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Retinal Vascular Signs As Risk Markers For Incident Stroke Or Cerebrovascular Death: A Population-based Assessment
Funder
National Health and Medical Research Council
Funding Amount
$410,199.00
Summary
Stroke remains a major cause of disability and death in Australia. Preliminary data from the Blue Mountains Eye Study suggest that blood vessel changes observed in the retina at the back of the eye may provide signs of an increased risk of stroke or death from stroke. Importantly, although stroke is strongly associated with elevated blood pressure, the risk associated with these blood vessel signs seems to be independent of blood pressure. The proposed study will conduct a detailed re-grading of ....Stroke remains a major cause of disability and death in Australia. Preliminary data from the Blue Mountains Eye Study suggest that blood vessel changes observed in the retina at the back of the eye may provide signs of an increased risk of stroke or death from stroke. Importantly, although stroke is strongly associated with elevated blood pressure, the risk associated with these blood vessel signs seems to be independent of blood pressure. The proposed study will conduct a detailed re-grading of retinal photographs taken on people who attended the Eye Study during 1992-4 and 5-year follow-up exams during 1997-9. We will grade these photographs manually (using a stereo-viewer), and with computer assistance to measure changes in the diameter of small arteries in the retina and other signs. By closely matching our grading technique to that used in a large American Study, we hope to develop reliable grading for these signs and will be able to compare our findings internationally. Our aim is to assess the frequency of abnormal retinal vessel changes in people of different age groups as well as the development and progression of these signs over time. Their relationship to well known vascular risk factors like smoking, blood pressure, obesity, diabetes and cholesterol will also be investigated. We hope to be able to discriminate those changes associated with an increased stroke risk from those due to normal ageing. We expect that the increased stroke risk associated with abnormal retinal vessel changes may be greater than shown in our early data. If confirmed, then these findings may provide a more sensitive and objective measure of stroke risk than relying on traditional risk factors, which are difficult to quantify and change with time. We may be able to develop simple rules so that doctors using an ophthalmoscope or examining a retinal photograph could identify high risk patients. These people could benefit from interventions to reduce their risk.Read moreRead less
Neurophysiological Basis For Sensorimotor Interventions In Rehabilitation After Stroke
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Stroke is estimated to cost the Australian government almost $2 billion annually, and is the most common cause of death after heart disease and cancer and one of the largest single causes of long-term disability. Of people who survive a stroke, a large number have some degree of residual motor dysfunction on one side of the body. Motor rehabilitation programmes are generally considered to enhance the recovery of motor function and to reduce the degree of long-term disability. However the rationa ....Stroke is estimated to cost the Australian government almost $2 billion annually, and is the most common cause of death after heart disease and cancer and one of the largest single causes of long-term disability. Of people who survive a stroke, a large number have some degree of residual motor dysfunction on one side of the body. Motor rehabilitation programmes are generally considered to enhance the recovery of motor function and to reduce the degree of long-term disability. However the rationale for the design of effective rehabilitation programmes is largely empirical, and there is uncertainty regarding the efficacy and cost-effectiveness of currently used therapies. The empirical nature of stroke rehabilitation has resulted in a diversity of techniques, many of which were pioneered 30-40 years ago, and which are generally aimed at enhancing brain plasticity as a means to facilitate motor recovery. However, despite the belief that brain plasticity is a key to recovery, it is still not known how best to develop this potential for reorganisation into practical interventions that could be introduced in stroke rehabilitation. The aim of the present study is to investigate the physiological bases for the action of commonly used sensorimotor rehabilitation strategies and identify those strategies which are most effective in bringing about corticomotor reorganisation, in the belief that such reorganisation is fundamental to motor recovery. Specifically we will investigate the changes in the organisation of the cortical projection to muscles of the upper limb as a result of passive movement, resisted and non-resisted movement, increased functional motor use and visuomotor training programmes. It is anticipated that the study will lead to a better understanding of the physiological basis for therapeutic interventions after stroke and will allow a more rational approach to the design of effective rehabilitation programmes for stroke patients.Read moreRead less
A Study Of Mechanisms Of Cognitive Decline In Type 2 Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$510,222.00
Summary
Diabetes mellitus and dementia are major public health problems. Diabetes may increase the risk of dementia. This study aims to uncover the mechanism by which diabetes may increase dementia risk. This may lead to finding new ways to prevent or treat diabetes-related dementia and thus reduce the public health burden of dementia.
