Showing posts with label Neurology. Show all posts
Showing posts with label Neurology. Show all posts
Tuesday, August 11, 2009
Seizures, Not Epilepsy Itself, May Raise Birth Risks
Epileptic seizures during pregnancy increase the likelihood of premature and small babies, says a new study. Read more
Wednesday, January 14, 2009
Pediatric MS Tied to Higher Relapse Rates
(HealthDay News) -- People who develop multiple sclerosis before age 18 tend to suffer almost three times the symptom relapses than those who develop the disease in adulthood, a new study says.
The study, headed by Dr. Mark P. Gorman of Brigham and Women's Hospital and Massachusetts General Hospital in Boston, found those who had MS as children experienced 1.13 relapses annually compared with 0.4 relapses for those who didn't develop the disease until adulthood.
Symptoms of MS, an inflammatory disease in which the protective coating covering nerve cells degenerates, usually first appears in people between ages 20 and 40. Fewer than 11 percent of MS patients report symptoms appearing before age 18, according to background information in the article, leading some to theorize that MS progresses slower in those who have it in childhood.
"The higher relapse rate in the pediatric-onset group in our study may therefore suggest that patients with pediatric-onset MS are coming to medical attention closer to the true biological onset of their disorder than patients with adult onset during a more inflammatory phase, as has been previously suggested," Gorman and colleagues wrote.
The findings were published in the January issue of Archives of Neurology.
More information
The U.S. National Institute of Neurological Disorders and Stroke has more about multiple sclerosis.
The study, headed by Dr. Mark P. Gorman of Brigham and Women's Hospital and Massachusetts General Hospital in Boston, found those who had MS as children experienced 1.13 relapses annually compared with 0.4 relapses for those who didn't develop the disease until adulthood.
Symptoms of MS, an inflammatory disease in which the protective coating covering nerve cells degenerates, usually first appears in people between ages 20 and 40. Fewer than 11 percent of MS patients report symptoms appearing before age 18, according to background information in the article, leading some to theorize that MS progresses slower in those who have it in childhood.
"The higher relapse rate in the pediatric-onset group in our study may therefore suggest that patients with pediatric-onset MS are coming to medical attention closer to the true biological onset of their disorder than patients with adult onset during a more inflammatory phase, as has been previously suggested," Gorman and colleagues wrote.
The findings were published in the January issue of Archives of Neurology.
More information
The U.S. National Institute of Neurological Disorders and Stroke has more about multiple sclerosis.
Wednesday, January 30, 2008
Alzheimers Research Target May Be a Dead End
(HealthDay News) -- A once-promising pathway for research into preventing and treating Alzheimer's disease may have been derailed by a surprise chemical finding, researchers report.
Scientists in laboratories around the world have been investigating drug candidates called amyloid inhibitors, which many experts believed could keep proteins such as amyloid-beta from sticking together in brain tissue.
This type of "sticky" protein plaque build-up is a hallmark of Alzheimer's disease. It also characterizes brain illnesses such as Huntington's disease and "mad cow" disease.
But the new study, published Jan. 27 in the journal Nature Chemical Biology, may sound an unexpected death knell for amyloid inhibitor research.
In the study, a team of chemists at the University of California, San Francisco, found that these candidate drugs form large, unwieldy clumps themselves, rendering them useless as targeted therapy against amyloid in the brain.
High-tech research in the lab is revealing that typical amyloid inhibitors "seem to act not in the way people expect them to and want them to," explained study senior author Brian Shoichet, professor of pharmaceutical chemistry at UCSF.
Once these drugs aggregate into clumps, "they no longer have the right pharmacology, they won't cross the [brain's] membrane barriers, and they inhibit everything -- any protein will bind with them," he said.
In other words, the drugs lose their ability to migrate to the brain to fight amyloid plaque. They also give up their targeted specificity against amyloid, Shoichet said. "They end up inhibiting everything -- any protein that sees them will be sequestered by them," he said. This molecular clumping process is largely inevitable, Shoichet added.
His advice to neuroscientists investigating these agents as potential Alzheimer's therapies: "They should stop."
Another expert agreed.
David Lynn is a Howard Hughes Institute investigator and professor of biological chemistry at Emory University in Atlanta. "I think that Brian's paper argues that [scientists] have been missing the boat here," he said. "It's not clear that you are ever going to get the concentrations that you need of these agents at the right site to be able to have any therapeutic intervention."
On the level of basic chemistry, attacking Alzheimer's and other protein-clumping diseases by preventing amyloid from concentrating has "always been a long shot," Lynn said. That's because amyloid proteins are incredibly "sticky," chemically speaking.
"To find things that will competitively stick and stop them from assembling is theoretically hard to imagine," Lynn said. It was thought that individual molecules of amyloid inhibitors might do so, but the new finding -- that the molecules inevitably bind together in a more impractical mass -- renders them therapeutically useless.
But other avenues of Alzheimer's research remain promising, Lynn said.
"There are certainly other strategies that have potential," he noted, including antibody-focused strategies aimed at eliminating plaques, or treatments focused on easing the downstream effects of amyloid buildup.
Both scientists stressed that it's still not certain whether protein plaques even cause Alzheimer's and other brain diseases, or whether they are merely byproducts of the disease process. "That's really another open area of research," Shoichet said.
"The problem with these diseases is that it is such a moving target," Lynn said. "And so, different people are looking at different things."
More information
There's much more on Alzheimer's disease at the Alzheimer's Association.
Scientists in laboratories around the world have been investigating drug candidates called amyloid inhibitors, which many experts believed could keep proteins such as amyloid-beta from sticking together in brain tissue.
This type of "sticky" protein plaque build-up is a hallmark of Alzheimer's disease. It also characterizes brain illnesses such as Huntington's disease and "mad cow" disease.
But the new study, published Jan. 27 in the journal Nature Chemical Biology, may sound an unexpected death knell for amyloid inhibitor research.
In the study, a team of chemists at the University of California, San Francisco, found that these candidate drugs form large, unwieldy clumps themselves, rendering them useless as targeted therapy against amyloid in the brain.
High-tech research in the lab is revealing that typical amyloid inhibitors "seem to act not in the way people expect them to and want them to," explained study senior author Brian Shoichet, professor of pharmaceutical chemistry at UCSF.
Once these drugs aggregate into clumps, "they no longer have the right pharmacology, they won't cross the [brain's] membrane barriers, and they inhibit everything -- any protein will bind with them," he said.
In other words, the drugs lose their ability to migrate to the brain to fight amyloid plaque. They also give up their targeted specificity against amyloid, Shoichet said. "They end up inhibiting everything -- any protein that sees them will be sequestered by them," he said. This molecular clumping process is largely inevitable, Shoichet added.
His advice to neuroscientists investigating these agents as potential Alzheimer's therapies: "They should stop."
Another expert agreed.
David Lynn is a Howard Hughes Institute investigator and professor of biological chemistry at Emory University in Atlanta. "I think that Brian's paper argues that [scientists] have been missing the boat here," he said. "It's not clear that you are ever going to get the concentrations that you need of these agents at the right site to be able to have any therapeutic intervention."
On the level of basic chemistry, attacking Alzheimer's and other protein-clumping diseases by preventing amyloid from concentrating has "always been a long shot," Lynn said. That's because amyloid proteins are incredibly "sticky," chemically speaking.
"To find things that will competitively stick and stop them from assembling is theoretically hard to imagine," Lynn said. It was thought that individual molecules of amyloid inhibitors might do so, but the new finding -- that the molecules inevitably bind together in a more impractical mass -- renders them therapeutically useless.
But other avenues of Alzheimer's research remain promising, Lynn said.
"There are certainly other strategies that have potential," he noted, including antibody-focused strategies aimed at eliminating plaques, or treatments focused on easing the downstream effects of amyloid buildup.
Both scientists stressed that it's still not certain whether protein plaques even cause Alzheimer's and other brain diseases, or whether they are merely byproducts of the disease process. "That's really another open area of research," Shoichet said.
"The problem with these diseases is that it is such a moving target," Lynn said. "And so, different people are looking at different things."
More information
There's much more on Alzheimer's disease at the Alzheimer's Association.
Tuesday, August 28, 2007
Food for the Aging Mind
Agricultural Research
08-27-07
Originally Published:20070801.
Scientists know that certain nutrients and other key chemical compounds are essential to human brain function. Serious deficiencies in some of these, such as vitamin B12 and iron, can lead to impaired cognitive function due to neurological, or nerve fiber, complications.
