Our Researchers

Belinda Brown

The influence of exercise intensity on the prevention of cognitive decline in older adults

Preliminary studies have demonstrated that an exercise regimen can protect against cognitive decline and reduce the risk of Alzheimer’s disease. Furthermore, new evidence from Dr Brown’s PhD project has identified intensity of exercise as a likely mediating factor associated with these benefits. Within individuals suffering from AD, it is unlikely that exercise can provide a therapeutic effect. Regardless, a large proportion of the aged community present as Memory Complainers, individuals at risk of developing AD, yet in whom, the disease course may still be responsive to intervention. Therefore the aim Dr Brown’s research is to assess the impact of a six month high- and low-intensity cycle-based exercise intervention on cognitive function and biological markers associated with Alzheimer's disease (measured in blood and by brain imaging) in 176 Memory Complainers. Furthermore the impact of genetic factors associated with Alzheimer’s disease risk on responses to exercise within this population will be assessed.

Catherine Blizzard

Spine and synapse plasticity and pathology in TDP-43 aggregated frontotemporal dementia: a novel therapeutic target?

Changes to synapses - the specialised structures that allow neurons to communicate with each other – may be an early disease-causing event in Frontotemporal Dementia (FTD). TDP-43, a DNA processing protein, is one of the main proteins that have been identified to play a role in FTD.  There is now convincing evidence that the dysfunction of TDP-43 can lead to the synaptic disturbances.  Her fellowship aims determine how TDP-43 changes lead to synaptic alterations, through in vitro primary culture techniques and a unique mouse model with sophisticated in vivo live imaging techniques, coupled with post mortem human FTD brain investigation.

Cindy Jones

Online resources - sexuality and dementia

Expression of sexuality by older people, particularly those with dementia, can be challenging and confronting for residential aged care staff. Not only is education on this topic often a low priority area for aged care organisations, there appears to be limited training programs available. Dr Jones' study will seek to evaluate the ease of use, quality and effectiveness of an online education intervention to increase knowledge and improve attitudes of residential aged care staff towards the expression of sexuality by older people including those with dementia.

Claire O'Connor

Understanding behaviour and function in frontotemporal dementia: developing better assessments and intervention approaches

Frontotemporal dementia (FTD) is a degenerative disease that causes changes to personality, behaviour, and language. A primarily younger-onset dementia (onset before 65 yrs), FTD also has a negative impact on a person’s everyday function, leading to difficulties with complex tasks such as shopping and paying bills, then progressing to difficulties with basic care tasks such as dressing and showering. This project will investigate whether these changes in behaviour and everyday function are related, will develop a novel tool to asses functioning of people in the severe stages of FTD, and will also investigate the benefit of an activity-based intervention for people with FTD living in the community with their carers. On a theoretical level, this project will contribute to the growing body of literature and knowledge in the field of FTD. On a practical level, it will lead to better care and support for people with FTD and their families.

Diane Moujalled

The role of RNA binding protein in frontotemporal dementia

Recent studies have identified a brain protein called ‘transactivation response DNA-binding protein-43’, or TDP-43, as having a key role in frontotemporal dementia. However, it is not yet clear how changes in TDP-43 lead to the loss of brain cell function and structure that is seen in frontotemporal dementia. Preliminary work from Dr Moujaled’s lab has shown that another important protein called hnRNP K may regulate the accumulation of mutated TDP-43 in brain cells. In the present study, Dr Moujaled aims to understand the molecular mechanism controlling TDP-43 accumulation in cells, to determine how mutations in TDP-43 may influence the action of hnRNP K, and to see how these contribute to the death of brain cells in people with frontotemporal dementia. If successful, the research may lead to new approaches to developing treatments for frontotemporal dementia and related neurodegenerative diseases.

Julia Gilmartin

Analgesic use, neuropsychiatric symptoms and quality of life in persons with Alzheimer’s disease and their carers

One of the major objectives for treating people with Alzheimer’s disease at present is to help reduce symptoms and maintain quality of life. It is well known that many people with Alzheimer’s disease and other forms of dementia experience moderate to severe chronic pain, and that analgesic (pain relieving) medication is effective at relieving and controlling this pain and improving quality of life. However, studies have highlighted lower use of analgesics among people with Alzheimer’s disease, despite untreated pain being associated with increased use of health care, and symptoms of agitation and aggression. There has also been limited research on the medicine use of carers of people with dementia, despite reports of depressive symptoms, anticipatory grief, and poor quality of life. Dr Gilmartin aims to investigate how analgesic use is associated with behavioural symptoms of Alzheimer’s disease and quality of life in both the individual with Alzheimer’s disease and their carer. Data collected as part of the Finnish ALSOVA study will be analysed, and it is anticipated that the findings of the study will inform Australian health professionals and patients to choose analgesic treatment options with the highest chance of positive outcomes, and therefore improve
the pain management of Australians with Alzheimer’s disease and their carers.

