DIETARY COCOA FLAVANOLS REVERSE AGE RELATED MEMORY DECLINE IN MICE

Dietary cocoa flavanols -- naturally occurring bioactives found in cocoa -- reversed age-related memory decline in healthy older adults, according to a study led by Columbia University Medical Center (CUMC) scientists. The study, published today in the advance online issue ofNature Neuroscience, provides the first direct evidence that one component of age-related memory decline in humans is caused by changes in a specific region of the brain and that this form of memory decline can be improved by a dietary intervention

As people age, they typically show some decline in cognitive abilities, including learning and remembering such things as the names of new acquaintances or where one parked the car or placed one's keys. This normal age-related memory decline starts in early adulthood but usually does not have any noticeable impact on quality of life until people reach their fifties or sixties. Age-related memory decline is different from the often-devastating memory impairment that occurs with Alzheimer's, in which a disease process damages and destroys neurons in various parts of the brain, including the memory circuits.

Previous work, including by the laboratory of senior author Scott A. Small, MD, had shown that changes in a specific part of the brain -- the dentate gyrus -- are associated with age-related memory decline. Until now, however, the evidence in humans showed only a correlational link, not a causal one. To see if the dentate gyrus is the source of age-related memory decline in humans, Dr. Small and his colleagues tested whether compounds called cocoa flavanols can improve the function of this brain region and improve memory. Flavanols extracted from cocoa beans had previously been found to improve neuronal connections in the dentate gyrus of mice.

Dr. Small is the Boris and Rose Katz Professor of Neurology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, the Sergievsky Center, and the Departments of Radiology and Psychiatry) and director of the Alzheimer's Disease Research Center in the Taub Institute at CUMC.

A cocoa flavanol-containing test drink prepared specifically for research purposes was produced by the food company Mars, Incorporated, which also partly supported the research, using a proprietary process to extract flavanols from cocoa beans. Most methods of processing cocoa remove many of the flavanols found in the raw plant.

In the CUMC study, 37 healthy volunteers, ages 50 to 69, were randomized to receive either a high-flavanol diet (900 mg of flavanols a day) or a low-flavanol diet (10 mg of flavanols a day) for three months. Brain imaging and memory tests were administered to each participant before and after the study. The brain imaging measured blood volume in the dentate gyrus, a measure of metabolism, and the memory test involved a 20-minute pattern-recognition exercise designed to evaluate a type of memory controlled by the dentate gyrus.

"When we imaged our research subjects' brains, we found noticeable improvements in the function of the dentate gyrus in those who consumed the high-cocoa-flavanol drink," said lead author Adam M. Brickman, PhD, associate professor of neuropsychology at the Taub Institute.

The high-flavanol group also performed significantly better on the memory test. "If a participant had the memory of a typical 60-year-old at the beginning of the study, after three months that person on average had the memory of a typical 30- or 40-year-old," said Dr. Small. He cautioned, however, that the findings need to be replicated in a larger study -- which he and his team plan to do.

Flavanols are also found naturally in tea leaves and in certain fruits and vegetables, but the overall amounts, as well as the specific forms and mixtures, vary widely.

The precise formulation used in the CUMC study has also been shown to improve cardiovascular health. Brigham and Women's Hospital in Boston recently announced an NIH-funded study of 18,000 men and women to see whether flavanols can help prevent heart attacks and strokes.

The researchers point out that the product used in the study is not the same as chocolate, and they caution against an increase in chocolate consumption in an attempt to gain this effect.

Two innovations by the investigators made the study possible. One was a new information-processing tool that allows the imaging data to be presented in a single, three-dimensional snapshot, rather than in numerous individual slices. The tool was developed in Dr. Small's lab by Usman A. Khan, an MD-PhD student in the lab, and Frank A. Provenzano, a biomedical engineering graduate student at Columbia. The other innovation was a modification to a classic neuropsychological test, allowing the researchers to evaluate memory function specifically localized to the dentate gyrus. The revised test was developed by Drs. Brickman and Small.

Besides flavanols, exercise has been shown in previous studies, including those of Dr. Small, to improve memory and dentate gyrus function in younger people. In the current study, the researchers were unable to assess whether exercise had an effect on memory or on dentate gyrus activity. "Since we didn't reach the intended VO2max (maximal oxygen uptake) target," said Dr. Small, "we couldn't evaluate whether exercise was beneficial in this context. This is not to saythat exercise is not beneficial for cognition. It may be that older people need more intense exercise to reach VO2max levels that have therapeutic effects."

The article is titled, "Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults," The other contributors are: Lok-Kin Yeung (CUMC), Wendy Suzuki (New York University, New York, NYU), Hagen Schroeter (Mars, Incorporated, McLean VA), Melanie Wall (CUMC and New York State Psychiatric Institute, New York NY), and Richard Sloan (CUMC and New York State Psychiatric Institute). The study was supported by grants from the National Institutes of Health (AG034618 and AG035015), the James S. McDonnell Foundation, the McKnight Brain Research Foundation, and Mars, Incorporated.

Hagen Schroeter is employed by Mars, Incorporated, a company with long-term research and commercial interests in cocoa flavanols and procyanidins. The other authors declare no financial or other conflicts of interest.

