Even with evidence of brain plaques associated with Alzheimer's disease, highly educated individuals manage to score higher on cognitive tests. Results from this study are published in the November issue of Archives of Neurology.
Currently there exists a popular notion - the "cognitive reserve" hypothesis - that people with greater thinking, learning, and memory capabilities can delay symptom of Alzheimer's disease even as the brain is changing. Since cognitive reserve is somewhat difficult to measure, researchers use education level as a proxy. "Adjusting for level of Alzheimer disease pathological burden determined at autopsy, greater education has been associated with better cognitive function during life," write Catherine M. Roe, Ph.D. and colleagues at the Washington University School of Medicine, St. Louis. "Education interacts with Alzheimer disease pathological burden such that a greater pathological burden is required to show an effect on cognition among persons with more education."
Between 2003 and 2008, the researchers analyzed 37 individuals diagnosed with Alzheimer's-like dementia and 161 individuals without dementia. Cognitive reserve measurements included education history as well as cognitive test scores. In addition, study participants received an injection of carbon 11-labeled Pittsburgh Compound B (PiB) prior to a 60-minute positron emission tomography (PET) brain scan. This contrast compound (PiB) has been shown to stick to beta-amyloid brain plaques that are linked to Alzheimer's disease, and thus researchers could identify the disease state in each patient.
Results of the study demonstrated that there were significant difference in the level of PiB uptake among patients with different years of education and cognitive test scores. For example, individuals with beta-amyloid plaques in the brain (organs that took up higher levels of PiB) showed increased performance on tests as education levels increased. For individuals without plaques, education was not significantly associated with cognitive scores.
"The results support the hypothesis that cognitive reserve influences the association between Alzheimer disease pathological burden and cognition," conclude Roes and colleagues. "Based on autopsy data, there may be a ceiling effect when extensive beta-amyloid pathological burden is present as in late-stage dementia of the Alzheimer type. Presumably, as the Alzheimer disease pathological burden increases, a greater proportion of highly educated participants reaches the threshold for dementia and the initial advantage provided by cognitive reserve decreases. Longitudinal imaging of beta-amyloid pathology in vivo will soon allow us to determine whether these inferences from cross-sectional studies are accurate."
Wednesday, January 21, 2009
Potential Protection For The Brain Against Alzheimer's Disease From A Special Type Of Collagen
Scientists from the Gladstone Institute of Neurological Disease (GIND), UCSF, and Stanford have discovered that a certain type of collagen, collagen VI, protects brain cells against amyloid-beta (Aβ ) proteins, which are widely thought to cause Alzheimer's disease (AD).
While the functions of collagens in cartilage and muscle are well established, before this study it was unknown that collagen VI is made by neurons in the brain and that it can fulfill important neuroprotective functions.
The team of investigators led by GIND director Lennart Mucke, MD, reported in a recent edition of the journal Nature Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's patients.
"We first noticed the increase in collagen VI in the brain of AD mouse models, which inspired us to look for it in the human condition and to define its role in the disease," said Dr. Mucke.
The Gladstone team had profiled changes in gene expression using DNA microarrays, which provides an unbiased method for identifying key biological pathways. By comparing all of the genes that are active in disease and normal tissue, one can get valuable information on new pathways and potential therapeutic targets.
The researchers looked at the dentate gyrus, a specific area of the brain that is critical to memory and particularly vulnerable in AD, and compared the genes that were turned on and off in normal mice and a mouse model of AD. This analysis revealed the striking increase in collagen VI in the brains of mice that model AD.
Building on this initial finding, the team examined brain tissue from AD patients and normal non-demented humans and found that collagen VI expression was also higher in the AD patients. They further discovered that the cellular source of the collagen VI in the brain was neurons, the very cells that the disease attacks and that we all need to think and remember.
"These findings were really surprising and exciting to us because nobody knew anything about collagen VI in the brain," said Jason Cheng, MD, co-lead author of the study. "We were particularly curious whether collagen VI contributed to neuronal damage in AD or was produced as a defense mechanism against it," added Dena Dubal, MD, PhD, co-lead author of the study.
To answer this and other questions, the scientists carried out a series of informative cell culture experiments. These experiments revealed found that Aβ added to neurons grown in culture increased the expression of collagen VI and that this process involved the immune regulatory cytosine TGFβ. What is more, the team discovered that increasing the amount of collagen VI in the cultures effectively protected the neurons against Aβ toxicity.
