Missing link found between brain, immune system; major disease implications

In a stunning discovery that overturns decades of textbook teaching, researchers have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. The discovery could have profound implications for diseases from autism to Alzheimer's to multiple sclerosis.

Maps of the lymphatic system: old (left) and updated to reflect UVA's discovery.

Credit: University of Virginia Health System

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). "It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."

"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role," Kipnis said. "Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation -- and they've done many studies since then to bolster the finding -- that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."

Even Kipnis was skeptical initially. "I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," he said. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."

'Very Well Hidden'

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges -- the membranes covering the brain -- on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'"

As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer's, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

---

Story Source:

The above post is reprinted from materials provided by University of Virginia Health System. Note: Materials may be edited for content and length.

---

Journal Reference:

1. Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Kevin S. Lee, Tajie H. Harris, Jonathan Kipnis. Structural and functional features of central nervous system lymphatic vessels. Nature, 2015; DOI: 10.1038/nature14432

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Missing link found between brain, immune system; major disease implications

In a stunning discovery that overturns decades of textbook teaching, researchers have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. The discovery could have profound implications for diseases from autism to Alzheimer's to multiple sclerosis.

Maps of the lymphatic system: old (left) and updated to reflect UVA's discovery.

Credit: University of Virginia Health System

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). "It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."

"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role," Kipnis said. "Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation -- and they've done many studies since then to bolster the finding -- that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."

Even Kipnis was skeptical initially. "I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," he said. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."

'Very Well Hidden'

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges -- the membranes covering the brain -- on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'"

As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer's, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

---

Story Source:

The above story is based on materials provided by University of Virginia Health System. Note: Materials may be edited for content and length.

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Healthy diets make brighter brains

A study following nearly 28,000 people aged 55 and older at high cardiovascular risk, which monitored their diets for 5 years and tested declines against thinking and memory tests, found a smaller drop in brain power for those who ate well.

Fish was part of healthy eating while red meat was among the unhealthy foods.

The American Academy of Neurology has published the results in the journal Neurology. The healthy eating linked to the stronger cognitive health was a diet with not much red meat, moderate alcohol and lots of fruits and vegetable, nuts and fish.

The 27,860 over-55s included for the analysis, from across 40 countries, were studied over an average of around 5 years.

Certain health conditions were excluded at the start of the study of people at high risk of cardiovascular disease. None of the participants had diabetes or a history of heart disease, stroke or peripheral artery disease; nor had any recently experienced serious disease outcomes such as a stroke or congestive heart failure.

Participants who experienced heart disease or stroke during the study were no longer followed for diet and mental power.

To take a baseline measure of cognitive health and monitor any decline, thinking and memory skills were tested at the start of the study, then 2 years and about 5 years later.

A maximum of 30 points was possible against these thinking and memory tests and cognitive decline was noted when scores dropped by 3 points or more, which happened for 17% overall - a total of 4,699 participants.

Cognitive decline lowest among those who reported healthiest diets

The proportion registering a decline was lower for people reporting the healthiest diets - 14% of these showed a drop in thinking and memory, compared with 18% of the people eating the least healthy diets.

Measuring cognitive health

This new study linking brain power and diet involved a test of cognitive health that is used during dementia diagnosis. The mini mental state examination (MMSE) measures:

• Orientation to time and place
• Word recall
• Language abilities
• Attention and calculation
• Visuospatial skills.

For the measure of diet, the participants were asked at the start of the study to say how often they ate certain foods, including vegetables, nuts and soy proteins, whole grains and deep-fried foods. They also reported levels of alcohol intake and gave data to produce a ratio of fish to meat and eggs in their diets.

The measure of diet quality was a modified version of the healthy eating index used by the US government.

Among the 5,687 people with the healthiest diet, 782 made up the 13.8% having cognitive decline, while of the 5,459 people with the least healthy diets, 987 accounted for the 18.1%.

The relative difference from these figures produces a 24% lower likelihood of a drop in thinking and memory for people eating well.

The researchers accounted for factors that could have affected the results, such as physical activity, high blood pressure and history of cancer.

Study author Dr. Andrew Smyth, of McMaster University in Hamilton, Ontario, Canada, and the National University of Ireland in Galway, says diet in later life is only part of the picture:

"Adoption of a healthy diet probably begins early in life, and a healthy diet might also go along with adoption of other healthy behaviors."

For their data, the authors examined participants from randomized drug trials in cardiovascular disease supported by pharmaceutical company Boehringer Ingelheim.

In background to their work, the authors cite previous brain health links to healthy diet but point out that using the large multinational prospective cohort study allows observation of "more precise associations between diet (assessed using standardized methodology) and cognitive outcomes."

