Our Researchers

Adam Walker

Neuroinflammation in frontotemporal dementia: The role of microglia in TDP-43-related disease

The brains of patients with frontotemporal dementia (FTD) show inflammation in affected regions, where neurodegeneration has occurred. In the brain, immune cells known as microglia are the main cell type that controls this inflammatory response. Microglia provide a protective surveillance function in the brain to allow rapid response to injury or disease but they can also take on toxic properties that drive neuron death. In FTD, it remains unclear whether inflammatory microglia are protective or toxic to neurons. In this study, microglia and inflammatory molecules will be analysed over time in recently-developed genetically-modified mice that develop disease similar to human FTD, and these mice will be treated with an experimental drug to prevent brain inflammation. Findings from this project will therefore determine if pharmacological alteration of the microglial inflammatory response could be used to modify disease development and progression in FTD. 

Alexander Wykes

Insights into cognitive neural circuits and treatment of Alzheimer's symptoms

A key hallmark of Alzheimer’s disease is the loss of neurons in brain regions associated with the control of memory and emotion. Neurons in these areas form complex circuits with other brain regions, sending and receiving chemical messages that orchestrate cognitive activity. In order to increase our understanding of these neural networks, Mr Wykes’ research is focused on characterising the function, biochemistry and anatomical connectivity of neurons located in the brainstem area known as the nucleus incertus. These neurons have been shown to promote memory consolidation and cognitive processes by using the amino acid transmitter, GABA, and the neuropeptide, relaxin-3, to modulate the activity of important forebrain areas including the hippocampus. Mr Wykes' studies will provide further insight into how the relaxin-3/nucleus incertus and related systems function in healthy and Alzheimer’s disease-affected brain, and in doing so identify potential therapeutic targets and approaches that may benefit individuals with Alzheimer’s disease and dementia.

Arne Ittner

A novel neuroprotective mechanism in Alzheimer's disease

Alzheimer’s disease is characterised by loss of memory because of dying brain cells and brain atrophy. In addition, proteins deposit in the brain tissue forming amyloid plaques. The amyloid plaques contain short protein fragments that are toxic to brain cells, causing them to die, a process called ‘amyloid toxicity’. Recent discoveries have shown that the toxic signal of amyloid is caused by changes of brain cell molecules (i.e. components that make up the cell). However, it remains completely unknown whether there are also molecules that can inhibit or even block these toxic signals. During his fellowship, Dr Ittner will assess a novel molecule, which may protect brain cells from amyloid toxic signals. Dr Ittner aims at finding out how exactly this molecule protects brain cells from amyloid toxic signals. His project will close a gap in knowledge of protective components in brain cells and will provide part of the understanding needed to design new ways for treating Alzheimer’s disease.

Bruce Wong

The inflammatory mediator Lactorferrin induces rapid and pronounced amyloidogenic processing of APP

The balance of iron and response to inflammation (e.g. through infection) in the cell are closely linked and has previously been implicated in Alzheimer’s disease. Lactoferrin, an iron transport protein produced in conditions such as increased inflammation was recently discovered by Dr Wong to also bind Amyloid Precursor Protein (APP). The binding of lactoferrin to APP promotes the production of β-amyloid; the main peptide found in senile plaques within the brains of Alzheimer’s disease patients. At first this interaction may be a way of protecting the body by temporarily locking the iron safely within the cell and out of harm’s way, however, more persistent presence of lactoferrin could lead to greater β-amyloid levels which is known to cause neuronal death in Alzheimer’s disease. By investigating the ability of lactoferin binding to APP, Dr Wong hopes to understand the significance of this interaction and identify a potential new drug target.

Caroline Bull

Psychological and nutritional determinants of telomere and genome integrity in dementia carers

Telomeres are regions of DNA that protect the ends of chromosomes from damage, and play a critical role in keeping our DNA healthy. Damaged and unstable chromosomes are associated with increased risk of cardiovascular disease, reduced immune function, neurodegeneration, and cancers. People who experience high levels of psychological stress, such as carers, have shorter telomeres than lower-stress individuals.

