Drinking Heavily and Smoke May Show ‘Early Aging’ of the Brain

May 19, 2013

Treatment for alcohol use disorders works best if the patient actively understands and incorporates the interventions provided in the clinic. Multiple factors can influence both the type and degree of neurocognitive abnormalities found during early abstinence, including chronic cigarette smoking and increasing age. A new study is the first to look at the interactive effects of smoking status and age on neurocognition in treatment-seeking alcohol dependent (AD) individuals. Findings show that AD individuals who currently smoke show more problems with memory, ability to think quickly and efficiently, and problem-solving skills than those who don’t smoke, effects which seem to become exacerbated with age. Results will be published in the October 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“Several factors — nutrition, exercise, comorbid medical conditions such as hypertension and diabetes, psychiatric conditions such as depressive disorders and post-traumatic stress disorder, and genetic predispositions — may also influence cognitive functioning during early abstinence,” explained Timothy C. Durazzo, assistant professor in the department of radiology and biomedical imaging at the University of California San Francisco, and corresponding author for the study.

“We focused on the effects of chronic cigarette smoking and increasing age on cognition because previous research suggested that each has independent, adverse affects on multiple aspects of cognition and brain biology in people with and without alcohol use disorders. This previous research also indicated that the adverse effects of smoking on the brain accumulate over time. Therefore, we predicted that AD, active chronic smokers would show the greatest decline in cognitive abilities with increasing age.”

“The independent and interactive effects of smoking and other drug use on cognitive functioning among individuals with AD are largely unknown,” added Alecia Dager, associate research scientist in the department of psychiatry at Yale University. “This is problematic because many heavy drinkers also smoke. Furthermore, in treatment programs for alcoholism, the issue of smoking may be largely ignored. This study provides evidence of greater cognitive difficulties in alcoholics who also smoke, which could offer important insights for treatment programs. First, individuals with AD who also smoke may have more difficulty remembering, integrating, and implementing treatment strategies. Second, there are clear benefits for thinking skills as a result of quitting both substances.”

Durazzo and his colleagues compared the neurocognitive functioning of four groups of participants, all between the ages of 26 and 71 years of age: never-smoking healthy individuals or “controls” (n=39); and one-month abstinent, treatment-seeking AD individuals, who were never-smokers (n = 30), former-smokers (n = 21) and active-smokers (n = 68). Evaluated cognitive abilities included cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions, and working memory.

“We found that, at one month of abstinence, actively smoking AD [individuals] had greater-than-normal age effects on measures of learning, memory, processing speed, reasoning and problem-solving, and fine motor skills,” said Durazzo. “AD never-smokers and former-smokers showed equivalent changes on all measures with increasing age as the never-smoking controls. These results indicate the combination of alcohol dependence and active chronic smoking was related to an abnormal decline in multiple cognitive functions with increasing age.”

“These results indicate the combined effects of these drugs are especially harmful and become even more apparent in older age,” said Dager. “In general, people show cognitive decline in older age. However, it seems that years of combined alcohol and cigarette use exacerbate this process, contributing to an even greater decline in thinking skills in later years.”

Durazzo agreed. “Chronic cigarette smoking, excessive alcohol consumption, and increasing age are all associated with increased oxidative damage to brain tissue,” he said. “Oxidative damage results from increased levels of free radicals and other compounds that directly injure neurons and other cells that make up the brain. Cigarette smoking and excessive alcohol consumption expose the brain to a tremendous amount of free radicals. We hypothesize that chronic, long-term exposure to cigarette smoke and excessive alcohol consumption interacts with the normal aging process to produce greater neurocognitive decline in the active-smoking AD group.”

Cigarette smoking is a “modifiable health risk” that is directly associated with at least 440,000 deaths every year in the United States, Durazzo noted. “Chronic smoking, and to a lesser extent, alcohol use disorders are also associated with an increased risk for Alzheimer’s disease,” he said. “So, the combination of these modifiable health risks may place an individual at even greater risk for development of Alzheimer’s disease. Given the above, in conjunction with the findings from our cognitive and neuroimaging research, we completely support programs that routinely offer smoking cessation programs to all individuals seeking treatment for alcohol/substance abuse disorders.”