Cognition can be defined as the ability to use simple-to-complex information to meet the challenges of daily living.
So, could careful attention to diet help protect the aging brain from problems with nerve cell signals involved in memory and cognition? A clear-cut answer could greatly affect the 77 million baby boomers who are now facing retirement. Their independence, quality of life, and even economic status will largely be defined by their ability to traffic information signals as they age.
In researching the nutrition-brain connection, new technologies are being used, such as those that take images of the brain or actually count individual brain cells. Behavioral tests that measure motor and cognitive skills-or lack thereof-are also providing insights. Yet the science of nutrition and brain function is relatively new and evolving.
Agricultural Research Service scientists at several locations nationwide are contributing to a growing body of research that explores the effect of diet and nutrition on the brain and its function across the lifespan.
Boosting Neuronal Function
The brain's billions of neurons "talk" to one another through chemical neurotransmitters that convey signals through neural pathways. These chemical transporters- which include norepinephrine, serotonin, and dopamine-are key to signal movement.
Although people naturally lose brain cells throughout their lives, the process of neuronal death does not necessarily accelerate with aging. "There is a lot of individual difference," says ARS neuroscientist James Joseph. "Loss of mental agility may be less due to loss of brain cells than to the cells' failure to communicate effectively."
Joseph heads the Neuroscience Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston. There, researchers are looking at the beneficial effects of certain dietary plant compounds to learn how they affect brain function.
"Vitamins and minerals in plant foods provide protective antioxidants," says Joseph. "But fruits, vegetables, nuts, seeds, and grains contain thousands of other types of compounds that contribute significantly to the overall dietary intake of antioxidants.
"A partial measure of the antioxidant effect is called 'ORAC,' for Oxygen Radical Absorbance Capacity. ORAC scores are now showing up in charts and on some food and beverage packages. They may be helpful in choosing foods to include in your diet."
Perhaps there is no better place in which to gauge the power of antioxidants than between the minute connections of the nerve cells.
Bucking Long-Held Dogma
Eight years ago, Joseph and colleagues began publishing a series of studies, done in rodents, that shed light on the relationship between various diets and the mechanisms behind cognitive losses in specific neighborhoods of the aging brain.
Many in the series are groundbreaking in that they challenge the long-accepted belief that the central nervous system, which includes the brain, is not capable of regenerating itself. Other published studies in the series echo similar findings based on primate and human brain research at the Salk Institute for Biological Studies, San Diego, California. Scientists there, using new technologies, disputed the notion that the brain does not make new neurons-a process called "neurogenesis"-into old age: It does, but at a much slower rate.
One of the first of Joseph's studies, published in the Journal of Neuroscience, showed a protective effect of consuming antioxidants. Study rats were fed-from adulthood to middle age-vitamin E, strawberry extracts, or spinach extracts, all with similar ORAC values. Animals receiving the high-antioxidant diets did not experience the age-related cognitive performance losses seen in control rats fed standard chow.
A later study, also published in the Journal of Neuroscience, showed a reversal of functional loss among rats on special diets. Each of three groups of rats, equivalent in age to 63-year-old humans, was fed a different high-antioxidant extract. A control group was fed standard chow.
After 8 weeks-equivalent to about 10 years in humans-the rats' performance levels were measured.
The rats fed the spinach, strawberry, or blueberry extracts effectively reversed age-related deficits in neuronal and cognitive function. In addition, the blueberryfed group far outperformed their peers while traversing a rotating rod to test balance and coordination.
"Despite their status as 'senior citizens,' those rats showed remarkable stamina on neuromotor function tests," says psychologist and coauthor Barbara Shukitt-Hale, also with the Neuroscience Laboratory.
Examination of the brain tissue of those blueberry-fed rats showed much higher levels of dopamine than were found in the other groups. Dopamine has many functions within the brain. In particular, it can affect the way the brain controls movements.
"We suspected that the combined antioxidant potency of compounds in blueberry extract may have reduced inflammatory compounds in the brains of these older animals," says Joseph.
"Inflammation ordinarily contributes to neuronal and behavioral shortfalls during aging."
Tests have since shown that blueberry compounds cross the blood-brain barrier and localize in rodent brain tissue.
Hard News: Brain Plaques
Later, the lab's researchers published an Alzheimer's disease model study in Nutritional Neuroscience. They studied mice that carried a genetic mutation for promoting increased amounts of amyloid beta, a protein fragment found within the telltale neuritic plaque, or "hardening of the brain," seen in Alzheimer's disease.
Although the exact cause of Alzheimer's is not completely understood, experts have recently identified one mechanism involving the insufficient breakdown and recycling of amyloid protein in the brain. That mechanism is both genetic and physiological. In those individuals, normally harmless amyloid protein turns into fragments of amyloid beta, which build up as plaque in the brain rather than being escorted into cellular recycling. That action leads to cell death and weakened neuronal communication.
In the mouse study, beginning at age 4 months-early adulthood-half the brainplaqued group was fed a diet that included blueberry extract for 8 months. The other half was fed standard rat chow and so was a control group of mice that didn't carry the amyloid-plaque mutation.
At 12 months-early middle age-all groups were tested for their performance in a maze.
The brain-plaqued mice that were fed the blueberry extract performed as well as the healthy control mice and performed much better than their brain-plaqued peers fed standard chow.
A look at the plaqued brains of both the blueberry-fed and chow-fed mice after death revealed no difference in the number of brain plaques in either group. "Amyloid-beta-induced plaques are only one aspect of Alzheimer's disease," says Joseph. "But the fact that we saw a dietinduced behavioral difference, despite a similarity in plaque density in both these animal groups, is significant."
The team found increased activity of a family of enzymes called "kinases" in the brains of the amyloid-plaqued mice that were fed blueberry extract. Two kinases found in particular, ERK and PKC, are important in mediating cognitive function, such as converting short-term memory to long-term.
"These kinase molecules are involved in signaling pathways for learning and memory," says Joseph. "It could be that the increased kinase activity within the plaque-ridden brains of the blueberry-fed mice enhanced the signaling in certain receptors."
Brain Cells Are Born
Another HNRCA rat study looked at the aged brain's ability to change physiologically- a condition scientists refer to as "neuronal plasticity." In addition to cell division and differentiation, or "mission assignment," brain tissue undergoes many other changes throughout aging.
For example, a newborn sprouts billions of nerve cells while soaking up information from the environment. But lower levels of synapse growth continue in waves throughout the lifespan.
Littleused synapses are eliminated, while others are strengthened in a neuronal pruning process, of sorts.
Repair mechanisms involve neural immune cells, called "microglia," that seek to heal and protect injured brain tissue; enzymes that regulate safe chemical levels; and genes that are expressed in response to inflammation.
The neuronal-plasticity study investigated the physiological link between nutrition and the memory-control hippocampal area of the aged brain. That region, in the center of the brain, is essential for what's called "working" or "short-term" memory. It receives and processes data, and then, if needed, passes it on for storage.
Neurogenesis also plays a role in the formation of new memories. The capacity of the hippocampus to produce new neurons is thought to be greatly diminished during aging. But this study suggested that old rats fed blueberry extracts for a short time had increased neurogenesis in the dentate gyrus area of their brain's hippocampus. The dentate gyrus is one of the few regions of the brain where neurogenesis occurs.
"We found changes in the proliferation of neurons in blueberry-fed rats," said Gemma Casadesus, formerly a graduate student with the Neuroscience Laboratory and now with Case Western Reserve University. In maze tests, blueberry-fed aged lab rats showed improvement in cognition over chow-fed peers. "There was an association between the proliferation of neuronal precursor cells and better performance of spatial memory," she says.
The researchers don't yet know whether the cognitive improvements seen in the aged blueberry-fed rats translate to humans. "But it's an important step in learning about the brain's ability to rescue itself from age-associated declines in physiological function," Casadesus says.
Can You Hear Me Now?
Neurons that can't get their messages through signaling pathways are like cell phones that can't get their signals through to other cell phones. Why does this happen?
As the brain matures, cell division becomes largely restricted to specific regions of the brain, and brain cells tend to become more vulnerable to two partners in crime: oxidative stress and inflammation.
In the body, free radicals-weakened atoms formed during activities of daily living-are missing an electron and want to bond with neighboring biomolecules to stabilize. The problem is that unless neutralized, free radicals cause cellular damage known as "oxidative stress."
Cellular antioxidant defense systems counterbalance these rogue molecules, but they're not 100 percent effective-particularly as the body and brain mature. And the brain is thought to be especially vulnerable to oxidative stress.
