Aspirin For The Prevention Of Cognitive Decline In The Elderly: A Neuro-Vascular Imaging Study (ENVIS-ion) From ASPREE
Funder
National Health and Medical Research Council
Funding Amount
$1,341,232.00
Summary
The ENVIS-ion trial will examine whether Aspirin is effective in delaying the onset of worsening of thinking and memory abilities in healthy older adults. Magnetic resonance imaging (MRI) of brain structure will detect markers of early worsening of thinking and memory abilities. Blood vessels in the back of the eye (retina) share many features with vessels in the brain. We will compare whether aspirin lessens changes over time of features shown with brain MRI and retinal photography.
Pressures Exerted On Upper Airway Walls By Surrounding Tissue Structures
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open a ....The obstructive sleep apnoea syndrome (OSA) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSA effects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in 5% of men over the age of 45 years. In the proposed studies we will examine the effect of the pressure in the tissues surrounding the throat on the ability of the throat to stay open and allow breathing. The major outcome of the animal studies is increased knowledge concerning mechanisms whereby collapsing forces are applied to the upper airway. This will give insights into potential factors influencing upper airway collapse during sleep in OSA patients. Of particular importance will be our studies on the effects of jaw position on the pressure exerted on the walls of the throat since the use of an intra-oral device to hold the jaw forward during sleep is one of the treatments used to prevent throat blockage during sleep. The studies in humans will examine, for the first time, the notion that the mass (weight) of the neck has a direct effect on the severity of sleep disordered breathing. If neck mass has a substantive influence on sleep disordered breathing then strategies aimed at reducing neck mass (fat) may provide a new therapeutic approach to the management of OSA patients.Read moreRead less
An FMRI Analysis Of The Functional Organization Within The Brain Of Experimental Superficial And Deep Orofacial Pain
Funder
National Health and Medical Research Council
Funding Amount
$307,526.00
Summary
This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a dee ....This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a deep pain that has a dull, aching quality that may be referred to related sites of the face, head and neck. It is also not known why jaw muscle pain is more common in females in comparison to males. Chronic jaw muscle pain is a major symptom of patients with Temporomandibular Disorders, the most common form of non-dental orofacial pain and that involves pain in or about the jaw joint and-or jaw muscles, and often limitation of jaw movement. Chronic jaw muscle pain can have a severe effect on quality of life but its diagnosis and management is difficult. Despite the widespread prevalence of chronic orofacial pains, we have little information on the central processing of chronic human orofacial pain. This proposal will improve our fundamental understanding of how jaw muscle pain is processed in the brain. The way that the central nervous system processes and represents jaw muscle pain will help explain why these pains present differently in the clinic and should provide important information on the differences between females and males in the representation of jaw muscle pain. This information on the central processing of chronic orofacial pain is crucial to inform the direction of novel or specific management strategies. Our long-term goal is to improve the diagnosis and management of patients with Temporomandibular Disorders, and the present application represents a major new direction of research.Read moreRead less
RISK AND PROTECTION FACTORS FOR NORMAL AND ABNORMAL BRAIN AGEING: A LONGITUDINAL EPIDEMIOLOGICAL MRI STUDY
Funder
National Health and Medical Research Council
Funding Amount
$153,020.00
Summary
Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed u ....Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we propose to perform MRI scans and blood tests on a quarter (n-500) of the 60-64 sample to obtain an epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3, wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain, both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and psychiatric disorder in old age.Read moreRead less
BioPolymer Fibres For Remodelling Mdx And Damaged Muscle
Funder
National Health and Medical Research Council
Funding Amount
$527,286.00
Summary
This project aims to generate new, smart polymers for use in re-building muscle that has degenerated due to disease and-or trauma damage. The merger of smart polymers with biologically based solutions and cells has great potential to improve outcomes of treatments of damaged muscle in diseases such as Muscular Dystrophy.
Hydrostatic Pressure Distributions In Peri-pharyngeal Tissues : Impact On Upper Airway Patency
Funder
National Health and Medical Research Council
Funding Amount
$508,935.00
Summary
The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our mo ....The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our model will be the influence of the properties of the tissue that form the walls of the throat. Our goal is to construct a computer model that will be useful in identifying specific features of throat function that make people susceptble to the development of OSAHS. In this manner we hope to provide a tool that can be used to develop new approaches to the treatment and prevention of OSAHS.Read moreRead less
Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
An Extended Follow-up Of Stroke Patients For Cognitive Impairment And Neuropsychiatric Disorders: Sydney Stroke Study
Funder
National Health and Medical Research Council
Funding Amount
$321,800.00
Summary
Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not bee ....Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not been studied. There have been few studies of the progressive changes in MRI in patients with cerebrovascular disease. The overlap of VaD and Alzheimer's disease (AD) remains a problem for taxonomists and clinicians. One approach to the study of VaD is to examine a high risk group of subjects longitudinally to determine the early features, the risk factors and progressive changes. With this in mind, we began studying a cohort of stroke patients who are at high risk of VaD, in 1997-1999, and are following them longitudinally. The follow-up is now in its third year, and three neuropsychological assessments and two MRI-MRS scans have been performed. We propose to extend the follow-up to 5 years, with repeat neuropsychiatric, neuropsychological and MRI-MRS investigations, and wherever possible to necropsy, to determine the nature of vascular pathology that underlies cognitive impairment. Our cohort of stroke patients is arguably the most comprehensively assessed such cohorts internationally, and presents an excellent opportunity for a long-term follow-up study.Read moreRead less
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.