Neurology
See below for NEUROLOGY/MULTIPLE SCLEROSIS
NEUROLOGY/DEMENTIA/ALZHEIMER'S DISEASE
Can statins protect against cognitive decline associated with dementia? - also offered as MBiomedSc
Supervisors: A/Professor Cassandra Szoeke
Project Site: Healthy Ageing Program, Dept of Medicine, Centre for Medical Research, Royal Melbourne Hospital
Contact: A/Professor Cassandra Szoeke T:61 3 8387 2224 F : 61 3 9387 9384 E: cszoeke@unimelb.edu.au
Project description: Cognitive impairment is becoming an increasingly researched field in ageing, particularly with dementia being in the top five leading causes of burden in Australia. Despite these already high and increasing prevalence rates, there is no curative treatment for AD. Therefore the identification of individuals who are at increased risk of AD and the implementation of preventive interventions is necessary until a treatment is found. Cardiovascular risk factors, including cholesterol, are typically thought to be associated with an increased risk of dementia. However the use of statins (cholesterol lowering medication) and its effect on cognitive performance has not been thoroughly investigated, particularly assessing duration of use. This research will help us identify the short term and long term effects of cholesterol-lowering medication on cognition, and whether statins can be used as prevention against dementia.
The project will provide a unique opportunity to work on an Australian dataset with midlife and late-life data collected (data over 20 years), and will suit a candidate with interest in commercialisation and ageing. There is also opportunity for publication.
Nutrient intake and cognitive decline - also offered as MBiomedSc
Supervisors: A/Professor Cassandra Szoeke
Project Site: Healthy Ageing Program, Dept of Medicine, Centre for Medical Research, Royal Melbourne Hospital
Contact: A/Professor Cassandra Szoeke T:61 3 8387 2224 F : 61 3 9387 9384 E: cszoeke@unimelb.edu.au
Project description: There is increasing evidence to suggest that diet may play an important role in preventing or delaying the on-set of Alzheimer’s disease (AD). Research has reported that a Mediterranean-type diet is associated with a lower risk of prevalent AD. One important pathological hallmark of AD is beta-amyloid (Aβ) peptide deposition in the brain, resulting in formation of plaques. However little is known about the possible association between nutrient intake and Aβ plasma. In this study, we will examine whether dietary intake of nutrients (data already collected from a food frequency questionnaire) is associated with plasma Aβ levels in a cross-sectional analysis of women aged 65 years and over. Aβ levels will be examined using Positron Emission Tomography (PET) scans (data already collected) in collaboration with imaging experts.
A major benefits of this project is that the nutritional data set has already been collected. The project will suit a candidate with interest in dietary factors and health, as well as media or commercialisation and industry interaction. This project also provides opportunity for publication.
Lifestyle Factors and Cognitive Health - also offered as MBiomedSc
Supervisors: A/Professor Cassandra Szoeke
Project Site: Healthy Ageing Program, Centre for Medical Research, Royal Melbourne Hospital
Contact: A/Professor Cassandra Szoeke E: cszoeke@unimelb.edu.au T: 8344 1835
Project description: Several studies have described the benefit of lifestyle change for healthy ageing and cognitive improvement. For example smoking and alcohol consumption have been linked to an increased rate of cognitive impairment and cardiovascular diseases. Studies investigating lifestyle factors have been limited by cohort sampling bias, cross sectional designs, short follow‐ups and small sample sizes. Furthermore the frequency and intensity of lifestyle alteration is still not defined. In this project we examine a 20 year longitudinal dataset to determine the influence of lifestyle factors on cognitive performance and health.
The main opportunities for this project are:
An opportunity for publication
Hands-on involvement in participant evaluation
Work with a large database with over 20 years of lifestyle data
This project would suit a candidate with an interest in neuropsychology
Examining neuropsychological trajectories using data collected from longitudinal study - also offered as MBiomedSc
Supervisors: A/Professor Cassandra Szoeke
Project Site: Healthy Ageing Program, Centre for Medical Research, Royal Melbourne Hospital
Contact: A/Professor Cassandra Szoeke E: cszoeke@unimelb.edu.au T: 8344 1835
Project description: In this study we will examine neuropsychological trajectories over the 16 years for which we have cognitive data and the many associated factors such as menopausal status, psychological status, health status, cognitive performance, APOE e4 status, and so on, to determine risk and protective factors for cognitive decline. The WHAP also has neuroimaging data (structural and functional) for about half of its cohort, which we may be able to explore in connection with cognition in this project.