"Weighing just 3 pounds, the brain accounts for only 2 percent of the body's total mass, yet it uses up to half of the body's total oxygen consumed during mental activity," says Joseph.
"Phytochemicals, together with essential nutrients in foods, provide a health-benefits cocktail of sorts. It is feasible that continued research in this area will point to dietary regimens that are effective in boosting neuronal function."
Inflammation is thought to be stoked by the overactivation of microglia-the neural immune cells mentioned earlier.
Microglia are usually dormant, but they migrate to the site of any brain injury. These sentries make up about 20 percent of the cell population in certain regions of the brain.
While seeking to protect and repair tissue, microglia cells produce and send out molecular stress signals, some by way of defensive cytokines, as a bugle call to other cells. Those signals begin a cascade of reactions, including the activation of genes that express proteins and other stress chemicals to help clear away cellular debris.
Microglial activation by amyloid beta is thought to be a key event in the progression of Alzheimer's disease. "When microglia are stuck in an always-on loop in response to plaque buildup in the brain, they become problematic in and of themselves," says Joseph.
This year, Francis Lau, a molecular biologist in the Neuroscience Laboratory, published a study that investigated whether blueberry extracts could have a preventive effect on inflammatory signals coming from activated microglia cells.
Microglial activation is considered the hallmark of inflammation in the central nervous system. For this study, Lau used a rodent microglial cell line that has previously served as a model to study plaqueinduced microglial activation.
Lau exposed groups of those test cells to various levels of blueberry extracts. He then challenged the cells with oxidative stress by exposing them to a toxin-lipopolysaccharide- that triggers secretion of inflammatory chemicals.
Neuroinflammation has been linked to the expression of genes that spew two inflammatory enzymes, iNOS and COX-2, and two cytokines, IL-1b and TNF-a.
Lau used real-time PCR (polymerase chain reaction) to find and measure expression of genes that produce iNOS and COX-2 in the stress-induced cell cultures. He found that the blueberry treatment significantly reduced that expression.
The blueberry extract also markedly lessened secretion of the two inflammatory cytokines. In fact, says Lau, "In cells exposed to the highest blueberry extract concentration, the amount of TNF-a cytokine found was next to nothing- essentially identical to that found in the control cells."
Looking to the Future
The food industry is now using a range of new and existing product ingredients to gain entrance into the emerging brainhealth market. Some are producing food labels that list ORAC values-for example, for use on containers of polyphenol-rich fruit juices and teas. So far, however, there has been no review conducted by the U.S. Food and Drug Administration on health benefits from eating berries.
Future studies at HNRCA will ideally include use of new diagnostic tools as well as human clinical trials. Neuroimaging equipment, for example, could be used to monitor the influence of various dietary factors on development of plaque within the human brain. Such studies aim to find the best dietary regimens to help adults preserve their mental capabilities while aging.-By Rosalie Marion Bliss, ARS.
This research is part of Human Nutrition, an ARS national program (#107) described on the World Wide Web at www. nps.ars.usda.gov.
James A. Joseph is with the USDA-ARS Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111; phone (617) 556-3178, fax (617) 556-3222, e-mail jim.joseph@ ars.usda.gov.
08-27-07
Originally Published:20070801.
Scientists know that certain nutrients and other key chemical compounds are essential to human brain function. Serious deficiencies in some of these, such as vitamin B12 and iron, can lead to impaired cognitive function due to neurological, or nerve fiber, complications.
Cognition can be defined as the ability to use simple-to-complex information to meet the challenges of daily living.
So, could careful attention to diet help protect the aging brain from problems with nerve cell signals involved in memory and cognition? A clear-cut answer could greatly affect the 77 million baby boomers who are now facing retirement. Their independence, quality of life, and even economic status will largely be defined by their ability to traffic information signals as they age.
In researching the nutrition-brain connection, new technologies are being used, such as those that take images of the brain or actually count individual brain cells. Behavioral tests that measure motor and cognitive skills-or lack thereof-are also providing insights. Yet the science of nutrition and brain function is relatively new and evolving.
Agricultural Research Service scientists at several locations nationwide are contributing to a growing body of research that explores the effect of diet and nutrition on the brain and its function across the lifespan.
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Boosting Neuronal Function
The brain's billions of neurons "talk" to one another through chemical neurotransmitters that convey signals through neural pathways. These chemical transporters- which include norepinephrine, serotonin, and dopamine-are key to signal movement.
Although people naturally lose brain cells throughout their lives, the process of neuronal death does not necessarily accelerate with aging. "There is a lot of individual difference," says ARS neuroscientist James Joseph. "Loss of mental agility may be less due to loss of brain cells than to the cells' failure to communicate effectively."
Joseph heads the Neuroscience Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston. There, researchers are looking at the beneficial effects of certain dietary plant compounds to learn how they affect brain function.
"Vitamins and minerals in plant foods provide protective antioxidants," says Joseph. "But fruits, vegetables, nuts, seeds, and grains contain thousands of other types of compounds that contribute significantly to the overall dietary intake of antioxidants.
"A partial measure of the antioxidant effect is called 'ORAC,' for Oxygen Radical Absorbance Capacity. ORAC scores are now showing up in charts and on some food and beverage packages. They may be helpful in choosing foods to include in your diet."
Perhaps there is no better place in which to gauge the power of antioxidants than between the minute connections of the nerve cells.
Bucking Long-Held Dogma
Eight years ago, Joseph and colleagues began publishing a series of studies, done in rodents, that shed light on the relationship between various diets and the mechanisms behind cognitive losses in specific neighborhoods of the aging brain.
Many in the series are groundbreaking in that they challenge the long-accepted belief that the central nervous system, which includes the brain, is not capable of regenerating itself. Other published studies in the series echo similar findings based on primate and human brain research at the Salk Institute for Biological Studies, San Diego, California. Scientists there, using new technologies, disputed the notion that the brain does not make new neurons-a process called "neurogenesis"-into old age: It does, but at a much slower rate.
One of the first of Joseph's studies, published in the Journal of Neuroscience, showed a protective effect of consuming antioxidants. Study rats were fed-from adulthood to middle age-vitamin E, strawberry extracts, or spinach extracts, all with similar ORAC values. Animals receiving the high-antioxidant diets did not experience the age-related cognitive performance losses seen in control rats fed standard chow.
A later study, also published in the Journal of Neuroscience, showed a reversal of functional loss among rats on special diets. Each of three groups of rats, equivalent in age to 63-year-old humans, was fed a different high-antioxidant extract. A control group was fed standard chow.
After 8 weeks-equivalent to about 10 years in humans-the rats' performance levels were measured.
The rats fed the spinach, strawberry, or blueberry extracts effectively reversed age-related deficits in neuronal and cognitive function. In addition, the blueberryfed group far outperformed their peers while traversing a rotating rod to test balance and coordination.
"Despite their status as 'senior citizens,' those rats showed remarkable stamina on neuromotor function tests," says psychologist and coauthor Barbara Shukitt-Hale, also with the Neuroscience Laboratory.
Examination of the brain tissue of those blueberry-fed rats showed much higher levels of dopamine than were found in the other groups. Dopamine has many functions within the brain. In particular, it can affect the way the brain controls movements.
"We suspected that the combined antioxidant potency of compounds in blueberry extract may have reduced inflammatory compounds in the brains of these older animals," says Joseph.
"Inflammation ordinarily contributes to neuronal and behavioral shortfalls during aging."
Tests have since shown that blueberry compounds cross the blood-brain barrier and localize in rodent brain tissue.
Hard News: Brain Plaques
Later, the lab's researchers published an Alzheimer's disease model study in Nutritional Neuroscience. They studied mice that carried a genetic mutation for promoting increased amounts of amyloid beta, a protein fragment found within the telltale neuritic plaque, or "hardening of the brain," seen in Alzheimer's disease.
Although the exact cause of Alzheimer's is not completely understood, experts have recently identified one mechanism involving the insufficient breakdown and recycling of amyloid protein in the brain. That mechanism is both genetic and physiological. In those individuals, normally harmless amyloid protein turns into fragments of amyloid beta, which build up as plaque in the brain rather than being escorted into cellular recycling. That action leads to cell death and weakened neuronal communication.
In the mouse study, beginning at age 4 months-early adulthood-half the brainplaqued group was fed a diet that included blueberry extract for 8 months. The other half was fed standard rat chow and so was a control group of mice that didn't carry the amyloid-plaque mutation.