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Federal Update on Alzheimer’s: Does this Make Sense?

May 18, 2013

Alzheimer’s disease is the most expensive disease facing our nation today and is set to increase like no other.Currently our country spends over $203 billion per year caring for those with Alzheimer’s, with two thirds of those costs paid by Medicare and Medicaid. Without any means of delaying, treating or curing this disease, costs are expected to skyrocket to over $20 trillion by 2050.

By comparison, our nation invests less than 1% of what we spend on caring for those with Alzheimer’s disease on promising research. To put it another way, for every $27,000 spent caring for those with Alzheimer’s, a mere $100 is spent on research. We must and should pay to provide the care we do today, but what we all want most is a world where it is unnecessary; a world without Alzheimer’s.

More Americans are dying either from or with Alzheimer’s, so overcoming this disease will save lives and is key to addressing our nation’s fiscal challenges.

Please urge your member of Congress to take the first steps in addressing this problem by supporting an additional $100 million for efforts to combat Alzheimer’s disease for FY 2014.

Congress simply can’t afford NOT to act.

Want to do more?

Last month close to 1,000 advocates held meetings with nearly every congressional office during the 2013 Alzheimer’s Advocacy Forum in Washington, DC. In everyone of those meetings advocates emphasized the critical need for additional resources and the passage of vital legislation to address the Alzheimer’s crisis. Members of Congress took notice, with many of them agreeing to support and promote these important initiatives, and others promising to seriously consider our proposals.

To capitalize on this momentum advocates and ambassadors from your local communities are currently planning follow-up meetings with elected officials in your district. If you’re interested in joining their efforts and sharing your story with members of Congress, please contact your local chapter today! It’s rewarding, and it matters.


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New Drug Reverses Memory Deficits and Slows Alzheimer’s in Mice

May 18, 2013

A drug developed by scientists at the Salk Institute for Biological Studies, known as J147, reverses memory deficits and slows Alzheimer’s disease in aged mice following short-term treatment. The findings, published May 14 in the journal Alzheimer’s Research and Therapy, may pave the way to a new treatment for Alzheimer’s disease in humans.

“J147 is an exciting new compound because it really has strong potential to be an Alzheimer’s disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment,” says lead study author Marguerite Prior, a research associate in Salk’s Cellular Neurobiology Laboratory.

Despite years of research, there are no disease-modifying drugs for Alzheimer’s. Current FDA-approved medications, including Aricept, Razadyne and Exelon, offer only fleeting short-term benefits for Alzheimer’s patients, but they do nothing to slow the steady, irreversible decline of brain function that erases a person’s memory and ability to think clearly.

According to the Alzheimer’s Association, more than 5 million Americans are living with Alzheimer’s disease, the sixth leading cause of death in the country and the only one among the top 10 that cannot be prevented, cured or even slowed.

J147 was developed at Salk in the laboratory of David Schubert, a professor in the Cellular Neurobiology Laboratory. He and his colleagues bucked the trend within the pharmaceutical industry, which has focused on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease.

Instead, the Salk team used living neurons grown in laboratory dishes to test whether their new synthetic compounds, which are based upon natural products derived from plants, were effective at protecting brain cells against several pathologies associated with brain aging. From the test results of each chemical iteration of the lead compound, they were able to alter their chemical structures to make them much more potent. Although J147 appears to be safe in mice, the next step will require clinical trials to determine whether the compound will prove safe and effective in humans.

“Alzheimer’s disease research has traditionally focused on a single target, the amyloid pathway,” says Schubert, “but unfortunately drugs that have been developed through this pathway have not been successful in clinical trials. Our approach is based on the pathologies associated with old age-the greatest risk factor for Alzheimer’s and other neurodegenerative diseases-rather than only the specificities of the disease.”