Explaining what biological explanations may lie behind the emerging evidence, the authors say: "Dietary intake may modify the risk of cognitive decline through multiple mechanisms, including increased risk of stroke (both overt and covert) and through deficiency of nutrients required for neuronal regeneration (for example, group B vitamins, and vitamin C)."

The risk factors for dementia listed by the US National Institute of Neurological Disorders and Stroke includes a number that can be modified by dietary and lifestyle measures.

The new study ends by stating:

"In conclusion, we report that higher diet quality is associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline."

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Could high blood sugar be a cause of Alzheimer's disease?

While nobody knows exactly what causes the complex brain changes that lead to Alzheimer's disease, scientists suspect one of the drivers is the accumulation of plaques of a faulty protein called beta-amyloid. Now, a new study of mice shows how too much sugar in the blood can speed up the production of the protein.

The researchers suggest their findings will lead to new treatments that reduce the harmful effects of high blood sugar on the brain.

Earlier studies have pointed to diabetes - where the body fails to control high blood sugar naturally with insulin - as a possible contributor to Alzheimer's disease, but the new study links high blood sugar itself to beta-amyloid.

Researchers from the School of Medicine at Washington University in St. Louis (WUSTL) report their findings inThe Journal of Clinical Investigation.

Lead author and postdoctoral research scholar Dr. Shannon Macauley says:

"Our results suggest that diabetes, or other conditions that make it hard to control blood sugar levels, can have harmful effects on brain function and exacerbate neurological conditions such as Alzheimer's disease."

She and her colleagues suggest their finding could lead to new treatment targets to reduce the harmful effects of high blood sugar on the brain.

Doubling of blood glucose led to 20% higher levels of beta-amyloid

For their study, the team used mice bred to develop a condition that is like Alzheimer's in humans - as they age their brains accumulate amyloid plaques.

When they infused glucose into the bloodstream of young mice, they found their brains produced beta-amyloid faster. A doubling of blood glucose led to 20% higher levels of beta-amyloid compared with mice that had normal blood glucose levels.

When the team repeated the experiment in older mice that already had amyloid plaques in their brains, beta-amyloid levels rose by 40%.

Closer examination revealed that sudden elevation of blood sugar increased brain cell activity, which stimulates them to make more beta-amyloid.

The team found that openings called KATP channels were an important feature of increased beta-amyloid. These ATP-sensitive potassium channels sit on the surface of brain cells and close when glucose levels get too high. When the channels are closed, the neurons are more likely to fire.

Under normal conditions, neurons fire to encode and send information - a basic function essential for learning and memory. But too much firing in certain areas of the brain increases beta-amyloid, which makes it more likely that plaques will form and encourage the development of Alzheimer's, the authors suggest.

KATP channel 'directly links glucose, brain cell activity and beta-amyloid'

In a final set of experiments, the team injected diazoxide straight into the brains of mice (to bypass the blood brain barrier). Diazoxide is a glucose-elevating drug that is used to treat low blood sugar.

The drug forced the KATP channels to stay open as glucose levels rose. Under these conditions, the brain cells produced beta-amyloid at the normal rate - it did not speed up.

The team concludes this result shows that the KATP channel directly links glucose levels with brain cell activity and rate of beta-amyloid production.

The researchers are already exploring the link further using diabetes drugs in Alzheimer's-like mice.

KATP channels feature in all kinds of cells, not just brain cells. For example, they feature in the pancreatic cells that make insulin - the enzyme the body uses to control blood sugar.

Commenting on the contribution of their findings, Dr. Macauley says:

"This observation opens up a new avenue of exploration for how Alzheimer's disease develops in the brain as well as offers a new therapeutic target for the treatment of this devastating neurologic disorder."

She and her colleagues are also looking into how raised glucose levels may interfere with how different parts of the brain work together in cognitive functioning.

Funds for the study came from the National Institutes of Health, the National Science Foundation and the JPB Foundation.

Meanwhile, Medical News Today recently learned how scientists at Johns Hopkins University found a molecule that links high blood sugar to metabolic disease. Writing in the Proceedings of the National Academy of Sciences, the team says the discovery could lead to new ways to prevent and treat diabetes.

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New 'MIND' diet linked to reduced risk of Alzheimer's

A new diet developed by researchers from Rush University Medical Center in Chicago, IL, could significantly reduce the risk of Alzheimer's disease, even for those who do not follow it precisely.

The MIND diet focuses specifically on berries rather than consumption of all fruits. Blueberries and strawberries, in particular, have been hailed for their brain benefits.