"This striking protective effect suggests that increased neuronal production of collagen VI is an important component of the brain's defense against Aβ," said Dr. Mucke. "It made us really curious about the underlying mechanisms."
To clinch these mechanisms, Dr. Mucke's team examined the direct interactions of collagen VI with Aβ. They looked at how Aβ attacks individual neurons in cell culture. Small poisonous Aβ assemblies, called oligomers, bind strongly to vulnerable neurons in the brain, but in the presence of collagen VI, this binding was blocked. Using immunohistochemistry and atomic force microscopy, they showed that collagen VI and Aβ form large aggregates with each other that may sequester the smaller, more toxic Aβ complexes away from neurons.
"We are eager to explore how this kind of process might be enhanced therapeutically and how we can best leverage it for the development of more effective treatments for this devastating condition," said Dr. Dubal.
While the functions of collagens in cartilage and muscle are well established, before this study it was unknown that collagen VI is made by neurons in the brain and that it can fulfill important neuroprotective functions.
The team of investigators led by GIND director Lennart Mucke, MD, reported in a recent edition of the journal Nature Neuroscience, that collagen VI is increased in brain tissues of Alzheimer's patients.
"We first noticed the increase in collagen VI in the brain of AD mouse models, which inspired us to look for it in the human condition and to define its role in the disease," said Dr. Mucke.
The Gladstone team had profiled changes in gene expression using DNA microarrays, which provides an unbiased method for identifying key biological pathways. By comparing all of the genes that are active in disease and normal tissue, one can get valuable information on new pathways and potential therapeutic targets.
The researchers looked at the dentate gyrus, a specific area of the brain that is critical to memory and particularly vulnerable in AD, and compared the genes that were turned on and off in normal mice and a mouse model of AD. This analysis revealed the striking increase in collagen VI in the brains of mice that model AD.
Building on this initial finding, the team examined brain tissue from AD patients and normal non-demented humans and found that collagen VI expression was also higher in the AD patients. They further discovered that the cellular source of the collagen VI in the brain was neurons, the very cells that the disease attacks and that we all need to think and remember.
"These findings were really surprising and exciting to us because nobody knew anything about collagen VI in the brain," said Jason Cheng, MD, co-lead author of the study. "We were particularly curious whether collagen VI contributed to neuronal damage in AD or was produced as a defense mechanism against it," added Dena Dubal, MD, PhD, co-lead author of the study.
To answer this and other questions, the scientists carried out a series of informative cell culture experiments. These experiments revealed found that Aβ added to neurons grown in culture increased the expression of collagen VI and that this process involved the immune regulatory cytosine TGFβ. What is more, the team discovered that increasing the amount of collagen VI in the cultures effectively protected the neurons against Aβ toxicity.
"This striking protective effect suggests that increased neuronal production of collagen VI is an important component of the brain's defense against Aβ," said Dr. Mucke. "It made us really curious about the underlying mechanisms."
To clinch these mechanisms, Dr. Mucke's team examined the direct interactions of collagen VI with Aβ. They looked at how Aβ attacks individual neurons in cell culture. Small poisonous Aβ assemblies, called oligomers, bind strongly to vulnerable neurons in the brain, but in the presence of collagen VI, this binding was blocked. Using immunohistochemistry and atomic force microscopy, they showed that collagen VI and Aβ form large aggregates with each other that may sequester the smaller, more toxic Aβ complexes away from neurons.
"We are eager to explore how this kind of process might be enhanced therapeutically and how we can best leverage it for the development of more effective treatments for this devastating condition," said Dr. Dubal.
Breakthrough In Screening For Alzheimer's Disease
CSIRO scientists have developed a new system to screen for compounds that can inhibit one of the processes that takes place during the progression of Alzheimer's disease.
In a paper published in the latest edition of the Journal of Alzheimer's Disease, folate is shown to be beneficial in the screening system.
Lead author, CSIRO's Dr Ian Macreadie says folate is already well known to have a protective effect against Alzheimer's disease which is believed to be caused by the loss of neurons in the brain due to a process whereby toxic multimers of a small protein called Aβ are formed.
"However, a team of scientists working within CSIRO's Preventative Health Flagship has discovered a rapid screening system to identify inhibitors of this process. Compounds that inhibit the formation of the toxic multimers may lead to the prevention or delay of the disease," Dr Macreadie says.
"Although many other research groups and drug companies around the world are trying to find compounds that act in the same way, the advance by the Flagship team involves using live yeast with the Aβ protein fused to a green fluorescent protein that comes from jellyfish.
