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
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