An aspirin a day
22/09/2005 07:08 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
izmeinaHeard this fascinating story on the radio last Sunday. Looks like we've finally found a reason to dump all those extra kilos and feed our stores of cheese to the rats.
Alzheimer's Disease: The Rise And Fall Of A Concept
Summary
The Director of the Research School of Biological Sciences and Institute of Advanced Studies at ANU in Canberra, Professor Jonathan Stone discusses some of the history of Alzheimer's and Dementia and talks about research findings that suggest that Alzheimer's is actually a vascular disease, which has important implications in treatment and prevention of the condition.
Robyn Williams: I’ve just returned from Ireland, from Trinity College, Dublin, where the British Association Festival of Science was on. While there, I looked up an old friend, Ian Robertson, who’s Professor of Psychology at Trinity. He has produced a set of seven steps to keep your mind nimble, steps which may even postpone the onset of dementia, but which at least will probably give your mind a lift. The steps include aerobic exercise, less fatty food, learning new skills and avoiding damaging free radicals. It’s all quoted in this week’s journal Nature, and we’ll have Professor Robertson on in next week’s Science Show.
But the question remains: why do so many people suffer from dementia, including Alzheimer’s disease?
Well the debate is about to be given a bit of a shake-up. Next week at the University of Sydney, Professor Jonathan Stone and Dr Karen Cullen will present lectures with a fresh interpretation of what’s going on. Professor Stone is here to give you a preview today.
Jonathan Stone: One of the quiet revolutions of the last century or so has been in how we die. For the individual, death is still a personal ordeal, something we must each face in a unique way. Statistically however, the causes and experience of death are changing. In particular, we are dying at progressively older ages, and age-related diseases are more common, more troubling and more important. This talk is about one of the most troubling of the trials of age, dementia. Dementia has been recognised for centuries, and has long been regarded as a normal feature of aging. In his ‘As You Like It’, Shakespeare traced the life of a man from mewling infant to whining schoolboy to sighing lover, to cursing soldier, to pompous middle age and piping old age and then:
Last scene of all,
That ends this strange eventful history,
Is second childishness and mere oblivion,
Sans teeth, sans eyes, sans taste, sans everything.
Act II, Scene vii
Until the great public health advances of the late 19th century however, most of the dying in all societies was done by children, overwhelmed by infectious diseases. Age-related conditions of dementia and blindness and muscular weakness and loss of teeth were mixed up in people’s understanding, as in Shakespeare’s stanza, as old age. And the first step of medical science in devising treatment for the problems of aging was to separate the several aspects of aging, among them dementia, so that each could be understood and treated separately.
By the latter half of the 19th century, neurologists had identified dementia as a condition separate from just ‘getting old’; and they had distinguished different types of dementia; the dementia caused by syphilis, for example, was distinguished from the dementia caused by vascular stroke. And that was distinguished from dementia pugilistica, which afflicts boxers who have fought too long. And the neurologists realised that many cases occur in advanced age, without any reason apparent other than age; and they called this senile dementia.
Early in the 20th century, the German neurologists Alois Alzheimer and Emil Kraepelin proposed the recognition of another form of dementia, characterised by three features. First, it appeared in people who were not old, still in their 40s or 50s. Second, it seemed to occur insidiously, without any other known cause of dementia. And third, Alzheimer provided a brilliant description of the pathology of the brain in his cases. Scattered throughout the brains of his patients he saw abnormal blobs of protein, which are now called plaques, sometimes they’re called senile plaques or amyloid plaques.
The plaques have become very important, and eventually confusing, to the understanding of dementia. They are abnormal regions where the complex circuitry of the brain has broken down and a range of abnormal proteins has been deposited, and they are used by pathologists throughout the world to diagnose a dementia as Alzheimer’s disease. Further, many scientists believe that the cause of the dementia lies in one of the many proteins found in the plaques. The protein thought to be the culprit is called amyloid. It is believed to deposit in brain tissue as nerve cells die; and to form a toxic breakdown product called beta-amyloid; which then poisons more nerve cells, which die and release their amyloid; and a destructive cycle follows.
