informal carers. However, these impacts are rarely considered when assessing the cost-effectiveness of dementia interventions, leading potentially to sub-optimal resource allocation decisions. The aim of the COCOON research project is to advance the methods used when assessing the cost-effectiveness of dementia interventions by incorporating carer outcomes. 

In this Fellowship, I will develop, with input from an advisory group, a new dementia-specific questionnaire to measure quality of life of informal carers, which will be tested for its appropriateness and performance in informal carers. I will then develop a way of scoring this new questionnaire that will account for the fact that some domains of quality of life are valued more than others. In the final part of the Fellowship, I will assess how carers’ quality of life can be combined with care recipients’ quality of life, by obtaining preferences from the Australian general population in terms of whether they should be weighted differently. Findings from this research project will enable the inclusion of carer outcomes in future cost-effectiveness analyses, leading to more equitable and efficient resource allocation decisions.          

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Louise Neale

Understanding relationships between neuroimaging markers and culturally relevant protective factors in Aboriginal communities: A way to enhance dementia prevention and diagnosis?

Research has shown higher dementia rates in Aboriginal and Torres Strait Islander communities compared to the broader population; however, there has been no study on underlying brain changes. Furthermore, lifecourse exposures (e.g., education, work opportunities) may be protective even when dementia-related disease/injury are present; yet little is understood about these relationships for Aboriginal and Torres Strait Islander people and how they predict cognitive function over time. This study aims to investigate relationships between brain structure and protective factors that contribute to healthy ageing and delay/prevent dementia; and will follow-up participants to predict cognitive outcomes. The project will involve co-developing a culturally relevant measure that captures protective lifecourse exposures. Two-hundred older Aboriginal and Torres Strait Islander people will then have Magnetic Resonance Imaging (MRI) scans. MRI brain structure measures will be examined in relation to the protective lifecourse exposure measure, to understand how they are related. This project will also develop a way to assess cognition via telephone or video conference, to easily follow up MRI participants 1 year later and investigate how the brain and protective factors predict cognitive decline. This project will inform culturally meaningful dementia prevention strategies and enhance dementia diagnosis for Aboriginal and Torres Strait Islander peoples.

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Marina Cavuoto

The influence of the Aquaporin-4 gene on the relationship between poor sleep and preclinical dementia: A multi-cohort study.

Poor sleep can contribute to dementia by disrupting the brain’s ability to remove toxic waste products that contribute to the development of Alzheimer's disease and other causes of dementia. The Aquaporin-4 (AQP4) gene plays an important role in the capacity of the brain to “flush out” waste. However, little is understood about the role of the AQP4 gene in the association between sleep and dementia. This could be crucial in identifying who would benefit most from sleep treatments designed to prevent dementia.

This study aims to investigate whether people with different variants of the AQP4 gene are more at risk of cognitive decline and early dementia biomarkers in the face of poor sleep. This will be done by looking at genetic sequencing in three different cohorts and comprehensively assessing sleep, and early dementia biomarkers, as well as cognitive assessments over time. The results of this research will identify whether certain people are at higher risk of negative brain health associated with poor sleep.

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Moyra Mortby

Understanding Neuropsychiatric Symptoms to inform timely diagnosis, patient management and lived experience of dementia

Changes in behaviours such as aggression, apathy and depression are common in dementia and contribute to more problems with doing everyday activities, more rapid memory loss, and more reliance on carers/family. They are often reported as a reason for entry into aged care. New research has shown that later-life behavioural changes before the onset of memory problems, known as Mild Behavioural Impairment (MBI), are an early warning sign for dementia. Research is now needed that will help us understand why some people are more vulnerable to MBI while others are resilient, how early detection of this dementia-risk marker can be used to help health care professionals and families manage the clinical presentation of MBI, how care service provision can be supported, and relationships safeguarded. A better understanding will help inform clinical diagnostics and care provision strategies. My research program provides the world-first opportunity to answer these important questions. I will do this by drawing on 20 years of data from the PATH Through Life Project and by leading the first Australian Survey of Knowledge and Understanding of MBI (ASKU-MBI). This understanding is urgently needed to improve early diagnosis and treatment of this dementia-risk marker in Australia.

