Our researchers

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Perminder Sachdev AM

Nanotechnology for the diagnosis and treatment of neurodegenerative disorders.

There is currently no treatment to prevent or modify the course of Alzheimer’s disease (AD) and other neurodegenerative dementias. Of the many obstacles to achieving the goal of prevention and cure of AD, we have identified two that can potentially be overcome with the latest developments in nanoscience. Firstly, the challenge of an easily available early diagnostic test can be met by the use of nanoparticles with superparamagnetic properties as imaging agents, tagged with appropriate ligands, for MRI and the newly emerging magnetic particle imaging (MPI). Secondly, nanoparticles, because of their ability to cross the brain’s protective barriers, can be harnessed as drug-delivery systems to deliver novel therapeutic agents directly to the site of pathology in the brain. This collaboration between clinical neuroscience and nanoscience therefore has the potential to transform the diagnostics and therapeutics of neurodegenerative disorders.

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Phillip Tully

The importance of blood pressure and its variability to dementia: an individual participant data meta-analysis from the VARIABLE BRAIN consortium.

High blood pressure is the leading modifiable risk factor for dementia and cerebrovascular diseases. A recent line of investigation in neurology and cardiology indicates that fluctuations in a person’s blood pressure over time are more strongly linked with cerebrovascular diseases than a person’s average blood pressure. This variability in blood pressure also impacts dementia, cognitive function and brain health, however, there have been few studies on this topic. Our aim is to test the hypothesis that fluctuations in blood pressure are associated with dementia and cognitive decline, and secondly, whether the use of certain blood pressure drugs can promote better brain health. To achieve our aims we will bring together researchers from North America, Europe, Asia and Australia, analysing data from 14 studies with information on cognitive function and blood pressure (total=43,219 persons). By thoroughly investigating blood pressure and brain health in this manner, we will help inform decisions on the best strategy to reduce dementia risk.

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Scott Ayton headshot

Scott Ayton

Investigating how presenilin causes neurodegeneration in Alzheimer’s disease.

Memory loss in Alzheimer’s disease results from damage, and ultimately the death of brain cells. The sequence of events that underlies this toxicity is unknown, and understanding this could lead to new drugs. Based on our recent clinical findings, and our new understanding of how Alzheimer-associated proteins might contribute to cell damage, we plan to use laboratory models to establish a new mechanism of toxicity, and trial new therapeutics based on this concept.

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Simon Bell

An international common data model for improving medicine management for people with dementia and comorbid conditions.

Australia’s Clinical Practice Guidelines and Principles of Care for People with Dementia highlight the importance of providing evidence-based care to improve quality of life, maintain function and maximise comfort. However, clinicians do not necessarily prescribe the same guideline-recommended medicines for people with and without dementia. Indeed, people with dementia are often excluded from randomised controlled trials. Fortunately, recent and widespread availability of electronic prescribing and dispensing data are transforming medicine safety and effectiveness research. We propose to develop the first large-scale international common data model (CDM) specifically for people with dementia. A CDM is a data platform that supports secondary use of linked health data through standardising definitions, terminologies, vocabularies and coding schemes. Using the CDM, we will conduct analyses of linked Australian, Hong Kong, UK and US data to generate new evidence regarding medicine safety and effectiveness for people with dementia. This will help fill a critical evidence gap.

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Stephanie Gibson

Ensuring safe and appropriate hospital discharge prescribing of opioids for people living with dementia.

Pain is a common symptom among people living with dementia. Opioid analgesics are often prescribed for pain at hospital discharge. However, opioids have been associated with a range of side-effects including constipation, delirium, falls, trauma and death. People with dementia may be at higher risk of medication-related harm and also prescribed effective pain relief less often compared to people without dementia. The decision not to prescribe opioids at hospital discharge reduces the risk of side-effects but increases the risk of inadequate pain management.

This study aims to investigate opioid prescriptions on hospital discharge and the risk of rehospitalisation and death in people living with dementia. It is a retrospective study linking diagnoses, medications, re-hospitalisations and death. The primary outcome will be time to rehospitalisation or death. The aim and implications of this research is to inform future strategies and recommendations to improve pain management and reduce the risk of opioid-related harm in people with dementia.

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Stephanie Wong

Financial vulnerabilities in younger onset dementia: insights for targeted interventions.

