from journal of medicine wrote: December 30, 2008 — Memory decline with age appears partly explained by increased blood glucose levels that cause decreased activity in the dentate gyrus, a new study published in the December issue of the Annals of Neurology suggests.
"Our experiments in humans, monkeys, and mice establish that blood glucose elevations target the dentate gyrus of the hippocampus, a region that is affected by normal aging," study author Scott A. Small, MD, from Columbia University, in New York, told Medscape Psychiatry.
Since blood glucose levels tend to rise with age, this study suggests that improving blood glucose regulation may be a good way to ameliorate age-related memory decline, said Dr. Small.
"Whether through physical exercise, diet, or drugs, this research suggests that improving glucose metabolism could help some people avert the cognitive slide that occurs in many of us as we age," he said.
Glucose levels that are too low, conversely, may inhibit cognitive function. In a separate small study published in the February 2009 issue of Appetite, researchers found transient impaired memory in dieters who depleted their glycogen stores by not eating any carbohydrates for a week.
"We saw decreased memory at the point when the dieters had exhausted their body's supply of glycogen, and memory returned when small amounts of carbohydrates were reintroduced a week later," Holly A. Taylor, PhD, from Tufts University, in Medford, Massachusetts, told Medscape Psychiatry.
Study in Mice, Humans, and Monkeys
Understanding cognitive decline in aging is becoming more important as people are living longer and "expect to live intellectually challenging lives," Dr. Small and colleagues write in the Annals of Neurology article.
Researchers have shown that the hippocampus, which is vital for memory, is targeted by Alzheimer's disease, stroke, and type 2 diabetes — diseases that occur in later life. But the underlying causes of age-related hippocampal dysfunction have remained largely unknown, said Dr. Small.
To investigate whether different regions of the hippocampus are targeted differently by diabetes and stroke, the researchers studied 240 nondemented seniors (58% women) who had a mean age of 79.7 years and were living in the community.
They used functional magnetic resonance imaging to obtain cerebral blood volume maps of hippocampal subregions and to ascertain whether the individuals had survived a stroke.
Of the 240 study subjects, 60 had type 2 diabetes and 74 had documented stroke. Each disease was associated with dysfunction in the hippocampus.
Further analysis showed, however, that in subjects with diabetes, the hippocampal dysfunction was mainly due to changes in the dentate gyrus, whereas in patients with stroke, it was due to changes in the CA1 subfield.
In a further experiment in rhesus monkeys, the researchers found that increased blood glucose levels affected the dentate gyrus in these animals.
Further, using a mouse model of diabetes, the researchers also found that compared with controls, diabetic mice had greater dysfunction in the dentate gyrus.
"Our study is the first to show in humans, monkeys, and mice that blood glucose differentially targets the dentate gyrus," said Dr. Small.
Their study suggests that moderating blood glucose levels, through physical exercise, diet, or medication, may aid in preventing cognitive decline, he added.
"I now recommend physical exercise to my aging patients as a way to preserve cognitive ability," he said. "There are a lot of other reasons why physical exercise is good for you, and this is an additional reason."
Low-Carb Diets May Hinder Memory
In the article published in Appetite, Dr. Taylor and colleagues note that little is known about how a low-carbohydrate diet may affect cognitive performance.
To look at this further, the researchers performed a 3-week study in 19 women, aged 22 to 55 years, who chose to follow either a low-carbohydrate diet similar to the Atkins diet or a low-calorie, balanced, weight-loss diet recommended by the American Dietetic Association.
Nine women chose to follow the low-carbohydrate diet, and 10 women chose the low-calorie, balanced diet.
Just prior to starting the diet, the women completed computer-based tests that assessed visuospatial memory, attention, and preoccupation with food. They were then tested again at 48 hours and 1, 2, and 3 weeks later.
Participants in both diet groups lost less than 2 kg over the 3-week period.
During complete withdrawal of carbohydrates in week 1, participants in the low-carbohydrate diet performed worse on memory tests than the women on the low-calorie, balanced diet.
"It was essentially a no-carbohydrate diet in week 1, which was not good for brain function," said Dr. Taylor. When very small amounts of carbohydrates were reintroduced in the second week, cognitive performance returned to normal.
Individuals following the low-carbohydrate diet also reported less confusion and performed better on a "very boring" task that assessed ability to pay attention, said Dr. Taylor.
Study limitations include its small size and the fact that the subjects were followed for only 3 weeks.
Nevertheless, "the results showed a clear difference in cognitive performance as a function of diet . . . [and] the data suggest that diet can affect more than just weight," Dr. Taylor said in a statement. "The brain needs glucose for energy, and diets low in carbohydrates can be detrimental to learning, memory and thinking."
The authors of the Annals of Neurology article and the Appetite article do not have any financial disclosure to report. The Annals of Neurology study was supported by the National Institutes of Health, the James S. McDonnell Foundation, the American Diabetes Association, and the McKnight Brain Research Foundation.
Ann Neurol. 2008;64:698-707. Abstract
Appetite. 2009;52:96-103. Abstract
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