This is the finding of a new study published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

The diet - called the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet - was created by nutritional epidemiologist Martha Clare Morris, PhD, and colleagues at Rush. It uses aspects of the DASH (Dietary Approaches to Stop Hypertension) diet - an eating plan based on studies supported by the National Institutes of Health - and the Mediterranean diet.

While both the Mediterranean and DASH diets have been shown to reduce the risk of cardiovascular problems, such as heart attack, stroke and high blood pressure, some studies have suggested the diets may also protect against dementia.

The newly created MIND diet, according to Morris and Colleagues, is easier to follow than the Mediterranean and DASH diets. It consists of 15 dietary components: 10 "brain-healthy food groups" and five unhealthy food groups.

Green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine make up the brain-healthy foods, while red meats, butter and stick margarine, cheese, pastries and sweets, and fried or fast food are the food groups that should be limited.

Unlike the DASH and Mediterranean diets - in which high consumption of all fruits is recommended - the MIND diet focuses specifically on berries. Morris explains that blueberries and strawberries, in particular, have been hailed for their brain benefits in past research.

Moderate adherence to MIND diet reduced Alzheimer's risk by 35%

For their study, the researchers analyzed the food intake of 923 Chicago residents between the ages of 58 and 98 who were part of the Rush Memory and Aging Project - an ongoing study that aims to identify factors that may protect cognitive health.

Dietary information was gathered from food frequency questionnaires the participants completed between 2004 and 2013. The researchers scored participants on how closely their food intake matched either the MIND diet, Mediterranean diet or DASH diet, and incidence of Alzheimer's disease was assessed over an average follow-up period of 4.5 years.

Fast facts about Alzheimer's

• More than 5 million people in the US are living with Alzheimer's, and this number is expected to rise to as many as 16 million by 2050
• Alzheimer's is the sixth leading cause of death in the US
• More than two thirds of Americans with Alzheimer's are women.

The researchers found that participants whose food intake closely followed either of the three diets were at lower risk of Alzheimer's. Participants who followed the Mediterranean diet were at 54% lower risk, those who followed the MIND diet were at 53% lower risk, while followers of the DASH diet had a 39% reduced risk for Alzheimer's.

However, the team found that participants who had a moderate adherence to the Mediterranean or DASH diets showed no reduced risk for Alzheimer's, while moderate adherence to the MIND diet still put participants at 35% lower risk of developing the disease.

Morris says one of the most exciting things about their findings is the fact that even following the MIND diet moderately well indicated significant protection against Alzheimer's. "I think that will motivate people," she adds.

However, the researchers note that to really benefit from the MIND diet, followers should not overindulge in unhealthy foods, particularly butter, cheese and fried foods.

On eliminating participants who changed their diet at some point during follow-up, the team found that participants who followed the MIND diet for a longer duration saw the highest protection against Alzheimer's. "As is the case with many health-related habits, including physical exercise," says Morris, "you'll be healthier if you've been doing the right thing for a long time."

While further studies are needed to confirm these findings, the researchers believe the MIND diet shows promise for reducing the risk of Alzheimer's. "We devised a diet and it worked in this Chicago study," Morris adds.

Talking to Medical News Today, Morris said there is no reason why people should wait to try the MIND diet, however. "The dietary components of the MIND diet are also the foundations of the Mediterranean and DASH diets - both of which have been found through randomized controlled trials to have many cardiovascular benefits," she said. "It is hard to come up with a potential downside to adopting these dietary habits."

Last week, MNT reported on a study published in Science Translational Medicine, in which Australian researchers reveal how a new ultrasound technique successfully restored memory in mouse models of Alzheimer's.

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Laughter may be the best medicine for age-related memory loss

We are all familiar with the saying, "laughter is the best medicine." And this motto may ring true when it comes to tackling age-related memory loss; a new study from Loma Linda University in California finds that humor may reduce brain damage caused by the "stress hormone" cortisol, which in turn, improves memory.

The research team, led by Dr. Gurinder Singh Bains, recently presented their findings at the Experimental Biology meeting in San Diego.

It is well known that too much stress can negatively affect health. Medical News Today recently reported on a study suggesting that stress may worsen allergies, while other research indicates that it makes the brain more susceptible to mental illness.

Past research has also shown that stress can worsen memory and learning ability in elderly individuals. This is because stress increases production of cortisol - a hormone that can cause damage to neurons in the brain.

Since it is well known that laughter can be a stress reliever, the research team wanted to determine whether humor may reduce brain damage caused by cortisol.

Watching a funny video 'reduced cortisol levels and boosted memory performance'

The researchers analyzed one group of elderly individuals who had diabetes and another group of elderly people who were healthy.