Mechanisms Of Cell Death In Focal Cerebral Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$229,624.00
Summary
Stroke most commonly results from interruption to a major artery in the brain. If not rapidly reversed the reduction in blood flow leads to the death of many cells in the brain tissue. There is currently considerable interest in developing treatments to be used in the early stages of stroke that can reduce cell death. As the extent of cell death is the major determinant of the long-term disabilities from stroke, such treatments are likely to provide considerable benenfits for affected individual ....Stroke most commonly results from interruption to a major artery in the brain. If not rapidly reversed the reduction in blood flow leads to the death of many cells in the brain tissue. There is currently considerable interest in developing treatments to be used in the early stages of stroke that can reduce cell death. As the extent of cell death is the major determinant of the long-term disabilities from stroke, such treatments are likely to provide considerable benenfits for affected individuals. Our study will investigate mechanisms underlying the death of brain cells in an animal model of stroke and in cells treated in culture. These studies will specifically focus on the role in cell death of alterations in mitochondria, a part of the cell that provides the energy needed for their normal function. The proposed investigations will identify molecular events that contribute to the mitochondrial dysfunction and examine the importance of these changes in brain tissue damage. The findings should contribute to the identication of new therapeutic approaches aimed at ameliorating the consequences of stroke.Read moreRead less
Retinal Vascular Signs As Predictors Of Systemic Disease Outcomes: 10-year Evolution In A Population-based Cohort
Funder
National Health and Medical Research Council
Funding Amount
$389,575.00
Summary
Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important sys ....Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important systemic health outcomes in the population-based cohort of residents attending the Blue Mountains Eye Study (BMES. Two types of retinal signs will be evaluated: firstly, the presence of specific clinical signs, such as focal narrowing of small retinal vessels (arterioles), nicking of retinal veins as arterioles cross them or presence of retinopathy (haemorrhages and other signs) secondly, measures of generalized retinal vessel calibre (narrowing) using a computer-assisted method developed for the U.S. studies. We will also develop new grading methods for two other signs. Late and will compare computer-assisted grading from 35mm slides to automated grading of vessels using a scanning device (being developed) to screen the eyes of older persons. This project builds upon our current 3-year NHMRC grant (ID153948; 2001-2003) Retinal vascular signs as risk markers for incident stroke or cerebrovascular death: A population-based assessment . In the last 2 years, this has explored different aspects of measurement and grading of these signs, has documented their relation to blood pressure and has begun to assess whether these features predict vascular events and other systemic outcomes in older Australians. The new project will assess the evolution of retinal microvascular signs over a 10-year period, using data and retinal photographs from the 10-year examinations of the BMES cohort, currently being collected, in a further current NHMRC grant (ID211069; 2002-2004).Read moreRead less
Cerebral Circulation In Sleep - Physiology & Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$779,650.00
Summary
Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both adults and children. As many as 200,000 Australian adults and 100,000 children are affected. OSA has major medical consequences, amongst the most serious being cardiovascular disease and stroke. This experimental study investigates the blood flow to the brain and heart in normal sleep, and in sleep disrupted by OSA, as many of the ....Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both adults and children. As many as 200,000 Australian adults and 100,000 children are affected. OSA has major medical consequences, amongst the most serious being cardiovascular disease and stroke. This experimental study investigates the blood flow to the brain and heart in normal sleep, and in sleep disrupted by OSA, as many of the problems associated with OSA may have their origin in disturbance of blood flow to the brain and heart.Read moreRead less
Cerebral Circulation In Sleep: Impact Of Endothelial Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$313,026.00
Summary
Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both children and adults. As many as 200,000 Australian adults and 300,000 children are affected. OSA has major medical consequences, amongst the most serious being cognitive deficits in children and vascular disease and stroke in adults. This experimental study investigates blood flow to the brain in normal sleep, and in sleep disrupte ....Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both children and adults. As many as 200,000 Australian adults and 300,000 children are affected. OSA has major medical consequences, amongst the most serious being cognitive deficits in children and vascular disease and stroke in adults. This experimental study investigates blood flow to the brain in normal sleep, and in sleep disrupted OSA, as many of the problems associated with OSA may have their origin in disturbance of blood flow to the brain.Read moreRead less
Nox4-containing NADPH-oxidase As A Protective Enzyme In The Cerebral Circulation
Funder
National Health and Medical Research Council
Funding Amount
$515,812.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activa ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activation of an enzyme, Nox4-containing NADPH-oxidase, to generate oxygen radicals which then relax the wall of blood vessels causing the arteries to let more blood through. We believe that this process plays an important role in the normal, healthy maintenance of blood supply to the brain. Furthermore, we propose that the activity of this enzyme is elevated and therefore protective in brain arteries during high blood presure - which is the major risk factor for stroke. We will specifically test whether the activity of this enzyme actually helps to limit the amount of brain death following stroke. We will use a variety of techniques to assess the importance of this enzyme in brain arteries in the living body, and also in isolated segments of brain artery from animals that are either healthy or have diseased brain arteries. The results are expected to provide major new insight into processes that help maintain brain blood flow under normal conditions and after a stroke, and the knowledge gained here should lead to safer therapies to prevent or treat stroke.Read moreRead less
MECHANISMS OF CEREBROVASCULAR REGULATION IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$216,430.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the degree of opening of the cerebral arteries. This mechanism involves activation of an enzyme, Rho-kinase, which is present in the wall of blood vessels. The applicants believe that this process plays an important role in the normal, healthy regulation of blood supply to the brain. Moreover, there are strong reasons for us to speculate that the function of this enzyme is abnormally high in two disease states that are associated with an increased risk of stroke - high blood pressure and subarachnoid haemorrhage. We will employ a variety of techniques to assess the importance of Rho-kinase in cerebral artery function in the living body, and also in isolated segments of artery. The results are expected to provide major new insight into mechanisms that regulate brain blood flow, and the knowledge gained here may lead to better therapies to prevent or treat stroke.Read moreRead less
The Impact Of CPAP Treatment On Carotid Artery Atherosclerosis In Heavy Snoring And Mild Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$697,512.00
Summary
Mild sleep disordered breathing, including habitual snoring, is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that habitual snoring may be an independent risk factor for the development of stroke. In this proposal we will explore the hypothesis that treatment for snoring will slow or stop the development of carotid artery atherosclerosis.