People with dementia have a higher risk of being financially exploited, and may also have difficulty managing their money. These financial issues have especially serious consequences for people with younger-onset dementia, as they are usually affected at a stage in their lives where they may still have significant financial responsibilities (e.g. paying mortgages, supporting children, running businesses). However, little is known about the different types of risk factors for financial exploitation and mismanagement in these individuals. Through a series of questionnaires and interviews with family members and tests in people with younger-onset dementia, this project will identify changes in cognition and behaviour that give rise to increased financial exploitation and mismanagement. By understanding what causes these financial problems, we can work to develop better ways to minimise exploitation and mismanagement while supporting financial independence in people with younger-onset dementia.

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Yen Ying Lim

High-frequency sampling of cognition in clinically normal adults at genetic risk of Alzheimer’s disease using mobile applications.

Detecting the earliest signs of memory problems is critical for identifying individuals at-risk for dementia so that they can be given the opportunity to sign up for clinical trials and make lifestyle changes. Accurately measuring memory change is hard as memory can vary from day-to-day. Most studies measure memory annually, which is problematic because it assumes that individuals are in a similar state of mind every year (not fatigued, not stressed). One alternative is to increase the number of times an individual is tested to get a more accurate estimation of their memory. Unfortunately, many studies cannot implement this approach, as studies do lengthy and expensive tests in a clinic. Using two smartphone apps that we developed, we aim to determine the feasibility and reliability of high-frequency memory assessments. These apps have the potential to be one of the first of their kind to be implemented across large Alzheimer’s studies.

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Zina Hijazi

The influence of cerebrovascular disease in dementia with Lewy bodies.

Dementia with Lewy bodies is a common type of dementia, and shares symptoms with Alzheimer’s disease and Parkinson’s disease. Trials have not found any treatments that can prevent deterioration in this condition. There is limited information as to the cause of symptoms experienced and the prognosis. Certain brain changes have been found to be more common in people with dementia. One such change is small bleeds in the brain, called cerebral microbleeds. This study will examine the prevalence and distribution of small bleeds in the brain of people with dementia with Lewy bodies, and explore the effect on symptoms of the condition. The results of the study will improve understanding of the potential influence of cerebral microbleeds in dementia with Lewy bodies, and therefore the clinical condition and management.

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Ben Summers headshot

Ben Summers

Protecting axon-glial interactions to guard against dementia

Alzheimer’s disease and vascular dementia can be associated with vascular related brain damage, often caused by brain cells being deprived of oxygen. White matter regions of the brain are particularly susceptible to this type of injury. They contain the long, thin nerve cell processes that act like the electrical wires of the brain, and the specialist insulating cells called oligodendrocytes, that wrap and insulate the nerves, and provide them with energy and nutrients. This project will study the interactions between nerve cells and oligodendrocytes under normal and low oxygen conditions. It will determine how oligodendrocytes die and determine whether blocking this pathway to enhance oligodendrocyte survival can improve nerve cell health in low oxygen conditions.  Additionally, this project will examine individual oligodendrocytes in order to understand which nerves they associate with, how they regulate nerve cell function to facilitate learning and memory, and how this is affected in dementia.

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Duncan Sinclair headshot

Duncan Sinclair

How does stress impact pathological processes in Alzheimer's disease?

Brain changes associated with stress may increase risk for Alzheimer’s disease, or make it worse. This makes the stress hormone system an exciting target for new drugs, but more work is required to understand how such drugs might work. This study will investigate how the stress hormone system impacts production and accumulation of a molecule, amyloid beta, which builds up abnormally in brain cells during Alzheimer’s disease. This study will also determine whether this happens ‘vice versa’, so that amyloid beta abnormalities change the sensitivity of brain cells to stress. By performing these experiments, we hope to lay the groundwork for new therapies for reducing risk for Alzheimer’s disease and slowing its progression.

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Hakuei Fujiyama headshot

Hakuei Fujiyama

Dr

Entrainment of brain oscillations to improve inhibitory function in people with MCI

Inhibitory control, a key aspect of executive cognitive control, declines early in the neurodegenerative processes that ultimately lead to dementia. It appears that changes in the brain networks are responsible for a decline in inhibitory control in individuals with mild cognitive impairment (MCI), a preclinical stage of dementia.  It has been suggested that non-invasive brain stimulation (NiBS) is a powerful tool to improve cognitive function in people with the AD. Here we will investigate whether the application of NiBS can improve inhibitory function in people with MCI. The aims of the project are (1) to investigate the efficacy of NiBS on inhibitory function in people with MCI, and (2) to reveal the underlying neurophysiological mechanisms in inhibitory processing changes induced by NiBS on brain networks. Thus, the project will answer the question of whether NiBS can ameliorate declines in inhibitory control by altering the functioning of specific brain networks.