Laughter may reduce neuron damage caused by "stress hormone" cortisol, therefore improving memory in older individuals.

Both groups were required to view a 20-minute humorous video, before completing a memory test that measured their visual recognition, learning ability and memory recall.

A third group of elderly individuals were asked to complete the memory test without watching the funny video. The team then compared the results of all three groups.

Cortisol levels for all participants were recorded before and after the experiments.

The investigators found that both groups who watched the humorous video showed a significant reduction in cortisol levels, compared with the group that did not view the video.

The groups that watched the funny video also showed greater improvement in memory recall, learning ability and sight recognition, compared with those who did not watch the video. The diabetic group demonstrated the greatest improvement in both cortisol levels and memory test scores.

'Laughter may improve memory and quality of life'

Study co-author Dr. Lee Burk says these findings suggests that the less stress a person has, the better their memory performance, and humor may be the key to reducing stress levels.

"Humor reduces detrimental stress hormones like cortisol that decrease memory hippocampal neurons, lowers your blood pressure, and increases blood flow and your mood state," he explains.

"The act of laughter - or simply enjoying some humor - increases the release of endorphins and dopamine in the brain, which provides a sense of pleasure and reward."

He says that these neurochemical changes in the brain also increase "gamma wave band frequency," which can improve memory.

"So, indeed," he adds, "laughter is turning out to be not only a good medicine, but also a memory enhancer adding to our quality of life."

Dr. Bains says the team's findings may offer benefits that can be applied to wellness programs for elderly individuals, adding:

"The cognitive components - learning ability and delayed recall - become more challenging as we age and are essential to older adults for an improved quality of life: mind, body and spirit.

Although older adults have age-related memory deficits, complimentary, enjoyable and beneficial humor therapies need to be implemented for these individuals."

Laughter may not be the only way to boost memory. Medical News Today recently reported on a study suggesting that green tea may improve working memory, while other research from Johns Hopkins University in Maryland found that caffeine may boost long-term memory.

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Brain training boosted older adults' mental skills

Researchers found that giving a group of older adults a brief course of mental or cognitive training helped to improve their reasoning ability and processing speed, and hold onto the gains for up to 10 years, compared with a group of untrained controls. Plus, those who received additional training for another 3 years improved even further.
Cognitive decline is not uncommon among older adults and can seriously affect their ability to lead a normal life and carry out everyday tasks.
Study leader George Rebok, a professor at Johns Hopkins University in Baltimore, MD, and an expert on aging and mental health, says:
"Showing that training gains are maintained for up to 10 years is a stunning result because it suggests that a fairly modest intervention in practicing mental skills can have relatively long-term effects beyond what we might reasonably expect."

He and his colleagues also found the seniors who received the brief cognitive training also reported experiencing less difficulty in carrying out everyday living tasks.
Prof. Rebok says even small delays in impairment of mental and functional ability can have a big effect on public health and help reduce the rising cost of caring for older adults.
They report their findings in a soon-to-be-published issue of the Journal of the American Geriatrics Society.

Seniors received training in memory, reasoning and processing speed skills

The results come from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which tested whether cognitive training sessions could help older adults maintain functional independence by improving basic mental skills.
This latest analysis is of 10 years of follow-up results from 2,832 participants whose average age was 73.6 years at the start of the study, when they were randomly assigned to one of three groups for memory, reasoning or speed-of-processing training, or to an untrained control group.
The participants who underwent cognitive training received 10 sessions, which lasted 60-75 minutes, over 5-6 weeks in small groups.
Those in the memory training group were taught how to remember word lists and sequences of items, texts, and themes and details of stories.
Those assigned to the reasoning group learned problem-solving skills that help with daily tasks, such as filling out order forms and reading bus timetables.
And the participants who received speed-of-processing training used computer programs to learn how to spot and find visual information quickly. This kind of training can boost scanning skills, such as noticing changes in traffic when driving or looking up phone numbers.

Cognitive training groups reported less difficulty with daily living

After 10 years of follow-up, the groups that received cognitive training reported experiencing less difficulty with carrying out daily living tasks, such as cooking, taking medications and managing finances.
After 10 years, 60% of the participants who had mental training were at the same level of functioning in carrying out daily living tasks, compared with only 50% of the untrained controls.
While memory performance showed improvement in the training group for up to 5 years after training, 10 years later there was no significant difference between the trained groups and the untrained controls.
However, reasoning and speed-of-processing training appeared to have a more lasting effect - trained participants still showed significant improvements in these skills, compared with controls at the 10-year follow-up.

