Alzheimer's disease (AD) affects as much as 10% of the world population above 65 years of age but after years of research it is still not understood exactly how the disease appears and, even less, how to treat it. But work just published in The EMBO Journal opens the door to new ways for disease intervention by showing that lipids found throughout the brain can dissolve the large insoluble protein plaques characteristic of the disease, releasing their soluble protofibrillar components, and also that it is the soluble components and not the insoluble plaques that provoke neural death. These results identify a new target for disease intervention - the soluble protofibrillar components - but also alert for the fact that the insoluble plaques are, nevertheless, reservoirs of toxicity and so will need to be controlled too, while also identifying a totally new influence in the disease - the patients' lipid metabolism - and in this way add a few important pieces to the puzzle that is AD.
Alzheimer's is a progressive fatal illness that results from the death of certain brain areas associated with cognitive functions such as memory and learning. Starting with forgetfulness as the disease progresses patients suffer major personality changes and, eventually, a terrifying loss of the "self" occurs. The disease is associated with an abnormal amyloid-beta (A??) protein that incapable of fold properly -all proteins need specific 3D structures to work properly - accumulates instead in large insoluble deposits (or amyloids) in the brain of patients exactly where neurons' death occurr. These insoluble plaques have a fibrillar structure and originate from the agglomeration of free A??-peptide after an intermediate state as soluble protofibrills.
Although initially it was thought that the large fibrillar plaques were behind the disease, more recent research seems to suggest that it is the intermediate protofibrillar form that is neurotoxic. Also recently there has been increasing suggestions of a link between AD and alterations in the lipid metabolism of patients, while some lipids - such as cholesterol - have been shown to affect the formation of the insoluble plaques.
Trying to understand better what is happening in the disease Ivo Cristiano Martins, Inna Kuperstein, Joost Schymkowitz, Frederic Rousseau and colleagues at the VIB Switch Laboratory, Vrije Universiteit Brussel, and the VIB Department of Molecular and Developmental Genetics,K.U.Leuven, Belgium decided to test the effect of different biological lipids on both the protofibrillar and the fibrillar forms of the aberrant A??-protein, while also analysing how all these factors affected the neurodegeneration characteristic of AD.
To start, the team of researchers exposed insoluble fibrillar plaques like those found in patients' brains to several naturally occurring lipids - such as cholesterol - to find that in their presence the plaques partially dissolved, releasing the soluble protofibrills that constitute them. This result showed, for the first time, that the formation of plaques was a reversible process and as such could be manipulated if necessary.
Martins, Kuperstein and colleagues then tested the neurotoxicity of the obtained protofibrills and show that they were able, not only of kill isolated neurons, but also of affect the brain of injected mice. The insoluble fibrills (plaques) were shown to be biologically inert on both cases. To further investigate the different neurotoxicities of the fibrillar versus the protofibrillar form of A??-peptide, mice were injected with one or the other and tested for memory and learning capacities (both cognitive capabilities affected in Alzheimer's). Again it was found that only the protofibrillar form deteriorated mice capabilities to perform. Interestingly, the damaging effect was temporary agreeing with the idea that the protofibrills eventually turned into the inert fibrillar plaques in a process similar to what occurs in AD.
Martins, Kuperstein and colleagues' work has several important implications. Their results confirm that it is the protofibrillar form of A??-peptide that is neurotoxic and not the insoluble fibrillar plaques but also reveals - by showing that plaque formation is reversible - that the plaques are, nevertheless, reservoirs of toxicity. They also suggest that disturbances in the metabolism of lipids have the potential to influence the development of AD and may be the reason behind the fact that many times the extension of the insoluble plaques in the brain of AD patients does not correlate with their disease severity.
As Ivo Martins - a Portuguese researcher and one of the main authors explains - "before our work the plaques were seen as relatively innocuous, the last stage of the disease, but what we show here is that they are in reality a" time bomb" ready to be activated by interacting with lipids"
A major implication of Martins and colleagues' work is to bring into the field two very exciting new avenues for disease intervention: control of the lipid metabolism and neutralization of the toxicity/formation of A?? protofibrills. And, in a world where Alzheimer's affects about 10 percent of people over 65 with as much as half of those over 85 suffering with the disease, new targets for therapy are undoubtedly good news. As Martins reveals "The next step, already under work in the our laboratory, is the production of drugs and /or antibodies capable of control the neurotoxic fibrils"
Piece researched and written by Catarina Amorim
Catarina.Amorim at linacre.ox.ac.uk
"Lipids revert inert Ab amyloid fibrils to neurotoxic protofibrils that affect learning in mice"
Ivo Martins, Joost Schymkowitz, Frederic Rousseau
The EMBO Journal (2008) 27, 224-233
Link to original article
понедельник, 20 июня 2011 г.
воскресенье, 19 июня 2011 г.
New Study Investigating Side Effects Of Dementia Drugs
Side effects associated with several commonly-prescribed dementia drugs may be putting elderly Canadians at risk, says Queen's University Geriatrics professor Sudeep Gill.
Cholinesterase inhibitors (Aricept, Exelon and Reminyl) are often prescribed for people with Alzheimer's disease and related dementias because they increase the level of a chemical in the brain that seems to help memory. Although such drugs are known to provoke slower heart rates and fainting episodes, the magnitude of these risks has not been clear until now.
"This is very troubling, because the drugs are marketed as helping to preserve memory and improve function," says Dr. Gill, who is an Ontario Ministry of Health and Long-term Care Career Scientist, working at Providence Care's St. Mary's of the Lake Hospital in Kingston. "But for a subset of people, the effect appears to be the exact opposite."
In a large study using province-wide data, Dr. Gill and his colleagues discovered that people who used cholinesterase inhibitors were hospitalized for fainting almost twice as often as people with dementia who did not receive these drugs. Experiencing a slowed heart-rate was 69 per cent more common amongst cholinesterase inhibitor users. In addition, people taking the dementia drugs had a 49 per cent increased chance of having permanent pacemakers implanted and an 18 per cent increased risk of hip fractures.
Unfortunately, Dr. Gill continues, this class of drugs is one of the few effective dementia treatments available today. Acknowledging that these drugs do have an important role in the management of dementia, he suggests that people who are already at a higher risk (for example, those who have had previous episodes of fainting or slowed heart rate) may want to ask their doctors to reassess the value of taking the drugs.
Slowing of the heart rate from cholinesterase inhibitors, if significant, may cause a person to faint and suffer fall-related injuries such as a broken hip - often debilitating and sometimes fatal for seniors. However, many physicians aren't aware of the connection between these problems and the dementia drugs, Dr. Gill notes.
If the association with dementia drugs is not identified, people who faint may be prescribed a permanent pacemaker: an invasive procedure that can involve serious complications for seniors. Both the injuries incurred from falling and the risks from pacemaker implants are "downstream consequences" of not recognizing this drug-induced phenomenon.
"This study does not suggest that dementia patients shouldn't take these drugs," says Dr. Gill. "What's critical is that patients, caregivers and physicians be aware of the potential side effects, and weigh these risks carefully against the potential for beneficial effects."
The findings are published in the journal, Archives of Internal Medicine. Scientists from the Institute for Clinical Evaluative Sciences, the University of Toronto and Harvard University are also on the research team.
The study uses data housed at the Institute for Clinical Evaluative Sciences (ICES). Ontario's first satellite unit of ICES was established at Queen's in 2007 to provide university researchers with electronic access to Ontario health datasets and population registries by secured and encrypted lines. Areas of focus at Queen's include cancer, pharmacological studies and dementia.
Source:
Jeff Drake
Queen's University
View drug information on ARICEPT; Exelon; Reminyl.
Cholinesterase inhibitors (Aricept, Exelon and Reminyl) are often prescribed for people with Alzheimer's disease and related dementias because they increase the level of a chemical in the brain that seems to help memory. Although such drugs are known to provoke slower heart rates and fainting episodes, the magnitude of these risks has not been clear until now.
"This is very troubling, because the drugs are marketed as helping to preserve memory and improve function," says Dr. Gill, who is an Ontario Ministry of Health and Long-term Care Career Scientist, working at Providence Care's St. Mary's of the Lake Hospital in Kingston. "But for a subset of people, the effect appears to be the exact opposite."
In a large study using province-wide data, Dr. Gill and his colleagues discovered that people who used cholinesterase inhibitors were hospitalized for fainting almost twice as often as people with dementia who did not receive these drugs. Experiencing a slowed heart-rate was 69 per cent more common amongst cholinesterase inhibitor users. In addition, people taking the dementia drugs had a 49 per cent increased chance of having permanent pacemakers implanted and an 18 per cent increased risk of hip fractures.
Unfortunately, Dr. Gill continues, this class of drugs is one of the few effective dementia treatments available today. Acknowledging that these drugs do have an important role in the management of dementia, he suggests that people who are already at a higher risk (for example, those who have had previous episodes of fainting or slowed heart rate) may want to ask their doctors to reassess the value of taking the drugs.
Slowing of the heart rate from cholinesterase inhibitors, if significant, may cause a person to faint and suffer fall-related injuries such as a broken hip - often debilitating and sometimes fatal for seniors. However, many physicians aren't aware of the connection between these problems and the dementia drugs, Dr. Gill notes.
If the association with dementia drugs is not identified, people who faint may be prescribed a permanent pacemaker: an invasive procedure that can involve serious complications for seniors. Both the injuries incurred from falling and the risks from pacemaker implants are "downstream consequences" of not recognizing this drug-induced phenomenon.
"This study does not suggest that dementia patients shouldn't take these drugs," says Dr. Gill. "What's critical is that patients, caregivers and physicians be aware of the potential side effects, and weigh these risks carefully against the potential for beneficial effects."
The findings are published in the journal, Archives of Internal Medicine. Scientists from the Institute for Clinical Evaluative Sciences, the University of Toronto and Harvard University are also on the research team.
The study uses data housed at the Institute for Clinical Evaluative Sciences (ICES). Ontario's first satellite unit of ICES was established at Queen's in 2007 to provide university researchers with electronic access to Ontario health datasets and population registries by secured and encrypted lines. Areas of focus at Queen's include cancer, pharmacological studies and dementia.
Source:
Jeff Drake
Queen's University
View drug information on ARICEPT; Exelon; Reminyl.
суббота, 18 июня 2011 г.
What is Dementia? What Causes Dementia? Symptoms of Dementia
The word dementia comes from the Latin de meaning "apart" and mens from the genitive mentis meaning "mind". Dementia is the progressive deterioration in cognitive function - the ability to process thought (intelligence).
Progressive means the symptoms will gradually get worse. The deterioration is more than might be expected from normal aging and is due to damage or disease. Damage could be due to a stroke, while an example of a disease might be Alzheimer's.
Dementia is a set of signs and symptoms
Dementia is a non-specific syndrome in which affected areas of brain function may be affected, such as memory, language, problem solving and attention. Dementia, unlike Alzheimer's, is not a disease in itself. When dementia appears the higher mental functions of the patient are involved initially. Eventually, in the later stages, the person may not know what day of the week, month or year it is, he may not know where he is, and might not be able to identify the people around him.
Dementia is significantly more common among elderly people. However, it can affect adults of any age.
What are the symptoms of dementia?
Memory loss - the patient may forget his way back home from the shops. He may forget names and places. He may find it hard to remember what happened earlier on during the day.
Moodiness - the patient may become more and more moody as parts of the brain that control emotion become damaged. Moods may also be affected by fear and anxiety - the patient is frightened about what is happening to him.
Communicative difficulties - the affected person finds it harder to talk read and/or write.
As the dementia progresses, the patient's ability to carry out everyday tasks diminishes and he may not be able to look after himself.
Diseases that cause dementia
Alzheimer's disease - This is by far the most common cause of dementia. The chemistry and structure of the brain of a person with Alzheimer's disease changes and his brain cells die prematurely.
Stroke (Vascular problems) - this means problems with blood vessels (veins and arteries). Our brain needs a good supply of oxygen-rich blood. If this supply is undermined in any way our brain cells could die - causing symptoms of vascular dementia. Symptoms may appear suddenly, or gradually. A major stroke will cause symptoms to appear suddenly while a series of mini strokes will not.
Dementia with Lewy bodies - spherical structures develop inside nerve cells. Brain cells are nerve cells; they form part of our nervous system. These spherical structures in the brain damage brain tissue. The patient's memory, concentration and ability to speak are affected. Dementia with Lewy bodies is sometimes mistaken for Parkinson's disease because the symptoms are fairly similar.
Fronto-temporal dementia - this includes Pick's disease. The front part of the brain is damaged. The patient's behavior and personality are affected first, later his memory changes.
Other diseases - progressive supranuclear palsy, Korsakoff's syndrome, Binswanger's disease, HIV and AIDS, and Creutzfeldt-Jakob disease (CJD). Dementia is also more common among patients who suffer from Parkinson's disease, Huntington's disease, Motor Neurone disease and Multiple Sclerosis. People who suffer from AIDS sometimes go on to develop cognitive impairment.
There are two main categories of dementia
Interesting mental health articles:
What is psychology? What are the branches of psychology?
What is psychotherapy? What are the benefits of psychotherapy?
What is ADHD (attention deficit hyperactive disorder)
What is Post-Traumatic Stress Disorder (PTSD)? What causes PTSD?
