Obesity in Middle-Age Could Lead to Dementia, Study Suggests

May 25, 2013

Rising levels of obesity in middle age could cause a major rise in the number of dementia sufferers, researchers have warned.

The risk of having dementia almost doubles with midlife obesity, the UK Health Forum said.

Dr Laura Webber and Tim Marsh found that by 2050 almost 7% of the population over 65 are predicted to suffer from dementia, costing £41 billion a year compared with £23 billion at present.

They said: “This study adds to the existing body of evidence which shows the importance of policies and interventions to prevent obesity and its related diseases in the population, including dementia.”

The study, presented at the European Congress on Obesity in Liverpool, also predicted that by 2050, nearly half of men and 31% of women will be obese.

Dr Simon Ridley, head of research at Alzheimer’s Research UK, said: “Research shows that obesity in midlife is a risk factor for dementia and these projections suggest that rising obesity in the UK could contribute to growing levels of dementia over the coming decades.

“Dementia already has an enormous impact on individuals, families and communities and it is concerning to see that this could become even greater than previously predicted.

“We know that age is the biggest risk factor for dementia, and while we can’t change our age, research suggests that lifestyle choices during midlife could help to keep our brains healthy as we age.”

Jessica Smith, research officer at the Alzheimer’s Society, said we “can’t afford to ignore” the risk of “piling on the pounds”.

She said: “It’s easy to see the immediate impact of piling on the pounds but we can’t afford to ignore the long-term effects.

“Evidence shows that obesity increases the risk of developing dementia. This study highlights the impact obesity will have on the numbers of people with the condition in the future.

“The changes that cause dementia develop over many years, so maintaining a healthy weight and exercising regularly – especially in midlife – are hugely important in reducing your risk.”

Citation

 

How Your Brain Focuses and Concentrates

May 25, 2013

Scientists at Newcastle University have shed new light on how the brain tunes in to relevant information.

Publishing in Neuron, the team reveal the interplay of brain chemicals which help us pay attention in work funded by the Wellcome Trust and BBSRC.

By changing the way neurons respond to external stimuli we improve our perceptual abilities. While these changes can affect the strength of a neuronal response, they can also affect the fidelity of that response.

Lead author Alex Thiele, Professor of Visual Neuroscience explains:

“When you communicate with others, you can make yourself better heard by speaking louder or by speaking more clearly. Neurons appear to do similar things when we’re paying attention. They send their message more intensely to their partners, which compares to speaking louder. But more importantly, they also increase the fidelity of their message, which compares to speaking more clearly.”

“Our earlier work has shown that attention is able to affect the intensity of responses — in effect the loudness — by means of the brain chemical acetylcholine. Now we have shown that the fidelity of the response is altered by a different brain chemical system.”

In the paper, the team reveal that the quality of the response is altered by means of glutamate coupling to NMDA receptors (a molecular device that mediates communication between neurons). Carried out in a primate model, these studies for the first time isolate different attention mechanisms at the receptor level.

The research builds on the team’s previous studies and has potentially significant implications not only for our understanding of how our brains work but also give an insight into conditions such as schizophrenia, Alzheimer’s disease and attention deficit disorder, and may aid in the development of treatments for them.

Citation

 

Anti-Cancer Drug Reverses Alzheimer’s Disease In Mice

May 25, 2013

An anti-cancer drug may reverse memory problems in an Alzheimer’s Disease mouse model, according to new research carried out at the University of Pittsburgh Graduate School of Public Health.

The study, published in the journal Science, examined previously published outcomes on the drug bexarotene – which is approved by the U.S. Food and Drug Administration for use in cutaneous T cell lymphoma.

The researchers established that the drug does notably improve cognitive deficits in mice expressing gene mutations associated with human Alzheimer’s disease, however, they could not verify the effect on amyloid plaques.

Senior author Rada Koldamova, M.D., Ph.D., associate professor in Pitt Public Health’s Department of Environmental and Occupational Health, said, “We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer’s disease.”