To test the efficacy of J147 in a much more rigorous preclinical Alzheimer’s model, the Salk team treated mice using a therapeutic strategy that they say more accurately reflects the human symptomatic stage of Alzheimer’s. Administered in the food of 20-month-old genetically engineered mice, at a stage when Alzheimer’s pathology is advanced, J147 rescued severe memory loss, reduced soluble levels of amyloid, and increased neurotrophic factors essential for memory, after only three months of treatment.

In a different experiment, the scientists tested J147 directly against Aricept, the most widely prescribed Alzheimer’s drug, and found that it performed as well or better in several memory tests.

“In addition to yielding an exceptionally promising therapeutic, both the strategy of using mice with existing disease and the drug discovery process based upon aging are what make the study interesting and exciting,” says Schubert, “because it more closely resembles what happens in humans, who have advanced pathology when diagnosis occurs and treatment begins.” Most studies test drugs before pathology is present, which is preventive rather than therapeutic and may be the reason drugs don’t transfer from animal studies to humans.

Prior and her colleagues say that several cellular processes known to be associated with Alzheimer’s pathology are affected by J147, including an increase in a protein called brain-derived neurotrophic factor (BDNF), which protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation. Postmortem studies show lower than normal levels of BDNF in the brains of people with Alzheimer’s.

Because of its broad ability to protect nerve cells, the researchers believe that J147 may also be effective for treating other neurological disorders, such as Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS), as well as stroke, although their study did not directly explore the drug’s efficacy as a therapy for those diseases.

The Salk researchers say that J147, with its memory enhancing and neuroprotective properties, along with its safety and availability as an oral medication, would make an “ideal candidate” for Alzheimer’s disease clinical trials. They are currently seeking funding for such a trial.

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How Pets Help Dementia Patients

May 17, 2013

Therapy dogs and other animals can stimulate social interaction and ease agitation in dementia patients. But it takes specially trained pets to bring the full benefit of animal therapy into elder care settings. Talk to animal therapy practitioners and researchers and you will hear stories about therapy dogs and dementia patients that bring tears to your eyes.

petsforever1You may hear of Diva, a German shepherd, who sought out an elderly, non-communicative man sitting alone and let him wind his fingers in her fur and hug her. Then there is the resident golden retriever-lab mix in an Alzheimer’s care unit who found his favorite patient agitated in a hallway — and gently took him by the sleeve to lead him back to his room. Or you’ll hear about Leonardo, a cat who curls up on the bed next to end-stage Alzheimer’s patients in hospice units.

But behind every successful animal-assisted therapy visit, there is also a lot of planning, training, and work to be done so that animal therapy is safe for people living in elder care settings.

The Benefits of Animal Therapy

“Even people with Alzheimer’s recognize a dog and they see that the dog is someone new in their environment. I think they see it as someone with whom they can interact without any worry,” explains Mara M. Baun, DNSc, a coordinator of the PhD in nursing program at the University of Texas Health Sciences Center at the Houston School of Nursing in Houston.

Baun has been researching the benefits of therapy animals for over a decade. In one of her studies, she and her team compared degrees of social interaction of adults in an Alzheimer’s unit with and without the presence of a dog.

“When they had the pet with them, they had more interactive behaviors, although some of them were aimed at the dog, not at the person,” she says. Her work has shown this effect is consistent whether the dog and dementia patients interact one-on-one or in a group setting.

In addition to stimulating a social response, dementia patients may benefit from the presence of therapy animals because of:

  • Reduced agitation. Agitation behaviors, common among dementia patients, are reduced in the presence of a dog.
  • Physical activity. Depending on a patient’s mobility, they may be able to groom the animal, toss a ball, or even go for a short walk.
  • Improved eating. Dementia patients have been shown to eat more following a dog’s visit.
  • Pleasure. Some patients simply enjoy the presence of the dog and its human companion, as well as the tricks therapy dogs can do.