Kim Kiely

The impact of sensory impairment on cognitive decline and dementia: A collaborative cohort study

Sensory loss and dementia are often reported to co-occur and are the two leading contributors to non-fatal disease burden for older Australians. Communication difficulties arising from sensory declines can exacerbate the impacts of cognitive impairment, lead to excess disability, and compromise effective dementia diagnosis, management, and treatment. Importantly, as both hearing and vision loss predict cognitive impairment and dementia incidence, their comorbidity may not simply be a coincidental result of general ageing processes but could reflect a causal connection. A range of mechanisms have been proposed to account for this relationship, but little research has explicitly tested these explanations. This project collates existing international clinical and longitudinal data to advance our understanding of the association between sensory disability and cognitive impairment. The aims of the project are to: i) highlight the combined effects of sensory and cognitive impairment on wellbeing, quality of life, daily functioning and independence, ii) use novel analytic approaches to examine the long-term coupling of sensory and cognitive ageing, iii) identify social, cognitive and biological mechanisms that explain the relationship, iv) ascertain whether hearing rehabilitation can reduce the impacts of hearing loss on impaired cognitive function, v) inform health policy relating to comorbid sensory and cognitive impairment.

Leone Chare

Clinical and pathological associations in Frontotemporal Dementia

Frontotemporal dementia is a common cause of early onset (<65 years of age) dementia, as common as Alzheimer’s disease in this age group. People with frontotemporal dementia can present in one of four different ways that can be differentiated by different behavioural, language and motor dysfunction, with marked diversity between patients. The neuropathology does not match the clinical presentations, with each clinical syndrome associated with a range of molecular pathologies. This makes prediction of the underlying pathology largely guesswork. With the advent of drugs that are aimed at targeting the different molecular pathologies, methods to predict these pathologies has become more urgent. This study aims to determine the associations between the clinical and pathological features that could assist in correct diagnosis and eventually the appropriate medical management of these dementias.

Lesley Cheng

The use of exosomal microRNA biomarkers for the diagnosis of Alzheimer’s disease

There is no consensus for a blood based test for early Alzheimer’s Disease (AD). Deregulation of gene expression has been found to be informative for understanding different biological states. microRNA (miRNA) are small non-coding RNA species that are transcriptionally processed in the host cell. Normally involved in post-transcriptional gene silencing, the deregulation of miRNA has been shown to influence pathogenesis of a number of diseases. miRNA has been found to travel in small membranous microvesicles known as exosomes which can be released extracellularly into the bloodstream. My research involves determining the changes of miRNA expression in exosomes which can be isolated from the blood and profiled using Next-Generation deep sequencing. The significance of this method is to determine a set of differential RNA biomarkers between healthy and AD patients. Samples are obtained from the Australian Imaging, Biomakers and Lifestyle Flagship Study of Aging (AIBL) which is an Australian Flagship study committed to discovering the biomarkers and lifestyle factors that determine the prevalence of AD. This project represents a vital step towards developing a cost-effective and non-invasive diagnostic test to detect the onset and monitor various stages of AD

Marina Cavuoto

Sleep disturbance and cognition in amnestic mild cognitive impairment and healthy older adults.

Sleep disturbance is a prominent feature of Alzheimer’s disease and is associated with dementia severity, reduced quality of life, increased carer burden, and the decision to place people into aged-care institutions. However, little research has been conducted on the sleep of people who may have the earliest changes associated with an Alzheimer’s process, namely amnestic mild cognitive impairment, nor in those older adults with high levels of memory complaint. Given the strong relationship between sleep and memory, gaining insight into the nature of sleep disturbance in people with memory difficulties and memory complaints provides the opportunity to understand the mechanisms of sleep disturbance in Alzheimer’s disease. It may also have important implications for the early detection, treatment and management of the disease.