Dr. Koldamova and her team were studying mice expressing human Apolopoprotein E4 (APOE4) – the only known genetic risk factor for late-onset Alzheimer’s disease, or APOE3 – known not to raise the risk for Alzheimer’s disease – when a Case Western Reserve University study was published last year.

It claimed that bexarotene elevates memory and rapidly cleared amyloid plaques from the brains of Alzheimer’s model mice expressing mouse Apolipoprotein E (APOE).

Amyloid plaques are made up of toxic protein fragments known as amyloid beta that are known to damage neurones in the brain and are believed to result in the memory deficits linked to Alzheimer’s disease, and eventually death.

Bexarotene is a compound chemically associated with vitamin A that triggers Retinoic X Receptors (RXR) found all over the body including neurons and other brain cells. Once they are activated, the receptors bind to DNA and control the expression of genes that guide many different biological functions.

Elevated levels of APOE are one result of RXR activations by bexarotene. The researchers started examining similar compounds over 10 years ago.

Co-author Iliya Lefterov, M.D., Ph.D., associate professor in Pitt Public Health’s Department of Environmental and Occupational Health said:

“We were already set up to repeat the Case Western Reserve University study to see if we could independently arrive at the same findings. While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains.”

The Pitt investigators believe that the drug functions through a different biological process, possibly by decreasing soluble oligomers which, like the plaques, are made up of the toxic amyloid beta protein pieces. Even though the oligomers are made up of amyloid beta they are able to move, unlike the plaques.

Dr. Koldamova explained:

“We did find a significant decrease in soluble oligomers. It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer’s disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism.”

In the current study experiments, mice with the Alzheimer’s gene mutations expressing human APOE3 or APOE4 were able to complete cognitive tests just as well as their non-Alzheimer’s counterparts 10 days after starting treatment with bexarotene.

The mice underwent a spatial test that used cues to detect a hidden platform in a water maze, and a long-term memory test of the mouse’s skills in distinguishing between two familiar objects following introduction to a third, new object.

Bexarotene treatment has no impact on the weight or general behavior of the mice. The drug was was successful in both male and female mice.

Citation

 

Anti-Cancer Drug Viewed as Possible Alzheimer’s Treatment Doesn’t Work in UF Study

May 25, 2013

An anti-cancer drug about to be tested in a clinical trial by a biomedical company in Ohio as a possible treatment for Alzheimer’s disease has failed to work with the same type of brain plaques that plague Alzheimer’s patients, according to results of a study by University of Florida researchers.

David Borchelt, Ph.D., a professor ofneuroscience affiliated with the Evelyn F. and William L. McKnight Brain Institute of the University of Florida, emphasized the importance of verifying promising research results before investing in clinical studies or testing potential therapies in people. Bexarotene has known side effects that include effects on the liver, blood and other metabolic systems.

“We wanted to repeat the study to see if we could build on it, and we couldn’t,” he said. “We thought it was important that something like this, which got a lot of publicity and patients were immediately looking to try to get access to this drug, that it was important to publish the fact that we couldn’t reproduce the most exciting part of the study. Maybe there should be some caution going forward in regard to patients.”

Borchelt and Kevin Felsenstein, Ph.D., an associate professor of neuroscience, said a drug called bexarotene that their team orally administered to mice did not reduce amyloid plaques, waxy buildups on the brain that are a key culprit in Alzheimer’s disease. Their findings will be published in the May 24, 2013 issue of the journal Science magazine, with two additional articles detailing similar results from other researchers.

The research follows up on a 2012 Science article that claimed bexarotene had reversed Alzheimer’s-like symptoms in mice afflicted with the plaques. Authors of that study also administered the drug orally.

The paper “indicated that with as little as three days of treatment, they basically cleared the amyloid deposits from these animals, as well as restored cognitive abilities,” Felsenstein said of the 2012 paper.

He said the results of the original study were surprising, given decades of research that had failed to find a therapy successful in dismantling amyloid plaques.