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 Hayley Lamonica headshot

Haley LaMonica

Dr

Developing and evaluating an online Healthy Brain Ageing psychoeducation and cognitive training intervention for older adults with Mild Cognitive Impairment

The Healthy Brain Ageing team at the University of Sydney’s Brain and Mind Centre has developed and tested a multi-faceted, face-to-face information and brain training program for older adults at higher risk of developing dementia. Our seven-week ‘Healthy Brain Ageing’ program can improve memory, depression symptoms and sleep quality. We aim to translate this program to a web-based format, thus increasing its accessibility and suitability to a broad range of older adults. We will redesign the program, taking into account specific needs of older adults with cognitive difficulties (e.g. navigating the Internet, engaging activities etc.). We will then scientifically evaluate whether the online program is effective and feasible compared to a ‘waitlist’ control group who will receive the program later on. This project represents an opportunity to develop and evaluate a cost-effective, accessible and deliverable intervention to reduce the impact of cognitive decline in older adults ‘at risk’ of dementia.

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Imogen Clark headshot

Imogen Clark

Dr

Therapeutic songwriting to support relationship quality among community dwelling people living with dementia and their family caregivers: A proof of concept randomised controlled trial

This project for community-dwelling people living with dementia and their family carers aims to examine the potential of group songwriting as a means for improving their social connection, mental health and wellbeing, and positive change in quality of life for both. Group songwriting, facilitated by a registered music therapist, is an innovative process involving social interaction, mental stimulation and emotional exploration with others in a similar situation to create original songs. The songwriting process is expected to help families and couples living with dementia to explore personal resources and challenges, and may assist them to continue living together in a loving and mutually supportive relationship for as long as possible. Songs written during the project will be performed and recorded to increase public awareness and understanding about what it is like to live with dementia.

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Isabella Choi headshot

Isabella Choi

Dr

Consumer co-creation of an e-health dementia risk profiling tool: exploring benefits and harms

Would you want to know your risk of dementia? How can this be communicated to you in a meaningful, non-distressing, and engaging way, which will motivate you to make changes to your lifestyle and health risk factors to reduce your dementia risk? This project addresses these questions by conducting focus groups with consumers to explore their attitudes towards knowing personal dementia risk and collaboratively designing an interactive online personal dementia risk profiling tool. We will test the resulting risk profiling tool in a trial with people at-risk of developing dementia to assess whether it facilitates an accurate understanding of risk, and its impacts on psychological distress and engagement in behaviours to reduce risk. The risk profiling tool could be later used in primary care, ehealth interventions, and dementia prevention programs, to empower people at risk of dementia to take action to reduce their modifiable risks and lessen the impact on society.

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Joyce Siette headshot

Joyce Siette

Dr

Evaluating social engagement services for older adults in community care: Role of social networks in cognitive decline

Current treatments for dementia are effective in only a subset of patients, and for these individuals it only manages to temporarily halt symptom progression. A ‘cure’ would involve reversal of a complex cognitive and non-cognitive syndromes, and likely require psychosocial changes early on in an individual’s life. Here, we aim to see if rich and meaningful social networks play a significant protective role in memory decline associated with old age. The proposed studies will inform future social engagement services through their evaluation of current social services offered in community care (e.g., meals on wheels, intergenerational interaction activities) and will form a new evidence base on how to best structure social networks in order to improve an individual’s quality of life.