At 12 months-early middle age-all groups were tested for their performance in a maze.
The brain-plaqued mice that were fed the blueberry extract performed as well as the healthy control mice and performed much better than their brain-plaqued peers fed standard chow.
A look at the plaqued brains of both the blueberry-fed and chow-fed mice after death revealed no difference in the number of brain plaques in either group. "Amyloid-beta-induced plaques are only one aspect of Alzheimer's disease," says Joseph. "But the fact that we saw a dietinduced behavioral difference, despite a similarity in plaque density in both these animal groups, is significant."
The team found increased activity of a family of enzymes called "kinases" in the brains of the amyloid-plaqued mice that were fed blueberry extract. Two kinases found in particular, ERK and PKC, are important in mediating cognitive function, such as converting short-term memory to long-term.
"These kinase molecules are involved in signaling pathways for learning and memory," says Joseph. "It could be that the increased kinase activity within the plaque-ridden brains of the blueberry-fed mice enhanced the signaling in certain receptors."
Brain Cells Are Born
Another HNRCA rat study looked at the aged brain's ability to change physiologically- a condition scientists refer to as "neuronal plasticity." In addition to cell division and differentiation, or "mission assignment," brain tissue undergoes many other changes throughout aging.
For example, a newborn sprouts billions of nerve cells while soaking up information from the environment. But lower levels of synapse growth continue in waves throughout the lifespan.
Littleused synapses are eliminated, while others are strengthened in a neuronal pruning process, of sorts.
Repair mechanisms involve neural immune cells, called "microglia," that seek to heal and protect injured brain tissue; enzymes that regulate safe chemical levels; and genes that are expressed in response to inflammation.
The neuronal-plasticity study investigated the physiological link between nutrition and the memory-control hippocampal area of the aged brain. That region, in the center of the brain, is essential for what's called "working" or "short-term" memory. It receives and processes data, and then, if needed, passes it on for storage.
Neurogenesis also plays a role in the formation of new memories. The capacity of the hippocampus to produce new neurons is thought to be greatly diminished during aging. But this study suggested that old rats fed blueberry extracts for a short time had increased neurogenesis in the dentate gyrus area of their brain's hippocampus. The dentate gyrus is one of the few regions of the brain where neurogenesis occurs.
"We found changes in the proliferation of neurons in blueberry-fed rats," said Gemma Casadesus, formerly a graduate student with the Neuroscience Laboratory and now with Case Western Reserve University. In maze tests, blueberry-fed aged lab rats showed improvement in cognition over chow-fed peers. "There was an association between the proliferation of neuronal precursor cells and better performance of spatial memory," she says.
The researchers don't yet know whether the cognitive improvements seen in the aged blueberry-fed rats translate to humans. "But it's an important step in learning about the brain's ability to rescue itself from age-associated declines in physiological function," Casadesus says.
Can You Hear Me Now?
Neurons that can't get their messages through signaling pathways are like cell phones that can't get their signals through to other cell phones. Why does this happen?
As the brain matures, cell division becomes largely restricted to specific regions of the brain, and brain cells tend to become more vulnerable to two partners in crime: oxidative stress and inflammation.
In the body, free radicals-weakened atoms formed during activities of daily living-are missing an electron and want to bond with neighboring biomolecules to stabilize. The problem is that unless neutralized, free radicals cause cellular damage known as "oxidative stress."
Cellular antioxidant defense systems counterbalance these rogue molecules, but they're not 100 percent effective-particularly as the body and brain mature. And the brain is thought to be especially vulnerable to oxidative stress.
"Weighing just 3 pounds, the brain accounts for only 2 percent of the body's total mass, yet it uses up to half of the body's total oxygen consumed during mental activity," says Joseph.
"Phytochemicals, together with essential nutrients in foods, provide a health-benefits cocktail of sorts. It is feasible that continued research in this area will point to dietary regimens that are effective in boosting neuronal function."
Inflammation is thought to be stoked by the overactivation of microglia-the neural immune cells mentioned earlier.
Microglia are usually dormant, but they migrate to the site of any brain injury. These sentries make up about 20 percent of the cell population in certain regions of the brain.
While seeking to protect and repair tissue, microglia cells produce and send out molecular stress signals, some by way of defensive cytokines, as a bugle call to other cells. Those signals begin a cascade of reactions, including the activation of genes that express proteins and other stress chemicals to help clear away cellular debris.
Microglial activation by amyloid beta is thought to be a key event in the progression of Alzheimer's disease. "When microglia are stuck in an always-on loop in response to plaque buildup in the brain, they become problematic in and of themselves," says Joseph.
This year, Francis Lau, a molecular biologist in the Neuroscience Laboratory, published a study that investigated whether blueberry extracts could have a preventive effect on inflammatory signals coming from activated microglia cells.
Microglial activation is considered the hallmark of inflammation in the central nervous system. For this study, Lau used a rodent microglial cell line that has previously served as a model to study plaqueinduced microglial activation.
Lau exposed groups of those test cells to various levels of blueberry extracts. He then challenged the cells with oxidative stress by exposing them to a toxin-lipopolysaccharide- that triggers secretion of inflammatory chemicals.
Neuroinflammation has been linked to the expression of genes that spew two inflammatory enzymes, iNOS and COX-2, and two cytokines, IL-1b and TNF-a.
Lau used real-time PCR (polymerase chain reaction) to find and measure expression of genes that produce iNOS and COX-2 in the stress-induced cell cultures. He found that the blueberry treatment significantly reduced that expression.
The blueberry extract also markedly lessened secretion of the two inflammatory cytokines. In fact, says Lau, "In cells exposed to the highest blueberry extract concentration, the amount of TNF-a cytokine found was next to nothing- essentially identical to that found in the control cells."
Looking to the Future
The food industry is now using a range of new and existing product ingredients to gain entrance into the emerging brainhealth market. Some are producing food labels that list ORAC values-for example, for use on containers of polyphenol-rich fruit juices and teas. So far, however, there has been no review conducted by the U.S. Food and Drug Administration on health benefits from eating berries.
Future studies at HNRCA will ideally include use of new diagnostic tools as well as human clinical trials. Neuroimaging equipment, for example, could be used to monitor the influence of various dietary factors on development of plaque within the human brain. Such studies aim to find the best dietary regimens to help adults preserve their mental capabilities while aging.-By Rosalie Marion Bliss, ARS.
This research is part of Human Nutrition, an ARS national program (#107) described on the World Wide Web at www. nps.ars.usda.gov.
James A. Joseph is with the USDA-ARS Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111; phone (617) 556-3178, fax (617) 556-3222, e-mail jim.joseph@ ars.usda.gov.
Friday, June 22, 2007
1st Gene Therapy Trial Effective Against Parkinson's
(HealthDay News) -- In an early trial, gene therapy has proven both safe and effective in easing the symptoms of Parkinson's disease, researchers say.
A dozen patients experienced a 25 percent to 30 percent improvement in their total symptoms without any side effects, the U.S. team noted in the June 23 issue of The Lancet.
"Safety and tolerability were met with flying colors. On that level, we are extremely encouraged," said Dr. Matthew During, senior author of the study and professor of molecular biology, immunology and medical genetics at Ohio State University. "All in all, we're very excited, but we have to be a little bit cautious, and we need to do a definitive study with the proper controls."
During completed the study while on the faculty of Weill Medical College of Cornell University in New York City. The trial was conducted with researchers from the Feinstein Institute for Medical Research, part of the North Shore-LIJ Health System, in New York. The study was funded by Neurologix, which was co-founded by During and another study author, Dr. Michael Kaplitt. The two remain as consultants to the company, and Kaplitt's father is chairman of the board of Neurologix.
Parkinson's disease affects some 1.5 million Americans, most of them over the age of 65, although younger patients are also affected, including actor and Parkinson's research advocate Michael J. Fox.
The illness is characterized by a loss of dopamine-producing brain cells, resulting in problems with motor function such as tremors, limb rigidity, slow movement and balance and coordination problems.
There are some treatments but no cure, and, as During pointe out, current treatments are far from ideal.
Patients eventually become resistant to drugs. Deep brain stimulation, which involves placing an electrode deep into the brain, has helped some patients who no longer respond to drugs. But the therapy has side effects and is only partially effective.
"There are wires and a huge battery pack in the chest. It's a bit Frankensteinian, and patients hate it," During said. "There's about a 30 to 40 percent adverse event rate. Although it works, it comes at a significant cost."