What is anorexia? What is bulimia?
What is anxiety? Anxiety symptoms and causes.
What is autism? What causes autism?
What is bipolar disorder?
What is depression? What causes depression?
What is dyspraxia? How is dyspraxia treated?
What is hypochondria?
What is mental health? What is mental disorder?
What is schizophrenia?
According to most experts, there are two main categories of dementia - cortical and subcortical dementias.
Cortical Dementia - The cerebral cortex is affected. This is the outer layer of the brain. The cerebral cortex is vital for cognitive processes, such as language and memory. Alzheimer's disease is a form of cortical dementia, as is CJD (Creutzfeldt-Jakob disease).
Subcortical Dementia - A part of the brain beneath the cortex (deeper inside) becomes affected or damaged. Language and memory are not usually affected. A patient with subcortical dementia will usually experience changes in his personality, his thinking may slow down, and his attention span may be shortened. Dementias which sometimes result from Parkinson's disease are subcortical dementias, as are those caused by AIDS and Huntington's disease.
A patient with multi-infarct dementia will have both the cortical and subcortical parts of the brain affected or damaged.
Diagnosis of dementia
Although there are some brief tests, a more reliable diagnosis needs to be carried out by a specialist, such as a geriatric internist, geriatric psychiatrist, neurologist, neuropsychologist or geropsychologist.
The following tests are commonly used:
AMTS (Abbreviated Mental Test Score) A score lower than six out of ten suggests a need for further evaluation.
MMSE (Mini Mental State Examination) A score lower than twenty-four out of thirty suggests a need for further evaluation)
3MS (Modified Mini-Mental State Examination)
CASI (Cognitive Abilities Screening Instrument)
It is important that the patient's score is interpreted in context with his socio-economic, educational and cultural background. The tester must also factor in the patient's present physical and mental state - does the patient suffer from depression, is he in great pain?
What is the treatment for dementia?
In the majority of cases dementia is incurable. Researchers are making inroads into treatments that may slow down dementia's progress. Cholinestaerase inhibitors are frequently administered during the early stages. Cognitive and behavioral therapies may also be useful. Several studies have found that music therapy helps patients with dementia. It is important to remember that the patient's caregiver also needs training and emotional support.
See our specialized news channels
Psychology / Psychiatry news
Attention Deficit Hyperactive Disorder (ADHD) news
Alzheimer's / Dementia news
Anxiety / Stress news
Autism news
Bipolar disorder news
Depression news
Dyslexia news
Eating disorders news
Mental health news
Neurology news
Schizophrenia news
In the USA, Tacrine (Cognex), donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) have been approved for the treatment of dementia caused by Alzheimer's disease - some physicians prescribe these drugs for vascular dementia as well. Selegiline, which is used for treating Parkinson's disease, has been found to slow down the progress of dementia.
In Canada, a country where two languages are spoken, English and French, researchers found that bilingual people who develop dementia do so four years later than monolingual people who develop dementia. The four year difference prevails even after factoring for such variables as cultural differences, education, employment, gender and immigration.
How common is dementia?
United Kingdom - According to a report by the Alzheimer's Society (UK), approximately 700,000 people in the United Kingdom have dementia, out of a total population of about 61 million. Your chances of having dementia are 1 in 100 during your late 60s, this rises to 6 in 100 in your late 70s, and 20 in 100 in your late 80s. As people live longer experts predict dementia will rise significantly. According to predictions, there will be 940,000 people with dementia in the United Kingdom by 2021.
Worldwide - According to a study published in The Lancet, approximately 24.3 million people had dementia worldwide in 2005, with 4.6 million new cases every year. The number of people with dementia will double every two decades and reach 81.1 million by 2040. The rate of increase is expected to be faster in developing countries which have rapidly-growing life expectancies. (Lancet. 2005 Dec 17;366(9503):2112-7)
Sources - The Alzheimer's Society (UK), NIH, Wikipedia, The Lancet
Written by
For the latest news on dementia, and to sign up to newsletters or news alerts, please visit our dementia news section.
View drug information on ARICEPT; Exelon; Selegiline tablets.
Progressive means the symptoms will gradually get worse. The deterioration is more than might be expected from normal aging and is due to damage or disease. Damage could be due to a stroke, while an example of a disease might be Alzheimer's.
Dementia is a set of signs and symptoms
Dementia is a non-specific syndrome in which affected areas of brain function may be affected, such as memory, language, problem solving and attention. Dementia, unlike Alzheimer's, is not a disease in itself. When dementia appears the higher mental functions of the patient are involved initially. Eventually, in the later stages, the person may not know what day of the week, month or year it is, he may not know where he is, and might not be able to identify the people around him.
Dementia is significantly more common among elderly people. However, it can affect adults of any age.
What are the symptoms of dementia?
Memory loss - the patient may forget his way back home from the shops. He may forget names and places. He may find it hard to remember what happened earlier on during the day.
Moodiness - the patient may become more and more moody as parts of the brain that control emotion become damaged. Moods may also be affected by fear and anxiety - the patient is frightened about what is happening to him.
Communicative difficulties - the affected person finds it harder to talk read and/or write.
As the dementia progresses, the patient's ability to carry out everyday tasks diminishes and he may not be able to look after himself.
Diseases that cause dementia
Alzheimer's disease - This is by far the most common cause of dementia. The chemistry and structure of the brain of a person with Alzheimer's disease changes and his brain cells die prematurely.
Stroke (Vascular problems) - this means problems with blood vessels (veins and arteries). Our brain needs a good supply of oxygen-rich blood. If this supply is undermined in any way our brain cells could die - causing symptoms of vascular dementia. Symptoms may appear suddenly, or gradually. A major stroke will cause symptoms to appear suddenly while a series of mini strokes will not.
Dementia with Lewy bodies - spherical structures develop inside nerve cells. Brain cells are nerve cells; they form part of our nervous system. These spherical structures in the brain damage brain tissue. The patient's memory, concentration and ability to speak are affected. Dementia with Lewy bodies is sometimes mistaken for Parkinson's disease because the symptoms are fairly similar.
Fronto-temporal dementia - this includes Pick's disease. The front part of the brain is damaged. The patient's behavior and personality are affected first, later his memory changes.
Other diseases - progressive supranuclear palsy, Korsakoff's syndrome, Binswanger's disease, HIV and AIDS, and Creutzfeldt-Jakob disease (CJD). Dementia is also more common among patients who suffer from Parkinson's disease, Huntington's disease, Motor Neurone disease and Multiple Sclerosis. People who suffer from AIDS sometimes go on to develop cognitive impairment.
There are two main categories of dementia
Interesting mental health articles:
What is psychology? What are the branches of psychology?
What is psychotherapy? What are the benefits of psychotherapy?
What is ADHD (attention deficit hyperactive disorder)
What is Post-Traumatic Stress Disorder (PTSD)? What causes PTSD?
What is anorexia? What is bulimia?
What is anxiety? Anxiety symptoms and causes.
What is autism? What causes autism?
What is bipolar disorder?
What is depression? What causes depression?
What is dyspraxia? How is dyspraxia treated?
What is hypochondria?
What is mental health? What is mental disorder?
What is schizophrenia?
According to most experts, there are two main categories of dementia - cortical and subcortical dementias.
Cortical Dementia - The cerebral cortex is affected. This is the outer layer of the brain. The cerebral cortex is vital for cognitive processes, such as language and memory. Alzheimer's disease is a form of cortical dementia, as is CJD (Creutzfeldt-Jakob disease).
Subcortical Dementia - A part of the brain beneath the cortex (deeper inside) becomes affected or damaged. Language and memory are not usually affected. A patient with subcortical dementia will usually experience changes in his personality, his thinking may slow down, and his attention span may be shortened. Dementias which sometimes result from Parkinson's disease are subcortical dementias, as are those caused by AIDS and Huntington's disease.
A patient with multi-infarct dementia will have both the cortical and subcortical parts of the brain affected or damaged.
Diagnosis of dementia
Although there are some brief tests, a more reliable diagnosis needs to be carried out by a specialist, such as a geriatric internist, geriatric psychiatrist, neurologist, neuropsychologist or geropsychologist.
The following tests are commonly used:
AMTS (Abbreviated Mental Test Score) A score lower than six out of ten suggests a need for further evaluation.
MMSE (Mini Mental State Examination) A score lower than twenty-four out of thirty suggests a need for further evaluation)
3MS (Modified Mini-Mental State Examination)
CASI (Cognitive Abilities Screening Instrument)
It is important that the patient's score is interpreted in context with his socio-economic, educational and cultural background. The tester must also factor in the patient's present physical and mental state - does the patient suffer from depression, is he in great pain?
What is the treatment for dementia?
In the majority of cases dementia is incurable. Researchers are making inroads into treatments that may slow down dementia's progress. Cholinestaerase inhibitors are frequently administered during the early stages. Cognitive and behavioral therapies may also be useful. Several studies have found that music therapy helps patients with dementia. It is important to remember that the patient's caregiver also needs training and emotional support.
See our specialized news channels
Psychology / Psychiatry news
Attention Deficit Hyperactive Disorder (ADHD) news
Alzheimer's / Dementia news
Anxiety / Stress news
Autism news
Bipolar disorder news
Depression news
Dyslexia news
Eating disorders news
Mental health news
Neurology news
Schizophrenia news
In the USA, Tacrine (Cognex), donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) have been approved for the treatment of dementia caused by Alzheimer's disease - some physicians prescribe these drugs for vascular dementia as well. Selegiline, which is used for treating Parkinson's disease, has been found to slow down the progress of dementia.
In Canada, a country where two languages are spoken, English and French, researchers found that bilingual people who develop dementia do so four years later than monolingual people who develop dementia. The four year difference prevails even after factoring for such variables as cultural differences, education, employment, gender and immigration.
How common is dementia?
United Kingdom - According to a report by the Alzheimer's Society (UK), approximately 700,000 people in the United Kingdom have dementia, out of a total population of about 61 million. Your chances of having dementia are 1 in 100 during your late 60s, this rises to 6 in 100 in your late 70s, and 20 in 100 in your late 80s. As people live longer experts predict dementia will rise significantly. According to predictions, there will be 940,000 people with dementia in the United Kingdom by 2021.
Worldwide - According to a study published in The Lancet, approximately 24.3 million people had dementia worldwide in 2005, with 4.6 million new cases every year. The number of people with dementia will double every two decades and reach 81.1 million by 2040. The rate of increase is expected to be faster in developing countries which have rapidly-growing life expectancies. (Lancet. 2005 Dec 17;366(9503):2112-7)
Sources - The Alzheimer's Society (UK), NIH, Wikipedia, The Lancet
Written by
For the latest news on dementia, and to sign up to newsletters or news alerts, please visit our dementia news section.
View drug information on ARICEPT; Exelon; Selegiline tablets.
пятница, 17 июня 2011 г.
Obesity Linked To Increased Risk For Dementia
Obesity may increase adults' risk for having dementia, according to researchers at the Johns Hopkins Bloomberg School of Public Health. Their analysis of published obesity and dementia prospective follow-up studies over the past two decades shows a consistent relationship between the two diseases. The results are published by The International Association for the Study of Obesity in the May, 2008 issue of Obesity Reviews.
"Our analysis of the data shows a clear association between obesity and an increased risk for dementia and several clinical subtypes of the disease," said Youfa Wang, MD, PhD, senior author of the study and associate professor with the Bloomberg School's Center for Human Nutrition. "Subjects with a healthy body mass index (BMI) and waist circumference saw a decreased risk for dementia than their counterparts with an elevated BMI or waist circumference." Wang adds, "Preventing or treating obesity at a younger age could play a major role in reducing the number of dementia patients and those with other commonly associated illnesses such as Alzheimer's disease by up to 20 percent in the United States."
Lead researcher May A. Beydoun, along with Wang and H.A. Beydoun attribute these findings to a systematic review of 10 previously published studies that examined the relationships between dementia or its subtypes and various measures of body fat. Based on a pooled analysis of their findings from 7 of the studies, baseline obesity compared to normal weight increased the risk of Alzheimer's disease by 80 percent on average. The team further concluded that being underweight also increases the risk of dementia and its subtypes. The studies cited in the meta-analysis were conducted in a number of countries, including the United States, Finland, Sweden and France, and contained middle-aged and older adults.
Previously published research defines dementia as not a single disorder, but a number of syndromes characterized by diverse behavioral, cognitive, and emotional impairments. The most common form is Alzheimer's disease, with an estimated 5 million adults living with the disease in the United States alone.
"Currently, Alzheimer's disease is the eighth leading cause of death among the elderly population in the United States. While more studies are needed to determine optimal weight and biological mechanisms associated with obesity and dementia, these findings could potentially decrease the number of people diagnosed with dementia and lead to an overall better quality of life," said May A. Beydoun, a former postdoctoral research fellow at the Johns Hopkins Bloomberg School of Public Health.
"Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis" was written by M. A. Beydoun, H. A. Beydoun and Y. Wang.
The research was funded by the Johns Hopkins Bloomberg School of Public Health.
