The study, published the first week of February in the online edition of the Proceeding of the National Academy of Sciences, is the first to show an association between the size of the hippocampus, a key brain structure for learning and memory, and the ability to control blood sugar levels in the body, according to the researchers.
The study assessed non-diabetic middle-aged and elderly people, some of whom had an impaired ability to use sugar (glucose) effectively. Those with impaired glucose tolerance (a pre-diabetic condition characterized by higher than normal blood sugar levels) had a smaller hippocampus and scored worse on tests for recent memory.
"We have demonstrated that impaired glucose regulation is associated with memory dysfunction and shrinkage of the hippocampus," says Antonio Convit, M.D., Associate Professor of Psychiatry and Medical Director for the Center for Brain Health at the School of Medicine, who led the study. "Our study suggests that this impairment may contribute to the memory deficits that occur as people age, and it raises the intriguing possibility that improving glucose tolerance could reverse some age-associated problems in cognition.”
The brain uses glucose almost exclusively as a fuel source. It was once generally believed that brain occupied a privileged position – it could get all of the glucose it needed regardless of what was happening in the rest of the body. However, in recent years this view has been changing as knowledge about brain metabolism grows. It is now known that the ability to get glucose from the blood to the tissues (including the brain) is reduced in diabetes. Dr. Convit speculates that perhaps during periods of increased metabolic demand, such as while trying to remember something, glucose levels drop in the parts of the brain doing the work in individuals with impaired glucose tolerance, leading to the memory problems reported in his study. Since the hippocampus is especially vulnerable to injury, the inadequate sugar supply may cause it to atrophy over time.
"For every person with Alzheimer's disease, there are some 8 people with memory problems sufficient to affect the quality of their lives who don't go on to develop dementia," says Dr. Convit. "Our work seeks to understand what other medical factors influence memory in aging." In fact, says Dr. Convit, there are now more than 20 reports in the medical literature demonstrating that diabetics experience memory and learning problems that cannot be explained away by the presence of other conditions such as cardiovascular disease, which are often associated with diabetes. Diabetics have very high levels of glucose in the blood because the sugar cannot enter their tissues, where it is broken down to do useful work.
The new study attempted to extend the observations about cognitive impairment in diabetics to otherwise healthy, non-diabetic aging men and women, some of whom may have impaired glucose tolerance. In the study, the NYU researchers measured how well blood glucose was regulated – namely, how fast glucose moved from the blood into the tissues where it is used, and performed MRI brain scans to measure the size of the hippocampus in 30 healthy middle-age and elderly men and women (ranging in age from 53 to 89), who were also given a series of tests to assess memory and overall cognition. All of these adults had fasting blood glucose levels in the non-diabetic range (levels below 126 mg/dl). Glucose regulation was assessed by standard intravenous glucose tolerance tests after an overnight fast. Memory was assessed by a series of tests in which patients were asked to recall paragraphs and, in addition, overall cognitive function was measured on a test called the Mini Mental Status Examination (MMSE).
Overall, the study demonstrated that poorer glucose regulation was associated with lower memory performance and smaller hippocampal volumes, which were adjusted for head size. These results were independent of age or overall cognitive performance, meaning that these variables did not affect the results, and suggest that delivery of glucose may influence hippocampal structure and function. These observations, like other new medical findings, need to be confirmed by other investigators, says Dr. Convit. "If our results are confirmed then they may have significant treatment implications given that diabetes and obesity are reaching epidemic proportions in the United States and there are a large number of middle aged and elderly individuals with impaired glucose metabolism and memory dysfunction."
In addition to Dr. Convit, the authors of the study are Oliver Wolf, Ph.D, who is currently a Senior Scientist at University of Duesseldorf, Germany; Chaim Tarshish (B.S.), and Mony de Leon, Ed.D., Director of the Center for Brain Health and Professor of Psychiatry.
The study was supported by grants from: The National Institutes of Health/National Institute on Aging and the General Clinical Research Center (GCRC) at the NYU School of Medicine.
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