"There's an unmet need for Parkinson's disease" treatment, he added.
Gene therapy has shown some promise in different areas of medicine, but there have been lingering concerns about its safety after one patient receiving gene therapy for a rare inherited disorder died in 1999. That case led to a temporary suspension of trials.
The current trial is the first-ever phase I clinical trial looking at gene therapy against Parkinson's disease. The study involved 11 men and one woman, averaging 58 years of age. Participants were divided into three groups of four and given low, medium or high dose injections of the glutamic acid decarboxylase (GAD) gene directly into brain cells. The gene, which is involved in dopamine production, was transferred to the cells using an adeno-associated virus.
There were no side effects associated with the gene therapy and, although the study was not undertaken to show effectiveness, the researchers have noted improvements in movement within three months of the procedure.
Brain scans showed changes in metabolism similar to those that occur after surgery for Parkinson's.
The benefits were equivalent to improvements seen with deep brain stimulation, although deep brain stimulation is given to both sides of the brain, and the gene therapy was only given to one side of the brain because of concerns about side effects.
"It's sort of a proof of concept that the adenovirus vector process is not going to be detrimental for patients or doesn't show signs that it will," said Dr. Gerald Frye, a professor of neuroscience and experimental therapeutics at the Texas A&M Health Science Center College of Medicine. "I am impressed that there weren't a lot of negative things that happened. That's really encouraging."
But Frye added that, right now, it's hard to gauge whether this will be superior or inferior to deep brain stimulation.
"The authors argue that not having to go in and modulate your stimulator is an advantage for gene therapy. But, I would say that the fact that you can modulate stimulation is an advantage," Frye said. "Once you put the gene in, you can't take it back out and turn it up or down."
More information
Learn more about Parkinson's at the National Parkinson Foundation.
A dozen patients experienced a 25 percent to 30 percent improvement in their total symptoms without any side effects, the U.S. team noted in the June 23 issue of The Lancet.
"Safety and tolerability were met with flying colors. On that level, we are extremely encouraged," said Dr. Matthew During, senior author of the study and professor of molecular biology, immunology and medical genetics at Ohio State University. "All in all, we're very excited, but we have to be a little bit cautious, and we need to do a definitive study with the proper controls."
During completed the study while on the faculty of Weill Medical College of Cornell University in New York City. The trial was conducted with researchers from the Feinstein Institute for Medical Research, part of the North Shore-LIJ Health System, in New York. The study was funded by Neurologix, which was co-founded by During and another study author, Dr. Michael Kaplitt. The two remain as consultants to the company, and Kaplitt's father is chairman of the board of Neurologix.
Parkinson's disease affects some 1.5 million Americans, most of them over the age of 65, although younger patients are also affected, including actor and Parkinson's research advocate Michael J. Fox.
The illness is characterized by a loss of dopamine-producing brain cells, resulting in problems with motor function such as tremors, limb rigidity, slow movement and balance and coordination problems.
There are some treatments but no cure, and, as During pointe out, current treatments are far from ideal.
Patients eventually become resistant to drugs. Deep brain stimulation, which involves placing an electrode deep into the brain, has helped some patients who no longer respond to drugs. But the therapy has side effects and is only partially effective.
"There are wires and a huge battery pack in the chest. It's a bit Frankensteinian, and patients hate it," During said. "There's about a 30 to 40 percent adverse event rate. Although it works, it comes at a significant cost."
"There's an unmet need for Parkinson's disease" treatment, he added.
Gene therapy has shown some promise in different areas of medicine, but there have been lingering concerns about its safety after one patient receiving gene therapy for a rare inherited disorder died in 1999. That case led to a temporary suspension of trials.
The current trial is the first-ever phase I clinical trial looking at gene therapy against Parkinson's disease. The study involved 11 men and one woman, averaging 58 years of age. Participants were divided into three groups of four and given low, medium or high dose injections of the glutamic acid decarboxylase (GAD) gene directly into brain cells. The gene, which is involved in dopamine production, was transferred to the cells using an adeno-associated virus.
There were no side effects associated with the gene therapy and, although the study was not undertaken to show effectiveness, the researchers have noted improvements in movement within three months of the procedure.
Brain scans showed changes in metabolism similar to those that occur after surgery for Parkinson's.
The benefits were equivalent to improvements seen with deep brain stimulation, although deep brain stimulation is given to both sides of the brain, and the gene therapy was only given to one side of the brain because of concerns about side effects.
"It's sort of a proof of concept that the adenovirus vector process is not going to be detrimental for patients or doesn't show signs that it will," said Dr. Gerald Frye, a professor of neuroscience and experimental therapeutics at the Texas A&M Health Science Center College of Medicine. "I am impressed that there weren't a lot of negative things that happened. That's really encouraging."
But Frye added that, right now, it's hard to gauge whether this will be superior or inferior to deep brain stimulation.
"The authors argue that not having to go in and modulate your stimulator is an advantage for gene therapy. But, I would say that the fact that you can modulate stimulation is an advantage," Frye said. "Once you put the gene in, you can't take it back out and turn it up or down."
More information
Learn more about Parkinson's at the National Parkinson Foundation.
Monday, November 13, 2006
Hydergine: Desire Better Brain-Power?
Q: Hydergine: Desire Better Brain-Power? What do you think of hydergine to boost mental powers?
A: Hydergine has been touted for some time as a "smart" drug for use in enhancing mental abilities and improving intelligence.
It has been around for more than 20 years and is marketed today as a nonspecific cerebral stimulant and prescribed to help relieve symptoms of age-related mental decline. Hydergine has been studied but found ineffective for the treatment of Alzheimer's disease.
Originally developed for the treatment of hypertension, hydergine didn't really help lower blood pressure and is no longer used for that purpose. However, some people who took it soon after its introduction noticed improvements in memory and mood, which they associated with use of the drug. At first, these changes were attributed to increased blood flow to the brain, but later research suggested that hydergine improved brain cell metabolism.
Today, hydergine is FDA approved only for the treatment of people over the age of 60 who show signs of mental decline. I'm told it is more widely used in Europe, and I understand that some in the anti-aging community advocate taking more than the 3 mg daily dose recommended by the FDA.
Frankly, I wouldn't bother. I tried hydergine myself some years ago to see what it could do, but I detected no benefits. While the drug seems safe enough, I don't see the point of using it - especially since it's expensive. I'm unconvinced that it makes good on the promises made for it by its Internet promoters.
Andrew Weil, M.D.
A: Hydergine has been touted for some time as a "smart" drug for use in enhancing mental abilities and improving intelligence.
It has been around for more than 20 years and is marketed today as a nonspecific cerebral stimulant and prescribed to help relieve symptoms of age-related mental decline. Hydergine has been studied but found ineffective for the treatment of Alzheimer's disease.
Originally developed for the treatment of hypertension, hydergine didn't really help lower blood pressure and is no longer used for that purpose. However, some people who took it soon after its introduction noticed improvements in memory and mood, which they associated with use of the drug. At first, these changes were attributed to increased blood flow to the brain, but later research suggested that hydergine improved brain cell metabolism.
Today, hydergine is FDA approved only for the treatment of people over the age of 60 who show signs of mental decline. I'm told it is more widely used in Europe, and I understand that some in the anti-aging community advocate taking more than the 3 mg daily dose recommended by the FDA.
Frankly, I wouldn't bother. I tried hydergine myself some years ago to see what it could do, but I detected no benefits. While the drug seems safe enough, I don't see the point of using it - especially since it's expensive. I'm unconvinced that it makes good on the promises made for it by its Internet promoters.
Andrew Weil, M.D.
Folic Acid to Boost Memory?
Q: Folic Acid to Boost Memory?Is it true that folic acid can prevent Alzheimer's disease? I heard that it improves memory.
A: New findings do suggest that folic acid may slow the declines in memory that can occur with age. Dutch researchers recently presented compelling evidence from a three-year study that included 818 adults between the ages of 50 and 70, none of whom were having any memory problems.
During the study, the participants took either a placebo or 800 mg folic acid (twice the amount recommended for women of childbearing age to protect against birth defects).
Results showed that those who took the folic acid had memory scores equal to people five and a half years younger. The folic acid group in the study also did better in information processing and muscle skills. The study was conducted by researchers at Wageningen University in the Netherlands and reported at the Alzheimer's Association International Conference on Dementia Prevention.
A: New findings do suggest that folic acid may slow the declines in memory that can occur with age. Dutch researchers recently presented compelling evidence from a three-year study that included 818 adults between the ages of 50 and 70, none of whom were having any memory problems.