Johns Hopkins Bloomberg School of Public Health
615 N. Wolfe St., W1600
Baltimore, MD 21205
United States
jhsph
"Our analysis of the data shows a clear association between obesity and an increased risk for dementia and several clinical subtypes of the disease," said Youfa Wang, MD, PhD, senior author of the study and associate professor with the Bloomberg School's Center for Human Nutrition. "Subjects with a healthy body mass index (BMI) and waist circumference saw a decreased risk for dementia than their counterparts with an elevated BMI or waist circumference." Wang adds, "Preventing or treating obesity at a younger age could play a major role in reducing the number of dementia patients and those with other commonly associated illnesses such as Alzheimer's disease by up to 20 percent in the United States."
Lead researcher May A. Beydoun, along with Wang and H.A. Beydoun attribute these findings to a systematic review of 10 previously published studies that examined the relationships between dementia or its subtypes and various measures of body fat. Based on a pooled analysis of their findings from 7 of the studies, baseline obesity compared to normal weight increased the risk of Alzheimer's disease by 80 percent on average. The team further concluded that being underweight also increases the risk of dementia and its subtypes. The studies cited in the meta-analysis were conducted in a number of countries, including the United States, Finland, Sweden and France, and contained middle-aged and older adults.
Previously published research defines dementia as not a single disorder, but a number of syndromes characterized by diverse behavioral, cognitive, and emotional impairments. The most common form is Alzheimer's disease, with an estimated 5 million adults living with the disease in the United States alone.
"Currently, Alzheimer's disease is the eighth leading cause of death among the elderly population in the United States. While more studies are needed to determine optimal weight and biological mechanisms associated with obesity and dementia, these findings could potentially decrease the number of people diagnosed with dementia and lead to an overall better quality of life," said May A. Beydoun, a former postdoctoral research fellow at the Johns Hopkins Bloomberg School of Public Health.
"Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis" was written by M. A. Beydoun, H. A. Beydoun and Y. Wang.
The research was funded by the Johns Hopkins Bloomberg School of Public Health.
Johns Hopkins Bloomberg School of Public Health
615 N. Wolfe St., W1600
Baltimore, MD 21205
United States
jhsph
четверг, 16 июня 2011 г.
New Neuroimaging Analysis Technique Identifies Impact Of Alzheimer's Disease Gene In Healthy Brains
Brain imaging can offer a window into risk for diseases such as Alzheimer's disease (AD). A study conducted at the University of Kansas School of Medicine demonstrated that genetic risk is expressed in the brains of even those who are healthy, but carry some risk for AD. The results of this study are published in the November 2009 issue of the Journal of Alzheimer's Disease.
Investigators used automated neuroimaging analysis techniques to characterize the impact of an AD-risk gene, apolipoprotein E (ApoE4), on gray and white matter in the brains of cognitively healthy elderly from the KU Brain Aging Project.
They found that healthy elderly individuals carrying a risk-allele of the ApoE4 gene had reduced cognitive performance, decreased brain volume in the hippocampus and amygdala (regions important for memory processing), and decreased white matter integrity in limbic regions. These type of brain changes are also found in people with AD. Therefore, brain changes, usually found in AD patients, are also evident in nondemented individuals who have a genetic risk of later developing AD.
Lead investigator, Robyn Honea, DPhil, Research Assistant Professor, University of Kansas School of Medicine, Department of Neurology, Alzheimer's and Memory Group, comments, "It is important to note that findings of imaging phenotypes of risk variants, such as with this gene, have been shown in a number of studies. The unique element of our study is that we used several new neuroimaging analysis techniques. In addition, the individuals in our study have been well-characterized in a clinical setting."
This research was conducted in the laboratory of Jeffrey M. Burns, MD, Associate Professor in the Department of Neurology at the University of Kansas Medical Center. He is the Director of the Alzheimer and Memory Center and the Alzheimer's Disease Clinical Research Program. Dr. Burns serves as the Principal Investigator of the Brain Aging Program.
Reference: Honea, Robyn A., Eric Vidoni, Amith Harsha and Jeffrey M. Burns. Impact of APOE on the Healthy Aging Brain: A Voxel-Based MRI and DTI Study. J Alzheimers Dis 18:3 (November 2009).
Source: Saskia van Wijngaarden
IOS Press
Investigators used automated neuroimaging analysis techniques to characterize the impact of an AD-risk gene, apolipoprotein E (ApoE4), on gray and white matter in the brains of cognitively healthy elderly from the KU Brain Aging Project.
They found that healthy elderly individuals carrying a risk-allele of the ApoE4 gene had reduced cognitive performance, decreased brain volume in the hippocampus and amygdala (regions important for memory processing), and decreased white matter integrity in limbic regions. These type of brain changes are also found in people with AD. Therefore, brain changes, usually found in AD patients, are also evident in nondemented individuals who have a genetic risk of later developing AD.
Lead investigator, Robyn Honea, DPhil, Research Assistant Professor, University of Kansas School of Medicine, Department of Neurology, Alzheimer's and Memory Group, comments, "It is important to note that findings of imaging phenotypes of risk variants, such as with this gene, have been shown in a number of studies. The unique element of our study is that we used several new neuroimaging analysis techniques. In addition, the individuals in our study have been well-characterized in a clinical setting."
This research was conducted in the laboratory of Jeffrey M. Burns, MD, Associate Professor in the Department of Neurology at the University of Kansas Medical Center. He is the Director of the Alzheimer and Memory Center and the Alzheimer's Disease Clinical Research Program. Dr. Burns serves as the Principal Investigator of the Brain Aging Program.
Reference: Honea, Robyn A., Eric Vidoni, Amith Harsha and Jeffrey M. Burns. Impact of APOE on the Healthy Aging Brain: A Voxel-Based MRI and DTI Study. J Alzheimers Dis 18:3 (November 2009).
Source: Saskia van Wijngaarden
IOS Press
среда, 15 июня 2011 г.
Lilly Halts Development Of Semagacestat For Alzheimer's Disease Based On Preliminary Results Of Phase III Clinical Trials
Eli Lilly and Company (NYSE: LLY) will halt development of semagacestat, a gamma secretase inhibitor being studied as a potential treatment for Alzheimer's disease, because preliminary results from two ongoing long-term Phase III studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.
The company's decision does not affect the ongoing clinical trials of solanezumab, Lilly's other compound in Phase III trials as a potential Alzheimer's treatment. While both drugs focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease, they have different mechanisms of action. Lilly also has two other compounds in earlier stages of clinical development; those studies are not affected by today's announcement.
In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease. Lilly has now reviewed data from a pre-planned interim analysis of semagacestat studies. This interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo. In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.
"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."
Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug they have received. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has appropriately informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.
Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research. Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols. These additional follow-up visits will help to answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.
The decision to halt development of semagacestat is expected to result in a third-quarter charge to earnings of approximately $.03 to $.04 per share. The company confirmed its previous 2010 earnings per share guidance range of $4.44 to $4.59 on a reported basis, or $4.50 to $4.65 on a non-GAAP basis.
"We are clearly disappointed by the results we are announcing today. However, Lilly's innovation strategy, based on advancing a pipeline of nearly 70 molecules currently in clinical development, does not rest on the success or failure of any single compound," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. "Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases."
About Alzheimer's disease
Alzheimer's disease is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when billions of neurons in the brain begin dying prematurely. Researchers don't know exactly what causes it, but the leading hypothesis is that amyloid beta plaques play an important role.
About semagacestat
Semagacestat is an oral agent designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques. The compound's safety and efficacy are being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.
About the IDENTITY trials
IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.
All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.
Use of approved treatments for Alzheimer's disease (including donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, RazadyneER), tacrine (Cognex) and memantine (Namenda)) is permitted during the study, provided that such medications had been given for at least 4 months and the dose had been unchanged for 2 months before study participants first received their study drug.
The primary objective of both IDENTITY trials was to determine whether semagacestat given orally would slow the decline associated with Alzheimer 's disease as compared with placebo. The study protocol calls for this to be evaluated periodically for 21 months after initiation of treatment for most patients. A participant's cognition and function are assessed using two 2 co-primary endpoints:
-- the Alzheimer's disease Assessment Scale - Cognitive subscore (referred to as the ADAS-Cog11); and
-- the Alzheimer's disease Cooperative Study - Activities of Daily Living Inventory (Referred to as the ADCS-ADL).
Source: Eli Lilly and Company
View drug information on ARICEPT; Exelon; Namenda.
The company's decision does not affect the ongoing clinical trials of solanezumab, Lilly's other compound in Phase III trials as a potential Alzheimer's treatment. While both drugs focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease, they have different mechanisms of action. Lilly also has two other compounds in earlier stages of clinical development; those studies are not affected by today's announcement.
In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease. Lilly has now reviewed data from a pre-planned interim analysis of semagacestat studies. This interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo. In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.
"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."
Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug they have received. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has appropriately informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.
Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research. Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols. These additional follow-up visits will help to answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.
The decision to halt development of semagacestat is expected to result in a third-quarter charge to earnings of approximately $.03 to $.04 per share. The company confirmed its previous 2010 earnings per share guidance range of $4.44 to $4.59 on a reported basis, or $4.50 to $4.65 on a non-GAAP basis.
"We are clearly disappointed by the results we are announcing today. However, Lilly's innovation strategy, based on advancing a pipeline of nearly 70 molecules currently in clinical development, does not rest on the success or failure of any single compound," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. "Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases."
About Alzheimer's disease
Alzheimer's disease is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when billions of neurons in the brain begin dying prematurely. Researchers don't know exactly what causes it, but the leading hypothesis is that amyloid beta plaques play an important role.
About semagacestat
Semagacestat is an oral agent designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques. The compound's safety and efficacy are being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.
About the IDENTITY trials
IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.
All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.
Use of approved treatments for Alzheimer's disease (including donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, RazadyneER), tacrine (Cognex) and memantine (Namenda)) is permitted during the study, provided that such medications had been given for at least 4 months and the dose had been unchanged for 2 months before study participants first received their study drug.
The primary objective of both IDENTITY trials was to determine whether semagacestat given orally would slow the decline associated with Alzheimer 's disease as compared with placebo. The study protocol calls for this to be evaluated periodically for 21 months after initiation of treatment for most patients. A participant's cognition and function are assessed using two 2 co-primary endpoints:
-- the Alzheimer's disease Assessment Scale - Cognitive subscore (referred to as the ADAS-Cog11); and
-- the Alzheimer's disease Cooperative Study - Activities of Daily Living Inventory (Referred to as the ADCS-ADL).
Source: Eli Lilly and Company
View drug information on ARICEPT; Exelon; Namenda.
вторник, 14 июня 2011 г.
Medical Care Corporation Enables Early Detection Of Memory Loss Due To Alzheimer's Disease
Medical Care Corporation (MCC), the leading provider of high accuracy memory assessment technology, announced that physicians now have a fast and accurate memory assessment procedure, the MCI Screen, which enables them to accurately separate normal declines due to aging from more serious signs of memory loss associated with an underlying medical condition.
Medical Care Corporation's MCI Screen is a brief memory assessment that allows physicians to detect abnormal recall patterns caused by medical conditions such as Alzheimer's disease (AD), vascular disease, depression and other disorders. The easy-to-administer test is 97 percent accurate in detecting Mild Cognitive Impairment (MCI), a transition stage between normal cognition and severe impairment associated with dementia. According to a study from the Mayo Clinic, 60 percent of those with MCI are diagnosed with AD within the next six years so detecting MCI enables physicians to intervene quickly and manage AD at an earlier stage.
The U.S. Preventative Services Task Force recommends cognitive assessment whenever there is evidence or suspicion of memory loss. Since the MCI Screen is quick and noninvasive, it functions as an efficient traffic-control mechanism that escorts the "worried well" out of the healthcare system while retaining those with real memory loss for further evaluation. This process allows physicians to prioritize resources and focus on those patients whose memory concerns are well founded.
About Medical Care Corporation
The MCI Screen's precision is achieved by using advanced mathematical analysis that characterizes recall patterns within a large database of carefully studied patients. The test's computerized algorithm determines whether or not the patient's recall pattern matches those with a healthy profile. Research confirming the accuracy of the MCI Screen has been published in the Proceedings of the National Academy of Science and in the National Alzheimer's Association's Journal of Alzheimer's and Dementia.
Source: Medical Care Corporation
Medical Care Corporation's MCI Screen is a brief memory assessment that allows physicians to detect abnormal recall patterns caused by medical conditions such as Alzheimer's disease (AD), vascular disease, depression and other disorders. The easy-to-administer test is 97 percent accurate in detecting Mild Cognitive Impairment (MCI), a transition stage between normal cognition and severe impairment associated with dementia. According to a study from the Mayo Clinic, 60 percent of those with MCI are diagnosed with AD within the next six years so detecting MCI enables physicians to intervene quickly and manage AD at an earlier stage.
The U.S. Preventative Services Task Force recommends cognitive assessment whenever there is evidence or suspicion of memory loss. Since the MCI Screen is quick and noninvasive, it functions as an efficient traffic-control mechanism that escorts the "worried well" out of the healthcare system while retaining those with real memory loss for further evaluation. This process allows physicians to prioritize resources and focus on those patients whose memory concerns are well founded.
About Medical Care Corporation
The MCI Screen's precision is achieved by using advanced mathematical analysis that characterizes recall patterns within a large database of carefully studied patients. The test's computerized algorithm determines whether or not the patient's recall pattern matches those with a healthy profile. Research confirming the accuracy of the MCI Screen has been published in the Proceedings of the National Academy of Science and in the National Alzheimer's Association's Journal of Alzheimer's and Dementia.