This understanding of dementia took over a century to build, but right at the start of these great developments, Alzheimer was convinced that he had identified a new form of dementia. His influential mentor, Kraepelin, agreed; gave the concept his backing; proposed naming the dementia after its discoverer, and Alzheimer’s disease, the best known of the dementias, was launched.
It had become clear by the 1970s however, that Alzheimer’s idea that he had identified a new, early-onset dementia, was not tenable. Study after study through the middle of the 20th century has shown that the early-onset cases were just early instances of age-related dementia. Alzheimer’s idea of a discrete early-onset condition has been quietly abandoned and the term Alzheimer’s disease is currently applied to age-related dementia, provided the brain shows plaques in sufficient number. A few genetically driven forms of early-onset dementia have been identified, but we now know, thanks to some clever DNA detective work done in the 1990s, that Alzheimer’s patients did not carry these genes.
Not yet abandoned, but under serious challenge, is the second of Alzheimer’s claims for his dementia, that it occurs without any sign of other known diseases. From the start there has been a debate whether age-related dementia can occur without diffuse disease of the blood vessels of the brain. Kraepelin discussed the issue, way back in 1910 and in recent studies, estimates of how often vessel disease occurs in age-related dementia vary from 30% to 90%, and some scientists have begun to argue that maybe Alzheimer’s disease is a vascular disease after all. The brain atrophies, they would argue, because its blood vessels break down, maybe getting blocked, maybe bleeding, in either case starving the brain tissue of blood.
Adding strength to this view is evidence from a quite unexpected source. This was evidence first reported in the 1980s that anti-inflammatory drugs taken for other reasons, usually arthritis, are highly protective against dementia. By the late 1990s, a score or more of studies had appeared, from Europe, from North America, Japan and Australia, all confirming the point. Take non-steroidal anti-inflammatories, like aspirin and indomethacin, take them for long enough and your chances of getting dementia are reduced by 30% some said, or 50% or more. How these drugs protect against dementia is still debated, but one possibility is that they protect blood vessels against oxidative damage. More recently, the statin drugs, which were developed specifically to reduce cholesterol levels and to reduce the atherosclerotic degeneration of vessels, have also proved to be protective against dementia. And finally on this point, there is an important literature on risk factors. Without any assumption about what causes a disease, epidemiologists can analyse what factors seem to be associated with high or low incidence: diet, age, lifestyle, genetics and so on. To cut a long story short, the risk factors for dementia are almost identical with the risk factors for diseases of the cardiovascular system, the heart and the blood vessels. The case for considering the dementia which Alzheimer and Kraepelin had described as a disease of blood vessels, is growing.
Yet another way of assessing our understanding of a disease is to ask whether it leads to successful treatment. The analysis of the amyloid protein of senile plaques has been very powerful, but has not yet led to treatment of dementia, to ways of delaying or preventing dementia. Ways of reducing amyloid deposits in the brain are being devised, and even applied in clinical trials, but not yet with benefit to patients. In the meantime, large-scale prevention is under way in people who, largely for other reasons, like arthritis or high cholesterol, are taking the non-steroidal anti-inflammatory drugs, or the statins. It may be time, respectfully but firmly, to stop looking for a treatment for Alzheimer’s disease because Alzheimer’s concept of an early onset dementia with a distinctive, plaque-related cause has failed; it was a distinction too far, which now I would argue inhibits the growth of understanding of how much protection against dementia is available already.