'Booster' sessions resulted in even greater improvements

Some of the trained participants also had four "booster" sessions just before the end of the first year, and just before the end of the third year of follow-up. These resulted in additional improvements in reasoning and speed-of-processing.
Prof. Rebok says:

"Our findings provide support for the development of other interventions for senior adults, particularly those that target cognitive abilities showing the most rapid decline with age and that can affect their everyday functioning and independence. Such interventions have potential to delay the onset of difficulties in daily functioning."

The researchers say more studies are needed to find out how such brief training can translate to such lasting effects on everyday functioning.
The team now plans to test whether more training over a longer period leads to even greater improvements, and also whether cognitive training can help older adults maintain safe driving skills.

Funds from various institutions, including the National Institute on Aging and private sources, helped finance the study.
Meanwhile in another study reported in October 2013, researchers showed that sleeping longer is linked to faster cognitive decline in older adults. They found people in their 60s and 70s who slept on average more than 9 hours a night showed double the amount of cognitive function decline, compared with people who slept 6-8 hours a night.

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Low vitamin D levels may damage the brain

Vitamin D plays an important role in maintaining bone health, but a new study led by University of Kentucky researchers claims that deficiency of this vitamin may cause damage to the brain and other organs.
The results, published in Free Radical Biology and Medicine, showed that when middle-aged rats were fed a diet low in vitamin D for several months, they developed free radical damage to the brain. They also performed less well in cognitive functioning tests for learning and memory.
The researchers say that several brain proteins were found to have significantly higher levels and that this contributes to significant nitrosative stress in the brain, possibly leading to cognitive decline.
The researchers claim that vitamin D deficiency is increasing in the US and its effects on an aging brain should not be underestimated.
Prof. Allan Butterfield, lead author of the paper, explains:

"Given that vitamin D deficiency is especially widespread among the elderly, we investigated how, during aging from middle-age to old-age, low vitamin D affected the oxidative status of the brain.
Adequate vitamin D serum levels are necessary to prevent free radical damage in brain and subsequent deleterious consequences."

Catch some rays

Often called the "sunshine vitamin," dietary sources of vitamin D are limited, and the study notes that when times are hard, individual food intake is not always the most nutritious.
The result of this is low levels of the vitamin, particularly among the elderly population. Coupled with the widespread use of sunscreens and popularity of wearing of long-sleeved clothing in the sunshine, levels of vitamin D are declining.
Low levels of vitamin D have previously been linked to Alzheimer's disease, the development of certain cancers and heart disease.
Prof. Butterfield recommends that everyone should allow themselves at least 10-15 minutes' exposure to sunshine every day to ensure that vitamin D levels are adequate.
He also suggests that vulnerable people should contact their physicians to have their levels tested. If they are low, individuals should consider taking supplements and eating more foods containing the vitamin, including oily fish, eggs and fortified milk.
Medical News Today recently reported that dancers from Birmingham's Royal Ballet in the UK have benefitted from vitamin D supplements, citing a report that showed greater improvements in muscle strength and fewer injuries for dancers taking them.
However, researchers from Johns Hopkins caution that too much can do more harm than good. Levels over 21 nanograms per milliliter increased levels of c-reactive protein, which is associated with hardening of blood vessels and an increased risk of cardiovascular problems.

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Common blood pressure drugs may slow dementia decline

A class of drug used to lower blood pressure could potentially slow the rate of cognitive decline in dementia and even boost brain power, according to a study published by BMJ Open.
Researchers from Ireland analyzed the cognitive decline and brain power of 361 patients with an average age of 77. All had been diagnosed with either Alzheimer's disease, vascular dementia, or a mixture of both.
Of these patients, 85 were already using the blood pressure-lowering (antihypertensive) drugs known as ACE inhibitors (angiotensin-converting enzyme inhibitors). This is a commonly used class of antihypertensive drug. Thirty of the patients who were newly prescribed ACE inhibitors during the first six months of treatment were also analyzed for their brain power activity.
Between the years 1999 and 2010, the researchers used the Standardized Mini Mental State Examination (SMMSE) or the Quick Mild Cognitive Impairment (Qmci) to test the cognitive decline of each patient. This was done on two separate occasions, six months apart.
The patients who were taking ACE inhibitors had slower rates of cognitive decline in the study compared with patients who were not taking the drugs.
The study also revealed that in patients who had been newly prescribed the ACE inhibitors over the six-month period, their brain power improved in comparison with both those already taking them and those not taking them at all.
However, the study authors add that this could be due to the newly prescribed patients having better control over their medication regimen, or due to better blood pressure control or improved blood flow to the brain.
The researchers say:

"This [study] supports the growing body of evidence for the use of ACE inhibitors and other [blood pressure-lowering] agents in the management of dementia.
Although the differences were small and of uncertain clinical significance, if sustained over years, the compounding effects may well have significant clinical benefits."