"The significance of this development is that the yeast trial we developed could lead to the discovery of new agents which may prove useful in preventing or delaying the onset of Alzheimer's disease."
Currently Alzheimer's disease is an incurable illness and the fourth leading cause of death in people aged 65 years and over.
Although folate is abundant in foods like leafy green vegetables, pulses and liver, CSIRO studies have shown that many Australians do not consume enough folate to benefit from its ability to prevent cell damage. Folate levels can, however, be readily restored by dietary folate supplementation.
In a paper published in the latest edition of the Journal of Alzheimer's Disease, folate is shown to be beneficial in the screening system.
Lead author, CSIRO's Dr Ian Macreadie says folate is already well known to have a protective effect against Alzheimer's disease which is believed to be caused by the loss of neurons in the brain due to a process whereby toxic multimers of a small protein called Aβ are formed.
"However, a team of scientists working within CSIRO's Preventative Health Flagship has discovered a rapid screening system to identify inhibitors of this process. Compounds that inhibit the formation of the toxic multimers may lead to the prevention or delay of the disease," Dr Macreadie says.
"Although many other research groups and drug companies around the world are trying to find compounds that act in the same way, the advance by the Flagship team involves using live yeast with the Aβ protein fused to a green fluorescent protein that comes from jellyfish.
"The significance of this development is that the yeast trial we developed could lead to the discovery of new agents which may prove useful in preventing or delaying the onset of Alzheimer's disease."
Currently Alzheimer's disease is an incurable illness and the fourth leading cause of death in people aged 65 years and over.
Although folate is abundant in foods like leafy green vegetables, pulses and liver, CSIRO studies have shown that many Australians do not consume enough folate to benefit from its ability to prevent cell damage. Folate levels can, however, be readily restored by dietary folate supplementation.
In Early Diagnosis Of Alzheimer's Disease, MRI Brain Scans Accurate
MRI scans that detect shrinkage in specific regions of the mid-brain attacked by Alzheimer's disease accurately diagnose the neurodegenerative disease, even before symptoms interfere with daily function, a study by the Florida Alzheimer's Disease Research Center (ADRC) in Miami and Tampa found.
The study, reported earlier this month in the journal Neurology, adds to a growing body of evidence indicating MRI brain scans provide valuable diagnostic information about Alzheimer's disease. The findings are important in light of many new disease-modifying drugs in trials -- treatments that may prevent mild memory loss from advancing to full-blown dementia if administered early enough.
"We advocate, based on these findings, that the criteria for the diagnosis of Alzheimer's disease should include MRI scans," said the study's lead author Ranjan Duara, MD, medical director of the Wien Center for Alzheimer's Disease and Memory Disorders at Mount Sinai Medical Center who is affiliated with the University of Miami Miller School of Medicine and University of South Florida College of Medicine. "By incorporating MRIs into the assessment of patients with memory problems, early diagnosis can be standardized and done far more accurately."
"This study demonstrates that MRI brain scans are accurate enough to be clinically useful, both in diagnosing Alzheimer's disease itself at an early stage and in identifying people at risk of developing Alzheimer's," said Florida ADRC Center Director Huntington Potter, PhD, a neuroscientist at the Byrd Alzheimer's Center and Research Institute, University of South Florida.
Alzheimer's disease, the most common cause of dementia, is characterized by memory loss, disorientation, difficulty with reasoning and the decline of language and thinking skills. Alzheimer's is diagnosed by a process of elimination since many other diseases and related disorders can mimic its symptoms, and autopsy is currently the only definitive way a diagnosis can be confirmed. The diagnosis often includes a medical history, mental status tests, neurological evaluations and blood tests. Physicians typically use brain scans only to exclude conditions that can also cause memory deficits, such as strokes and brain tumors.
The Florida researchers used a new visual rating system to evaluate the severity of shrinkage, or atrophy, in the brain's medial temporal lobe - specifically in three structures essential for the conscious memory of facts and events. They compared the MRI brain scans of 260 people - a group with probable Alzheimer's disease, two groups with varying degrees of mild cognitive impairment (mild memory problems), and a control group of normal elderly with no discernable memory loss. They found that scores generated by this MRI-facilitated test accurately distinguished each group from the other and correlated with the types of memory problems most frequently caused by Alzheimer's disease. The more extensive the brain atrophy, the more advanced the clinical stage of Alzheimer's disease.