The project will involve older adults who are aged 65 years and above who are healthy (with and without complaints about their memory) and those with early memory problems but who do not have dementia. The aim is to determine whether measures of sleep quality are associated with memory performance in these groups. Participants will be asked to undertake a number of in-home sleep monitoring sessions, as well tests of memory and attention.

Marion Turnbull

Neurotrophin regulation of Alzheimer’s disease pathology

Research over the last 50 years has indicated that overproduction of the protein called amyloid beta and irregular accumulations of tau proteins in brain cells are responsible for the development and progression of Alzheimer’s disease. However the factors that initiate the production and accumulation of these toxic proteins are poorly understood. Ms Turnbull’s research aims to see if a decrease in the availability of a class of chemicals in the brain called neurotrophins, which are observed in people with Alzheimer’s disease, are associated with the early stages of the development of amyloid beta and tau protein build-up. She aims to understand the molecular mechanisms linking neurotrophin reduction to the dysregulation of amyloid-beta production and tau accumulation. She will also investigate whether a compound called c29 peptide may be able to reduce the production of amyloid beta and reduce tau accumulation in the event of decreased neurotrophin activity in a mouse model of Alzheimer’s disease.

Megan Lenehan

Education in Later-Life and its effects on the Trajectory of Age-Related Cognitive Decline

This research aims to investigate whether formal education undertaken after the age of 50 could have a protective effect on a person’s cognitive function as they age. Approximately 400 healthy adults aged
between 50 and 79 years will have their memory, mental processing speed and attention skills assessed annually over a period of three years. Most participants will undertake a minimum 12 months part-time study at the University of Tasmania, but some participants will not engage in any further university study. The two groups will then be compared to see whether the additional education results in reduced rate of cognitive decline over time.

Michele Callisaya

Pilot Randomized Controlled Trial of exercise to preserve brain health in Type 2 Diabetes Mellitus

Type 2 Diabetes is known to be a significant risk factor for dementia, and it has been suggested that vascular disease may be the common cause of both conditions. Greater physical activity is associated with better brain function and is also recommended for people with Type 2 Diabetes to reduce cardiovascular risk. However, it is currently unknown whether an exercise intervention can preserve or improve brain health in people with Type 2 Diabetes. The aim of Dr Callisaya’s project is to examine whether a six-month exercise program can preserve brain health in people aged 50-70 years with Type 2 Diabetes. Dr Callisaya will also evaluate whether this occurs by improving vascular health. If successful, this study will provide a strong basis for targeting people with Type 2 Diabetes (as a high-risk group) with structured exercise interventions to reduce their dementia risk. It will also provide new insights into the vascular basis of both conditions.

Michelle Kelly

Development of a Social Cognition Assessment Battery for Older Adults

People with dementia often have difficulty with social interaction which can at times lead to misunderstandings, confusion and aggression. This can negatively affect relationships with caregivers, friends and family, and can reduce quality of life for all concerned. Impaired social interaction can be due to problems with interpreting social cues such as facial expressions, or problems with understanding another person’s feelings or intentions. Currently, clinicians working with people with dementia do not routinely assess social skills, possibly due to the limited availability of tests that can be used for this purpose. Dr Kelly’s project aims to develop a bedside screening test for social skills that is suitable for people with dementia. The test will be given to a group of people with dementia and a group of people without dementia. Differences in performance will allow us to determine whether the test is sensitive to the social difficulties we see in people with dementia.

Mitchell Goldsworthy

Identifying neurophysiological markers of early cognitive decline in Alzheimer’s disease

The early detection of patients with Alzheimer's disease is key to more effective early intervention. Current biomarkers for Alzheimer's disease are typically expensive with limited widespread applicability, and are not suited for detecting the subtle changes in brain function that may occur during the initial stages of the disease. There is increasing evidence in animal models of Alzheimer’s disease that subtle changes in synaptic function occur at an early stage of disease progression, affecting the connections between neurons and influencing their capacity to adapt to behavioural and environmental changes. This capacity for neuronal adaptation (a process broadly defined as neuroplasticity) is an important factor mediating learning and memory, and its disruption may be an early sign of Alzheimer’s disease pathology. Recent advances in the combined use of non-invasive brain stimulation techniques and electroencephalography (a non-invasive method for assessing the electrical activity of the brain) have enabled researchers to assess neuronal connectivity and neuroplasticity within brain regions affected early during the development of Alzheimer’s disease. Therefore, this research will investigate whether this highly novel and relatively inexpensive approach might be useful for detecting markers of early brain dysfunction and cognitive decline in Alzheimer’s disease patients.