CHEMICAL IN COFFEE MAY HELP PREVENT OBESITY RELATED DISEASE

Researchers at the University of Georgia have discovered that a chemical compound commonly found in coffee may help prevent some of the damaging effects of obesity.

In a paper published recently in Pharmaceutical Research, scientists found that chlorogenic acid, or CGA, significantly reduced insulin resistance and accumulation of fat in the livers of mice who were fed a high-fat diet.

"Previous studies have shown that coffee consumption may lower the risk for chronic diseases like Type 2 diabetes and cardiovascular disease," said Yongjie Ma, a postdoctoral research associate in UGA's College of Pharmacy and lead author of the paper. "Our study expands on this research by looking at the benefits associated with this specific compound, which is found in great abundance in coffee, but also in other fruits and vegetables like apples, pears, tomatoes and blueberries."

During the past 20 years, there has been a dramatic increase in obesity in the United States. More than one-third of U.S. adults and approximately 17 percent of children are obese, according to the Centers for Disease Control and Prevention, and the annual medical cost of obesity is more than $147 billion.

Aside from weight gain, two common side effects of obesity are increased insulin resistance and the accumulation of fat in the liver. Left untreated, these disorders can lead to diabetes and poor liver function.

To test the therapeutic effects of CGA, researchers fed a group of mice a high-fat diet for 15 weeks while also injecting them with a CGA solution twice per week.

They found that CGA was not only effective in preventing weight gain, but it also helped maintain normal blood sugar levels and healthy liver composition.

"CGA is a powerful antioxidant that reduces inflammation," said Ma, who works in the laboratory of professor Dexi Liu in the department of pharmaceutical and biomedical sciences. "A lot of evidence suggests that obesity-related diseases are caused by chronic inflammation, so if we can control that, we can hopefully offset some of the negative effects of excessive weight gain."

But the authors are quick to point out that CGA is not a cure-all. Proper diet and regular exercise are still the best methods to reduce the risks associated with obesity.

The mice in this study received a high dose of CGA, much higher than what a human would absorb through regular coffee consumption or a diet rich in fruits and vegetables.

However, the researchers do believe that CGA may form the foundation of a treatment for those who need extra help. They plan to conduct more research to develop an improved CGA formulation specifically for human consumption.

"We're not suggesting that people start drinking a lot of coffee to protect themselves from an unhealthy lifestyle," said Ma, who is also a member of UGA's Obesity Initiative. "But we do think that we might be able to create a useful therapeutic using CGA that will help those at risk for obesity-related disease as they make positive lifestyle changes."

MEDITATION MUST SLOW THE AGE RELATED LOSS OF GRAY MATTER IN THE BRAIN

Since 1970, life expectancy around the world has risen dramatically, with people living more than 10 years longer. That's the good news.

The bad news is that starting when people are in their mid-to-late-20s, the brain begins to wither -- its volume and weight begin to decrease. As this occurs, the brain can begin to lose some of its functional abilities.

So although people might be living longer, the years they gain often come with increased risks for mental illness and neurodegenerative disease. Fortunately, a new study shows meditation could be one way to minimize those risks.

Building on their earlier work that suggested people who meditate have less age-related atrophy in the brain's white matter, a new study by UCLA researchers found that meditation appeared to help preserve the brain's gray matter, the tissue that contains neurons.

The scientists looked specifically at the association between age and gray matter. They compared 50 people who had mediated for years and 50 who didn't. People in both groups showed a loss of gray matter as they aged. But the researchers found among those who meditated, the volume of gray matter did not decline as much as it did among those who didn't.

The article appears in the current online edition of the journal Frontiers in Psychology.

Dr. Florian Kurth, a co-author of the study and postdoctoral fellow at the UCLA Brain Mapping Center, said the researchers were surprised by the magnitude of the difference.

"We expected rather small and distinct effects located in some of the regions that had previously been associated with meditating," he said. "Instead, what we actually observed was a widespread effect of meditation that encompassed regions throughout the entire brain."

As baby boomers have aged and the elderly population has grown, the incidence of cognitive decline and dementia has increased substantially as the brain ages.

"In that light, it seems essential that longer life expectancies do not come at the cost of a reduced quality of life," said Dr. Eileen Luders, first author and assistant professor of neurology at the David Geffen School of Medicine at UCLA. "While much research has focused on identifying factors that increase the risk of mental illness and neurodegenerative decline, relatively less attention has been turned to approaches aimed at enhancing cerebral health."

Each group in the study was made up of 28 men and 22 women ranging in age from 24 to 77. Those who meditated had been doing so for four to 46 years, with an average of 20 years.

The participants' brains were scanned using high-resolution magnetic resonance imaging. Although the researchers found a negative correlation between gray matter and age in both groups of people -- suggesting a loss of brain tissue with increasing age -- they also found that large parts of the gray matter in the brains of those who meditated seemed to be better preserved, Kurth said.

The researchers cautioned that they cannot draw a direct, causal connection between meditation and preserving gray matter in the brain. Too many other factors may come into play, including lifestyle choices, personality traits, and genetic brain differences.

"Still, our results are promising," Luders said. "Hopefully they will stimulate other studies exploring the potential of meditation to better preserve our aging brains and minds. Accumulating scientific evidence that meditation has brain-altering capabilities might ultimately allow for an effective translation from research to practice, not only in the framework of healthy aging but also pathological aging."