Source: Medical Care Corporation
понедельник, 13 июня 2011 г.
MPs And Peers Must Unite To Prevent Social Care System 'Breaking At The Seams', UK
Baroness Sally Greengross called on the government to act with urgency to mend the crumbling social care system after being elected Chairman of the All-Party Parliamentary Group (APPG) on Dementia.
In her first act as Chairman, the crossbench peer spoke of the need for the government to push on with plans for a commission on social care. She proposed a meeting of APPGs concerned with older people, disability and carers issues to discuss the problem and create an influential voice on the matter.
Speaking after the APPG on Dementia's AGM on Wednesday (7 July), she said:
'The social care system we have in this country is breaking at the seams. Millions of people, including many thousands with dementia, are currently being forced to pay huge fees for often substandard care.'
'The Government has acknowledged this but we now need to see promises turned into action. By bringing together the APPGs, we can create a powerful voice to represent the views of millions of often unheard people and keep the pressure up. There is no quick fix solution but we must make sure the wheels keep turning until we reach our destination - quality care at a fair price.'
Ruth Sutherland, Acting Chief Executive of Alzheimer's Society, which acts as the secretariat for the APPG on Dementia, said:
'One in three people over 65 will die with dementia. People with dementia are some of the hardest hit by the current social care system. Many are forced to pay a 'dementia tax' of tens of thousands of pounds for essential care. These people cannot afford for the government to let this issue slip. They have a right to have the best quality of life possible and not have to bankrupt themselves trying to achieve it.'
'APPGs are an invaluable source of pressure on the government demonstrating how working together can create the best results. We will do everything we can to support Baroness Greengross and her fellow members in their fight for change.'
Baroness Greengross replaces Jeremy Wright MP as Chairman of the APPG. She holds top positions in a number of older people's organisations and committees including the APPG on Intergenerational Futures, the International Longevity Centre - UK think tank and Eurolink Age. MPs David Blunkett, Mike Freer, Tracey Crouch, Tim Farron and Mike Hancock were also elected as Vice Chairmen.
Source:
Alzheimer's Society
In her first act as Chairman, the crossbench peer spoke of the need for the government to push on with plans for a commission on social care. She proposed a meeting of APPGs concerned with older people, disability and carers issues to discuss the problem and create an influential voice on the matter.
Speaking after the APPG on Dementia's AGM on Wednesday (7 July), she said:
'The social care system we have in this country is breaking at the seams. Millions of people, including many thousands with dementia, are currently being forced to pay huge fees for often substandard care.'
'The Government has acknowledged this but we now need to see promises turned into action. By bringing together the APPGs, we can create a powerful voice to represent the views of millions of often unheard people and keep the pressure up. There is no quick fix solution but we must make sure the wheels keep turning until we reach our destination - quality care at a fair price.'
Ruth Sutherland, Acting Chief Executive of Alzheimer's Society, which acts as the secretariat for the APPG on Dementia, said:
'One in three people over 65 will die with dementia. People with dementia are some of the hardest hit by the current social care system. Many are forced to pay a 'dementia tax' of tens of thousands of pounds for essential care. These people cannot afford for the government to let this issue slip. They have a right to have the best quality of life possible and not have to bankrupt themselves trying to achieve it.'
'APPGs are an invaluable source of pressure on the government demonstrating how working together can create the best results. We will do everything we can to support Baroness Greengross and her fellow members in their fight for change.'
Baroness Greengross replaces Jeremy Wright MP as Chairman of the APPG. She holds top positions in a number of older people's organisations and committees including the APPG on Intergenerational Futures, the International Longevity Centre - UK think tank and Eurolink Age. MPs David Blunkett, Mike Freer, Tracey Crouch, Tim Farron and Mike Hancock were also elected as Vice Chairmen.
Source:
Alzheimer's Society
воскресенье, 12 июня 2011 г.
Alzheimer's Disease May Be Predicted By New Brain Marker
Duke University Medical Center researchers have used imaging technology to identify a new marker that may help identify those at greatest risk for cognitive decline and the development of Alzheimer's disease.
The study focused on people with mild cognitive impairment (MCI), a condition that affects an estimated four to five million individuals in the United States. People with MCI are at increased risk for developing Alzheimer's disease in the future and approximately 30-50 percent of MCI subjects will develop Alzheimer's if followed over a three- to five-year period.
Duke researchers used functional magnetic resonance imaging, also known as fMRI, on people with MCI to track regions of the brain that become active or inactive when participating in tasks that involve memory. They then followed these individuals over time to document progression to Alzheimer's.
"A single baseline fMRI measure of deactivation could help predict which individuals will convert to Alzheimer's over the next several years," said the study's lead author, Jeffrey R. Petrella, M.D. "On the other hand, the fMRI scans of MCI subjects who did not convert looked more like those of healthy normal people, and could therefore be reassuring," said Petrella, who is director of the Alzheimer's Imaging Research Laboratory and associate professor of radiology at Duke.
The results of this study, published in PLoS ONE, focus on an area of the brain known as the posteromedial cortex, which has recently been implicated in personal memory.
"Our theory is that the posteromedial cortex may be our brain's 'cruise control' that normally deactivates when we are trying to remember things, so resources can be sent to other areas of the brain that encode memories. However, in people with mild cognitive impairment or Alzheimer's disease, the deactivation does not happen and the posteromedial cortex remains active," said Dr. Petrella.
The process of brain deactivation is similar to some other common bodily functions. For example, when a person is participating in a marathon, the gastrointestinal system temporarily turns off so blood can be redirected to areas which need it more, namely the muscles that are keeping the runner in motion.
In this study, researchers conducted fMRI scans on 75 people, including 34 with mild cognitive impairment, 13 with Alzheimer's disease and 28 with normal cognition. Study participants completed standard neuropsychological testing and were monitored with fMRI while performing a memory task matching names and faces. Patients were then followed for three and a half years to determine how their cognition changed over time.
"At present we treat all people with mild memory loss the same, even though some MCI subjects may convert in a year and others may take five years," said study co-author P. Murali Doraiswamy, M.D., chief of the division of biological psychiatry at Duke. "This is because there is no single test that can definitively predict who will develop late-onset Alzheimer's or not. The ability to probe brain circuits at a deeper level may help us diagnose risk with greater certainty."
The researchers found that approximately a third of the MCI subjects converted to Alzheimer's in three and half years after their initial scans. The conversion to Alzheimer's was determined by study doctors using routine clinical and memory tests. fMRI level of deactivation was found to significantly predict which MCI subjects converted to Alzheimer's.
While other studies have focused on the brain's ability to turn on certain regions, this research determined that losing the ability to turn off a region of the brain may be a more sensitive marker of future cognitive decline
"The Holy Grail in this field is to predict with 100 percent accuracy whether a 50-year old who forgets names will get dementia or not. We are not there yet but are inching closer and closer everyday. The combination of genetic, biochemical and imaging biomarkers will soon become the gold standard," said Doraiswamy.
Dr. Petrella added, "Although we tend of think of Alzheimer's as a disease causing shrinkage of discrete memory centers, at its earliest stages it really disrupts neural circuits. The diagnostic tests of the future will examine not just structure but also the interplay between the many nodes in the brain's memory circuits."
The study was supported by the National Institute on Aging.
Click here to view an animation illustrating the continuum from a healthy brain to one with Alzheimer's disease.
Click here to view the complete study manuscript on the PLoS ONE website.
Source: Melissa Sccwarting
Duke University Medical Center
The study focused on people with mild cognitive impairment (MCI), a condition that affects an estimated four to five million individuals in the United States. People with MCI are at increased risk for developing Alzheimer's disease in the future and approximately 30-50 percent of MCI subjects will develop Alzheimer's if followed over a three- to five-year period.
Duke researchers used functional magnetic resonance imaging, also known as fMRI, on people with MCI to track regions of the brain that become active or inactive when participating in tasks that involve memory. They then followed these individuals over time to document progression to Alzheimer's.
"A single baseline fMRI measure of deactivation could help predict which individuals will convert to Alzheimer's over the next several years," said the study's lead author, Jeffrey R. Petrella, M.D. "On the other hand, the fMRI scans of MCI subjects who did not convert looked more like those of healthy normal people, and could therefore be reassuring," said Petrella, who is director of the Alzheimer's Imaging Research Laboratory and associate professor of radiology at Duke.
The results of this study, published in PLoS ONE, focus on an area of the brain known as the posteromedial cortex, which has recently been implicated in personal memory.
"Our theory is that the posteromedial cortex may be our brain's 'cruise control' that normally deactivates when we are trying to remember things, so resources can be sent to other areas of the brain that encode memories. However, in people with mild cognitive impairment or Alzheimer's disease, the deactivation does not happen and the posteromedial cortex remains active," said Dr. Petrella.
The process of brain deactivation is similar to some other common bodily functions. For example, when a person is participating in a marathon, the gastrointestinal system temporarily turns off so blood can be redirected to areas which need it more, namely the muscles that are keeping the runner in motion.
In this study, researchers conducted fMRI scans on 75 people, including 34 with mild cognitive impairment, 13 with Alzheimer's disease and 28 with normal cognition. Study participants completed standard neuropsychological testing and were monitored with fMRI while performing a memory task matching names and faces. Patients were then followed for three and a half years to determine how their cognition changed over time.
"At present we treat all people with mild memory loss the same, even though some MCI subjects may convert in a year and others may take five years," said study co-author P. Murali Doraiswamy, M.D., chief of the division of biological psychiatry at Duke. "This is because there is no single test that can definitively predict who will develop late-onset Alzheimer's or not. The ability to probe brain circuits at a deeper level may help us diagnose risk with greater certainty."
The researchers found that approximately a third of the MCI subjects converted to Alzheimer's in three and half years after their initial scans. The conversion to Alzheimer's was determined by study doctors using routine clinical and memory tests. fMRI level of deactivation was found to significantly predict which MCI subjects converted to Alzheimer's.
While other studies have focused on the brain's ability to turn on certain regions, this research determined that losing the ability to turn off a region of the brain may be a more sensitive marker of future cognitive decline
"The Holy Grail in this field is to predict with 100 percent accuracy whether a 50-year old who forgets names will get dementia or not. We are not there yet but are inching closer and closer everyday. The combination of genetic, biochemical and imaging biomarkers will soon become the gold standard," said Doraiswamy.
Dr. Petrella added, "Although we tend of think of Alzheimer's as a disease causing shrinkage of discrete memory centers, at its earliest stages it really disrupts neural circuits. The diagnostic tests of the future will examine not just structure but also the interplay between the many nodes in the brain's memory circuits."
The study was supported by the National Institute on Aging.
Click here to view an animation illustrating the continuum from a healthy brain to one with Alzheimer's disease.
Click here to view the complete study manuscript on the PLoS ONE website.
Source: Melissa Sccwarting
Duke University Medical Center
суббота, 11 июня 2011 г.
New Ethical Guidelines Needed For Dementia Research
How do we handle the ethical dilemmas of research on adults who can't give their informed consent? In a recent article in the journal Bioethics, ethicist Stefan Eriksson proposes a new approach to the dilemma of including dementia patients and others with limited decision making capabilities in research.
There is a need for research on persons with impaired decision making, for example dementia patients. Without their participation we stand to loose knowledge necessary for future treatments that can benefit these groups. There are ethical guidelines to guard their interests, but they are somewhat ill-guided, says Stefan Eriksson, associate professor of research ethics at the Centre for Research Ethics & Bioethics (CRB).
We are sometimes led to believe that these guidelines conclusively state that research on these groups is permitted only in exceptional cases, but they don't, he says.
According to Stefan Eriksson, today's guidelines are often arbitrary. On one hand, research that benefits some groups, for example one's own age group, is allowed. On the other hand, research that benefits other groups, for example one's own children or community is not allowed. The previous will or interests expressed by person has little or no weight in these situations.
Another problem that Stefan Eriksson highlights is that some ethical standards simply make no sense for these groups. For example, the idea of a 'minimal risk standard' builds on the idea that there is something ordinary or routine about the risks we take in our daily lives. Such risks should then be acceptable in research as well. This kind of reasoning doesn't work for someone with for example Alzheimer's. The same is true for 'very slight impact' and 'routine examination', notions that doesn't translate well to a person with dementia who might very well react in a very different way than a person without dementia.
The guidelines that researchers act according to allows for vulnerable persons to be exploited, says Stefan Eriksson.
Instead of trying to translate the norm to those who fall outside it, we need to address the real issues at stake and re-write the guidelines that apply today Stefan Eriksson says. We need to rid them of notions of exceptionality, minimal risk and group beneficence. We also need to monitor this kind of research more closely and provide legal obligations to compensate for any injuries suffered. He concludes:
But we also need to consider other issues, such as how surrogate decision-makes can be of use to these persons and how to find ways to estimate a dementia patient's capacity for autonomy. We need to continue the debate and do more research on the ethics of research on persons with limited decision-making capacity.
Source: Uppsala Universitet
There is a need for research on persons with impaired decision making, for example dementia patients. Without their participation we stand to loose knowledge necessary for future treatments that can benefit these groups. There are ethical guidelines to guard their interests, but they are somewhat ill-guided, says Stefan Eriksson, associate professor of research ethics at the Centre for Research Ethics & Bioethics (CRB).