Monica Cations

A community case-control study examining environmental and lifestyle risk factors for younger onset dementia.

The aim of this project is to examine lifestyle and environmental risk factors for the development of Younger Onset Dementia (YOD). Dementia that develops before 65 years of age is unexpected, distressing and can have devastating consequences for the person, their partner and family. However, there is little known about this group, which is increasing in size due to the Baby Boomer generation. There are many preventable causes of YOD and this project aims to better understand these. In particular, we aim to investigate the long term effects of serious head injury, alcohol and/or substance misuse, vascular risk factors, exposure to heavy metals and psychological trauma. Ultimately, we hope that this project will enable prevention strategies and possibly treatment plans to be developed, reducing the overall burden of YOD in Australia.

Mouna Haidar

Neuromodulatory Control of Memory Circuits in Dementia and Alzheimer’s Disease

Alzheimer’s disease primarily affects the memory-related areas of the brain, and ongoing research into where and how this damage occurs can provide insights into the nature of the disease and its improved treatment. Ms Haidar’s research aims to determine the effects of Alzheimer’s disease on an area of the brain called the ‘nucleus incertus’ (NI). This area is located in the brainstem (at the base of the neck), and produces a chemical called relaxin-3, which is thought to play a role in the regulation of memory and other cognitive functions that are effected in dementia. Mouna’s research is investigating if the NI/relaxin-3 system is damaged at different stages of disease progression in a mouse model of dementia, and she hopes to determine whether alterations in NI/relaxin-3 networks might contribute to memory loss, and ultimately, if relaxin-3 related drugs might be therapeutic.

Moyra Mortby

Apathy in Mild Cognitive Impairment and Clinically Normal elderly: a biomarker of and risk factor for brain structure, cognitive trajectories and apathetic symptom progression?

Apathy is a common neuropsychiatric symptom linked to Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). Apathy is associated with increased functional and cognitive disability, reduced quality of life, increased progression from MCI to AD, earlier institutionalisation and more caregiver burden. While the brain structures associated with apathy in AD are well understood, little is known about them in MCI or people who do not meet the clinical criteria for dementia. With estimates predicting the worldwide incidence of AD to rise to 115.4 million people by 2050, it is vital to identify risk factors early and better understand how the development and progression of AD can be prevented. This project will investigate whether apathy in people who do not meet the clinical criteria for dementia is associated with changes to brain structures and whether these brain structures can help us to better understand how 1) apathy contributes to the risk of developing dementia; 2) treatment of apathy can be improved; and 3) the personal, emotional, social and financial burden of apathy can be reduced. A better understanding may provide a useful biomarker for earlier and more accurate AD diagnosis, improved understanding of apathetic symptom progression, and apathy-related increased dementia risk.

Nupur Kain

Regiospecific Loss of Essential Sphingolipids in the Early Stages of Alzheimer’s disease

Ms Kain’s research will investigate the biochemical changes in the brain that preceed cognitive symptoms in people with Alzheimer’s disease. This research is based on her earlier study that showed a sharp decline in levels of a neurochemical called sphingosine 1-phosphate (S1P) in the hippocampus (the memory region) and temporal gyrus in the brain’s of people with Alzheimer’s disease. She will also look at the influence of a common genetic variation called APO-E4 on changes in these levels and the association with amyloid beta accumulation in brain tissue samples of people without Alzheimer’s disease. Future work will include determining the effect of S1P levels on cognitive function in mice with and without Alzheimer’s disease.

Rachel Atkinson

The role of frontotemporal lobar dementia proteins in nerve cell process function and dysfunction

Ms Atkinson’s project is looking at a number of proteins that are implicated in frontotemporal degeneration, the second most common form of younger onset dementia. She will seek to determine whether these proteins play a role in maintaining nerve cell processes in the brain, and whether it is these maintenance roles that become dysfunctional in frontotemporal lobe degeneration. She will use genetic techniques in animals and in test tubes to examine how these proteins are involved in the function of nerve cell processes, and use human tissue to confirm her results. Deciphering the mechanisms by which these proteins cause nerve cells to dysfunction is vital for the development of new approaches to treatment.