The researchers warn, however, that previous research has indicated that ACE inhibitors may be harmful in some cases, so if future benefit of the drugs in dementia is proven, it may be limited to certain groups of patient.
The study authors call for further research and a controlled trial to confirm their findings. They say:
"If these data can be reproduced in a randomized trial of sufficient length, incorporating appropriate outcome measures, such as an amyloid positron emission tomography (PET), then these agents are likely to have significant benefits in delaying or even preventing dementia."

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Alzheimer's Prevalence May Triple By 2050, USA

The USA could be facing an Alzheimer's explosion as the baby boom generation ages, placing a massive burden on society, researchers from the Rush Institute for Healthy Aging at Rush University Medical Center, Chicago, reported in the journal Neurology.

The authors specifically mentioned a tripling of the number of Americans with Alzheimer's disease by 2050.

Co-author Jennifer Weuve, MPH, ScD, said:

"This increase is due to an aging baby boom generation. It will place a huge burden on society, disabling more people who develop the disease, challenging their caregivers, and straining medical and social safety nets. Our study draws attention to an urgent need for more research, treatments and preventive strategies to reduce this epidemic."

The team gathered and examined data from 10,802 people who lived in Chicago between 1993 and 2011. They were all Caucasians and African-Americans, aged 65 or more. The researchers interviewed them and assessed them for dementia once every three years. They took into account compounding factors, such as level of education, race and age.

The authors then combined the data with US death rates, education and current/future population estimates from the US Census Bureau.

The study predicts that by 2050 there will be 13.8 million people with Alzheimer's disease, compared to 4.7 million in 2010. Seven million of them in 2050 will be at least 85 years of age.

Weuve said:

"Our detailed projections use the most up-to-date data, but they are similar to projections made years and decades ago. All of these projections anticipate a future with a dramatic increase in the number of people with Alzheimer's and should compel us to prepare for it."

In an Abstract in the journal, the authors concluded "The number of people in the United States with AD dementia will increase dramatically in the next 40 years unless preventive measures are developed."

Alzheimer's numbers set to triple by 2050 globally too

In April 2012, the World Health Organization (WHO) predicted that today's population of 35.6 million people with Alzheimer's worldwide will rise to at least 115 million by 2050.

WHO added that by 2030, at least 65 million people will have dementia, 58% of whom will be from developing nations - these countries will have more than 70% of the global population with dementia.

Over $600 billion are spent globally on the treatment and care of people with dementia. Caregivers often have to leave their jobs to look after a person with Alzheimer's disease.

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Novel Protein Discovered That May Help Detect Lou Gehrig's Disease And Dementia

Researchers at Mayo Clinic have discovered an abnormal protein that accumulates in the brains of many patients affected with two common neurodegenerative disorders - amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, and frontotemporal dementia. They say their findings have uncovered a potentially new therapeutic target and biomarker that would allow clinicians to confirm diagnosis of the diseases. The study is published online in the journal Neuron.

The Mayo research team, led by scientists at Mayo Clinic's campus in Florida, discovered the abnormal protein pathology that they call C9RANT. An error in the highly regulated cellular process through which proteins are generated causes the abnormal production of C9RANT. The team developed an antibody that can detect the specific, insoluble protein that clumps together and is present in patients with mutations in the C9ORF72 gene, which was previously identified by Mayo Clinic researchers as the most common genetic cause of ALS and frontotemporal dementia.

"This new finding sheds light on how the mutation causes these disorders, and it provides us with a marker that helps us track disease progression in patients with this disorder and potentially combat the disease," says senior author Leonard Petrucelli, Ph.D., a molecular neuroscientist and director of the Department of Neuroscience at Mayo Clinic in Florida.

If it is shown that, as suspected, these protein clumps are the cause of neuronal death and toxicity in these diseases, it may be possible to design therapies to break the clumps apart or to prevent the protein from accumulating in the first place, Dr. Petrucelli says.

Because the protein is found throughout the central nervous system in patients with ALS and frontotemporal dementia - but not in other neurodegenerative diseases - the researchers hope that in the future it can be tested through a spinal tap.

After Alzheimer's disease, frontotemporal dementia is the most common form of early onset neurodegenerative dementia. It is characterized by changes in personality, behavior and language due to loss of gray matter in the brain's frontal lobe. ALS destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing.