The project will suit a candidate with interest in neuropsychology. Benefits of this project include the opportunity for publication and that the data set has already been collected.
Subjective memory complaints, frailty and dementia - also offered as MBiomedSc
Supervisors: A/Professor Cassandra Szoeke
Project Site: Healthy Ageing Program, Centre for Medical Research, Royal Melbourne Hospital
Contact: A/Professor Cassandra Szoeke, E: cszoeke@unimelb.edu.au T: 8344 1835
Project description: The early detection of those likely to develop dementia is essential. Subjective memory complaints have been associated with low mood and subjective cognitive decline. However better selection of those with subjective memory complaints to distinguish the worried well from those with disease is required. Some imaging studies have shown that increased amyloid in those subjective memory complaints despite no objective memory change. In this study we will examine 15 years of cognitive decline with subjective memory complaints and frailty measures, adjusting for mood.
Major benefits from this study are:‐
There is opportunity for publication
You will work with a well-known longitudinal database with over 20 years of data already collected
What causes a neuron to die? Investigating the essential role of selenium nutrition in neurodegenerative disease including Alzheimer’s
Supervisors: Dr. Blaine R. Roberts
Project Site: Florey Inst. Neuroscience, Melbourne Brain Centre
Contact: Dr. Blaine R. Roberts blaine.roberts@florey.edu.au
Project description: Selenium is an essential trace element required for normal development. Curiously, out of the entire human genome of ~22,000 genes we only have 25 genes that encode for selenium containing proteins. This indicates an evolutionarily conserved function for selenium proteins. We have recently connected a newly discovered pathway for cell death known as ferroptosis to a key antioxidant selenium enzyme. The enzyme is known as glutathione peroxidase 4 (GPX4) and is a master regulator of ferroptoisis. Ferroptosis was discovered as a new form of cell death in cancer cells. Oxidative stress and selenium nutrition are intimately linked to the incidence and progression of cancer. The brain has a unique requirement for selenium and the levels of selenium in brain tissue are implicated in the pathogenesis of Alzheimer’s disease.
This project involves the use of modern cutting edge ‘omics’ technology (e.g. Proteomics and Metallomics) to investigate the role of selenium containing proteins in human Alzheimer’s disease tissue.
NEUROLOGY/MULTIPLE SCLEROSIS
Validation of computerized tools for the assessment of tremor severity in Multiple Sclerosis - also offered as MBiomedSc
Supervisors: Dr Anneke van der Walt, Dr Thushara Perera
Project Site: Department of Medicine, Royal Melbourne Hospital and Bionics institute
Contact: Dr Anneke van der Walt, Anneke.vanderwalt@mh.org.au
Project description: Tremor in MS (MST) is difficult to treat and the development of new interventions is limited by the absence of universal measuring systems. At present, therapeutic outcomes are measured by a variety of clinical rating scales that are subjective and lack sufficient sensitivity. With increasing use of interventional treatments such as Botulinum toxin injections or Deep Brain Stimulation for MST, it has become critical to develop precise measurement instruments.
This project aims to compare two computerized techniques used to measure MS tremor severity. The first is a 3D motion tracker, called TREMBAL, developed by the Bionics institute. The second is a simple joystick-based computer game. The aim of the project is to demonstrate that the simple joystick computer game is equivalent to the 3D motion tracker analysis.
During the project, you will be able to analyse data from MS patients with and without tremor, using both methods. This project requires MATLAB and statistical skills.
Functional MRI of speech in multiple sclerosis: understanding the organisation of speech production and its relation to cerebellar dysfunction
Supervisors: Dr Anneke van der Walt, Dr Scott Kolbe, Dr Adam Vogel
Project Site: Department of Medicine at Royal Melbourne Hospital, UoM, Centre for Neuroscience of Speech at The University of Melbourne
Contact: Dr Anneke van der Walt, Anneke.vanderwalt@mh.org.au
Project description: Dysarthria is the most common communication disorder in MS, with a prevalence ranging from 40% to 55%. Yet, it has not often been the focus of MS studies. There are virtually no studies investigating the correlation of other cerebellar scores with dysarthria severity in MS. The underlying pathophysiology of dysarthria in MS is also not well understood with mixed reports of cerebellar, brainstem pathology and cortical pathology contributing to the changes in voice production.