I became involved in trying to understand the causes of dementia a decade or so ago, when a private charitable trust based in Sydney, the Sir Zelman Cowen Universities Fund, asked me to help manage its research grants program, in which work on dementia had high priority. Through that program I became aware of the work of a young neuropathologist at the University of Sydney, Karen Cullen, who showed me some of her material from the brains of patients diagnosed with Alzheimer’s disease. In a critical step she had deliberately searched for signs of bleeding in these brains, using a range of techniques to detect blood residue and to relate it to plaque. Her material showed that every plaque in every brain she studied, in young brains where the plaques were uncommon, in older brains, in demented brains where the plaques aver very numerous, every plaque is the site of a small bleed, a tiny stroke. Her finding confirms the growing evidence that the Alzheimer-like dementias involve vascular disease, and show precisely what is happening: blood vessels break down in the aging brain, as they do in aging skin for example, creating first one, then a few, then many dead patches of brain, which we see after death as plaques. A finding as striking as this is rarely accepted without argument, and Karen’s work has struck its share of dismissal and delay. But the papers describing her findings will shortly appear in international journals, and we hope, a door to prevention, and delay of dementia, half open for over a decade, will be opened more widely.
For Karen’s observations suggest that Alzheimer-like dementias occur because of the breakdown of cerebral capillaries, the smallest blood vessels of the brain. Each breakdown is a microstroke, too small to cause symptoms, which is why the sufferers often have no clinical history of stroke. But as these microstrokes accumulate, their effects accumulate, and the familiar, sad pattern of cognitive loss, loss of memory, then personality, follows. Age-related dementia, her results suggest, is a vascular disease. That is why the anti-inflammatory and statin drugs are protective. That is why the risk factors for cardiovascular disease and dementia overlap so extensively. That is where prevention and delay are already available. That is where advances in the design and deployment of drugs which preserve blood vessels should give the long-awaited tools to delay and prevent this slow, troubling destruction of personality, known to family and carers as ‘the long goodbye’.
And that is why I now take a small aspirin tablet every day, at least I do whenever I remember.
Robyn Williams: And I might remember too. Well that should shake up the conventional wisdom, don’t you think? Professor Jonathan Stone is director of the Research School of Biological Sciences at the Australian National University in Canberra. The talks launching this new look at Alzheimer’s will be held next Thursday at the University of Sydney.
And next week on Ockham’s Razor, Peter Lavelle will take a radical look at infidelity.
I’m Robyn Williams.
Guests on this program:
Professor Jonathan Stone
Director
Research School of Biological Sciences
Institute of Advanced Studies
Australian National University
Canberra
Alzheimer's Disease: The Rise And Fall Of A Concept
Summary
The Director of the Research School of Biological Sciences and Institute of Advanced Studies at ANU in Canberra, Professor Jonathan Stone discusses some of the history of Alzheimer's and Dementia and talks about research findings that suggest that Alzheimer's is actually a vascular disease, which has important implications in treatment and prevention of the condition.
Robyn Williams: I’ve just returned from Ireland, from Trinity College, Dublin, where the British Association Festival of Science was on. While there, I looked up an old friend, Ian Robertson, who’s Professor of Psychology at Trinity. He has produced a set of seven steps to keep your mind nimble, steps which may even postpone the onset of dementia, but which at least will probably give your mind a lift. The steps include aerobic exercise, less fatty food, learning new skills and avoiding damaging free radicals. It’s all quoted in this week’s journal Nature, and we’ll have Professor Robertson on in next week’s Science Show.
But the question remains: why do so many people suffer from dementia, including Alzheimer’s disease?
Well the debate is about to be given a bit of a shake-up. Next week at the University of Sydney, Professor Jonathan Stone and Dr Karen Cullen will present lectures with a fresh interpretation of what’s going on. Professor Stone is here to give you a preview today.
Jonathan Stone: One of the quiet revolutions of the last century or so has been in how we die. For the individual, death is still a personal ordeal, something we must each face in a unique way. Statistically however, the causes and experience of death are changing. In particular, we are dying at progressively older ages, and age-related diseases are more common, more troubling and more important. This talk is about one of the most troubling of the trials of age, dementia. Dementia has been recognised for centuries, and has long been regarded as a normal feature of aging. In his ‘As You Like It’, Shakespeare traced the life of a man from mewling infant to whining schoolboy to sighing lover, to cursing soldier, to pompous middle age and piping old age and then:
Last scene of all,
That ends this strange eventful history,
Is second childishness and mere oblivion,
Sans teeth, sans eyes, sans taste, sans everything.
