Lewy Bodies In Patients With Dementia – Determining Common And Unique Mechanisms In Relation To Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
Alzheimer’s disease is the most common type of dementia but often has multiple mixed pathologies. For example, Alzheimer post mortem brains may have abnormal accumulation of Lewy bodies in certain parts of the brains, and could be diagnosed as Lewy body disease. This may represent a skewed representation of some dementia subtypes. This project will identify the biological determinants of dementia patients with Lewy body disease for better understanding and future therapeutic targeting.
Dementia Related Deficits In Striatal Cholinergic Function And Decision-making
Funder
National Health and Medical Research Council
Funding Amount
$414,370.00
Summary
This proposal will provide essential new information on the role of deficits in decision-making associated with Parkinson’s disease dementia. We will use an innovative animal model to assess the influence of neurodegeneration and neuroinflammation the consequent loss of function in the neuronal systems supporting the learning and memory processes that contribute to goal-directed action, particularly the way new learning interacts with existing memory to guide choice and decision-making.
Feasibility Of Minimally Invasive Deep Brain Stimulation Via An Endovascular Stent-electrode.
Funder
National Health and Medical Research Council
Funding Amount
$122,032.00
Summary
Neurocognitive decline in Parkinson's disease refers to the non-motor symptoms of the disease; these symptoms have increasingly become recognised as both prevalent, and evolving early in the disease course. While motor symptoms are treated with drugs and electrodes, the changes to patients� cognition, the progressive dementia, the psychosis and other symptoms progress with poor treatment. This research is designed to identify and understand targets so better treatments can be created.
Retinal Microvascular Signs In Acute Stroke: Prognostic Significance And Relevance To Underlying Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$375,425.00
Summary
This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that asses ....This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that assess size of the small retinal arteries compared to veins (the arteriole-to-venule ratio) and will document other abnormalities, such as microaneurysms, haemorrhages, tortuosity and focal and generalised vessel narrowing and wall opacity. In normal populations these signs are associated with hypertension, inflammation and endothelial dysfunction and predict future stroke. These signs, and their significance have not been systematically studied in acute stroke. This may offer a window into the brain for important subgroups of stroke such as lacunar stroke. It is increasingly hard (and remains technically very difficult) to study the cause of lacunar stroke, affecting 10,000 Australians each year, as lacunar stroke has a lower fatality rate (and thus few opportunities for post mortem studies) but a high disability rate. Lacunar stroke is known to be due to small vessel disease but the exact nature of this disease is unknown. Echocardiography (to identify heart and major blood vessel abnormalities) and carotid duplex scanning (to identify critical stenosis of the major blood supply to the brain) are commonly normal in this type of stroke, and brain scanning with computerised tomography (CT) or magnetic resonance (MR) merely shows the outcome of the small vessel disease. The eye develops as part of the brain and thus retinal vascular abnormalities could add important knowledge to our understanding of stroke and add clinically useful data in the assessment of patients with stroke.Read moreRead less
Post-stroke Hyperglycaemia – Treatment With Exenatide In Acute Ischaemic Stroke (TEXAIS) Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,266,149.00
Summary
Raised blood glucose levels (hyperglycaemia) after a stroke is common. It reduces the efficacy of stroke treatments and results in worse outcomes. Insulin is not useful as a treatment for this as it causes frequent hypoglycaemia and does not improve clinical outcomes. Exenatide is a common diabetes drug that is simple to use and lowers blood glucose without hypoglycaemia. It will be tested in the Treatment with Exenatide in Acute Ischaemic Stroke (TEXAIS) trial.
Dementia In Type 2 Diabetes – Studying Causal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$514,786.00
Summary
Type 2 diabetes mellitus (T2D) is an important risk factor for dementia, and knowledge regarding the biological pathways linking the two disorders can provide great insight into the causes of dementia overall. I plan to study the links between T2D and dementia using analytical modelling to tease out causal pathways. My overall vision is to establish a sound knowledge base upon which effective interventions can be devised to prevent or delay dementia, using T2D-related dementia as a model.
The Role Of Brain Inflammation In Leptin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$730,123.00
Summary
Melanocortin neurons control body weight and are regulated by leptin. In obesity leptin cannot regulate the melanocortin system. We will test if leptin action on melanocortin neurons is limited by increased expression of suppressor of cytokine signalling 3 (SOCS3) in obese mice. As an alternative we will test if there are changes in the blood brain barrier, or an increased density of support and immune cells around melanocortin neurons of obese mice that might restrict inputs to these neurons.
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less
Investigating Underlying Mechanisms Linking Type 2 Diabetes With Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$701,950.00
Summary
With type-2 diabetes representing a major risk factor for neurodegenerative diseases such as Alzheimer's disease, it is important to understand the underlying mechanisms. This project will provide significant insight into how T2D impacts the brain with a focus on how deficiencies in brain inuslin signaling drives neurodegeneration. We will also evaluate novel inuslin like molecules at improving brain insulin siganling and preventing or slowing down the neurodegenerative process.
Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understandin ....Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understanding the mechanisms underpinning this success have the potential to further improve surgical approaches and outcomes and provide insights that will better enable weight loss therapies for all overweight and obese Australians.Read moreRead less