To explore this, we have recruited and assessed patients with MS with and without arm tremor by performing a functional Brain MRI during which participants performed several reading, speaking and listening tasks.
This study aims to 1) analyse functional brain MRI and 2) understand the network changes observed by comparing it to clinical speech analysis and cerebellar disability scores. We hypothesize that the affected functional brain networks will be different in patients with and without other cerebellar features (such as arm tremor).
During this project, you will gain experience in analysing functional MRI images and develop the neuroanatomical knowledge to interpret these results. You will become familiar with statistical approaches to correlative analyses. This work will add to the current knowledge about communication problems in people with M
Measuring long-term disability outcomes in Multiple Sclerosis - also offered as MBiomedSc
Supervisors: Dr Tomas Kalincik; Dr Vilija Jokubaitis; Prof Helmut Butzkueven
Project Site: Department of Medicine / Royal Melbourne Hospital / The University of Melbourne
Contact: Tomas Kalincik; E: tomas.kalincik@unimelb.edu.au
Project description: Prevention of irreversible disability is the most important goal of multiple sclerosis disease modifying therapy. However, assessment of disability outcomes in multiple sclerosis therapeutic trials is complicated by the great individual and time-dependent variability of disability and measurement error. In particular, the design of modern clinical trials with 1–3 year follow-up infers long-term irreversible disability outcomes from short-term disability measures. We have previously shown that the currently used definitions of disability accrual are suboptimal, as they are not associated with long-term disability outcomes in up to 25% of the recorded events.
This project develops a new metric of short-term change in disability that is highly predictive of long-term irreversible disability accrual, suitable for use in clinical trials of therapies. It builds on the definition of confirmed disability progression (Kalincik et al., Brain 2015, 138:3287) and utilizes MSBase, a large global observational multiple sclerosis cohort of more than 39,000 patients.
This project will suit students with interest in statistics and health outcomes research. During the project, you will improve your statistical skills, learning some of the more complex statistical techniques. Knowledge of elementary statistics is a requisite. You will contribute to the evidence-based clinical management of multiple sclerosis.
Therapy of progressive forms of multiple sclerosis - also offered as MBiomedSc
Supervisors: Dr Tomas Kalincik; Dr Vilija Jokubaitis; Prof Helmut Butzkueven
Project Site: Department of Medicine / Royal Melbourne Hospital / The University of Melbourne
Contact: Tomas Kalincik; E: tomas.kalincik@unimelb.edu.au
Project description: Treatment options for relapsing and progressive forms of multiple sclerosis differ greatly. While more than 10 disease modifying therapies are available for treatment of relapsing multiple sclerosis, effective management of progressive multiple sclerosis is lacking. It is possible that the immunomodulatory therapies effective in relapsing multiple sclerosis are also suitable for treatment of progressive multiple sclerosis; however, conclusive evaluation of this hypothesis is needed. Due to the very slow disability accrual in progressive multiple sclerosis, evaluation of treatment efficacy in prospective randomised trials in impractical. On the other hand, large observational cohorts provide the opportunity to generate these much needed answers.
This project compares effectiveness of different available disease modifying therapies in progressive multiple sclerosis forms. We hypothesise that the highly potent immunosuppressive therapies modify disability trajectories in progressive multiple sclerosis. The project utilizes MSBase, a large global observational multiple sclerosis cohort of more than 39,000 patients, which we have recently used to develop an objective definition of secondary progressive multiple sclerosis (Lorscheider et al., Brain, in press). It uses advanced statistical modelling, including propensity score-based comparisons and marginal structural models, in order to control multiple biases inherent in observational data.
This project will suit students with interest in statistics and health outcome research. During the project, you will improve your statistical skills, learning some of the more complex statistical techniques. Sound knowledge of elementary statistics is a requisite. The generated evidence will influence clinical management of multiple sclerosis globally.