The researchers even found brain atrophy in some people without memory complaints at the study's onset who demonstrated memory decline when assessed a year or two later. This suggests MRIs could predict who will get the disease well before signs of dementia become apparent by other diagnostic methods as well as rule out an Alzheimer's diagnosis in people experiencing memory problems, Dr. Duara said. "If you don't have changes in these three particular areas of the brain, then you don't have Alzheimer's."
Researchers at centers like Miami's Wien Center and USF's Byrd Institute are developing new Alzheimer's drugs that attack mechanisms leading to the death of nerve cells and their connections. The emergence of these disease-modifying treatments has made an earlier diagnosis of Alzheimer's increasingly important, Dr. Duara said. "Having an accurate diagnosis will allow us to start using drugs earlier. The earlier treatment begins, the more likely you are to stop disease progression and benefit the patient."
Most participants in the MRI study were enrolled in the clinical arm of the Florida ADRC, which is supported by a grant from the National Institute on Aging.
The Florida ADRC, the first statewide, multi-center ADRC in the United States, was critical for the successful implementation of the study, said Dr. Potter, the study's senior author. "To validate any new diagnostic test or treatment, you need a large number of diverse volunteers for good comparisons. Alzheimer's research is a partnership between the scientific community and study volunteers; we need both to solve the complexities of Alzheimer's disease."
The study, reported earlier this month in the journal Neurology, adds to a growing body of evidence indicating MRI brain scans provide valuable diagnostic information about Alzheimer's disease. The findings are important in light of many new disease-modifying drugs in trials -- treatments that may prevent mild memory loss from advancing to full-blown dementia if administered early enough.
"We advocate, based on these findings, that the criteria for the diagnosis of Alzheimer's disease should include MRI scans," said the study's lead author Ranjan Duara, MD, medical director of the Wien Center for Alzheimer's Disease and Memory Disorders at Mount Sinai Medical Center who is affiliated with the University of Miami Miller School of Medicine and University of South Florida College of Medicine. "By incorporating MRIs into the assessment of patients with memory problems, early diagnosis can be standardized and done far more accurately."
"This study demonstrates that MRI brain scans are accurate enough to be clinically useful, both in diagnosing Alzheimer's disease itself at an early stage and in identifying people at risk of developing Alzheimer's," said Florida ADRC Center Director Huntington Potter, PhD, a neuroscientist at the Byrd Alzheimer's Center and Research Institute, University of South Florida.
Alzheimer's disease, the most common cause of dementia, is characterized by memory loss, disorientation, difficulty with reasoning and the decline of language and thinking skills. Alzheimer's is diagnosed by a process of elimination since many other diseases and related disorders can mimic its symptoms, and autopsy is currently the only definitive way a diagnosis can be confirmed. The diagnosis often includes a medical history, mental status tests, neurological evaluations and blood tests. Physicians typically use brain scans only to exclude conditions that can also cause memory deficits, such as strokes and brain tumors.
The Florida researchers used a new visual rating system to evaluate the severity of shrinkage, or atrophy, in the brain's medial temporal lobe - specifically in three structures essential for the conscious memory of facts and events. They compared the MRI brain scans of 260 people - a group with probable Alzheimer's disease, two groups with varying degrees of mild cognitive impairment (mild memory problems), and a control group of normal elderly with no discernable memory loss. They found that scores generated by this MRI-facilitated test accurately distinguished each group from the other and correlated with the types of memory problems most frequently caused by Alzheimer's disease. The more extensive the brain atrophy, the more advanced the clinical stage of Alzheimer's disease.
The researchers even found brain atrophy in some people without memory complaints at the study's onset who demonstrated memory decline when assessed a year or two later. This suggests MRIs could predict who will get the disease well before signs of dementia become apparent by other diagnostic methods as well as rule out an Alzheimer's diagnosis in people experiencing memory problems, Dr. Duara said. "If you don't have changes in these three particular areas of the brain, then you don't have Alzheimer's."
Researchers at centers like Miami's Wien Center and USF's Byrd Institute are developing new Alzheimer's drugs that attack mechanisms leading to the death of nerve cells and their connections. The emergence of these disease-modifying treatments has made an earlier diagnosis of Alzheimer's increasingly important, Dr. Duara said. "Having an accurate diagnosis will allow us to start using drugs earlier. The earlier treatment begins, the more likely you are to stop disease progression and benefit the patient."
Most participants in the MRI study were enrolled in the clinical arm of the Florida ADRC, which is supported by a grant from the National Institute on Aging.