During the study, the participants took either a placebo or 800 mg folic acid (twice the amount recommended for women of childbearing age to protect against birth defects).
Results showed that those who took the folic acid had memory scores equal to people five and a half years younger. The folic acid group in the study also did better in information processing and muscle skills. The study was conducted by researchers at Wageningen University in the Netherlands and reported at the Alzheimer's Association International Conference on Dementia Prevention.
Banishing Balance Problems?
Q: Banishing Balance Problems?
You often suggest exercises to improve balance among seniors. How common are balance problems among older people and what is the cause?
A: Balance problems are very common among people over the age of 65 and are responsible for many serious injuries. It's estimated that this year one out of every four seniors living at home will fall.
Proper balance depends on the collaboration of three of your senses: your eyes, your sense of spatial orientation (the inner sense that tells you which way your feet or hands are pointing even with your eyes closed), and the vestibular system which encompasses the fluid-filled semicircular canals in the inner ear and informs the brain and eyes about the position of your head.
Each of these three senses diminishes with age, making balance more difficult.
Balance problems can also stem from the effects of alcohol, certain prescription drugs (ask your doctor if any of the drugs you take can have effects on balance), and such diseases as diabetes, which can cause numbness in the legs and feet, and arthritis, which can limit flexibility and range of motion.
Unfortunately, fear of falling often leads older people to become less active when, in fact, becoming moreactive can help reduce the risk. To improve balance, I recommend T'ai chi, which has been proven to reduce the odds of falling as well as the risk of injury if you do fall.
You can also learn balance exercises at the gym (have a trainer show you how to use balance boards or inflatable exercise balls). Physical therapy can further help you reduce the risk of falls with exercises tailored to whatever problem is impairing your balance.
You might also consider yoga, with its many balance poses, and Feldenkrais therapy to improve body awareness.
In addition, a new study from Indiana University at Bloomington has shown that exercises that speed up swaying may help forestall balance problems later in life.
We all sway when we stand on our feet but this happens so subtly that we're usually not aware of it.
Younger people generally sway backward and forward while older people tend to sway side to side, a less stable pattern. The Indiana researchers taught balance exercises to a group of adults between the ages of 55 and 60 who were in pretty good shape.
After doing three balance exercises four days a week for 15 minutes a day, all the participants improved their sway speed by an average of 16 percent, and, as a result, their stability.
One of the exercises required standing on one leg for 15 seconds with the other leg bent so the thigh was parallel to the floor; a second required balancing with one leg lifted to the side, and a third involved lifting one leg straight back while reaching forward with the opposite arm - all exercises that can be learned and practiced at home.
Andrew Weil, M.D.
You often suggest exercises to improve balance among seniors. How common are balance problems among older people and what is the cause?
A: Balance problems are very common among people over the age of 65 and are responsible for many serious injuries. It's estimated that this year one out of every four seniors living at home will fall.
Proper balance depends on the collaboration of three of your senses: your eyes, your sense of spatial orientation (the inner sense that tells you which way your feet or hands are pointing even with your eyes closed), and the vestibular system which encompasses the fluid-filled semicircular canals in the inner ear and informs the brain and eyes about the position of your head.
Each of these three senses diminishes with age, making balance more difficult.
Balance problems can also stem from the effects of alcohol, certain prescription drugs (ask your doctor if any of the drugs you take can have effects on balance), and such diseases as diabetes, which can cause numbness in the legs and feet, and arthritis, which can limit flexibility and range of motion.
Unfortunately, fear of falling often leads older people to become less active when, in fact, becoming moreactive can help reduce the risk. To improve balance, I recommend T'ai chi, which has been proven to reduce the odds of falling as well as the risk of injury if you do fall.
You can also learn balance exercises at the gym (have a trainer show you how to use balance boards or inflatable exercise balls). Physical therapy can further help you reduce the risk of falls with exercises tailored to whatever problem is impairing your balance.
You might also consider yoga, with its many balance poses, and Feldenkrais therapy to improve body awareness.
In addition, a new study from Indiana University at Bloomington has shown that exercises that speed up swaying may help forestall balance problems later in life.
We all sway when we stand on our feet but this happens so subtly that we're usually not aware of it.
Younger people generally sway backward and forward while older people tend to sway side to side, a less stable pattern. The Indiana researchers taught balance exercises to a group of adults between the ages of 55 and 60 who were in pretty good shape.
After doing three balance exercises four days a week for 15 minutes a day, all the participants improved their sway speed by an average of 16 percent, and, as a result, their stability.
One of the exercises required standing on one leg for 15 seconds with the other leg bent so the thigh was parallel to the floor; a second required balancing with one leg lifted to the side, and a third involved lifting one leg straight back while reaching forward with the opposite arm - all exercises that can be learned and practiced at home.
Andrew Weil, M.D.
Saturday, September 16, 2006
Commentary on Nutritional Treatment
from Willam Walsh, Ph.D., Senior Scientist, Pfeiffer Treatment Center http://www.hriptc.org/(The following information is taken from Dr. William Walsh's discussion on Safe Harbor's "Integrative Psychiatry" email list for professionals.
To preserve Dr. Walsh's wealth of information, we have posted his comments here, with the notation of added commentary [with the date] as discussion goes on.)
SAMe
SAMe is very promising for undermethylated persons and a bad idea for those who suffer from a genetic tendency for overmethylation. I don't particularly like the "allopathic" method you referred to which is simply trial & error. SAMe can do great harm if given to the wrong person.
I hate going to funerals. (17 Dec, 2002)The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP, methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body.
Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine.
The TMG route is secondary to the 5-methyl-tetrahydrofolate/B-12 reaction which the primary route for restoring methionine. Methionine and SAMe supplements directly introduce new methyl groups into the body.
TMG can provide a methyl group only to the extent that there is insufficient folate/B-12 to do the job. In some persons, the methylation effect of TMG is very minimal. In addition, persons who are undermethylated have a SAM cycle which is "spinning very slowly", much like a superhighway with little traffic.
The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body. A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient.
TMG is a great way to treat individuals with dangerously high homocysteine levels. TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine. Use of TMG is an "insurance policy" against this happening. (Jan 22, 2003)
A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe.
Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)..... you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We've found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It's often hard to improve on Mother Nature. (Jan 20, 2003)
SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person. The incidence of overmethylation in our patient database of 1,500 bipolar cases is about 18%. Bipolar disorder is not a single condition, but a collection of very different biochemical disorders under the same umbrella diagnosis. SAMe works great for truly undermethylated patients, but all hell breaks out if given to someone who is overloaded (genetically) with methyl groups. The right way to do this is to (a) first determine the person's innate methylation tendency & then (b) act accordingly. (Jan 31, 2003)
Schizophrenia
Severe wheat gluten intolerance can cause classic symptoms of schizophrenia, and amounts to about 4% of all schizophrenia diagnoses in the U.S. These persons usually become quite normal when placed on a gluten-free diet.I've done medical histories for more than 2,000 persons diagnosed with schizophrenia and have always been struck by the high frequency of schizophrenia in other relatives. Interestingly, the schizophrenia would often skip a generation.
NIMH data suggests that the overall incidence of schizophrenia in the USA is between 1% and 4%, depending on the definitions. However, the incidence of schizophrenia for children who have a schizophrenic parent is about 16%. This number doesn't change much for children of schizophrenics adopted at birth. I don't think there is "a schizophrenia gene", partly because this is a garbage term which encompasses several completely different conditions.
There are a number of biochemical ingredients which predispose to each phenotype of SZ..... these may be either genetic or acquired. However, I'm absolutely certain there is a genetic component in most cases.
Carl Pfeiffer was the first to develop meaningful chemical classifications of schizophrenia (and separate treatments for each phenotype). Carl Pfeiffer of Princeton, N.J. saw more than 20,000 schizophrenics in his lifetime. He found that 90% of all SZ patients could be classified into 3 large groups, with completely different etiologies & treatment approaches. These he termed "histapenia", "histadelia", and "pyroluria". The remaining 10% fit into several splinter groups.
One of the splinter groups was gluten intolerance, which represents 4% (1 case in 25). This is a rare form of schizophrenia, but if you've got it, it's everything!Multiple food & chemical sensitivities are also associated with histapenia (low histamine, overmethylation), the largest of all SZ groups, amounting to about 48% of all cases.