We are sometimes led to believe that these guidelines conclusively state that research on these groups is permitted only in exceptional cases, but they don't, he says.
According to Stefan Eriksson, today's guidelines are often arbitrary. On one hand, research that benefits some groups, for example one's own age group, is allowed. On the other hand, research that benefits other groups, for example one's own children or community is not allowed. The previous will or interests expressed by person has little or no weight in these situations.
Another problem that Stefan Eriksson highlights is that some ethical standards simply make no sense for these groups. For example, the idea of a 'minimal risk standard' builds on the idea that there is something ordinary or routine about the risks we take in our daily lives. Such risks should then be acceptable in research as well. This kind of reasoning doesn't work for someone with for example Alzheimer's. The same is true for 'very slight impact' and 'routine examination', notions that doesn't translate well to a person with dementia who might very well react in a very different way than a person without dementia.
The guidelines that researchers act according to allows for vulnerable persons to be exploited, says Stefan Eriksson.
Instead of trying to translate the norm to those who fall outside it, we need to address the real issues at stake and re-write the guidelines that apply today Stefan Eriksson says. We need to rid them of notions of exceptionality, minimal risk and group beneficence. We also need to monitor this kind of research more closely and provide legal obligations to compensate for any injuries suffered. He concludes:
But we also need to consider other issues, such as how surrogate decision-makes can be of use to these persons and how to find ways to estimate a dementia patient's capacity for autonomy. We need to continue the debate and do more research on the ethics of research on persons with limited decision-making capacity.
Source: Uppsala Universitet
пятница, 10 июня 2011 г.
Update On NICE Guidance On The Use Of Drugs To Treat Alzheimer's Disease, UK
The National Institute for Health and Clinical Excellence (NICE) has today published the next draft of its guidance on the use of donepezil, rivastigmine, galantamine and memantine for the treatment of Alzheimer's disease.
The Appraisal Committee is recommending that donepezil, galantamine and rivastigmine should be considered as options in the treatment of people with Alzheimer's disease of moderate severity only (that is, those with a mini mental state examination [MMSE] score of between 10 and 20 points). Memantine is not recommended as a treatment option for people with moderately-severe to severe Alzheimer's disease except as part of clinical studies.
The draft recommendations are subject to an appeal period which closes on 15 June: the consultation document has been published earlier than anticipated, for information, following a leak of the document to national newspapers. During this period registered stakeholder organisations including those representing healthcare professionals, patients and carers can decide if they wish to appeal against the draft guidance. If no appeals are received, the guidance will be issued to the NHS. If appeals are received these will be considered by the Institute. NICE is expecting to issue final guidance to the NHS in July 2006.
The guidance which NICE issued on the use of donepezil, galantamine and rivastigmine for Alzheimer's disease in 2001 is still in force and will continue to apply until NICE issues updated guidance. When published, the guidance will apply to newly diagnosed patients only. Patients currently using these drugs should continue to do so, on the basis on which they were initiated.
NICE is currently also consulting on a clinical guideline on the management of dementia which addresses the wider issue of care of patients with dementia (including Alzheimer's disease). This guideline is expected to be published in December 2006. More details can be found at nice.uk/page.aspx?o=guidelines.inprogress.dementia.
nice.uk
The Appraisal Committee is recommending that donepezil, galantamine and rivastigmine should be considered as options in the treatment of people with Alzheimer's disease of moderate severity only (that is, those with a mini mental state examination [MMSE] score of between 10 and 20 points). Memantine is not recommended as a treatment option for people with moderately-severe to severe Alzheimer's disease except as part of clinical studies.
The draft recommendations are subject to an appeal period which closes on 15 June: the consultation document has been published earlier than anticipated, for information, following a leak of the document to national newspapers. During this period registered stakeholder organisations including those representing healthcare professionals, patients and carers can decide if they wish to appeal against the draft guidance. If no appeals are received, the guidance will be issued to the NHS. If appeals are received these will be considered by the Institute. NICE is expecting to issue final guidance to the NHS in July 2006.
The guidance which NICE issued on the use of donepezil, galantamine and rivastigmine for Alzheimer's disease in 2001 is still in force and will continue to apply until NICE issues updated guidance. When published, the guidance will apply to newly diagnosed patients only. Patients currently using these drugs should continue to do so, on the basis on which they were initiated.
NICE is currently also consulting on a clinical guideline on the management of dementia which addresses the wider issue of care of patients with dementia (including Alzheimer's disease). This guideline is expected to be published in December 2006. More details can be found at nice.uk/page.aspx?o=guidelines.inprogress.dementia.
nice.uk
четверг, 9 июня 2011 г.
Alzheimer's Disease Research Seeks Volunteers For Dietary Study
The Indiana University Center for Alzheimer's disease and Related Disorders seeks volunteers for a clinical study on the effects of a fatty acid on patients with Alzheimer's.
The fatty acid, docosahexaenoic acid or DHA, which is found in small amounts in the diet, is essential for normal brain and eye development. Center researchers want to evaluate whether chronic use of DHA changes the progression of Alzheimer's. This research will help physicians learn more about the usefulness of DHA for future prevention and treatment of the disease.
Volunteers, who must have been diagnosed with Alzheimer's disease, will participate in the study for 18 months and will be seen approximately six times during the course of the study at the IU Medical Center. Study medication, procedures, exams and compensation for time and travel are provided.
For more information, call 317-278-8307.
Center for Alzheimer Disease and Related Disorders
The fatty acid, docosahexaenoic acid or DHA, which is found in small amounts in the diet, is essential for normal brain and eye development. Center researchers want to evaluate whether chronic use of DHA changes the progression of Alzheimer's. This research will help physicians learn more about the usefulness of DHA for future prevention and treatment of the disease.
Volunteers, who must have been diagnosed with Alzheimer's disease, will participate in the study for 18 months and will be seen approximately six times during the course of the study at the IU Medical Center. Study medication, procedures, exams and compensation for time and travel are provided.
For more information, call 317-278-8307.
Center for Alzheimer Disease and Related Disorders
среда, 8 июня 2011 г.
Gingko Biloba Not Effective Against Alzheimer's
A randomized clinical trial involving over 3,000 elderly people in the US found that the popular herbal supplement Gingko biloba fared no better
than placebo at preventing dementia or Alzheimer's disease.
The research was the work of the Ginkgo Evaluation of Memory (GEM) Study Investigators who are based at centers throughout the US, including the
University of Pittsburgh, Pennsylvania, where lead author Dr Steven T DeKosky, was working at the time of the investigation. The findings are
published in the 19 November issue of the Journal of the American Medical Association, JAMA.
Ginkgo biloba is taken by many people because of claims that it benefits memory and cognition and in some parts of the world it is prescribed for
such. But there have been no substantial clinical trials to evaluate the effectiveness of the supplement in the primary prevention of dementia, wrote the
authors.
More than 5 million people in the United States are currently affected by dementia and Alzheimer's in particular. This chronic disease is a leading
cause of age-associated disability requiring long term care, according to DeKosky and colleagues.
The randomized, placebo-controlled clinical trial included 3,069 community-dwelling volunteers aged 75 and over and took place at five US medical
research centers between 2000 and 2008. About half the volunteers were given a twice daily dose of 120mg extract of Ginkgo biloba and the other
half took a placebo.
None of the participants showed signs more advanced than mild cognitive impairment at the start (2,587 had normal cognition while 482 had mild
cognitive impairment). They were followed for a median period of 6.1 years during which time they underwent 6-monthly assessments for
dementia.
The results showed that:
During the period of the study, 523 participants were diagnosed with dementia: 16.1 per cent (246) in the placebo group and 17.9 per cent (277)
in the Ginkgo biloba group.
92 per cent of all the dementia cases were classed as possible or probable Alzheimer's Disease (AD), or AD with evidence of the tell-tale signs of
AD in the brain (vascular disease that shows as changes in the blood vessels).
The overall prevalence rate of dementia did not differ significantly between the two groups: 3.3 dementia cases per 100 persons per year of
exposure for the Gingko biloba group and 2.9 per 100 for the placebo group.
There was a similar lack of significance for Alzheimer's prevalence: 3.0 persons per 100 per year of exposure in the Gingko biloba group and 2.6
per 100 in the placebo group.
Ginkgo biloba appeared to have no impact on the rate of progression to dementia in the participants who had mild cognitive impairment.
There were no significant differences between the groups in the rate of side effects.
The authors concluded that:
"Based on the results of this trial, Ginkgo biloba cannot be recommended for the purpose of preventing dementia."
They also said that these findings confirm the idea that randomized trials play a crucial part in the evaluation of new traditional pharmaceutical and
complementary therapies alike and show that it is important to include older people in randomized trials of treatments that claim to be effective at
preventing or delaying dementia.
In an accompanying editorial, Dr Lon S Schneider from the University of Southern California, Los Angeles, wrote that two decades of research using
standardized extracts of Ginkgo biloba have yielded no definitive answer about its effectiveness. Preclinical scientific reports sing its praises but have
failed to identify the active compounds and the claims have not been proved in clinical research.
"The clinical research, in turn, has not adequately defined potential cognitive indications, potentially effective dosing ranges, pharmacodynamic
markers, or convincing evidence for efficacy for any one cognitive condition," wrote Schneider.
"The GEM study adds to the substantial body of evidence that Ginkgo biloba extract as it is generally used does not prevent dementia in individuals
with or without cognitive impairment and is not effective for Alzheimer disease," he added.
"Ginkgo biloba for Prevention of Dementia: A Randomized Controlled Trial."
Steven T. DeKosky; Jeff D. Williamson; Annette L. Fitzpatrick; Richard A. Kronmal; Diane G. Ives; Judith A. Saxton; Oscar L. Lopez; Gregory Burke;
Michelle C. Carlson; Linda P. Fried; Lewis H. Kuller; John A. Robbins; Russell P. Tracy; Nancy F. Woolard; Leslie Dunn; Beth E. Snitz; Richard L.
Nahin; Curt D. Furberg; for the Ginkgo Evaluation of Memory (GEM) Study Investigators.
JAMA, Vol. 300 No. 19, pp 2253-2262, November 19, 2008.
Click here for Article.
Sources: JAMA.
Written by: , PhD
than placebo at preventing dementia or Alzheimer's disease.
The research was the work of the Ginkgo Evaluation of Memory (GEM) Study Investigators who are based at centers throughout the US, including the
University of Pittsburgh, Pennsylvania, where lead author Dr Steven T DeKosky, was working at the time of the investigation. The findings are
published in the 19 November issue of the Journal of the American Medical Association, JAMA.
Ginkgo biloba is taken by many people because of claims that it benefits memory and cognition and in some parts of the world it is prescribed for
such. But there have been no substantial clinical trials to evaluate the effectiveness of the supplement in the primary prevention of dementia, wrote the
authors.
More than 5 million people in the United States are currently affected by dementia and Alzheimer's in particular. This chronic disease is a leading
cause of age-associated disability requiring long term care, according to DeKosky and colleagues.
The randomized, placebo-controlled clinical trial included 3,069 community-dwelling volunteers aged 75 and over and took place at five US medical
research centers between 2000 and 2008. About half the volunteers were given a twice daily dose of 120mg extract of Ginkgo biloba and the other
half took a placebo.
None of the participants showed signs more advanced than mild cognitive impairment at the start (2,587 had normal cognition while 482 had mild
cognitive impairment). They were followed for a median period of 6.1 years during which time they underwent 6-monthly assessments for
dementia.
The results showed that:
During the period of the study, 523 participants were diagnosed with dementia: 16.1 per cent (246) in the placebo group and 17.9 per cent (277)
in the Ginkgo biloba group.
92 per cent of all the dementia cases were classed as possible or probable Alzheimer's Disease (AD), or AD with evidence of the tell-tale signs of
AD in the brain (vascular disease that shows as changes in the blood vessels).
The overall prevalence rate of dementia did not differ significantly between the two groups: 3.3 dementia cases per 100 persons per year of
exposure for the Gingko biloba group and 2.9 per 100 for the placebo group.
There was a similar lack of significance for Alzheimer's prevalence: 3.0 persons per 100 per year of exposure in the Gingko biloba group and 2.6
per 100 in the placebo group.
Ginkgo biloba appeared to have no impact on the rate of progression to dementia in the participants who had mild cognitive impairment.
There were no significant differences between the groups in the rate of side effects.
The authors concluded that:
"Based on the results of this trial, Ginkgo biloba cannot be recommended for the purpose of preventing dementia."
They also said that these findings confirm the idea that randomized trials play a crucial part in the evaluation of new traditional pharmaceutical and
complementary therapies alike and show that it is important to include older people in randomized trials of treatments that claim to be effective at
preventing or delaying dementia.
In an accompanying editorial, Dr Lon S Schneider from the University of Southern California, Los Angeles, wrote that two decades of research using
standardized extracts of Ginkgo biloba have yielded no definitive answer about its effectiveness. Preclinical scientific reports sing its praises but have
failed to identify the active compounds and the claims have not been proved in clinical research.
"The clinical research, in turn, has not adequately defined potential cognitive indications, potentially effective dosing ranges, pharmacodynamic
markers, or convincing evidence for efficacy for any one cognitive condition," wrote Schneider.
