This feasibility study aims to enhance services currently available to care recipient/carer couples living with early-stage dementia attending a general medical practice or a Queensland Health memory clinic. Healthcare professionals working in the two settings have been trained and supported to deliver a structured education and support program to the couples. The five program sessions focus on identifying/managing dementia related changes, establishing a support network, and encouraging social outlets. The couple document how they will live well with dementia in their SHARE plan, which they update and share with their family and friends. Post-intervention evaluations show that couples that have completed the program are very satisfied with program content and location, feel better informed, are planning for the future, and have expanded their support networks. These are significant findings as older people living with dementia often try to manage alone until a crisis occurs, at which point choices are limited.
How do microglia-synapse dynamics change with Alzheimer's disease?
Historically, microglia are referred to as the immune cells of the central nervous system. This project explores the emerging role of microglia in facilitating changes to neuronal connections, synaptic plasticity or the ability of the brain to remodel throughout the lifespan in response to a changing environment. Using state of the art imaging techniques this project explores microglia-synapse interactions in real-time, to elucidate their role in Alzheimer’s disease. Using our innovative approach to understanding the role of microglia at the synapse, our findings may represent a major advance in our understanding how synaptic connections are regulated and are likely to be fundamental in informing any therapeutic manipulation of microglia to induce neuroplasticity in models of health and disease.
Heat shock proteins in Alzheimer's disease
It is now well known that Alzheimer’s disease involves the aggregation and deposition of proteins within the brain, which may suggest the importance of molecular chaperones in the manifestation of these protein-aggregate diseases. Heat shock proteins (HSP’s) play an important role in cellular homeostasis by repairing and refolding damaged or stress denatured proteins. HSP’s, known for their chaperoning ability, have now been associated with Alzheimer's disease pathogenesis and its potential as a pharmacologically modulated target in Alzheimer's disease treatment. Jessica is investigating the activation of heat shock protein 72 in the brain as a potential therapy against the cognitive decline associated with Alzheimer’s disease. Furthermore, the somewhat epidemic of obesity and Type 2 Diabetes within our society has been linked to a higher risk of cognitive decline. Jessica is therefore also investigating the role of a Western Diet and its resultant insulin resistance on the progression of Alzheimer’s disease and the treatment effects of heat shock protein 72 activation.
Harnessing the power of exosomes to understand Alzheimer’s disease
Every year, the number of people living with Alzheimer’s disease increases due to our aging population and the lack of effective drugs currently available. This increase is a global problem and if we are to successfully intervene we need a clearer understanding of what’s driving the disease. Alzheimer’s disease is characterised by impairment in clearance of toxic molecules from brain cells which leads to cell death and ultimately memory deficits in affected individuals. We recently discovered a novel relationship between these toxic molecules and tiny vesicles trafficked around the brain, called exosomes. This project aims to determine the role of exosomes in Alzheimer’s disease with goal of understanding their contribution to disease progression. This study will reveal the potential that exosomes hold as drug targets and will provide the field with a new perspective on the onset and progression of Alzheimer's disease.
Development and pilot testing the Dignity in Care Survey for acute and subacute care settings
Health and aged care services strive to provide ‘person-centred’ or ‘consumer-directed’ care, but there is no agreed tool used across health and aged care to measure these concepts. The purpose of this research study is to develop a questionnaire that could be used to measure patients’ and carers’ experience of receiving care that is consistent with the 10 Principles of Dignity in Care. These 10 Principles are short, simple and powerful expressions of how health and aged care consumers interpret the 'person-centred' and 'consumer-focused' models of care. The research team will develop three versions of a Dignity in Care Questionnaire: a version for use by older people (including people with dementia) who are admitted to hospital; a version for use by their carer (i.e., their family/friend/advocate); and a version for use by health care staff. The validity and reliability of the Dignity in Care Questionnaire will be evaluated and if acceptable, will be recommend for use in Australian hospitals.
Does sleep predict future memory decline? A five-year follow-up study of a community-based cohort of older adults
This study proposes to follow-up a sample of community-based older adults, five years after their initial involvement in a baseline study that collected information on sleep and memory measures. The aim of the current project is to determine whether aspects of sleep are associated with memory decline over time. Study involvement will include assessment of sleeping patterns by wearing an activity monitor (similar to a Fitbit) on the wrist for two weeks to obtain an objective measure of sleeping patterns; completing questionnaires about perceived sleep quality; and undertaking an assessment of memory and other aspects of thinking. The analyses will examine whether sleep at baseline, or change in sleep patterns from baseline to follow-up, are associated with memory decline over time. This study is proposed as a pilot study which is hoped will provide the basis for applying for further research funding for a larger-scale project. The results will have important implications for understanding memory decline in ageing, improving the early detection of AD, and providing the opportunity for developing memory interventions targeting sleep.
Dementia Stigma Reduction (DESeRvE): A randomised controlled trial to reduce dementia related stigma in the general public
Dementia is a stigmatised condition and dementia-related stigma is undoubtedly harmful with the ability to cause negative effects on people with dementia and their carers. Stigma can lead to low self-esteem, isolation and poorer mental health in people with dementia, and increased burden in caregivers. Stigma can also prevent people from seeking help. This results in people missing out on timely diagnosis and the utilisation of health and social services. Timely diagnosis is beneficial to people with dementia and carers as it provides time to better plan for future care, delays institutionalisation, reduces costs to the health system, and leads to timely treatment and slower cognitive decline. It is therefore vital to develop programs to reduce the stigma of dementia. In this study, we are developing and evaluating the short-term effectiveness of an online intervention programme (Dementia Stigma Reduction (DESeRvE)) aimed at the general public to reduce dementia-related stigma.