This new discovery stems from a key finding, reported simultaneously in 2011 by Mayo researchers and scientists from the National Institutes of Health, that an unusual mutation - a short DNA sequence repeated hundreds to thousands of times - was found in almost 12 percent of familial frontotemporal dementia and more than 22 percent of familial ALS samples studied.

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Longer Use Of Hormonal Contraception During Midlife Predicts Better Cognitive Function Later

Premenopausal use of hormonal contraceptives may improve the cognitive abilities of women in midlife and for years afterward. This finding may have implications for prevention of declining cognitive function that occurs with advancing age and in diseases such as Alzheimer's. The beneficial effects of hormones increase the longer a woman uses them, as described in a study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website.*

Kelly Egan, University of Wisconsin School of Medicine and Public Health, and Carey Gleason, PhD, William S. Middleton Memorial Veterans Hospital, Madison, WI, present the results of cognitive performance tests administered to women enrolled in the Wisconsin Registry for Alzheimer's Prevention in the article "Longer Duration of Hormonal Contraceptive Use Predicts Better Cognitive Outcomes Later in Life."

"This study provides preliminary evidence that hormonal contraceptives may have a protective cognitive effect, even years after use is discontinued," says Editor-in-Chief Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health.

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Alzheimer's Disease Discovered 100 Years Ago, November 4th

According to the Alzheimer's Association, Alzheimer's disease was discovered 100 years ago on Saturday, November 4, 1906. Currently 4.5 million people in America have Alzheimer's and that figure is expected to grow to as many as 16 million by 2050.

On November 4, 1906, German physician Alois Alzheimer presented the case of a 51-year-old woman who had shown severe memory, language and behavior problems to his medical colleagues. When Dr. Alzheimer performed the woman's autopsy, he found a dramatically shrunken brain and unusual abnormalities in and around cells. Not long afterward, the brain disease he described was named Alzheimer. Alzheimer's disease is a progressive brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate and carry out daily activities.

For more information on Alzheimer's disease contact the Alzheimer's Association, http://www.alz.org or call 800-272-3900.

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Exelon Patch, The First Transdermal Therapy For Alzheimer's Disease, May Provide Promising New Approach To Treatment Of Dementia

An international study of the first transdermal patch for patients with Alzheimer's - a degenerative brain disease estimated to affect more than 15 million people worldwide - has shown that it may provide a promising new treatment approach1.

The six-month IDEAL trial of 1,195 patients with Alzheimer's disease showed that the Exelon Patch provided benefits across a range of symptoms and the target dose was well tolerated. Results were presented today at the 10th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association in Madrid, Spain.

Patients receiving Exelon Patch (rivastigmine transdermal patch) had significant improvements in memory and were better able to maintain everyday activities1 than those receiving placebo. They could also complete a concentration task up to 20 seconds faster compared to those taking placebo, and physicians considered Exelon Patch patients to have done better overall.

In addition, over 70% of caregivers in the IDEAL study preferred the patch to capsules as a method of drug delivery for reasons including helping them follow the treatment schedule, overall ease of use and less interference with daily life2, according to a questionnaire in the study.

"The patch represents an important new option for people with Alzheimer's disease and their families," said lead study investigator Professor Bengt Winblad of the Karolinska Institute in Stockholm, Sweden. "The target rivastigmine patch dose provided similar efficacy to that achieved at the highest doses of the capsule with three times fewer reports of nausea and vomiting. A transdermal patch may prove to be the best way to deliver rivastigmine to treat Alzheimer's."

Transdermal patches are designed to provide controlled, continuous delivery of drug through the skin. This maintains steady drug levels in the bloodstream, which may reduce side effects and consequently allow access to higher doses. In addition, patches may help caregivers to monitor treatment compliance because they provide visual reassurance that the medication has been taken.

"Although Alzheimer's disease treatments have been available in oral forms for some time, we believe a patch may offer unique advantages for patients with this condition," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "If approved, the Exelon Patch could potentially improve therapy compliance and help patients and their caregivers in reaching a better quality of life."

Exelon is a cholinesterase inhibitor already approved in many countries for the treatment of mild to moderate Alzheimer's disease and dementia associated with Parkinson's disease. The IDEAL results will support the regulatory submission of the Exelon Patch to health authorities, planned by the end of 2006.


About the IDEAL study

IDEAL (Investigation of Transdermal Exelon in Alzheimer's disease) was a 24-week, multi-center, randomized, double-blind, placebo- and active-controlled trial to compare the efficacy, safety and tolerability of the once-daily Exelon Patch with conventional twice-daily Exelon capsules in patients with moderate Alzheimer's disease. The primary outcomes measures were the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADSC-CGIC).