Making Animal Therapy Work in Elder Care Settings

If the idea of animal therapy is appealing, it’s worth knowing that there is a lot of work that goes into matching the right animal and human handler team with the right patients. Here are some of the issues involved:

  • Temperament. An animal’s personality will dictate whether they can be a good therapy animal. You want an animal that is not easily startled and is comfortable interacting with unpredictable strangers in a calm manner. Dogs are the easiest to train for these types of situations, says Cheri Weston Swenson, MSN, a therapy animal handler and an evaluator for Delta Society Pet Partners Teams in Minneapolis-St Paul, Minn. Still, she knows teams that work with Delta Society-registered guinea pigs, rabbits, horses, and even chickens.
  • Individual strengths. Each animal has their own strengths. Swenson says her cat, Leonardo, does best when he is interacting one-on-one — but her dog, Victor, is fine in group situations. Some animals are better suited to children than dementia patients.
  • Training. Swenson trains her dogs to be comfortable with hospital equipment, tubing, wheelchairs, and the crowded situations they might encounter in an Alzheimer’s unit. Therapy animals should also be able to sit, stay, do tricks on command, introduce themselves nicely (such as putting their head gently on a knee), and pass over tantalizing smells. At the same time, human companions must cultivate their ability to be good advocates for their pets in difficult situations.
  • Registration or certification. “I am almost never asked about our qualifications and that bothers me,” says Swenson. “We want to uphold a high standard for therapy animals and their handlers.” She recommends seeking out therapy animals and human companions who are registered with the Delta Society, Pet Therapy International, or Therapy Dogs International. Delta Society, for which she is an evaluator, retests both humans and pets every two years — a good thing, says Swenson, who has observed that even the most committed teams can become lax during that time.
  • Cleanliness. Swenson bathes her indoor animals at least once a month and spends about 30 minutes grooming them before a visit — this includes cleaning their ears and mouth, clipping their nails, washing their feet, and brushing them thoroughly.
  • Infection control. Infectious agents such as MRSA, C. difficile, E. coli, and Salmonella are a concern in elderly care settings, affecting both dementia patients and the therapy dog teams that visit them. In addition to properly cleaning the therapy animals before and after a visit, infection control measures include:
    • Cleaning the hands of everyone who will touch the animal before and after contact.
    • Preventing animals that eat a raw foods diet from being therapy animals.
    • Avoiding contact with the animal’s mouths.
    • Using sheets and barriers, such as rolled towels, to keep some distance between the animals and the dementia patients’ bedding or furniture. Fresh sheets and towels must be used in each room.
  • Giving treats. Swenson says feeding is a universal bonding behavior, and many of the people her animals visit want to give a treat. She carries small hand-held shovels into which they can place a treat (which she provides) for the animal to retrieve — but then the therapy dogs are required to do some kind of trick in exchange. Other animal and pet teams do not allow treats, however.
  • Flexibility. With dementia patients, visits can be unpredictable, says Swenson. She has seen her dog surprised to find that a patient he knows well may, on occasion, push him away. Both human and animal have to be able to adjust to changing situations.

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Baun adds that some facilities try to have a resident animal. This can work, she says, but the animal must have off-time — just like every other worker — as well as a place of its own to rest and a clear understanding at the staff-level about who is responsible for the animal’s well-being. The best situations occur when a staff member brings a suitable animal in with him during the day and then they go home together at night.

Properly trained and prepared therapy animals can be a real blessing to dementia patients in elder care settings — it’s a great option to look into for your loved one. Start with the national organizations recommended by Swenson to learn about local options.

Find more information in the Everyday Health Alzheimer’s Disease Center.

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Brain Rewires Itself After Damage or Injury

May 16, 2013

When the brain’s primary “learning center” is damaged, complex new neural circuits arise to compensate for the lost function, say life scientists from UCLA and Australia who have pinpointed the regions of the brain involved in creating those alternate pathways — often far from the damaged site.

The research, conducted by UCLA’s Michael Fanselow and Moriel Zelikowsky in collaboration with Bryce Vissel, a group leader of the neuroscience research program at Sydney’s Garvan Institute of Medical Research, appears this week in the early online edition of the Proceedings of the National Academy of Sciences.