“We can shut down the production of amyloid in these animal models and the deposits in these animal models don’t disappear,” Felsenstein said. “These deposits have been described by some as cement, and it will take a lot to get rid of them. The fact that something could actually make them disappear in literally a couple of days is — again — very remarkable.”

Interested to see how bexarotene might work to break down amyloid plaques, Felsenstein and Borchelt selected mice approximately the same age as those used in the 2012 study and orally administered the drug to the mice. Tests confirmed the drug had reached its target genes in the mice, and that it elevated levels of a protein called apolipoprotein E. Some scientists believe one of the forms of this protein may prevent the buildup of amyloid brain plaques in people who don’t have Alzheimer’s disease.

But elevated levels of the protein in the mice studied by UF researchers seemed to have no effect on the animals’ amyloid plaques. Samples taken after seven days of treatment with bexarotene showed no significant difference in the number or size of plaques in the animals’ brains. Two teams of researchers from other institutions also were unable to replicate the breakdown of amyloid plaques.

Felsenstein emphasized that his team does not claim the previous study indicating bexarotene’s effectiveness is “totally wrong.”

“We’re just saying right now it’s extremely difficult to replicate and there may be little nuances, that there’s something that we don’t quite understand,” he added. Felsenstein and Borchelt both work at UF’s Center for Translational Research in Neurodegenerative Disease.

The other two research groups  who published papers in this week’s journal Science were led by Bart De Strooper, Ph.D., M.D., director of the VIB Center for the Biology of Disease in Belgium, and Sangram S. Sisodia, Ph.D., director of the Center for Molecular Neurobiology at the University of Chicago.

Citation

 

A New Strategy Required in the Search for Alzheimer’s Drugs?

May 24, 2013

In the search for medication against Alzheimer’s disease, scientists have focused on — among other factors — drugs that can break down Amyloid beta (A-beta). After all, it is the accumulation of A-beta that causes the known plaques in the brains of Alzheimer’s patients. The starting point for the formation of A-beta is APP. Alessia Soldano and Bassem Hassan (VIB/KU Leuven) were the first to unravel the function of APPL — the fruit-fly version of APP — in the brain of healthy fruit flies.

Alessia Soldano (VIB/KU Leuven): “We have discovered that APPL ensures that brain cells form a good network. We now have to ask ourselves the question whether this function of APPL is also relevant to Alzheimer’s disease.”

Bassem Hassan (VIB/KU Leuven): “Since we show that APP and APPL show similar activities in cultured cells, we suspect that APP in the human brain functions in the same manner as APPL in the brain of fruit flies. Hopefully we can use this to ask and eventually answer the question whether A-beta or APP itself is the better target for new drugs.”

Plaques in the brain: cause or effect

The brain of a person with Alzheimer’s disease is very recognizable due to the so-called plaques. A plaque is an accumulation of proteins that are primarily made up of Amyloid beta (A-beta), a small structure that splits off from the Amyloid Precursor Protein (APP). We have been dreaming for a long time of a drug that can break down A-beta, but we should be asking ourselves whether this is really the best strategy. After all, it is not yet clear whether the plaques are a cause or effect of Alzheimer’s disease. In order to answer this question, it is important to determine the function of APP in healthy brains.

Optimum communication between brain cells

Alessia Soldano and Bassem Hassan study APPL, the fruit-fly version of APP. APPL is found throughout the fruit-fly brain, but primarily in the so-called alpha-beta neurons that are vital to learning processes and memory. The alpha-beta neurons must form functional axons for optimum functioning. Axons are tendrils projecting from the neuron, which are essential for communication between neurons. The VIB scientists had previously shown that APPL is important for memory in flies. Now, they have discovered that — in the developing brain of a fruit fly — APPL ensures that the axons are long enough and grow in the correct direction. APPL is therefore essential in the formation of a good network of neurons. The question is whether or not it is a good strategy to target a protein with such an important function in the brain in order to combat Alzheimer’s disease.

Citation

 

Multiple Research Teams Unable to Confirm Bexarotene Alzheimer’s Study

May 24, 2013

Teams of highly respected Alzheimer’s researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.