IDEAL was conducted in 21 countries and involved 100 centers and 1,195 patients aged 50-85 years old with a score of 10-20 in the Mini-Mental State Examination (MMSE), the most widely-used test for assessing memory problems or dementia. Patients received Exelon either in capsules (6 mg twice-daily) or patches in two sizes, namely Patch 10 (providing 9.5 mg over 24 hours) or Patch 20 (17.4 mg/24 h)1.

Both patch sizes showed superior efficacy to placebo. The target dose of Patch 10 showed similar efficacy to the highest doses of Exelon capsules with three times fewer reports of nausea (7.2 percent vs. 23.1 percent) and vomiting (6.2 percent vs. 17.0 percent), which are well-known side effects of cholinesterase inhibitors. Patch 20 showed numerically but not statistically improved cognitive scores versus capsules and similar tolerability to capsules.

Local skin tolerability was good. The percentage of patients who reported moderate or severe redness of the skin at any point of the study was only 7.6 percent and 6.2 percent of patients receiving Patch 10 and 20, respectively. The patch also demonstrated very good skin adhesion over 24 hours in a range of everyday situations such as bathing and in hot weather.

About Exelon

Since 1997, Exelon (rivastigmine tartrate) has been widely used to treat mild to moderate Alzheimer's disease in more than 70 countries. Exelon is the only cholinesterase inhibitor to be also approved to treat both Alzheimer's disease and dementia associated with Parkinson's disease (PDD) in Europe and US.

Exelon belongs to a class of drugs known as cholinesterase inhibitors (ChEIs) which increase the activity of the neurotransmitter acetylcholine in the brain. Among the widely-used ChEIs, Exelon is the only treatment that inhibits both enzymes involved in the breakdown of this neurotransmitter - acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). This may offer additional benefits over treatments which inhibit AChE alone. Exelon can maintain both memory and thinking, help with behavioural problems, and affect how patients cope with the activities of daily living. It may help them communicate better, interact socially, and participate in hobbies and activities of daily living3,4.

About Alzheimer's disease

Alzheimer's disease is a progressive, degenerative disease that alters the brain, causing impaired memory, thinking and behaviour. Affecting approximately 15 million people worldwide and two to six percent of those over 65 years of age, it is the most common form of dementia and the third leading cause of death in this age group behind cardiovascular disease and cancer5. The worldwide direct costs for dementia in 2003 are estimated at $156 billion5.

This release contains certain forward-looking statements relating to the Novartis Group's business, which can be identified by the use of forward-looking terminology such as "may", "will", "could", "if approved", "planned by", or similar expressions, or by express or implied discussions regarding potential future regulatory submissions for Exelon or the Exelon Patch, or regarding potential future revenue from Exelon or the Exelon Patch. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Exelon or the Exelon Patch to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any regulatory submissions regarding the Exelon Patch will be made as planned or, if made, will be successful. Neither can there be any guarantee regarding potential future revenue from Exelon or the Exelon Patch. In particular, management's expectations regarding commercialization of Exelon or the Exelon Patch could be affected by, among other things, additional analysis of Exelon clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays in government regulation generally; the ability of Novartis to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; as well as factors discussed in Novartis AG's Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis has been a leader in the neuroscience area for more than 50 years, having pioneered early breakthrough treatments for Alzheimer's disease, Parkinson's disease, attention deficit/hyperactivity disorder, epilepsy, schizophrenia and migraine. Novartis continues to be active in the research and development of new compounds, and is committed to addressing unmet medical needs and to supporting patients and their families affected by these disorders.

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

References
1. Winblad B, Cummings J, et al. IDEAL: a 24 week placebo controlled study of the first transdermal patch in Alzheimer's disease - rivastigmine patch versus capsule. Oral Presentation at the 10th International Congress of Alzheimer's and Related Disorders (ICAD), Madrid, Spain, 19 July 2007.
2. Winblad B, Beusterien KM, et al. Caregivers prefer patches to capsules: results from a 24-week placebo controlled study of rivastigmine (IDEAL trial). Poster presented at the 10th International Congress of Alzheimer's and Related Disorders (ICAD), Madrid, Spain, 19 July 2007.
3. Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychopharmacol 1998;1:55-65.
4. R�sler M, Anand R, Cicin-Sain A et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. Br Med J 1999;318:633-40.
5. Wimo A, Jonsson L, Winblad B, An Estimate of the Worldwide Prevalence and Direct Costs of Dementia in 2003, dementia and Geriatrics Cognitive Disorders, 2006, 21: 175-181.

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