"The GEM study adds to the substantial body of evidence that Ginkgo biloba extract as it is generally used does not prevent dementia in individuals
with or without cognitive impairment and is not effective for Alzheimer disease," he added.
"Ginkgo biloba for Prevention of Dementia: A Randomized Controlled Trial."
Steven T. DeKosky; Jeff D. Williamson; Annette L. Fitzpatrick; Richard A. Kronmal; Diane G. Ives; Judith A. Saxton; Oscar L. Lopez; Gregory Burke;
Michelle C. Carlson; Linda P. Fried; Lewis H. Kuller; John A. Robbins; Russell P. Tracy; Nancy F. Woolard; Leslie Dunn; Beth E. Snitz; Richard L.
Nahin; Curt D. Furberg; for the Ginkgo Evaluation of Memory (GEM) Study Investigators.
JAMA, Vol. 300 No. 19, pp 2253-2262, November 19, 2008.
Click here for Article.
Sources: JAMA.
Written by: , PhD
вторник, 7 июня 2011 г.
Scientists zero in on memory-related proteins at the core of Alzheimer's disease
Reporting in two companion papers in the October 19 issue of the Journal of Neuroscience, investigators from the Gladstone Institute of Neurological Disease show in genetically engineered mouse models of the disease that the accumulation of Alzheimer-related neurotoxic amyloid-beta (A??) peptides can deplete key proteins in a specific memory center of the brain. They also report that this process can be worsened by increased activity of an enzyme called Fyn.
The inability of Alzheimer's patients to remember events from a few days ago may be linked to the lack of proteins that strengthen the contact points, or synapses, between neurons in the brain, according to study findings.
Much research points to the idea that, far from having a single cause, Alzheimer's disease is typically brought on by a combination of risk factors. In keeping with that model, these papers show that the depletion of memory proteins can require the interaction of different disease-promoting molecules, explains GIND Director Lennart Mucke, MD, the Joseph B. Martin Distinguished Professor in Neuroscience at the University of California, San Francisco, and senior author of the papers.
The researchers found that memory proteins can be depleted not only by high levels of A?? but also by low levels of A?? in combination with high levels of Fyn activity.
"Like partners in crime, A?? and Fyn appear to cooperate to cause Alzheimer-like changes in the brain," says Mucke. The findings may eventually help identify novel therapeutic targets and biomarkers for emerging treatments.
Scientists in Mucke's laboratory were among the first to generate genetically engineered mice that produce human A??, providing a powerful tool to study the devastating disease. Using a technique called gene expression imaging to profile molecular changes in millions of neurons throughout the brain, they unexpectedly found Ab-induced deficits in a very specific neuronal population in the hippocampus, a brain region that serves as a gateway to the complex system that helps lay down new memories.
"The most striking changes within the brain were found in hippocampal granule cells, the specialized neurons that help convert new information into a format for long-term storage," says Jorge J. Palop, PhD, lead author of one of the papers. "That conversion requires proteins that help strengthen the synapses between neurons." These important proteins, which included two called Arc and Fos, were found to be depleted in mice that produced Alzheimer's-related Ab peptides in the brain.
The investigators have good leads on exactly how the memory proteins are depleted in Alzheimer's disease, adds Jeannie Chin, PhD, lead author of the companion paper. They have discovered that changing the activity of the enzyme Fyn can drastically alter the susceptibility of granule cells to the Ab-induced depletion of memory proteins.
"Fyn is strategically located at the synapses, where it regulates the activity of several memory-related proteins," explains Chin. The scientists found that increases in Fyn activity markedly enhanced the susceptibility of granule cells to the A??-induced depletion of memory proteins and, in fact, triggered prominent deficits in memory retention, even in mice with low levels of human A??.
Further studies are now underway to determine whether treatments aimed at A?? and at Fyn-related pathways will together enhance the level and function of memory proteins, thereby providing synergistic benefit in the fight against Alzheimer's disease.
Palop, Chin and Mucke will present their work at Neuroscience 2005, the Society for Neuroscience's 35th Annual Meeting, to be held in Washington, DC, November 12-16.
The research was supported in part by grants from the National Institutes of Health and by fellowships from the John Douglas French Alzheimer's Foundation and the Academy of Finland.
One paper is titled "Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice." Co-authors are GIND staff members Jorge J. Palop, Jeannie Chin, Nga Bien-Ly, Catherine Massaro, Bertrand Z. Yeung, Gui-Qiu Yu and Lennart Mucke.
The companion paper is titled "Fyn Kinase Induces Synaptic and Cognitive Impairments in a Transgenic Mouse Model of Alzheimer's Disease." Co-authors are GIND staff members Chin, Palop, Jukka Puoliv?li, Massaro, Bien-Ly, Hilary Gerstein, Kimberly Scearce-Levie, and Mucke, as well as Eliezer Masliah of the UC San Diego Department of Neurosciences and Pathology.
Palop, Chin, and Mucke are additionally associated with the UCSF Department of Neurology, and Massaro and Mucke are associated with the UCSF Neuroscience Program.
The Gladstone Institute of Neurological Disease is one of three research institutes of The J. David Gladstone Institutes, a private, nonprofit biomedical research institution. It is affiliated with UCSF, a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care. For further information, visit gladstone.ucsf and ucsf.
John Watson
jwatsongladstone.ucsf
415-734-2019
Gladstone Institutes
gladstone.ucsf
The inability of Alzheimer's patients to remember events from a few days ago may be linked to the lack of proteins that strengthen the contact points, or synapses, between neurons in the brain, according to study findings.
Much research points to the idea that, far from having a single cause, Alzheimer's disease is typically brought on by a combination of risk factors. In keeping with that model, these papers show that the depletion of memory proteins can require the interaction of different disease-promoting molecules, explains GIND Director Lennart Mucke, MD, the Joseph B. Martin Distinguished Professor in Neuroscience at the University of California, San Francisco, and senior author of the papers.
The researchers found that memory proteins can be depleted not only by high levels of A?? but also by low levels of A?? in combination with high levels of Fyn activity.
"Like partners in crime, A?? and Fyn appear to cooperate to cause Alzheimer-like changes in the brain," says Mucke. The findings may eventually help identify novel therapeutic targets and biomarkers for emerging treatments.
Scientists in Mucke's laboratory were among the first to generate genetically engineered mice that produce human A??, providing a powerful tool to study the devastating disease. Using a technique called gene expression imaging to profile molecular changes in millions of neurons throughout the brain, they unexpectedly found Ab-induced deficits in a very specific neuronal population in the hippocampus, a brain region that serves as a gateway to the complex system that helps lay down new memories.
"The most striking changes within the brain were found in hippocampal granule cells, the specialized neurons that help convert new information into a format for long-term storage," says Jorge J. Palop, PhD, lead author of one of the papers. "That conversion requires proteins that help strengthen the synapses between neurons." These important proteins, which included two called Arc and Fos, were found to be depleted in mice that produced Alzheimer's-related Ab peptides in the brain.
The investigators have good leads on exactly how the memory proteins are depleted in Alzheimer's disease, adds Jeannie Chin, PhD, lead author of the companion paper. They have discovered that changing the activity of the enzyme Fyn can drastically alter the susceptibility of granule cells to the Ab-induced depletion of memory proteins.
"Fyn is strategically located at the synapses, where it regulates the activity of several memory-related proteins," explains Chin. The scientists found that increases in Fyn activity markedly enhanced the susceptibility of granule cells to the A??-induced depletion of memory proteins and, in fact, triggered prominent deficits in memory retention, even in mice with low levels of human A??.
Further studies are now underway to determine whether treatments aimed at A?? and at Fyn-related pathways will together enhance the level and function of memory proteins, thereby providing synergistic benefit in the fight against Alzheimer's disease.
Palop, Chin and Mucke will present their work at Neuroscience 2005, the Society for Neuroscience's 35th Annual Meeting, to be held in Washington, DC, November 12-16.
The research was supported in part by grants from the National Institutes of Health and by fellowships from the John Douglas French Alzheimer's Foundation and the Academy of Finland.
One paper is titled "Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice." Co-authors are GIND staff members Jorge J. Palop, Jeannie Chin, Nga Bien-Ly, Catherine Massaro, Bertrand Z. Yeung, Gui-Qiu Yu and Lennart Mucke.
The companion paper is titled "Fyn Kinase Induces Synaptic and Cognitive Impairments in a Transgenic Mouse Model of Alzheimer's Disease." Co-authors are GIND staff members Chin, Palop, Jukka Puoliv?li, Massaro, Bien-Ly, Hilary Gerstein, Kimberly Scearce-Levie, and Mucke, as well as Eliezer Masliah of the UC San Diego Department of Neurosciences and Pathology.
Palop, Chin, and Mucke are additionally associated with the UCSF Department of Neurology, and Massaro and Mucke are associated with the UCSF Neuroscience Program.
The Gladstone Institute of Neurological Disease is one of three research institutes of The J. David Gladstone Institutes, a private, nonprofit biomedical research institution. It is affiliated with UCSF, a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care. For further information, visit gladstone.ucsf and ucsf.
John Watson
jwatsongladstone.ucsf
415-734-2019
Gladstone Institutes
gladstone.ucsf
понедельник, 6 июня 2011 г.
Alzheimer Patients Brain Tracked By PET Scanner During Disease And After Death
For the first time the brain of a patient with Alzheimer's disease who displayed detectable amyloids with a PET scanner was regularly scanned as his disease progressed, and then his brain was analyzed after he died, researchers from the Karolinska Institutet, Sweden, reveal in the medical journal Brain. The authors say their study reveals important data on the pathological course of Alzheimer's disease.
Alzheimer's disease, also known as SDAT (Senile Dementia of the Alzheimer Type), or simply Alzheimer's, is a progressive neurologic brain disease which leads to irreversible loss of neurons and intellectual abilities, including reasoning and memory. Eventually, the patient is unable to function professionally, socially or independently. Plaques or tangles develop within the structure of the brain during the course of the disease, causing brain cells to die. The accumulation in the brain of beta-amyloid proteins form amyloid plaques.
The authors explain that we do not know how the plaques form in the brain in the early stages of the disease. We don't even know whether the plaques are the primary cause of Alzheimer's, and what the pathogenic impact might be of other alterations in the brain.
In 2002, Professor Professor Agneta Nordberg carried out the first PET scan ever of amyloid plaque on a living patient with 11C-PIB, an amyloid-binding compound. It was performed at the Karolinska Institutet on a patient with Alzheimer's disease; he was 56 years old at the time. The progression of his disease was tracked with periodic PET scans and memory tests. After death, the researchers performed neurochemical and pathological analyses of his brain tissue.
Their findings provide us with a detailed picture of how Alzheimer's develops. During the early stages of the disease, when the patient experienced only slight memory loss, high concentrations of amyloid plaques were detected. Amyloid plaque levels, in fact, did not change as the disease progressed, right until the patient died. However, the PET scans were able to show that his brain's metabolism declined with time. The decline in brain metabolism occurred in parallel to his rate of memory loss.
The scientists also discovered that an accumulation of plaque is accompanied by a fall in the brain's neuronal nicotinic receptors, which are key for the proper functioning of memory. We now know that these receptors are affected during the early stages of Alzheimer's.
The scientists also believe that inflammation of parts of the brain of a patient with Alzheimer's may have a different cause and occur at different times from the accumulation of amyloid. They found brain inflammation in areas of the brain with low levels of plaques. The authors inform that further research with living patients on this subject is currently underway.
Over 1,000 individuals have undergone PET scans to see what amyloid concentrations they have in their brains. The American Alzheimer's Association in its latest diagnostic guidelines includes PIB-PET as a recommended early clinical diagnostic biomarker for discovering Alzheimer's disease.
In order to fully understand the importance of the PET scans, a follow-up examination of brain tissue should be carried out after the patient has died, the researchers wrote.
Professor Nordberg said:
"If we combine different examinations, we will be able to affirm that complex changes take place at the same time in the brain during the development of Alzheimer's disease. Our study shows that new, modern imaging technology known as molecular imaging makes it possible to discover the disease at an early stage. This opens up new opportunities for early diagnosis and for understanding the causes of the disease and identifying patients who can be expected to respond well to future Alzheimer's therapy."
"Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer's disease"
Ahmadul Kadir,Amelia Marutle, Daniel Gonzalez, Michael Sch?¶ll, Ove Almkvist, Malahat Mousavi, Tamanna Mustafiz, Taher Darreh-Shori, Inger Nennesmo and Agneta Nordberg
Brain (2010) doi: 10.1093/brain/awq349
Written by
Alzheimer's disease, also known as SDAT (Senile Dementia of the Alzheimer Type), or simply Alzheimer's, is a progressive neurologic brain disease which leads to irreversible loss of neurons and intellectual abilities, including reasoning and memory. Eventually, the patient is unable to function professionally, socially or independently. Plaques or tangles develop within the structure of the brain during the course of the disease, causing brain cells to die. The accumulation in the brain of beta-amyloid proteins form amyloid plaques.
The authors explain that we do not know how the plaques form in the brain in the early stages of the disease. We don't even know whether the plaques are the primary cause of Alzheimer's, and what the pathogenic impact might be of other alterations in the brain.