Those results, presented online Feb. 9, 2012, suggested that the drug bexarotene (marketed as Targretin®) could rapidly reverse the buildup of beta amyloid plaques (Aβ) — a pathological hallmark of Alzheimer’s disease — in the brains of mice. According to the authors of the 2012 report, drug treatment quickly removed most of the plaques and brought rapid reversal of the pathological, cognitive and memory deficits related to the onset of Alzheimer’s.

However, the new reports from extensive and carefully controlled studies did not show any reduction in the number of plaques or total area occupied by the plaques during or after treatment. These results are described in three “technical comments” — one of which comes from researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St Louis and University of Tubingen in Germany — to be published in the May 24, 2013, issue of Science.

“The drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis,” according to that group’s comment. “We have failed to support earlier findings by Cramer et al that Targretin is efficacious in reducing plaque burden in transgenic mouse models of cerebral Aβ deposition.”

Comment co-author Sangram Sisodia, PhD, professor of neurosciences at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.

“We were surprised and excited, even stunned, when we first saw these results presented at a small conference,” said Sisodia. “The mechanism of action made some sense, but the assertion that they could reduce the areas of plaque by 50 percent within three days, and by 75 percent in two weeks, seemed too good to be true.”

“We all went back to our labs and tried to confirm these promising findings,” Sisodia added. “We repeated the initial experiments — a standard process in science. Combined results are really important in this field. None of us found anything like what they described in the 2012 paper.”

The researchers found no effects on plaque burden in three different strains of mice that were treated with bexarotene.

The discrepancy, besides being disappointing, also raises concerns about patient safety. The Food and Drug Administration approved bexarotene in December 1999 for a very specific use: treatment of refractory cutaneous T-cell lymphoma, a type of skin cancer. Once approved, the drug became legally available by prescription for “off-label” uses as well.

“Anecdotally, we have all heard that physicians are treating their Alzheimer’s patients with bexarotene, a cancer drug with severe side effects,” said co-author Robert Vassar, PhD, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. “This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene.”

Bexarotene has never been tested as a treatment for Alzheimer’s disease in humans, not even to determine the optimal dose or duration of treatment. This drug has significant side effects, including major blood-lipid abnormalities, pancreatitis, liver function test abnormalities, thyroid axis alterations, leucopenia, headaches, fatigue, weight gain, depression, nausea, vomiting, constipation and rash.

The two other technical comments came from research teams led by Kevin Felsenstein, Todd Golde, David Borchelt and colleagues at the University of Florida and by Bart DeStrooper and colleagues at the University of Leuven, Belgium.

There is no cure or effective treatment for Alzheimer’s disease, which is a progressive type of dementia that occurs when nerve cells in the brain die. When Alzheimer’s was first identified in 1906, it was considered a rare disorder. Today, Alzheimer’s is the most common cause of dementia. An estimated 5.3 million Americans have the disease.

This work was supported by the Cure Alzheimer’s Fund. Additional authors include Karthikeyan Veeraraghavalu of the University of Chicago; Rudolph Tanzi, Can Zhang and Sean Miller of Massachusetts General Hospital; Jasmin K. Hefendehl and Mathias Jucker of the University of Tübingen; Tharinda W. Rajapaksha and Robert Vassar of Northwestern University Feinberg School of Medicine; and Jason Ulrich and David M. Holtzman from the Washington University School of Medicine.

Citation

 

Stay Safe in the Sun – Important Changes About Sunscreen from the FDA

May 23, 2013

As summer approaches and everyone is clamoring to get outdoors, we know that sun protection is essential to prevent not only sun burns, but also premature skin aging and even cancer. The best protection for your skin, as many know, is sunscreen. But the labels on these sunscreen bottles can also be misleading, and it seems we may not have all the information we need on sunscreen. Be mindful of these quick facts below for a safe summer under the sun.

(Photo : Hacklock, CC BY-NC-SA 2.0) Summer is coming, and SPF may not mean what you think it does.