For this group, SZ symptoms often worsen if exposed to the offending substances, & nice improvements often occur if they are identified & avoided. However, the food sensitivities usually disappear after about 1 year of aggressive Folate/B-12/B-3 treatment, which is the primary route to a normal life for these patients.
We've known for more than 20 years that the metallothionein protein system does not perform well in most ADHD patients. About 68% of them exhibit very poor control of Cu & Zn, based on lab data from more than 6,000 patients diagnosed with ADD/ADHD. Autism is different in that about 90% of patients exhibit Cu/Zn imbalances that are generally much more severe than in ADHD.For several months, we have extended our metallothionein-promotion protocol to ADHD, behavior, depression, and schizophrenic patients who exhibit Cu/Zn imbalance.
The informal results so far are very encouraging. However, we've not yet done a formal outcome study for these populations, and thus have no statistics yet.We are considering applying MT-Promotion to Alzheimers & Parkinsons patients in the near future. Both disorders involve serious oxidative stress and abnormal trace metal levels. In addition, recent research has revealed a striking metallothionein deficiency in the brains of Alzheimers patients. (Feb 25, 2003)I've evaluated more than 3,500 patients with a diagnosis of bipolar or schizophrenia. The predominance of auditory hallucinations, serious self abuse, aggressiveness, inability to continue school, and social isolation...... all point in the direction of classic "paranoid schizophrenia", although many of these patients are labeled "bipolar disorder with psychotic features". Most severely mentally ill persons with a history of exceptional artistic or musical talent test as overmethylated. The biochemical recipe for these patients usually consists of (1) overmethylation, (2) low folate levels, and (3) elevated blood copper levels. All three of these chemical imbalances impact dopamine and norepinephrine in the brain, and together can cause rather extraordinary abnormalities in these important neurotransmitters. In my opinion, the key to successful treatment is biochemical treatment to overcome these chemical imbalances...... fortunately this can be accomplished using aggressive therapy with nutrients to normalize the chemical factors.Most mental breakdowns are triggered by severe stress, but the underlying cause is genetic and involves brain chemistry. Many persons self-medicate with alcohol, marijuana, or other illegal drugs in a desperate attempt to feel better. Many patients and their families erroneously believe that the EtOH or drug experiences were the underlying cause of the condition. They are wrong! This adult-onset condition will strike eventually in most cases, even if substance abuse never occurs.Traditional medicine can provide medication support which can usually eliminate (temporarily) most/all psychosis symptoms. However, these patients are usually plagued by drug side effects and are a mere shadow of their original selves. Common side effects are (a) fatigue, (b) inability to focus/concentrate for more than a few minutes, (c) change in personality, (d) massive weight gain, etc. The most popular drugs for these patients are Zyprexa, Seroquil, Risperdal, Geodon, and Clozaril..... the so-called atypical antipsychotics. Since most patients hate these medications, poor compliance is a major problem.I've seen many young schizophrenics and bipolar patients achieve complete recoveries through biochemical (nutrient) therapy. This rarely occurs with traditional medication therapy. (May 12, 2003)Some of schizophrenics who spontaneously get better are those who experience a toxic psychosis. I have a friend who had a toxic psychosis after an accidental overdose of a medication during childbirth. For 6 hours she was a full blown paranoid schizophrenic..... No symptoms in the following 20 years. Also, schizophrenia comes in mild, moderate, and severe versions. Many persons with a very mild genetic tendency for SZ can experience an environmental insult which pushes them into a temporary mental illness. Most will become quite ok with or without therapy.The real problem is the millions of SZ persons who have moderate to severe SZ which does not go away easily. (May 27, 2003)
Taurine
Yes, I've read a few articles and a book that talked about Taurine's slow metabolism and tendency to build up over time. Because of this, I've believed that high doses of Taurine (1,000 to 2,000 mg/day) are ok in the beginning..... but that the dosages need to be reduced within 2 weeks to about 400 to 500 mg/day..... to achieve the same effect.I believe that Taurine is especially effective for (1) combating seizure tendency and (2) reducing liver stress in processing fats. There have been several reports of intolerances and side effects from use of Taurine, and I feel that indiscriminant high doses are unwise.About 12 months ago, there was a fad among several alternative practitioners in which high doses of Taurine were given to every autistic patient. One of the reasons given was "to assist the liver cope with stresses associated with toxic metal overload". This seems to be a poor reason, since Taurine's action in the liver appears to be limited to fat metabolism, and most autistics are slender malabsorbers with low lipid levels. (June 24, 2003)
Womb Trauma
There is an exquisite and fragile biological/biochemical process during gestation in which short, dense immature brain cells are pruned, grow into fully-developed brain cells, and then (remarkably) experience growth inhibition to complete the process. The molecular biology of this process is becoming very well defined, and it is clear that many environmental events can hinder or disrupt early brain development. The primary culprits are oxidative stress, teratological chemicals, and infections. The least appreciated of these harmful factors is oxidative stress which can deplete key proteins and enzymes required for normal brain development.Environmental harm to a developing fetus can result from (a) biochemical inadequacies of the mother, and (b) external environmental insults. We're all familiar with birth defects that can result from Thalidomide, Thorazine, Prolixin, Haldol, and other psychiatric medications. Also the dangers of mercury, lead, and other toxics are well established, and we know that a mother's improper diet (e.g. inadequate folic acid) can be harmful. Although lower on the radar screen, fetal oxidative stresses can be equally devastating.What I'm leading up to.... is the scientific fact that serious emotional or physical stresses experienced by the mother can impair early brain development, especially if the mother is not biochemically intact. For example high emotional stresses or physical trauma to the mother will weaken the activity of metallothionein (MT) and glutathione (GSH) proteins, andincrease oxidative stress in the brain. MT-1 and MT-2 are directly involved in growth of immature brain cells. MT-3 is a key protein required for pruning and growth inhibition. These proteins also have the job of defending against oxidative stress in the brain and are consumed in the process. Maternal emotional stresses and psychic traumae deplete the embryonic brain of MT proteins and can compromise brain development.Womb trauma is real and the concept of "a cry so deep" is not psycho-babble guesswork. Rather, it is solidly supported by scientific fields such as embryology and molecular biology. (Aug 1, 2003)If fetal or early infant traumae have resulted in a brain that hasn't completely matured..... therapies to promote MT and GSH appear very promising..... especially in tandem withbehavioral therapies which stimulate the development of new brain cells.If the net result of the traumae is biochemical or neurotransmitter differences, then biochemical therapy aimed at normalizing brain chemistry would be indicated.If the traumae resulted in diminished ability to tolerate environmental toxins (for example an incompetent blood-brain barrier), then avoidance of such toxins would be an important aspect of treatment.If the traumae resulted in an innate inability to cope with emotional stresses, then counseling or other psychological services could be very beneficial.If the traumae resulted in a brain that is structurally different, this may represent "brain damage" that may be refractory to all treatments. (Aug 1, 2003)
Zinc
There have been several recent published articles which indicate that zinc and zinc metallothionein proteins (1) tend to prevent brain strokes, (2) tend to assist brain recovery after strokes, and (3) that deficiency of Zn or Zn-MT is associated with increased stroke likelihood. An occasional test for plasma Zn could help identify the proper dosage. Most adults can safely start with 25 to 50 mg/day of Zn. Without indication of B-6 deficiency, it might be a good idea to limit pyridoxine hydrochloride (usual form of B-6) to about 200 mg/day. B-6 is very helpful in enhancing the utilization of Zn.After use of these nutrients with thousands of persons, I'm not aware of a single case of harm. However, it is a good idea to introduce zinc gradually & to take Zn during the PM only. (June 3, 2003
Every 5 years or so, the zinc experts of the world convene for a symposium in which they share new advances in Zn technogy & research..... It's usually headed up by the eminent Prof. Prasad.One of the topics is laboratory testing to indicate an individual's Zn status. They consider about 10 different methods including packed cells, taste tests, etc...... The last two symposia resulted in the consensus that none of the testing options is wonderful, but that the best of the commercially available tests is plasma zinc. Taste tests didn't make the top three methods.However the Zn experts also stated that the most definitive determination of zinc depletion is the presence of symptoms of Zn depletion which disappear after Zn supplementation.My organization has evaluated the Zn status of 18,000 patients and we've tried all of these methods. Our standard protocol involves plasma Zn, being careful to use acid-etched, trace-metal-free tubes.We find that virtually all treatment-naive ASD persons are very Zn depleted and overloaded in "free" (unbound by ceruloplasmin) copper. Our patient population for ASD is 2,800. Our database of 5,600 ADHD patients indicates that about 75% are depleted in Zn. The remaining 25% have problems associated with pyrrole disorders, methylation disorders, EFA disorders, toxic overloads, etc. (July 22, 2003)
The high level of zinc depletion in ASD appears to stem from a genetic weakness in the metallothionein protein system.Cu/Zn ratios in hair are very helpful in ADHD and behavior disorders..... but far less useful in ASD, depression, and schizophrenia. Tracking plasma Zn, serum Cu and serum ceruloplasmin levels can be very helpful in guiding dosages aimed at normalizing Zn.