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Nathan D'Cunha

Evaluation of a multicomponent post-diagnostic support program for people living with dementia and their carers

The availability and accessibility of post-diagnostic support for people living with dementia and carers is of central importance in dementia care. People with dementia and their carers require access to timely education, emotional and practical support, lifestyle advice, and meaningful activities, to maximise their quality of life and to potentially delay cognitive decline. Allied health professionals at Canberra Health Services at the University of Canberra Rehabilitation Hospital and the University of Canberra have designed an evidence-based 12-week multicomponent program, tailored to people with dementia and carers, which includes physical activity, social engagement, nutrition assessment, education, and capacity building. The team engaged with Dementia Australia advocates to refine the program and set priorities for research. The research project will assess the value of the multicomponent dementia support program, perform a pilot study to measure impact and effectiveness, and explore barriers to access to post-diagnostic dementia support services for people with dementia and carers. The project has the potential to become part of standard care in the ACT region, and to set an example for dementia care services Australia-wide.

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Paul Jansons

Feasibility and pilot randomised controlled trial of a co-designed home-based personalised rehabilitative strategy program delivered via Voice-Controlled Intelligent Personal Assistants in older adults aged 60 years and older with mild cognitive impairmen

A personalised cognitive strategy program delivered by an Amazon Alexa Echo Show 8 (Alexa) using natural conversations may be more acceptable than some of the traditional digital health approaches such as internet browsers, tablets and smart phones. Alexas present an ideal method to deliver personalised strategies such as medication/appointment reminders or assist people with mild cognitive impairment (MCI) and dementia to carry out activities of daily living such as meal preparation, as they can be automated to provide voice reminders and instructions which can prompt users to carry out scheduled activities throughout the day, and enable regular feedback to the prescribing health professional. We will conduct a co-designed 12-week trial of a home-based personalised rehabilitative strategy program delivered via an Alexa in older adults aged 60 years and older with MCI and/or dementia. We anticipate that a 12-week Alexa delivered home-based personalised rehabilitative strategy program will be feasible, acceptable and improve depression, cognition and activities of daily living compared to a control group. Data from this project will explore the delivery of this project to reduce healthcare inequalities in people with dementia by providing high quality and cost-effective services to underserved populations, such as low-income individuals and people in remote and rural areas.

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Rose Chesworth

The cause of Alzheimer’s disease (AD) is unclear, and there is a significant need for better treatment of the disorder. Inflammation in the brain i.e. neuroinflammation, is an established hallmark of AD, but it is unclear precisely how neuroinflammation interacts with and/or exacerbates other types of AD pathology. We hypothesise that neuroinflammation exacerbates other types of AD pathology. This hypothesis has not been investigated before, and we hypothesise that these complex interactions may present a new treatment avenue. We will test this hypothesis using a novel mouse model which combines neuroinflammation with AD pathology. We will also examine a novel treatment for neuroinflammation, AD pathology and cognitive impairment in a mouse model. Our research will determine if interactions between neuroinflammation and AD pathology are a critical component of AD aetiology, and if these interactions could be a new treatment target. 

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Sau Chi Cheung

Supporting changed behaviours: Positive behaviour support in younger-onset dementia

Changed behaviours (e.g., aggression, socially-inappropriate behaviours) commonly occur in younger-onset dementia which typically affects people below the age of 65 years. These changed behaviours can have significant negative impacts on the person with dementia and their families such as reduced quality of life and increased stress for family carers. Medication is currently the most common intervention, though is often ineffective and causes side effects. Although behaviour support interventions, such as Positive Behaviour Support (PBS) are most effective, there is a serious lack of options for these in Australia.

Through five weekly education sessions, questionnaires and interviews, we will examine how acceptable and useful a family-directed PBS education program is in equipping family carers with more effective behaviour support. Our project will equip carers with the relevant skills to manage changed behaviours on a day-to-day basis, and thus reduce the negative impacts of changed behaviours. We will also examine the effectiveness of online delivery and develop facilitator guidelines to increase our ability to reach families supporting a person with dementia across Australia, particularly in regions with limited services. Our findings will improve dementia care in the community and the services available for families supporting a person with dementia with changed behaviours.

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Andrew McKinnon

Delineating relationships between sleep-wake disturbances, brain changes, dementia risk factors and the accumulation of dementia pathology

Dementia is the leading cause of disability in persons over the age of 65 in Australia, with Alzheimer’s disease alone accounting for more than 40% of all dementia cases. By addressing risk factors for developing dementia including hypertension, depression, and physical inactivity, one-third of Alzheimer’s Disease cases and up to 40% of all dementia cases may be preventable. Sleep disturbances including poor sleep quality, and shorter sleep duration, as well as sleep disorders such as sleep apnoea are present in up to 60% of older adults over the age of 60, and in up to 70% of those with dementia. These types of sleep problems are emerging as another significant yet modifiable (e.g. treatment with melatonin or CPAP devices) risk factor for dementia. However, to date how these sleep problems relate over time to brain and cognition changes, underlying dementia processes, and other risk factors has not been thoroughly investigated. We will address this gap through comprehensively characterising sleep problems in older adults with early dementia or at risk for dementia. Furthermore, we will develop tools that will provide personalised risk profile reports that can be implemented by clinicians to guide strategies for dementia management and prevention for individual patients.