The researchers found that parts of the prefrontal cortex take over when the hippocampus, the brain’s key center of learning and memory formation, is disabled. Their breakthrough discovery, the first demonstration of such neural-circuit plasticity, could potentially help scientists develop new treatments for Alzheimer’s disease, stroke and other conditions involving damage to the brain.

For the study, Fanselow and Zelikowsky conducted laboratory experiments with rats showing that the rodents were able to learn new tasks even after damage to the hippocampus. While the rats needed more training than they would have normally, they nonetheless learned from their experiences — a surprising finding.

“I expect that the brain probably has to be trained through experience,” said Fanselow, a professor of psychology and member of the UCLA Brain Research Institute, who was the study’s senior author. “In this case, we gave animals a problem to solve.”

After discovering the rats could, in fact, learn to solve problems, Zelikowsky, a graduate student in Fanselow’s laboratory, traveled to Australia, where she worked with Vissel to analyze the anatomy of the changes that had taken place in the rats’ brains. Their analysis identified significant functional changes in two specific regions of the prefrontal cortex.

“Interestingly, previous studies had shown that these prefrontal cortex regions also light up in the brains of Alzheimer’s patients, suggesting that similar compensatory circuits develop in people,” Vissel said. “While it’s probable that the brains of Alzheimer’s sufferers are already compensating for damage, this discovery has significant potential for extending that compensation and improving the lives of many.”

The hippocampus, a seahorse-shaped structure where memories are formed in the brain, plays critical roles in processing, storing and recalling information. The hippocampus is highly susceptible to damage through stroke or lack of oxygen and is critically inolved in Alzheimer’s disease, Fanselow said.

“Until now, we’ve been trying to figure out how to stimulate repair within the hippocampus,” he said. “Now we can see other structures stepping in and whole new brain circuits coming into being.”

Zelikowsky said she found it interesting that sub-regions in the prefrontal cortex compensated in different ways, with one sub-region — the infralimbic cortex — silencing its activity and another sub-region — the prelimbic cortex — increasing its activity.

“If we’re going to harness this kind of plasticity to help stroke victims or people with Alzheimer’s,” she said, “we first have to understand exactly how to differentially enhance and silence function, either behaviorally or pharmacologically. It’s clearly important not to enhance all areas. The brain works by silencing and activating different populations of neurons. To form memories, you have to filter out what’s important and what’s not.”

Complex behavior always involves multiple parts of the brain communicating with one another, with one region’s message affecting how another region will respond, Fanselow noted. These molecular changes produce our memories, feelings and actions.

“The brain is heavily interconnected — you can get from any neuron in the brain to any other neuron via about six synaptic connections,” he said. “So there are many alternate pathways the brain can use, but it normally doesn’t use them unless it’s forced to. Once we understand how the brain makes these decisions, then we’re in a position to encourage pathways to take over when they need to, especially in the case of brain damage.

“Behavior creates molecular changes in the brain; if we know the molecular changes we want to bring about, then we can try to facilitate those changes to occur through behavior and drug therapy,” he added. I think that’s the best alternative we have. Future treatments are not going to be all behavioral or all pharmacological, but a combination of both.”

Fanselow and Vissel have worked closely over the last several years. For more information on Fanselow’s research, visit the Fanselow Lab website. For more on the Garvan Institute of Medical Research, visit their website.

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Eating a High-Carb Diet Increases Your Chances of Alzheimer’s

May 15, 2013

There are a number of reasons why a high-carb diet is not wise, but new research has added yet another reason why you cut down on the pasta: You are more likely to develop Alzheimer’s disease.

A new study that was recently released found that older adults who load up on carbs have close to four times the risk of developing mild cognitive impairment.

Researchers also said that sugars played a role in the development of MCI, which very often serves as a precursor to Alzheimer’s, according to study results published in the Journal of Alzheimer’s Disease. By comparison, eating additional proteins and some fats can offer protection from MCI, USA Today said, citing the journal.

imagesA team of scientists from Mayo Clinic tracked 1,230 people aged 70-89 and asked if they would provide information on what kinds of foods they at the previous year.