This study will investigate telomere length and DNA damage of family dementia carers, together with a panel of psychological, physiological, diet and lifestyle measures. This novel, comprehensive approach will allow us to determine which specific diet and lifestyle factors help protect the genome against stress-related damage in carers.

Findings from this study will help to define practical, effective measures to empower carers to protect their DNA health, reduce risk for chronic disease and improve their overall health and wellbeing.

Deborah Brooks

Bereavement without death: Improving psychosocial support of family carers of people with dementia who have moved into residential aged care

Placing a relative with dementia into residential care has been described by carers as being amongst the most difficult and stressful times of their lives. Many experience a range of feelings such as stress, anxiety, guilt, grief and loss. Some have reported the separation to be ‘bereavement without death’. However most formal supports for carers end once the person has been admitted into care. Although the need for ongoing support for carers has been highlighted by researchers and carers alike, there is currently little research evidence as to what would be most effective. This study aims to: a) gain an in-depth understanding of the support needs of carers of people with dementia following residential care placement, and b) develop and test the effectiveness of a psychosocial intervention to improve the psychological health and emotional well-being of family carers during this time.

Donel Martin

The neural correlates of memory improvement following transcranial direct current stimulation combined with cognitive training

There is currently an urgent need for the development of an effective intervention for people at increased risk for dementia. My team has developed a novel intervention for this purpose involving the combination of mild electrical brain stimulation and targeted brain training exercises. We are currently testing the effectiveness of this intervention for improving memory in people at increased risk for dementia in an ongoing world-first randomised controlled trial. In this study we plan to use neuroimaging for the first-time to investigate the neural mechanisms associated with memory improvement following this intervention. This will be an important next step in the intervention’s development, as the results will help to inform which aspects of the intervention should be modified in order to further maximise memory improvements. If proven effective, this intervention could potentially be completed at home under medical supervision to help maintain memory functioning with normal ageing.

Elizabeth Cridland

Investigating the efficacy of an online intervention aiming to increase respite use amongst carers of people with dementia: Roles of motivational enhancement and professional delivery

The benefits of respite for both carers and people with dementia are well established. However, research indicates many carers and people with dementia are reluctant to use respite services and strategies. This project aims to understand these barriers and learn more about ways to facilitate carers’ use of respite services and strategies by developing and comparing three online programs. The first program will include motivation enhancing activities, such as developing a ‘respite goal’, and will be delivered by a health professional. The second program will include motivation enhancing activities in a self-paced format (i.e., not delivered by a health professional). The third program will provide education about respite services and strategies only. By directly comparing the outcomes of these programs, project findings will provide valuable information to inform the design of future online programs to support carers of people with dementia accessing respite services and strategies.

Fleur Harrison

Apathy in older community-dwelling persons: improving assessment, investigating its association with immune markers, differentiating from depression and fatigue and modelling its longitudinal course

Apathy, or loss of motivation leading to disability, is experienced by many community-dwelling older people, and is one of the most common symptoms of neurological and psychiatric disorders. People with apathy have poorer functioning, cognition and quality of life, yet it is relatively poorly understood and commonly unrecognised. There may be underlying biological causes for apathy, which if understood could help in its diagnosis and treatment. This project thus aims to: provide an in-depth synthesis of previously published studies looking at whether apathy may be associated with the presence of biomarkers; investigate whether apathy, depression and fatigue are distinct phenomena, by examining their longitudinal associations with biomarkers such as cytokines using data from epidemiological cohort studies; and compare methods of measuring apathy by interview, questionnaire and experimental tasks.

Isabella Hoi Kei Leung

Computerised cognitive training in insidious late life cognitive decline

A randomised clinical trial is currently being conducted at the Brain and Mind Centre, University of Sydney. The Trajectories trial will examine the efficacy of computerised cognitive training in reducing the rate of decline in memory and other cognitive abilities (Phase I). Trajectories will also examine whether booster doses of the computerised cognitive training are able to maintain cognitive gains in the long-term (Phase II). Recruited individuals are those aged 60 and over with clinical memory decline (but do not meet the diagnostic criteria for dementia and free from other neurological and psychological disorders). Magnetic Resonance Imaging (MRI), neuropsychological testing and behavioural outcomes will be measured at baseline and each time point of the trial (at baseline, after phase I and after phase II). Further, this trial will investigate whether baseline qualities (brain volume, gene expressions) may determine for whom computerised cognitive training benefits most i.e. baseline predictors of response.