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Kevin KaiEn Chen headshot

Kevin Kai-En Chen

Dr

Stabilising the retromer protein coplex with molecular chaperones for Alzheimer's and Parkinson's diseases

Many neurodegenerative diseases, including Alzheimer’s and Parkinson’s, are inherently disorders of protein homeostasis. Targeting of neuronal proteostasis for the treatment of neurodegenerative diseases and dementia is thus emerging as an area of significant interest for pharmaceutical development. But our understanding of these pathways, in neurons in particular, and our ability to pharmacologically manipulate these pathways is severely limited. One of the central mechanisms controlling neuronal proteostasis is the transport of proteins within the endolysosomal membrane controlled by a molecular machinery called the retromer complex. Retromer dysfunction has been strongly linked to neurodegenerative diseases, and such defects in cells and animal disease models can be rescued by the over-expression of retromer. Recent studies have confirmed that a retromer-enhancing small molecule chaperone can reverse both amyloid β and α-synuclein accumulation in neuronal cell models.

This project seeks to determine the molecular mechanism of chaperone interaction with retromer, and being to identify new molecules with greater specificity and activity. The implications will be a better understanding of the molecular basis of retromer stabilisation, providing a novel platform for the validation of retromer as a therapeutic target for neurodegenerative diseases and leads towards the development of future drug design.

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Kirrily Rogers headshot

Kirrily Rogers

Ms

Together but alone: caregiver grief and loss in dementia syndromes

Dementia is defined by loss – loss of specific brain cells due to diseases like Alzheimer’s disease cause changes in a person’s abilities and thinking skills. The losses that accompany dementia produce a form of grief that starts before the person dies and is expressed by family caregivers as loss of relationships, lifestyle, and future plans. Most research exploring grief in dementia has focused on Alzheimer’s dementia (AD) rather than other types of dementia, such as frontotemporal dementia (FTD). FTD is defined by behaviour change, which is known to result in higher levels of caregiver burden. To understand the contribution of grief to caregiver burden, this research aims to look at differences in grief experiences for spousal caregivers of people with AD and FTD. This will form the basis of interventions to support caregivers of people with different types of dementia with the goal of reducing overall caregiver burden.

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Linda Steele headshot

Linda Steele

Dr

Safe and just futures for people living with dementia in residential aged care ('Safe and Just Futures')

People living with dementia experience disproportionate rates of institutional violence in Residential Aged Care Facilities (RACFs). ‘Safe and Just Futures’ engages people living with dementia, care partners, lawyers, advocates, RACF regulatory bodies and services around stories and solutions for a safer and more just dementia care. It develops workable recommendations for more appropriate and effective legal responses to protect and enhance quality of life for people living with dementia in RACFs. This action research project takes an approach that combines dignified, respectful and non-discriminatory reparation and support for individual victims with large-scale reform to the RACF regulatory frameworks and practices and public hearings of past and historical abuses. The project seeks to:

  1. Promote reforms to regulatory frameworks and RACF practices to promote safer and more just care of people living with dementia; and
  2. Recognise and remedy harms experienced by people living with dementia and others affected by these incidents.
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Luba Sominsky

Dr

Neuroinflammation in the development of dementia

Ageing brings an increased vulnerability to cognitive decline and dementia. However, what places some individuals at a higher risk to develop dementia is not well understood. Recent studies suggest that obesity is associated with brain inflammation and significantly increases the likelihood to develop ageing-related cognitive decline. This project will determine whether obesity-induced cognitive decline is driven by increased activation of microglia, the brain immune cells, and if by suppressing the activity of these cells cognitive dysfunction can be improved. This study will significantly advance our understanding of the role microglia have in ageing-related cognitive decline and the development of dementia, particularly in the context of obesity. Findings from this project aim to provide a novel target for therapeutic interventions that may benefit individuals with dementia.   

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Mark Hackett headshot

Mark Hackett

Dr

Investigation of age-related alteration to hippocampal elemental and biochemical homeostasis and neuro-vascular function, as a means to identify new therapeutic strategies to minimise or delay dementia onset in the elderly

Australia is facing a crisis from the enormous health care costs associated with Alzheimer’s disease and dementia. New research into pathways that contribute to the disease are urgently needed, to identify lifestyle strategies or therapies to prevent, minimise or delay dementia. Of all the organs, the brain has the highest energy demands, which makes blood vessels, the suppliers of vital energy and nutrients to the brain, essential to healthy brain function. Several researchers have proposed that damage to blood vessels in the brain, may upset finely balanced biochemical relationships, potentially driving the progression of dementia. However, identifying when and where such events occur has been difficult. My aim in this project is to use newly developed imaging techniques, made possible with incredibly bright synchrotron light, to study changes in biochemical and metal levels that occur inside brain cells after damage to blood vessels.