Stopping development of MCI is key

Among the group only the 940 people who showed no appreciable signs of cognitive impairment were asked to return in 15 months for follow-up examination. By the fourth year of the study, 200 of the 940 were beginning to show small signs of cognitive impairment, including problems with memory, judgment, thinking and language.

Lead author Rosebud Roberts, a professor in the department of epidemiology at the clinic, which is located in Rochester, Minn., said not everyone who develops MCI progresses to Alzheimer’s disease, which affects some 5.2 million adults around the country. Those numbers are expected to triple by 2050, as Baby Boomers continue to age.

“The research field is trying to find things that can help reduce risk factors for pre-dementia problems,” Roberts said, according to USA Today. “If we can stop people from developing MCI, we hope we can stop people from developing dementia. Once you hit the dementia stage, it’s irreversible.”

Among the foods regarded as complex carbohydrates: rice, pasta, bread and cereals. The digestive system turns them into sugars. Fruits, vegetables and milk products are simple carbs.

“A high-carbohydrate intake could be bad for you because carbohydrates impact your glucose and insulin metabolism,” says Roberts. “Sugar fuels the brain, so moderate intake is good. However, high levels of sugar may actually prevent the brain from using the sugar – similar to what we see with Type 2 diabetes.”

He said high sugar levels – which are prevalent in high-carb diets – could affect blood vessels in the brain, and might also play a role in the development of beta amyloid plaques, which are proteins that are toxic to brain health and are found in the brains of people who are affected by Alzheimer’s. Scientists don’t yet know what causes the disease; however, they do suspect a buildup of beta amyloid is a leading cause.

Study offers some hope

Here are some of the study’s primary findings:

– People whose diets were the highest in fat (nuts and healthy oils, for instance) were 42 percent less likely to develop cognitive impairment, while those who had the highest intake of protein (chicken, meat, fish) saw their risk reduced by 21 percent.

– Many popular diets, including the Mediterranean (fish, protein from poultry and lots of plant-based foods and healthy fats) and Atkins (low-carb diet featuring plenty of meats), make pitches for multiple health benefits that are derived from lowering carb intake, which includes a reduced risk for heart disease, diabetes and improved brain health.

“This (study) is consistent with what we’ve seen in past published research on how a lower carbohydrate diet can help to reduce the risk of Alzheimer’s,” Colette Heimowitz, vice president of Nutrition and Education for Atkins Nutritionals Inc., told the paper.

While there currently is no treatment for Alzheimer’s besides drugs, Roberts said the study at least offers some hope because “it shows a modifiable way we can reduce risk for the disease.

“It is important to eat a balance of protein, carbohydrates and fat,” he added.

 

Obesity-Related Dementia Is Projected To Rise In England

May 15, 2013

The rise in obesity in England if unchecked could lead to an estimated increase indementia prevalence in over 65 year olds by 2050 from 5% to 7% (4,894 cases per 100,000 in 2010 to 6,662 cases per 100,000), conclude researchers at this year’s European Congress on Obesity (ECO), taking place in Liverpool, UK (12-15 May).

Dementia is characterised by a decline in cognitive function in areas such as memory, attention and language and increases with age making it a significant challenge to healthcare. Some recent studies suggest that obesity in mid-life increases the risk of dementia later in life. In this new study, the authors estimated the impact of changing rates of obesity on future rates of dementia and its cost to the English government.

The researchers’ projected obesity trends to 2050, and used computer modelling to simulate a ‘virtual population’ and estimate the prevalence and cost burden of obesity-related dementia. The researchers tested three scenarios. Firstly, they looked at the effect on dementia if the present rising trend in prevalence of obesity continues. Secondly, they looked at the effect of a smaller rise in obesity prevalence (a modelled 5% reduction).

Thirdly, they looked at the effect if obesity levels remained constant at present levels – this allowed the researchers to distinguish between the effect of an ageing population and the rising incidence of obesity.