Incomplete Protection

Many consumers may not know that some sunscreens only protect against UVB (the type of ultraviolet light that causes burns) and not UVA (another type that causes DNA damage and ages the skin). Both types of rays can cause cancer, and many bottles and spray cans of sunblock are not labeled clearly, leading to far more risk for consumers. In December, the Food and Drug Administration (FDA) required all labeling to indicate if sunscreen was “broad spectrum,” blocking both UVA and UVB. Additionally, no sunscreen blocks 100 percent of ultraviolet light, so sunblock needs to be reapplied often while also monitoring exposure to the sun.

Misunderstanding Of SPF

The FDA has stated that any sunscreen that is not broad spectrum or has an SPF between two and 14 has no effect in preventing cancer or screen aging, and only prevents burns. What’s more, the SPF labeling system does not relate to protection increases. A sunblock with SPF 100, for instance, only increases protection from UVB by one percent from 98 to 99 percent, compared to a sunblock with SPF 50. The FDA is considering requiring all sunscreens with a higher than 50 rating for SPF to be labeled “50+” because of the murky nature of the health benefit of increased protection.

SPF only takes into account the blocking of UVB rays and not UVA, leading people to think that if they use high SPF products, they will be gaining stronger protection from aging and cancer. There is no labeling system for determining UVA blocking ability because scientists know far less about UVA’s effects than UVB’s.

Waterproof Claims Are False

There are no sunscreens that are waterproof. The product can only be water-resistant, which means the chemicals that block UVA and UBV rays may still easily wash off the skin. New FDA regulations require that labels clearly indicate that a sunscreen is water-resistant, and show how much time in the water would wash away sun protection.

Sprays Are A Completely Different Animal

In recent years, many companies have come out with sunscreen sprays that make it easy and fast to apply sunblock all over one’s body. The FDA suggests two coats of spray-on sunscreen to assure that coverage is complete. Additionally, the active chemicals in spray-on sunscreens are different and have a modified formulation than traditional rub-on sunblock lotions, so the effectiveness of such protection is being investigated by the government as well. There are also current investigations to determine if the chemicals are safe for inhalation if the chemicals are sprayed in the air. For now, when applying spray sunscreen to the face, put a nice amount in the palm of your hand and then apply the sunscreen to your face.

In the end, it is important to be smart and safe about sun protection. Skin cancer rates have been rising, even with sunscreen use at an all time high. Much of this may be due to too much faith in the ability of sunscreen to protect from UV damage or the improper use of sunscreens when outdoors.

Citation

 

Grape Juice, Berries, and Walnuts Affect Brain Aging

May 23, 2013

J Nutr. 2009 Sep;139(9):1813S-7S. doi: 10.3945/jn.109.108266. Epub 2009 Jul 29.

Grape juice, berries, and walnuts affect brain aging and behavior.

Joseph JA, Shukitt-Hale B, Willis LM.

Source

USDA-Agricultural Research Service, Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. jim.joseph@ars.usda.gov

Abstract

Numerous studies have indicated that individuals consuming a diet containing high amounts of fruits and vegetables exhibit fewer age-related diseases such as Alzheimer’s disease.

Research from our laboratory has suggested that dietary supplementation with fruit or vegetable extracts high in antioxidants (e.g. blueberries, strawberries, walnuts, and Concord grape juice) can decrease the enhanced vulnerability to oxidative stress that occurs in aging and these reductions are expressed as improvements in behavior.

Additional mechanisms involved in the beneficial effects of fruits and vegetables include enhancement of neuronal communication via increases in neuronal signaling and decreases in stress signals induced by oxidative/inflammatory stressors (e.g. nuclear factor kappaB).

Moreover, collaborative findings indicate that blueberry or Concord grape juice supplementation in humans with mild cognitive impairment increased verbal memory performance, thus translating our animal findings to humans.

Taken together, these results suggest that a greater intake of high-antioxidant foods such as berries, Concord grapes, and walnuts may increase “health span” and enhance cognitive and motor function in aging.

Citation

 

«Older Posts