In 2002, Professor Professor Agneta Nordberg carried out the first PET scan ever of amyloid plaque on a living patient with 11C-PIB, an amyloid-binding compound. It was performed at the Karolinska Institutet on a patient with Alzheimer's disease; he was 56 years old at the time. The progression of his disease was tracked with periodic PET scans and memory tests. After death, the researchers performed neurochemical and pathological analyses of his brain tissue.
Their findings provide us with a detailed picture of how Alzheimer's develops. During the early stages of the disease, when the patient experienced only slight memory loss, high concentrations of amyloid plaques were detected. Amyloid plaque levels, in fact, did not change as the disease progressed, right until the patient died. However, the PET scans were able to show that his brain's metabolism declined with time. The decline in brain metabolism occurred in parallel to his rate of memory loss.
The scientists also discovered that an accumulation of plaque is accompanied by a fall in the brain's neuronal nicotinic receptors, which are key for the proper functioning of memory. We now know that these receptors are affected during the early stages of Alzheimer's.
The scientists also believe that inflammation of parts of the brain of a patient with Alzheimer's may have a different cause and occur at different times from the accumulation of amyloid. They found brain inflammation in areas of the brain with low levels of plaques. The authors inform that further research with living patients on this subject is currently underway.
Over 1,000 individuals have undergone PET scans to see what amyloid concentrations they have in their brains. The American Alzheimer's Association in its latest diagnostic guidelines includes PIB-PET as a recommended early clinical diagnostic biomarker for discovering Alzheimer's disease.
In order to fully understand the importance of the PET scans, a follow-up examination of brain tissue should be carried out after the patient has died, the researchers wrote.
Professor Nordberg said:
"If we combine different examinations, we will be able to affirm that complex changes take place at the same time in the brain during the development of Alzheimer's disease. Our study shows that new, modern imaging technology known as molecular imaging makes it possible to discover the disease at an early stage. This opens up new opportunities for early diagnosis and for understanding the causes of the disease and identifying patients who can be expected to respond well to future Alzheimer's therapy."
"Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer's disease"
Ahmadul Kadir,Amelia Marutle, Daniel Gonzalez, Michael Sch?¶ll, Ove Almkvist, Malahat Mousavi, Tamanna Mustafiz, Taher Darreh-Shori, Inger Nennesmo and Agneta Nordberg
Brain (2010) doi: 10.1093/brain/awq349
Written by
воскресенье, 5 июня 2011 г.
Study On Antioxidants And Memory Concerns Underway At Rush University Medical Center
Rush University Medical Center is conducting a clinical trial to evaluate whether taking Cerefolin®NAC reduces the inflammation and oxidative stress that is associated with memory decline in older persons. Cerefolin NAC is a commercially available food supplement available by prescription. It is a combination of high dose vitamin B12, B6, and folic acid along with n-acetylcysteine, an antioxidant.
Researchers will evaluate whether taking Cerefolin NAC causes a greater reduction in homocysteine, oxidative stress, and inflammation blood marker levels than a standard multivitamin. Homocysteine is an amino acid associated with inflammation.
"Finding treatments with the ability to reduce inflammation responses in the brain may help delay the onset of Alzheimer's disease," Said Dr. Raj Shah, medical director of the Rush Alzheimer's Disease Center. "The results of this study will help determine how to design future studies to see if Cerefolin NAC can make a difference in maintaining memory."
Rush University Medical Center will be the only site conducting this study. The study seeks 100 participants over age 60 with memory concerns who have a slightly higher risk for having an elevated homocysteine level. Participants must not have a diagnosis of Mild Cognitive Impairment, Alzheimer's disease, or a dementia.
One-half of participants will receive Cerefolin NAC and one-half will receive a placebo. All participants will receive a multivitamin. During the six month double-blind clinical trial, investigators will measure blood markers, will assess memory, walking, mood, and functional abilities, and will monitor side-effects over the course of four study visits with the participant.
"Alzheimer's disease is a public health crisis now and in the future. Alzheimer's disease currently affects over 4.5 million persons in the United States and over 200,000 in Illinois alone," said Shah. "It is projected to affect over 13 million persons by 2050 if nothing can be found to prevent the symptoms of the disease."
rush
Researchers will evaluate whether taking Cerefolin NAC causes a greater reduction in homocysteine, oxidative stress, and inflammation blood marker levels than a standard multivitamin. Homocysteine is an amino acid associated with inflammation.
"Finding treatments with the ability to reduce inflammation responses in the brain may help delay the onset of Alzheimer's disease," Said Dr. Raj Shah, medical director of the Rush Alzheimer's Disease Center. "The results of this study will help determine how to design future studies to see if Cerefolin NAC can make a difference in maintaining memory."
Rush University Medical Center will be the only site conducting this study. The study seeks 100 participants over age 60 with memory concerns who have a slightly higher risk for having an elevated homocysteine level. Participants must not have a diagnosis of Mild Cognitive Impairment, Alzheimer's disease, or a dementia.
One-half of participants will receive Cerefolin NAC and one-half will receive a placebo. All participants will receive a multivitamin. During the six month double-blind clinical trial, investigators will measure blood markers, will assess memory, walking, mood, and functional abilities, and will monitor side-effects over the course of four study visits with the participant.
"Alzheimer's disease is a public health crisis now and in the future. Alzheimer's disease currently affects over 4.5 million persons in the United States and over 200,000 in Illinois alone," said Shah. "It is projected to affect over 13 million persons by 2050 if nothing can be found to prevent the symptoms of the disease."
rush
суббота, 4 июня 2011 г.
How Stroke And Head Injury Can Increase Risk Of Alzheimer's Disease, Outlined By Study
Researchers from the MassGeneral Institute for Neurodegenerative Disorders (MGH-MIND) have discovered how the death of brain cells caused by a stroke or head injury may cause generation of amyloid-beta protein - the key component of senile plaques seen in the brains of patients with Alzheimer's disease. Their report appears in the journal Neuron.
"We have discovered how a stroke can trigger a series of biochemical events that increase amyloid-beta production in the brain," says Giuseppina Tesco, MD, PhD, of the MGH-MIND Genetics and Aging Research Unit, the paper's lead author. "These findings raise the prospect of novel therapies that could interfere with this process and reduce the risk of Alzheimer's disease in stroke or head trauma patients."
It has been known for several years that strokes and head injuries can increase the risk of Alzheimer's disease, but the mechanism underlying that increased risk has not been understood. Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein, which is toxic to brain cells. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes - beta-secretase, also known as BACE, and gamma-secretase - which releases the amyloid-beta fragment. The usual processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.
The MGH-MIND team previously reported that cellular BACE levels are normally controlled by the enzyme's breakdown in compartments called lysosomes, a process that is disrupted if a molecular signal on the enzyme is altered. That signal binds to GGA proteins, which are required for the transport of several types of enzymes into lysosomes. One of these proteins, GGA3, can be degraded by caspase, an enzyme takes part in the cell-death process called apoptosis.
In a series of experiments the MGH-MIND researchers revealed how cell death caused by a brain injury, including a stroke, can lead to the production of amyloid-beta. Damaged brain cells undergo apoptosis, releasing caspase which also breaks down GGA3. Without enough GGA3 to help transport BACE to lysosomes, levels of BACE rise and lead to increased amyloid-beta production. Amyloid-beta itself is toxic to brain cells, so it may cause further apoptosis, leading to a vicious cycle of continued cell death and amyloid-beta production.
The importance of GGA3's control of BACE levels was supported by the observation that, in brain tissue from Alzheimer's patients, reductions in GGA3 corresponded with elevations in BACE, particularly in those areas most affected by the disease.
"Our findings also shed new light on how the aged brain becomes more vulnerable to AD, since any insult to the brain - head injury, stroke, or the mini-strokes called TIAs - can set off this process and turn up BACE activity," says Rudolph Tanzi, PhD, director of the Genetics and Aging Research Unit and senior author of the Neuron paper. "Therapies that protect GGA3 from caspase cleaving might be able to reduce the risk of AD or the more transient type of dementia that can occur after such injuries." Tanzi is a professor of Neurology at Harvard Medical School, where Tesco is an assistant professor.
The research was supported by grants from the National Institute of Health, the National Institute of Mental Health, the American Health Assistance Foundation, the Cure Alzheimer's Fund, and the John French Douglas Foundation Fellowship. Additional co-authors of the Neuron paper are Young Ho Koh, PhD, Eugene Kang, MPH, Andrew Cameron, Shinjita Das, and Mikko Hiltunen, PhD, of MGH-MIND; Miguel Sena-Esteves, PhD, MGH Neuroscience Center; Shao-Hua Yang, MD, PhD, and James Simpkins, PhD, University of North Texas; and Zhenyu Zhong, PhD, and Yong Shen, MD, PhD, Sun Health Research Institute.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.
Contact: Sue McGreevey
Massachusetts General Hospital
"We have discovered how a stroke can trigger a series of biochemical events that increase amyloid-beta production in the brain," says Giuseppina Tesco, MD, PhD, of the MGH-MIND Genetics and Aging Research Unit, the paper's lead author. "These findings raise the prospect of novel therapies that could interfere with this process and reduce the risk of Alzheimer's disease in stroke or head trauma patients."
It has been known for several years that strokes and head injuries can increase the risk of Alzheimer's disease, but the mechanism underlying that increased risk has not been understood. Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein, which is toxic to brain cells. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes - beta-secretase, also known as BACE, and gamma-secretase - which releases the amyloid-beta fragment. The usual processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.
The MGH-MIND team previously reported that cellular BACE levels are normally controlled by the enzyme's breakdown in compartments called lysosomes, a process that is disrupted if a molecular signal on the enzyme is altered. That signal binds to GGA proteins, which are required for the transport of several types of enzymes into lysosomes. One of these proteins, GGA3, can be degraded by caspase, an enzyme takes part in the cell-death process called apoptosis.
In a series of experiments the MGH-MIND researchers revealed how cell death caused by a brain injury, including a stroke, can lead to the production of amyloid-beta. Damaged brain cells undergo apoptosis, releasing caspase which also breaks down GGA3. Without enough GGA3 to help transport BACE to lysosomes, levels of BACE rise and lead to increased amyloid-beta production. Amyloid-beta itself is toxic to brain cells, so it may cause further apoptosis, leading to a vicious cycle of continued cell death and amyloid-beta production.
The importance of GGA3's control of BACE levels was supported by the observation that, in brain tissue from Alzheimer's patients, reductions in GGA3 corresponded with elevations in BACE, particularly in those areas most affected by the disease.
"Our findings also shed new light on how the aged brain becomes more vulnerable to AD, since any insult to the brain - head injury, stroke, or the mini-strokes called TIAs - can set off this process and turn up BACE activity," says Rudolph Tanzi, PhD, director of the Genetics and Aging Research Unit and senior author of the Neuron paper. "Therapies that protect GGA3 from caspase cleaving might be able to reduce the risk of AD or the more transient type of dementia that can occur after such injuries." Tanzi is a professor of Neurology at Harvard Medical School, where Tesco is an assistant professor.
The research was supported by grants from the National Institute of Health, the National Institute of Mental Health, the American Health Assistance Foundation, the Cure Alzheimer's Fund, and the John French Douglas Foundation Fellowship. Additional co-authors of the Neuron paper are Young Ho Koh, PhD, Eugene Kang, MPH, Andrew Cameron, Shinjita Das, and Mikko Hiltunen, PhD, of MGH-MIND; Miguel Sena-Esteves, PhD, MGH Neuroscience Center; Shao-Hua Yang, MD, PhD, and James Simpkins, PhD, University of North Texas; and Zhenyu Zhong, PhD, and Yong Shen, MD, PhD, Sun Health Research Institute.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.
Contact: Sue McGreevey
Massachusetts General Hospital
пятница, 3 июня 2011 г.
Alzheimer's Society Comment On New Research Into The Effects Of Amyloid On Blood Clots In Alzheimer's
Research published in the journal Neuron has shown that the amyloid protein, a hallmark of Alzheimer's disease, increases the likelihood of the formation of blood clots.
The study worked with mouse models of the disease to determine how the presence of the amyloid protein affected accumulation of fibrinogen, a key component of blood clots.
People with Alzheimer's disease are more susceptible to stroke and bleeding in the brain. Previous research has shown that amyloid is found in the lining of blood vessels in the brain, causing the vessels to become more fragile. This new study provides new information about how amyloid affects the blood vessels, and increases the risk of stroke in people with Alzheimer's disease.
Alzheimer's Society comment:
'Many people with Alzheimer's disease actually have a condition called mixed dementia, a combination of Alzheimer's disease and vascular dementia, which is linked to interruptions in the blood flow to the brain. We already know that the amyloid protein is found in blood vessels in the brain in Alzheimer's, and that it increases the risk of stroke and bleeding in the brain.'
'This study provides a better understanding of how this amyloid might also be linked to the formation of blood clots, which increase the chance of damage to nerve cells. However, there is much we still do not understand. Research into dementia is drastically underfunded. We must invest more if we are to move forward in our understanding and treatment of this devastating condition.'
Professor Clive Ballard
Director of Research
Source
Alzheimer's Society
The study worked with mouse models of the disease to determine how the presence of the amyloid protein affected accumulation of fibrinogen, a key component of blood clots.
People with Alzheimer's disease are more susceptible to stroke and bleeding in the brain. Previous research has shown that amyloid is found in the lining of blood vessels in the brain, causing the vessels to become more fragile. This new study provides new information about how amyloid affects the blood vessels, and increases the risk of stroke in people with Alzheimer's disease.