Act II, Scene vii
Until the great public health advances of the late 19th century however, most of the dying in all societies was done by children, overwhelmed by infectious diseases. Age-related conditions of dementia and blindness and muscular weakness and loss of teeth were mixed up in people’s understanding, as in Shakespeare’s stanza, as old age. And the first step of medical science in devising treatment for the problems of aging was to separate the several aspects of aging, among them dementia, so that each could be understood and treated separately.
By the latter half of the 19th century, neurologists had identified dementia as a condition separate from just ‘getting old’; and they had distinguished different types of dementia; the dementia caused by syphilis, for example, was distinguished from the dementia caused by vascular stroke. And that was distinguished from dementia pugilistica, which afflicts boxers who have fought too long. And the neurologists realised that many cases occur in advanced age, without any reason apparent other than age; and they called this senile dementia.
Early in the 20th century, the German neurologists Alois Alzheimer and Emil Kraepelin proposed the recognition of another form of dementia, characterised by three features. First, it appeared in people who were not old, still in their 40s or 50s. Second, it seemed to occur insidiously, without any other known cause of dementia. And third, Alzheimer provided a brilliant description of the pathology of the brain in his cases. Scattered throughout the brains of his patients he saw abnormal blobs of protein, which are now called plaques, sometimes they’re called senile plaques or amyloid plaques.
The plaques have become very important, and eventually confusing, to the understanding of dementia. They are abnormal regions where the complex circuitry of the brain has broken down and a range of abnormal proteins has been deposited, and they are used by pathologists throughout the world to diagnose a dementia as Alzheimer’s disease. Further, many scientists believe that the cause of the dementia lies in one of the many proteins found in the plaques. The protein thought to be the culprit is called amyloid. It is believed to deposit in brain tissue as nerve cells die; and to form a toxic breakdown product called beta-amyloid; which then poisons more nerve cells, which die and release their amyloid; and a destructive cycle follows.
This understanding of dementia took over a century to build, but right at the start of these great developments, Alzheimer was convinced that he had identified a new form of dementia. His influential mentor, Kraepelin, agreed; gave the concept his backing; proposed naming the dementia after its discoverer, and Alzheimer’s disease, the best known of the dementias, was launched.
It had become clear by the 1970s however, that Alzheimer’s idea that he had identified a new, early-onset dementia, was not tenable. Study after study through the middle of the 20th century has shown that the early-onset cases were just early instances of age-related dementia. Alzheimer’s idea of a discrete early-onset condition has been quietly abandoned and the term Alzheimer’s disease is currently applied to age-related dementia, provided the brain shows plaques in sufficient number. A few genetically driven forms of early-onset dementia have been identified, but we now know, thanks to some clever DNA detective work done in the 1990s, that Alzheimer’s patients did not carry these genes.
Not yet abandoned, but under serious challenge, is the second of Alzheimer’s claims for his dementia, that it occurs without any sign of other known diseases. From the start there has been a debate whether age-related dementia can occur without diffuse disease of the blood vessels of the brain. Kraepelin discussed the issue, way back in 1910 and in recent studies, estimates of how often vessel disease occurs in age-related dementia vary from 30% to 90%, and some scientists have begun to argue that maybe Alzheimer’s disease is a vascular disease after all. The brain atrophies, they would argue, because its blood vessels break down, maybe getting blocked, maybe bleeding, in either case starving the brain tissue of blood.
Adding strength to this view is evidence from a quite unexpected source. This was evidence first reported in the 1980s that anti-inflammatory drugs taken for other reasons, usually arthritis, are highly protective against dementia. By the late 1990s, a score or more of studies had appeared, from Europe, from North America, Japan and Australia, all confirming the point. Take non-steroidal anti-inflammatories, like aspirin and indomethacin, take them for long enough and your chances of getting dementia are reduced by 30% some said, or 50% or more. How these drugs protect against dementia is still debated, but one possibility is that they protect blood vessels against oxidative damage. More recently, the statin drugs, which were developed specifically to reduce cholesterol levels and to reduce the atherosclerotic degeneration of vessels, have also proved to be protective against dementia. And finally on this point, there is an important literature on risk factors. Without any assumption about what causes a disease, epidemiologists can analyse what factors seem to be associated with high or low incidence: diet, age, lifestyle, genetics and so on. To cut a long story short, the risk factors for dementia are almost identical with the risk factors for diseases of the cardiovascular system, the heart and the blood vessels. The case for considering the dementia which Alzheimer and Kraepelin had described as a disease of blood vessels, is growing.