Identifying early molecular changes underlying familial Alzheimer’s disease
To reduce the enormous social and financial impacts of Alzheimer’s disease (AD) we must understand why and how AD occurs and be able to detect the pathological process (through biomarkers) so that intervention is possible before brain damage becomes too great. There is no firm consensus on what begins the decades long progression to AD. New technologies allow precise engineering of genomes and detailed gene expression analysis of tissues. However, there has not yet been any detailed analysis of the early brain changes in a fAD mutation model. The least studied fAD gene is SORL1. It is uncertain whether fAD mutations in SORL1 are dominant. My project will be to introduce fAD mutations into zebrafish SORL1 and then analyse their effects on transcriptome expression in young brains. This will also suggest biomarkers for early detection of the pathological processes leading to AD and will resolve the question of SORL1 fAD mutation loss or change of function.
The pathway to diagnosis: Experiences of caregivers of people with dementia
This study will provide valuable, up-to-date data on the experiences of caregivers on pathway to dementia diagnosis; one of only a few studies of its kind internationally. The findings of this research will provide important insight regarding gaps which may exist in provision of dementia care and services in the pre-diagnosis phase. Identifying such gaps will help to determine where improvements in care and future research are needed most. The research gives voice to the concerns and preferences of consumers to inform the development of strategies to reduce delays and overcome the barriers to obtaining a timely diagnosis. Understanding the path that people travel to the point of diagnosis will allow service providers and policy makers to target efforts to ensure that diagnosis is coordinated and supported.
Involvement of SIRT3 and related energy metabolite changes in the Alzheimer brain
Free radicals caused damage to lipids, proteins and DNA are hallmarks of Alzheimer’s disease (AD). This damage causes energy generation to falter and therefore damaged mitochondria can lead to impaired memory and cognitive function over time. Given that this is a important hallmark of AD, and neurons are especially sensitive to insults that result from energy depletion and free radical damage, proteins such as sirtuins which are involved in the cell’s response to oxidative stress as well as energy metabolites such as NAD which are used as substrates for these proteins and others involved in DNA repair, may play a key role in the pathogenesis of neurodegeneration. Therefore, the aim of this study is to look at sirtuin protein and related energy metabolite changes in control and AD post mortem brain tissue and potentially uncover new avenues to preserve or boost energy levels to maintain brain bioenergetics.
Exploration of the associations between cognitive performance and dual-tasking, gait and physical performance in community-dwelling older adults and individuals with Alzheimer's disease
Alzheimer’s disease is a condition that affects memory and the ability to reason. It is recognised that mild cognitive impairment, that is decreases in memory, ability to learn, or short attention span, is a strong predictor of developing Alzheimer’s disease later on in life. Early intervention has been shown to lead to better quality of life for people with Alzheimer’s disease and therefore screening for risk factors of Alzheimer’s disease, such as mild cognitive impairment, could be expected to lead to better management and slower progression of the condition. The purpose of this study is to explore brain, physical, and cognitive function in individuals with or without memory complaints, and individuals with diagnosed Alzheimer’s disease. The work is expected to help identify possible treatment targets, and refine screening tools to detect the signs of impending cognitive decline earlier and thus help enable improved care to individuals with Alzheimer’s disease.
Fast, accurate and accessible quantification of tau and amyloid PET Scans
β-amyloid deposits and tau tangles are present in the brain of a person diagnosed with Alzheimer’s disease. Brain imaging (known as PET scans) are used to detect these proteins and provide invaluable insight into the development of the disease. Presently, trained experts interpret PET scans manually, which is a tedious task. In this project, we propose to develop a tool that automatically quantifies β-amyloid and tau burden and offer an easier visualisation of the images. These reports will enable clinicians to provide a more confident and accurate diagnosis, allowing earlier and more appropriate care of patients. Importantly, this research will enable the introduction of consistent PET analysis to all scanning sites throughout Australia, including those situated in remote areas.
Improving dementia diagnosis among people from Culturally and Linguistically Diverse (CALD) backgrounds through e-interpreting
This project explores the use of web-based videoconferencing technology with interpreters (i.e., e-interpreting) in cognitive assessments with people from Culturally and Linguistically Diverse (CALD) backgrounds. Ten memory clients who are from CALD backgrounds will be recruited. Participants will receive two cognitive assessments (one using face-to-face and the other using e-interpreting) and complete a survey after each assessment. There will also be surveys with clinicians, interpreters and IT staff, as well as data collection of cost associated with the use of e-interpreting. These data will be used to evaluate the feasibility, acceptability, reliability, and cost-effectiveness of e-interpreting. A protocol for using e-interpreting in cognitive assessments will also be developed. This project has potential for more timely diagnoses of dementia among people from CALD backgrounds and for improved cost-effectiveness of the current health system.
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.
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.
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.
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.
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.
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.
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.