Jenni Ilomaki

How do people with and without dementia use anticoagulants? Systematic literature review and analyses of PBS data

Oral anticoagulants are medicines used to prevent stroke, heart attack and other blood clots. People with dementia are less likely to be prescribed anticoagulants than people without dementia, although they are equally likely to experience stroke. The most commonly prescribed anticoagulant is warfarin. Warfarin may cause serious adverse effects including bleeding in gastrointestinal tract or brain. Newer direct oral anticoagulants (DOACs) offer potential advantages to people with dementia as they don’t require a regular blood test, have fewer interactions and have more convenient dosing. However, the safety of DOACs has not been established for people with dementia. People with dementia were excluded from participating in clinical trials of DOACs. This research will investigate how anticoagulants are being prescribed to Australians with dementia. This will help to target interventions to minimise the risks associated with anticoagulant use. This research will assist clinicians to better care for people with dementia.

Kevin Huynh

The role of plasmalogen and other lipids in Alzheimer's disease

Early diagnosis and treatment of Alzheimer’s disease is believed to offer the best outcomes for patients. However, current methods to identify the disease before symptoms are evident are both expensive and invasive. Lipids (fats) are important molecules that are present in our cells and blood. Previous work has demonstrated differences in how lipids are regulated in Alzheimer’s disease. In this project, we will use new technology to measure over 500 lipids in a single drop of blood. We will perform these measurements on 5,000 samples from 1000 individuals to identify lipids which good markers of the disease. These will be used to develop a method for the early detection of Alzheimer’s disease.

Linda Schnitker

The development and evaluation of an educational program for the care of older people with dementia in emergency departments

Outcomes from this project will contribute to improving the way older people with dementia are cared for in emergency departments (ED). It will enable translating available evidence into clinical practice by developing adaptable educational programs for ED staff. We will work closely with experts - people living with dementia and carers and health care professional in emergency medicine and nursing, and dementia care- to develop this program by reviewing the literature and using experts’ ED clinical experiences. The program will enable older people with dementia presenting to EDs to receive guideline-supported care and improved health outcomes. For example, this educational intervention will ensure that people with dementia are screened for delirium and properly assessed for pain (so that pain is identified and managed) in ED. Finally the educational program’s implementation in two Australian EDs will occur. Feedback gathered from attendees will be used to further improve the program.

Marie Lou Camara

A novel approach to enhance cognitive function and promote synaptic plasticity

Alzheimer's disease (AD) is a severe burden on the Australian health care system and affects about 30% of the population over 65 years of age. While we have made significant advances in understanding the mechanisms of AD pathology, we are yet to develop an effective therapeutic that tackles not only the issues of memory loss but also the underlying brain neurodegeneration, such as the degeneration of the basal forebrain cholinergic neurons. Our lab has generated a cell permeable peptide (c29) that enhances the signalling potential of the low reserves of growth factors, a feature of the brains of people with AD, as well as promoting neuronal survival. This project will make new versions of the c29 peptide to improve its drug-like properties and will test the ability of c29 to enhance cognitive functioning in mice, with the aim of demonstrating the promise of this molecule as a therapeutic to treat AD.

Michelle Kelly

Does social competence impact quality of life for people with a diagnosis of dementia

The symptoms associated with dementia are many and varied. Until now, much of the research has focused on changes in memory and the ability to perform activities that we do every day such as cooking and driving. However, many people with dementia and their carers report other subtle changes in behaviour, such as those that occur in social situations and in relationships. Performing well in social situations requires people to be able to pick up on social cues such as facial expressions and subtle vocal and language changes that suggest someone is meaning something else than what they are saying. Failure to interpret these social cues correctly can be damaging to relationships with caregivers and can lead to social isolation. Whilst researchers have been able to show that some people with a diagnosis of dementia do have trouble with social cues (known as social cognition), they have not yet looked at whether problems with social cognition are related to overall quality of life. This project will examine whether impairments in social cognition affect quality of life and the quality of relationships with the caregiver. Results from this project may provide us with the information required to develop management strategies to help maintain relationships for longer.