Yet another way of assessing our understanding of a disease is to ask whether it leads to successful treatment. The analysis of the amyloid protein of senile plaques has been very powerful, but has not yet led to treatment of dementia, to ways of delaying or preventing dementia. Ways of reducing amyloid deposits in the brain are being devised, and even applied in clinical trials, but not yet with benefit to patients. In the meantime, large-scale prevention is under way in people who, largely for other reasons, like arthritis or high cholesterol, are taking the non-steroidal anti-inflammatory drugs, or the statins. It may be time, respectfully but firmly, to stop looking for a treatment for Alzheimer’s disease because Alzheimer’s concept of an early onset dementia with a distinctive, plaque-related cause has failed; it was a distinction too far, which now I would argue inhibits the growth of understanding of how much protection against dementia is available already.
I became involved in trying to understand the causes of dementia a decade or so ago, when a private charitable trust based in Sydney, the Sir Zelman Cowen Universities Fund, asked me to help manage its research grants program, in which work on dementia had high priority. Through that program I became aware of the work of a young neuropathologist at the University of Sydney, Karen Cullen, who showed me some of her material from the brains of patients diagnosed with Alzheimer’s disease. In a critical step she had deliberately searched for signs of bleeding in these brains, using a range of techniques to detect blood residue and to relate it to plaque. Her material showed that every plaque in every brain she studied, in young brains where the plaques were uncommon, in older brains, in demented brains where the plaques aver very numerous, every plaque is the site of a small bleed, a tiny stroke. Her finding confirms the growing evidence that the Alzheimer-like dementias involve vascular disease, and show precisely what is happening: blood vessels break down in the aging brain, as they do in aging skin for example, creating first one, then a few, then many dead patches of brain, which we see after death as plaques. A finding as striking as this is rarely accepted without argument, and Karen’s work has struck its share of dismissal and delay. But the papers describing her findings will shortly appear in international journals, and we hope, a door to prevention, and delay of dementia, half open for over a decade, will be opened more widely.
For Karen’s observations suggest that Alzheimer-like dementias occur because of the breakdown of cerebral capillaries, the smallest blood vessels of the brain. Each breakdown is a microstroke, too small to cause symptoms, which is why the sufferers often have no clinical history of stroke. But as these microstrokes accumulate, their effects accumulate, and the familiar, sad pattern of cognitive loss, loss of memory, then personality, follows. Age-related dementia, her results suggest, is a vascular disease. That is why the anti-inflammatory and statin drugs are protective. That is why the risk factors for cardiovascular disease and dementia overlap so extensively. That is where prevention and delay are already available. That is where advances in the design and deployment of drugs which preserve blood vessels should give the long-awaited tools to delay and prevent this slow, troubling destruction of personality, known to family and carers as ‘the long goodbye’.
And that is why I now take a small aspirin tablet every day, at least I do whenever I remember.
Robyn Williams: And I might remember too. Well that should shake up the conventional wisdom, don’t you think? Professor Jonathan Stone is director of the Research School of Biological Sciences at the Australian National University in Canberra. The talks launching this new look at Alzheimer’s will be held next Thursday at the University of Sydney.
And next week on Ockham’s Razor, Peter Lavelle will take a radical look at infidelity.
I’m Robyn Williams.
Guests on this program:
Professor Jonathan Stone
Director
Research School of Biological Sciences
Institute of Advanced Studies
Australian National University
Canberra
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no subject
Date: 2005-09-22 02:56 pm (UTC)