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Arne Ittner

A neuroprotective signaling axis in Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia and neither an effective treatment nor a cure are currently known. This is partly due to a gap in knowledge on how brain cells deteriorate in Alzheimer’s disease. The last decades of research have established that amyloid and tau, two factors that are common in Alzheimer’s, work together in damaging brain cells. Whether there are protective factors that reduce this damage remained largely unknown. Recently, we have found a protective signal that targets tau and reduces damage to brain cells and memory.

This project aims to understand how this protective signal works in detail, how it helps maintain healthy brain function, and how it can be boosted to prevent memory loss associated with Alzheimer’s disease. This study employs latest technologies in assessing brain molecules and their function, brain activity, and strength of memory performance. As a result, we will better understand how protective factors in the brain are connected and how they can be activated and harnessed to reduce brain damage and memory loss in Alzheimer’s disease.

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Deborah Brooks

Bridging the support void. Can the Residential Care Transition Module improve the psychological health of family carers during the residential care placement process in Australia?

Many people with dementia eventually move into residential care. Making this decision and coping with admission processes can be stressful and distressing. These feelings may be heightened by the COVID-19 pandemic if families are not able to visit care facilities due to lockdown and/or are concerned about transmission. However, carers report that formal supports to help families cope during this time are lacking. This study aims to test delivery of a telephone/video counselling intervention during the residential care placement process to help reduce stress and distress for family carers. The Residential Care Transition Module (RCTM) consists of six telephone or video-link counselling sessions delivered to family carers over 12 weeks by a trained health or social care professional. It includes education about dementia and residential care facilities, dementia-specific grief counselling, stress reduction techniques, and referral to support networks. The proposed pilot study will test whether delivery of the RCTM following Aged Care Assessment Team approval for residential care is feasible and potentially beneficial in reducing family carer stress, anxiety, depression, guilt, and grief, and improving social support during the course of placement. This may help carers to better cope and adjust once their relative has been admitted into residential care.

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Dhanisha Jhaveri

Cholinergic regulation of adult hippocampal neurogenesis and cognitive functions.

Early pathogenic events in Alzheimer’s disease (AD) include a progressive loss in brain’s capacity to generate new neurons (i.e. neurogenesis) in the area important for learning and memory and degeneration of cells that produce a neurochemical, acetylcholine that is vital for cognitive functions. However, whether and how these two processes are linked remains an open question. In this project, we will investigate a direct link between these two cellular processes and cognitive functions and explore whether these deficits can be rescued by stimulating a select receptor that we have identified boosts the production of new neurons. Using a multi-modal approach involving animal models to monitor and manipulate specific neuronal populations, together with assessing cognitive functions, our research will provide the experimental evidence establishing the role of cholinergic neurons and a select cholinergic receptor in regulating adult neurogenesis and neurogenesis-dependent cognitive functions. The outcomes of this study may provide the mechanistic basis for the development of a new approach harnessing therapeutic potential of brain’s endogenous neuroplasticity mechanism to delay the onset or slow the progression of dementia.

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Janet van Eersel

Preclinical development of specific tau-binding compounds to target underlying disease mechanisms for the treatment of dementia

Alzheimer’s disease and Frontotemporal Dementia are two of the most common causes of dementia. Unfortunately, there is currently no effective treatment or cure for either of these disorders. Therefore, the development and testing of new therapies is urgently required. Although these two dementias are quite distinct from one another, in both conditions, a protein known as Tau is thought to play a central role in the disease process. One mechanism by which Tau is thought to be involved, is via excessive interactions with another protein known as Fyn. Together, Fyn and Tau set off a cascade of events that lead to overstimulation of neuronal brain cells, eventually causing cell death. My work postulates that if interactions between Tau and Fyn could be disrupted or reduced in the brains of dementia patients, this would provide therapeutic benefits. Therefore, my research project aims to identify compounds that can disrupt interactions between Tau and Fyn by utilising a cutting-edge technology that can screen up to 14 billion compounds at once. Identified hits will then be tested in cell culture models to determine their potential usefulness. This will lay the groundwork for pre-clinical testing and, hopefully in the future, clinical trial testing in patients