The Florida ADRC, the first statewide, multi-center ADRC in the United States, was critical for the successful implementation of the study, said Dr. Potter, the study's senior author. "To validate any new diagnostic test or treatment, you need a large number of diverse volunteers for good comparisons. Alzheimer's research is a partnership between the scientific community and study volunteers; we need both to solve the complexities of Alzheimer's disease."
Friday, November 14, 2008
Diagnostic criteria for depressive episode
The main symptoms:
• lowering of mood, evident in comparison with the inherent patient norm, the dominant daily, and most of the day and continued at least 2 weeks regardless of the situation;
• marked reduction of interest or pleasure from activities that are usually associated with positive emotions;
• reducing energy and increased fatigue.
Additional symptoms:
• reducing the efficiency of focus;
• lowering self-esteem and sense of self-doubt;
• idea of guilt and self-effacement (even in light depressions);
• dark and pessimistic vision of the future;
• ideas or actions relating to self or suicide;
• disturbed sleep;
• broken appetite.
It should be noted that depression at the moment remains the most common mental disorder that requires adequate drug therapy. It is widespread depression leads on the one hand, to underestimate the role of development in the clinical picture of various diseases, including dementia, on the other - to hyper diagnostic depression and inadequate appointment of antidepressants.
Fruit and vegetable juices help prevent Alzheimer's
Drinking fruit and vegetable juice several times a week may help prevent Alzheimer's disease, showed the results of a new study, reported AFP.
The study was conducted 9 years in Seattle and has affected nearly 2 thousand people, led by professor at the University of Tennessee (USA) Key Dej. People filled out questionnaires about their lifestyles and preferences in foods. The state of health was recorded.
Research has shown that the risk of developing Alzheimer's disease is reduced by 76% among those who used the fruit or vegetable juice at least three times a week. Among those who used the juice once a week, the risk of the disease decreased by 16%.
Earlier Society believed that the prevention of Alzheimer's great role played by vitamins C and E. But now it is clear that the case not only in them. The author of the study believed that the disease could hinder development and natural antioxidants - polyphenols contained in tea, wine and soke.
Remarkably, the study did not identify any specific fruit or vegetable juices that help prevent Alzheimer's disease better than others.
Alzheimer's - a progressive disease in which patients gradually lose their memory and become unable to care for themselves. Medicines for him does not exist, modern drugs provide only temporary improvement.
It is believed that the disease causes sticky protein called beta-amyloid. It is contained in the brain, but healthy cells are able to get rid of its surplus. However, in patients with Alzheimer beta-amyloid accumulates, forming lump, which cover the cage.
In the U.S. Alzheimer's affects about 4.5 million people in Western Europe - 5.4 million.
Alzheimer's Disease: I think more
The most terrible disease XXI century may become senile marauds. Life expectancy in developed countries is constantly growing: the projections demographers, for example, half of girls born in 2000, live to 100 years. At the same time, after 65 years, the man threatened senile dementia - Alzheimer's disease. If scientists did not find drugs against the disease, it has been 50 years in the world will be 45 million marauds - more than cancer patients.
The American scientist Steven Austad believes that the average person will survive until the 150 the anniversary because, in his view, thanks to modern technology will soon be constructed of high quality and biologically adapted to the body «spare parts». According to another American scientist Jay Olshansky, the average length of human life in the XXII century, despite the gene therapy and cloning, will not exceed 130 years.
Studies have long shown that they have achieved so old age thanks to good health, and many continue to keep it until the end of his days
Long, who studied Dr. Thomas Perlz from Harvard Medical School, managed to avoid many of senile diseases - stroke, cardiovascular disease and others. According to Dr. Perzl sharp rise in long-livers in the United States over the past 10 years caused massive changes in lifestyle: Americans have to monitor their weight is healthy food, less smoke and more in sports. It is the combination of good heredity, a good environment and healthy lifestyles, according to scientists, and ensures longevity.
Physiology of aging studies have shown that the aging process involves two closely related system of the body: endocrine (hormone responsible for the formulation) and immunity (protecting the body against infection). From the age of the body resistance to disease drops. Scientists attribute this to age in violation of endocrine balance: a substance produced by the beginning of a larger, others - in smaller numbers. So, even if the medicine man learns to replace all the fastest frayed organs (heart, lungs, liver), it is unlikely to make him immortal.
Another more wear body, which can not yet be replaced - it is the brain. According to Lynn Adler, a pioneer in the study of long-livers in the United States, the most important problem associated with aging - a violation of the functions of the brain and senile dementia caused by the disease, first described in detail by German doctor Alloiz Alzheimer and called his name.
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