Management of Zn & Cu levels is a challenging problem in ASD. Sometimes rather extraordinary Zn dosages are required to normalize blood Zn levels.Virtually all ASD persons are Zn depleted., but not all exhibit an elevated Cu/Zn ratio. A minority of ASD patients exhibit normal or low Cu levels in serum, but have vastly inadequate levles of ceruloplasmin. Thus, the level of "unbound" Cu can be very high, even though all standard measures of Cu appear to be low. Some of these patients seem to have a mild version of Wilson's Disesase. (July 24, 2003)
Wednesday, July 19, 2006
Journal Editor Criticizes Authors of Migraine Study
(HealthDay News) -- The authors of a new study linking migraines with aura to an increased risk for heart woes came under attack Tuesday by the editor of the medical journal that published their research the same day.The editor-in-chief of the Journal of the American Medical Association criticized six researchers, led by a Harvard professor, for not disclosing that they have done consulting work or received research funding from makers of treatments for migraines or heart-related problems, the Associated Press reported.
The research, published in the July 19 issue of the journal, came a week after the journal announced a crackdown on researchers who don't reveal industry ties.
Dr. Catherine DeAngelis, JAMA editor-in-chief, said her editors did not know about the ties until the AP brought it to their attention.
"We'll get killed," the wire service quotes her as saying, referring to the potential damage to the journal's reputation.
During the past two months, there have been two cases of JAMA authors not disclosing their consulting relationships with drug companies, one involving antidepressants and the other arthritis drugs.
DeAngelis told the AP that she would have added the authors' financial association with the pharmaceutical companies if she had known about them, especially in the latest incident.
Dr. Tobias Kurth, the study's lead author and an assistant professor of medicine at Harvard School of Public Health in Boston, said the researchers were not trying to mislead the journal because they believed their financial ties were irrelevant. The study does not promote drug treatment, he added.
The research found specifically that women aged 45 and older who have migraines with aura are at an increased risk for heart attacks, strokes, angina and death due to cardiovascular disease but that there was no increased risk for women with a history of migraine without aura.
"This study confirmed an association between migraine with aura and stroke that was previously identified, and also demonstrated that migraine was a risk factor for ischemic heart disease as well," said Dr. Richard B. Lipton, co-author of an editorial accompanying the study and director of the Montefiore Headache Center in New York City.
"We expanded it beyond ischemic stroke," added Kurth. "The heart part is new, but it's not a different mechanism. It just shows a higher risk of overall cardiovascular disease."
About 18 percent of women and 6 percent of men have migraine in any given year, with some 28 million Americans suffering from the condition.
Migraine headaches are especially severe and can involve nausea, vomiting, sensitivity to light and sound. In some cases, the event also involves an aura -- visual and sensory "warning signs" just before the attack.
Migraines with auras, which comprise the minority of migraine attacks, have already been linked to an increased risk of ischemic stroke. Their association with other cardiovascular problems has not been established.
To evaluate the risk between migraine (with and without aura) with risk of vascular events, the authors looked at data on nearly 28,000 women aged 45 and older who were participating in the Women's Health Study.
Women who reported having active migraine with aura had about double the risk of major cardiovascular disease and heart attacks, almost double the risk for ischemic stroke and a 70 percent higher risk for ischemic cardiovascular death.
This translated into 18 additional major cardiovascular disease events attributable to migraine with aura per 10,000 women per year.
Women who had migraines without aura did not face increased risk in any of these areas. That's good news, since most migraine sufferers do not experience aura.
"It's important to understand that, for most migraine patients, this is not an issue," Kurth said. "Migraine without aura was not associated with any increased risk of vascular events, and this is the vast majority of migraine sufferers."
The biological mechanisms linking aura and cardiovascular risk remain unclear.
"There's pretty good evidence that migraine with or without aura have separate genetic risk factors," Lipton explained. "One of the migraine-with-aura genes is associated with elevated levels of high blood pressure and other risk factors. So, one possibility is that there's a genetic link between migraine with aura and heart disease."
For women who do experience aura with their migraines, there are some common-sense strategies.
"Over the last 20 years, there has been an enormous emphasis on knowing your risk factors for heart disease and reducing them," Lipton said. "This study suggests that migraine with aura should be added to that list of risk factors, at least in women over 45."
Scientists don't know, however, if treating the migraine itself will decrease the risk.
While researchers search for that answer, women should pay attention to known risk factors.
"Women with migraine with aura should be especially careful about addressing those risk factors that they can modify for heart disease, such as cholesterol and high blood pressure," Lipton said.
"Patients and treating physicians should be particularly cautious about other modifiable risk factors for cardiovascular disease, in particular smoking," Kurth added.
And research needs to confirm the findings in men and in younger women to see if they, too, should heed heightened precautions.
More information
The National Institute of Neurological Disorders and Stroke can tell you more about migraine.
Weight Loss May Yield Alzheimer's Clues
MONDAY, July 17 (HealthDay News) -- Gradual weight loss can precede dementia and begin as early as 10 years prior to memory loss, concludes a Mayo Clinic study involving women with and without dementia.
The findings may provide clues to the origins of dementia, say the researchers, who were expected to present the findings Sunday at the International Conference on Alzheimer's Disease and Related Disorders, in Madrid, Spain.
The Mayo team compared the long-term medical records of 560 people diagnosed with the onset of dementia between 1990 and 1994. These patients were compared to a group of patients who did not have dementia.
Both groups averaged about the same weight -- 140 pounds -- at the beginning of the study. Women who did not develop dementia maintained that weight over the next 30 years.
In contrast, "The women who later developed dementia started off at the same weight as those who didn't develop dementia, but their weight drifted downward to 136 pounds 10 years before symptom onset and 128 pounds at symptom onset," Dr. David Knopman, lead researcher and neurologist, said in a prepared statement.
He and his colleagues said it's unclear what caused the weight loss in the women who later developed dementia, but they have some theories.
"The weight loss findings raise scientific questions about the cause or causes of the weight loss. This points to changes in the brain that develop years before the actual memory loss. We think that there are several possible explanations," Knopman said.
"The women might have less initiative and lose interest in eating, they might develop a duller sense of taste and smell, or they might experience an earlier sense of satiety (feeling full). Also, because, we didn't observe the anticipatory weight loss in men, the weight loss could have something specific to do with postmenopausal hormonal changes," he said.
Pinpointing the brain mechanisms that influence weight loss in women who develop dementia may help researchers better understand how it develops, Knopman said.
More information
The American Medical Association has more about dementia.
The findings may provide clues to the origins of dementia, say the researchers, who were expected to present the findings Sunday at the International Conference on Alzheimer's Disease and Related Disorders, in Madrid, Spain.
The Mayo team compared the long-term medical records of 560 people diagnosed with the onset of dementia between 1990 and 1994. These patients were compared to a group of patients who did not have dementia.
Both groups averaged about the same weight -- 140 pounds -- at the beginning of the study. Women who did not develop dementia maintained that weight over the next 30 years.
In contrast, "The women who later developed dementia started off at the same weight as those who didn't develop dementia, but their weight drifted downward to 136 pounds 10 years before symptom onset and 128 pounds at symptom onset," Dr. David Knopman, lead researcher and neurologist, said in a prepared statement.
He and his colleagues said it's unclear what caused the weight loss in the women who later developed dementia, but they have some theories.
"The weight loss findings raise scientific questions about the cause or causes of the weight loss. This points to changes in the brain that develop years before the actual memory loss. We think that there are several possible explanations," Knopman said.
"The women might have less initiative and lose interest in eating, they might develop a duller sense of taste and smell, or they might experience an earlier sense of satiety (feeling full). Also, because, we didn't observe the anticipatory weight loss in men, the weight loss could have something specific to do with postmenopausal hormonal changes," he said.
Pinpointing the brain mechanisms that influence weight loss in women who develop dementia may help researchers better understand how it develops, Knopman said.
More information
The American Medical Association has more about dementia.
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