Alzheimer's Society comment:
'Many people with Alzheimer's disease actually have a condition called mixed dementia, a combination of Alzheimer's disease and vascular dementia, which is linked to interruptions in the blood flow to the brain. We already know that the amyloid protein is found in blood vessels in the brain in Alzheimer's, and that it increases the risk of stroke and bleeding in the brain.'
'This study provides a better understanding of how this amyloid might also be linked to the formation of blood clots, which increase the chance of damage to nerve cells. However, there is much we still do not understand. Research into dementia is drastically underfunded. We must invest more if we are to move forward in our understanding and treatment of this devastating condition.'
Professor Clive Ballard
Director of Research
Source
Alzheimer's Society
четверг, 2 июня 2011 г.
Biomarkers For Alzheimer's Disease Can Be Trusted In Clinical Trials
The best-established biomarkers for Alzheimer's disease have a low natural variation over two years. The results suggest the inclusion of these biomarkers in clinical trials of novel drugs against Alzheimer's disease.
The results are presented by researchers at the Sahlgrenska Academy at G?¶teborg University, Sweden, in the November 2007 issue of the Journal of Alzheimer's Disease.
"We show that the best-established diagnostic biomarkers for Alzheimer's disease stay at basically the same level during two years in patients with early Alzheimer's disease. This means that the biomarkers could be useful for detecting even minor biochemical changes induced by treatment in the clinical trials of novel drugs against Alzheimer's," says Henrik Zetterberg, Associate Professor at the Sahlgrenska Academy.
Dr Zetterberg and colleagues analyzed cerebrospinal fluid from more than 80 patients with mild cognitive impairment. Some of these patients developed full-blown Alzheimer's disease. The measured levels of the tau and amyloid-b proteins were compared in samples drawn from the same patients two years apart.
"If a novel drug candidate actually stops or slows down the neurodegenerative disease process in Alzheimer's disease, we should expect a normalized tau concentration in cerebrospinal fluid in patients on active treatment. Such a change should be readily detectable also in a small and inexpensive pilot study, given the low intra-individual variation in biomarker levels over time that was detected in our study," Dr Zetterberg says.
Alzheimer's disease is an age-related brain-damaging disorder that results in progressive cognitive impairment and death. Three decades of progress have resulted in a profound understanding of the molecular mechanisms underlying the disease. In the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid-b.
Journal: Journal of Alzheimer's Disease, 12:3 (November 2007)
Article title: Intra-Individual Stability of CSF Biomarkers for Alzheimer's Disease over Two Years
Authors: Henrik Zetterberg, Mona Pedersen, Karin Lind, Maria Svensson, Sindre Rolstad, Carl Eckerstr?¶m, Steinar Syversen, Ulla-Britt Mattsson, Chrisina Ysander, Niklas Mattsson, Arto Nordlund, Hugo Vanderstichele, Eugeen Vanmechelen, Michael Jonsson, ?…ke Edman, kaj Blennow and Anders Wallin
Source: Associate Professor Henrik Zetterberg
IOS Press
The results are presented by researchers at the Sahlgrenska Academy at G?¶teborg University, Sweden, in the November 2007 issue of the Journal of Alzheimer's Disease.
"We show that the best-established diagnostic biomarkers for Alzheimer's disease stay at basically the same level during two years in patients with early Alzheimer's disease. This means that the biomarkers could be useful for detecting even minor biochemical changes induced by treatment in the clinical trials of novel drugs against Alzheimer's," says Henrik Zetterberg, Associate Professor at the Sahlgrenska Academy.
Dr Zetterberg and colleagues analyzed cerebrospinal fluid from more than 80 patients with mild cognitive impairment. Some of these patients developed full-blown Alzheimer's disease. The measured levels of the tau and amyloid-b proteins were compared in samples drawn from the same patients two years apart.
"If a novel drug candidate actually stops or slows down the neurodegenerative disease process in Alzheimer's disease, we should expect a normalized tau concentration in cerebrospinal fluid in patients on active treatment. Such a change should be readily detectable also in a small and inexpensive pilot study, given the low intra-individual variation in biomarker levels over time that was detected in our study," Dr Zetterberg says.
Alzheimer's disease is an age-related brain-damaging disorder that results in progressive cognitive impairment and death. Three decades of progress have resulted in a profound understanding of the molecular mechanisms underlying the disease. In the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid-b.
Journal: Journal of Alzheimer's Disease, 12:3 (November 2007)
Article title: Intra-Individual Stability of CSF Biomarkers for Alzheimer's Disease over Two Years
Authors: Henrik Zetterberg, Mona Pedersen, Karin Lind, Maria Svensson, Sindre Rolstad, Carl Eckerstr?¶m, Steinar Syversen, Ulla-Britt Mattsson, Chrisina Ysander, Niklas Mattsson, Arto Nordlund, Hugo Vanderstichele, Eugeen Vanmechelen, Michael Jonsson, ?…ke Edman, kaj Blennow and Anders Wallin
Source: Associate Professor Henrik Zetterberg
IOS Press
среда, 1 июня 2011 г.
Of Mice And Men And Other News Tips From The Journal Of Neuroscience
1. With and without the 3 Mints
Angela Ho, Wade Morishita, Deniz Atasoy, Xinran Liu, Katsuhiko Tabuchi, Robert E. Hammer, Robert C. Malenka, and Thomas C. Sudhof
You can tell a lot about a protein by what it hangs out with. The three Mints (also called X11-like proteins) bind to multiple synaptic proteins, and knock-out studies have suggested that they may indeed be necessary in synaptic transmission. But different isoforms can complement each other's function; thus, it has been difficult to come to firm conclusions using single knock-outs. This week, Ho et al. deleted the Mints using constitutive and conditional knock-out strategies. Deletion of Mint 1 and 2, the two isoforms specifically expressed in neurons, caused most mice to die at birth. The 20% that survived had ataxia and reduced body weight. In the double knock-outs, whole-cell recording of hippocampal neurons revealed lowered synaptic strength, a twofold decrease in the frequency of miniature EPSCs, and enhanced paired-pulse facilitation, indicative of a presynaptic action of Mint 1 and 2. Similar results were obtained with acute ablation of Mint 1/2/3.
2. Born-Again Neurons in Mice and Men
John J. Ohab, Sheila Fleming, Armin Blesch, and S. Thomas Carmichael and Jadranka Macas, Christian Nern, Karl H. Plate, and Stefan Momma
Stroke doesn't only cause cell death, but it also attempts at recovery through neuronal regeneration in tissues near the infarct, according to two separate studies published this week. Using histological analyses in a large collection of postmortem human brains, Macas et al. found increased numbers of neuronal precursor cells, even in patients of advanced age who had suffered ischemia. Because recent studies have coupled neurogenesis to the formation of new blood vessels, Ohab et al. tested the link in a model of focal stroke in mice. These authors showed that stroke induced the long-distance migration of thousands of newly born neuroblasts from the subventricular zone to peri-infarct cortex. The new cells associated with peri-infarct blood vessels in a region of active vascular remodeling. When Ohab et al. added stromal-derived factor 1 and angiopoietin 1, which are produced by the vasculature, the number of newly formed neurons increased.
3. Localizing Vocal Emotions
Jane E. Warren, Disa A. Sauter, Frank Eisner, Jade Wiland, M. Alexander Dresner, Richard J. S. Wise, Stuart Rosen, and Sophie K. Scott
The sound of laughter or cheering typically makes us smile or laugh. Warren et al. wanted to know how this happens. A facial expression showing an emotion can produce a so-called "mirror" response or similar facial expression in an observer. The authors used functional magnetic resonance imaging to determine whether similar mirror responses were also triggered by vocal expressions of emotion. Study participants were asked to listen to human voices conveying positive valence such as amusement and triumph. Listening to these "positive-valence" vocalizations activated specific premotor areas in the left posterior inferior frontal region, an area involved in control of facial movement. The activation was not attributable to facial movement per se. Thus, listening to vocal expressions of emotions appears to automatically engage preparation for orofacial gestures corresponding to the emotional content of the stimulus.
4. Ginkgo biloba and Oligomeric AB in Worms
Yanjue Wu, Zhixin Wu, Peter Butko, Yves Christen, Mary P. Lambert, William L. Klein, Christopher D. Link, and Yuan Luo
Ginkgo biloba, the ancient plant that fed dinosaurs, is widely used in patients with Alzheimer's disease AD). This week, Wu et al. examined the effects of a standard preparation of plant extract, EGb 761, in Caenorhabditis elegans. Nematodes do not express endogenous B amyloid (AB), the peptide that oligomerizes and form deposits in AD brains. Nonetheless, transgenic expression of AB causes striking pathology in C. elegans, such as muscle paralysis and problems with chemotaxis, which were alleviated by EGb 761. Rescue of these behaviors was accompanied by a reduction in AB oligomers. The beneficial effects of G. biloba are thought to result from neuroprotective and antioxidant properties. But in the transgenic C. elegans, reducing oxidative stress with the antioxidant L-ascorbic acid was not nearly as effective in suppressing paralysis as EGb 761. Thus, the beneficial effects of the extract may result from block of AB oligomerization.
Contact: Sara Harris
Society for Neuroscience
Angela Ho, Wade Morishita, Deniz Atasoy, Xinran Liu, Katsuhiko Tabuchi, Robert E. Hammer, Robert C. Malenka, and Thomas C. Sudhof
You can tell a lot about a protein by what it hangs out with. The three Mints (also called X11-like proteins) bind to multiple synaptic proteins, and knock-out studies have suggested that they may indeed be necessary in synaptic transmission. But different isoforms can complement each other's function; thus, it has been difficult to come to firm conclusions using single knock-outs. This week, Ho et al. deleted the Mints using constitutive and conditional knock-out strategies. Deletion of Mint 1 and 2, the two isoforms specifically expressed in neurons, caused most mice to die at birth. The 20% that survived had ataxia and reduced body weight. In the double knock-outs, whole-cell recording of hippocampal neurons revealed lowered synaptic strength, a twofold decrease in the frequency of miniature EPSCs, and enhanced paired-pulse facilitation, indicative of a presynaptic action of Mint 1 and 2. Similar results were obtained with acute ablation of Mint 1/2/3.
2. Born-Again Neurons in Mice and Men
John J. Ohab, Sheila Fleming, Armin Blesch, and S. Thomas Carmichael and Jadranka Macas, Christian Nern, Karl H. Plate, and Stefan Momma
Stroke doesn't only cause cell death, but it also attempts at recovery through neuronal regeneration in tissues near the infarct, according to two separate studies published this week. Using histological analyses in a large collection of postmortem human brains, Macas et al. found increased numbers of neuronal precursor cells, even in patients of advanced age who had suffered ischemia. Because recent studies have coupled neurogenesis to the formation of new blood vessels, Ohab et al. tested the link in a model of focal stroke in mice. These authors showed that stroke induced the long-distance migration of thousands of newly born neuroblasts from the subventricular zone to peri-infarct cortex. The new cells associated with peri-infarct blood vessels in a region of active vascular remodeling. When Ohab et al. added stromal-derived factor 1 and angiopoietin 1, which are produced by the vasculature, the number of newly formed neurons increased.
3. Localizing Vocal Emotions
Jane E. Warren, Disa A. Sauter, Frank Eisner, Jade Wiland, M. Alexander Dresner, Richard J. S. Wise, Stuart Rosen, and Sophie K. Scott
The sound of laughter or cheering typically makes us smile or laugh. Warren et al. wanted to know how this happens. A facial expression showing an emotion can produce a so-called "mirror" response or similar facial expression in an observer. The authors used functional magnetic resonance imaging to determine whether similar mirror responses were also triggered by vocal expressions of emotion. Study participants were asked to listen to human voices conveying positive valence such as amusement and triumph. Listening to these "positive-valence" vocalizations activated specific premotor areas in the left posterior inferior frontal region, an area involved in control of facial movement. The activation was not attributable to facial movement per se. Thus, listening to vocal expressions of emotions appears to automatically engage preparation for orofacial gestures corresponding to the emotional content of the stimulus.
4. Ginkgo biloba and Oligomeric AB in Worms
Yanjue Wu, Zhixin Wu, Peter Butko, Yves Christen, Mary P. Lambert, William L. Klein, Christopher D. Link, and Yuan Luo
Ginkgo biloba, the ancient plant that fed dinosaurs, is widely used in patients with Alzheimer's disease AD). This week, Wu et al. examined the effects of a standard preparation of plant extract, EGb 761, in Caenorhabditis elegans. Nematodes do not express endogenous B amyloid (AB), the peptide that oligomerizes and form deposits in AD brains. Nonetheless, transgenic expression of AB causes striking pathology in C. elegans, such as muscle paralysis and problems with chemotaxis, which were alleviated by EGb 761. Rescue of these behaviors was accompanied by a reduction in AB oligomers. The beneficial effects of G. biloba are thought to result from neuroprotective and antioxidant properties. But in the transgenic C. elegans, reducing oxidative stress with the antioxidant L-ascorbic acid was not nearly as effective in suppressing paralysis as EGb 761. Thus, the beneficial effects of the extract may result from block of AB oligomerization.
Contact: Sara Harris
Society for Neuroscience
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