They found that, based on past and current data, obesity trends are projected to increase in England reaching 46% in males and 31% in females by 2050. The Health Survey for England 2011 shows male obesity to be currently at 24% and female at 26%.

This increase in obesity, could, say the researchers, have an impact upon the future incidence of dementia. In particular it is mid-life obesity that confers an almost doubling of the risk of later life dementia (Loef and Walach, 2013). By 2050, almost 7% of the population over 65 years are predicted to suffer from dementia. Holding BMI rates constant at today’s levels would result in a reduction of almost 10% of new cases of dementia in 2050 compared with if current trends continued unabated to 2050.

However, the researchers caution that, since dementia typically takes two to three decades to evolve the impact of any BMI intervention upon dementia will take 25 years to show effect. Reducing BMI will have an impact on other diseases such as heart disease, stroke, type 2 diabetes sooner than the impact on dementia. The annual total cost of dementia (health, social, informal care and lost productivity) is currently estimated at £23bn per year by the Alzheimer’s Research Trust1. Webber and Marsh project that based on current trends this will increase to £41bn per year by 2050.

With obesity rates projected to double by 2050, dementia-related costs are expected to increase. A modelled 5% reduction in BMI across the population would avoid an estimated £600 million in dementia-related costs in England. If the rise in obesity rates was halted and BMI levels were held at 2010 levels over the same period, an estimated £940 million in costs could be avoided.

“These are preliminary findings and we need to develop the modelling methods further to get a fuller picture. 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.”

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Cancer Drug Prevents Build-up of Toxic Brain Protein in Alzheimer’s

May 14, 2013

Researchers at Georgetown University Medical Center have used tiny doses of a leukemia drug to halt accumulation of toxic proteins linked to Parkinson’s disease in the brains of mice. This finding provides the basis to plan a clinical trial in humans to study the effects.

They say their study, published online May 10 in Human Molecular Genetics, offers a unique and exciting strategy to treat neurodegenerative diseases that feature abnormal buildup of proteins in Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington disease and Lewy body dementia, among others.

“This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain,” says the study’s senior investigator, neuroscientist Charbel E-H Moussa, MB, PhD. Moussa heads the laboratory of dementia and Parkinsonism at Georgetown.

When the drug, nilotinib, is used to treat chronic myelogenous leukemia (CML), it forces cancer cells into autophagy — a biological process that leads to death of tumor cells in cancer.

“The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death,” Moussa says. “We reasoned that small doses — for these mice, an equivalent to one percent of the dose used in humans — would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else.”

Moussa, who has long sought a way to force neurons to clean up their garbage, came up with the idea of using cancer drugs that push autophagy in tumors to help diseased brains. “No one has tried anything like this before,” he says.

Moussa, and his two co-authors — graduate student Michaeline Hebron and Irina Lonskaya, PhD, a postdoctoral researcher in Moussa’s lab — searched for cancer drugs that can cross the blood-brain barrier. They discovered two candidates — nilotinib and bosutinib, which is also approved to treat CML. This study discusses experiments with nilotinib, but Moussa says that use of bosutinib is also beneficial.

The mice used in this study over-express alpha-Synuclein, the protein that builds up in Lewy bodies in Parkinson’s disease and dementia patients and which is found in many other neurodegenerative diseases. The animals were given one milligram of nilotinib every two days. (By contrast, the FDA approved use of up to 1,000 milligrams of nilotinib once a day for CML patients.)

“We successfully tested this for several diseases models that have an accumulation of intracellular protein,” Moussa says. “It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson’s disease as well as Lewy body dementia.”

The team also showed that movement and functionality in the treated mice was greatly improved, compared with untreated mice.

In order for such a therapy to be as successful as possible in patients, the agent would need to be used early in neurodegenerative diseases, Moussa hypothesizes. Later use might retard further extracellular plaque formation and accumulation of intracellular proteins in inclusions such as Lewy bodies.

Moussa is planning a phase II clinical trial in participants who have been diagnosed with disorders that feature build-up of alpha Synuclein, including Lewy body dementia, Parkinson’s disease, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).

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