Mitchell McMaster

Body, Brain, Life Project for Mild Cognitive Impairment (BBL-MCI): A randomised controlled trial of multidomain dementia prevention for mild cognitive impairment

Mild cognitive Impairment (MCI) is a condition in which there are problems in memory, thinking, planning and/or language, as diagnosed by doctor. These problems are not severe enough to be diagnosed with dementia, however people with MCI have a high risk of developing dementia in the future. BBL-MCI is a 12-week program to educate participants about dementia and make lifestyle changes to diet, physical exercise, brain exercise and improve overall health to lower dementia risk.

Muireann Irish

"Beauty and the brain" - A novel approach to anhedonia in dementia

Try to imagine a world in which you could no longer experience beauty or pleasure in your daily life. Anhedonia refers to a loss of pleasure and has typically been studied in psychiatric disorders. Many of the diagnostic features of frontotemporal dementia, however, suggest the presence of anhedonia, such as social withdrawal, loss of interest in previous hobbies and activities, and apathy. The implications of anhedonia are stark, yet no study to our knowledge has systematically investigated anhedonia in younger-onset dementia. We will measure the experience of pleasure in response to viewing pieces of art and listening to music. Neuroimaging analyses will allow us to determine the association between damage to the brain in dementia and anhedonia. Our study will provide critical data regarding the subjective experience of the individual living with dementia and the utility of music and art to improve overall wellbeing and quality of life.

Nasser Bagheri

Hotspots of dementia risk in Australian communities: an approach to better targeting preventive interventions

Chronic illnesses such as dementia, diabetes and cardiovascular disease are predicted to rise significantly in Australia over the next few decades, posing challenges that will need to be met by effective preventive medicine strategies and health services planning.

This project will develop and apply new methodologies to identify hotspots of dementia risk in local communities using general practice records and spatial analysis techniques. This will allow interventions to be targeted at the right place, at the right time, and to the right people. It will also examine the possible link between hotspot areas and built environment characteristics and lifestyle. We hypothesise that dementia risk hotspots will be highly clustered in environments with higher densities of fast-food outlets, lower socio-economic areas, and fewer green spaces that support physical activity. This work will provide an innovative tool to help address the predicted dramatic rise of dementia in Australian communities and the technique can be used for other chronic diseases.

Shelley Forrest

Development of staging criteria to distinguish preclinical tauopathies from primary age-related tauopathy (PART)

The Rosemary Foundation Travel Fellowship will enable Dr Forrest to present her research at the 10th International Conference on Frontotemporal Dementias in Munich, 2016. She will also spend time in the laboratory of prominent neuropathologist, Associate Professor Kovacs at the Institute of Neurology, Medical University of Vienna. Associate Professor Kovacs is internationally recognised for his contributions in the neuropathology of normal aging, diseases characterised by the deposition of a protein called tau such as frontotemporal dementia and Alzheimer’s disease and other neurodegenerative diseases. He is a member of an international consortium that recently developed harmonised classification criteria for two novel tau-depositing pathologies. Both of these newly classified tau pathologies have implications for defining ‘normal’ age-related changes in the brain, and tau-related mechanisms in frontotemporal dementia versus Alzheimer’s disease. Visiting the Kovacs laboratory will provide Dr Forrest with the opportunity to gain first hand experience in the identification and characterisation of these novel pathologies, and broaden her knowledge of better-established tau pathologies.

Susan Slatyer

Meeting the support needs of family carers of people living with dementia in the community: Potential translation into practice

Family carers of people with dementia can experience significant stress and consequent poor health. The Carer Support Needs Assessment Tool is a questionnaire that is used within the context of a person-centred approach. The approach was developed for use in palliative care to help family carers identify and prioritise their needs and access appropriate support. In a recent trial in home-based palliative care, use of this approach resulted in a significant reduction in carer strain. This project aims to translate the approach for use in home-based care for people with dementia. Community care coordinators from one aged-care provider are implementing the approach with 35 family carers. Family carers’ and care providers’ perspectives are being evaluated. If found to be useful, this innovative practice change offers a novel way for community-based health care providers to engage with family carers of people with dementia and empower them to sustain their caregiving role.