Sugar has a bad rep. Stirred into your coffee or baked into your Danish, that sweet white powder contributes to obesity, which in turn is a risk factor of aging and diabetes mellitus. (In fact, "mellitus" is Latin for "honey-sweet.")

But besides these physiological negatives, unregulated sugar in the blood (aka glucose) dulls the sharpness of memory. "An inability to quickly bring down high levels of glucose in the blood is associated with poor memory," observed research psychiatrist Antonio Convit at New York University, "and may help explain some of the recollection loss that occurs as we age."

Convit is medical director of NYU's Center for Brain Health. He is senior author of a paper in the Proceedings of the National Academy of Sciences (PNAS), released online Feb. 11, 2003. Its title: "Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly."

"Our finding," he told BioWorld Today, "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."

In monkeys, apes and humans, the highly convoluted hippocampus - named for its fanciful resemblance to a sea horse - snuggles deep in the temporal lobe. There, fueled by glucose, it operates like the brain's mission-control center, a gateway to conscious memory and learning of new information.

Convit and his co-authors brought together 30 nondiabetic, middle-aged and elderly people, ages 53 to 89, some of whom had an impaired ability to use glucose effectively. "We evaluated them consecutively in an outpatient setting," he recounted. "All had superior educations. Of the 30, women comprised 57 percent. Participants with impaired glucose tolerance (a pre-diabetic condition marked by higher than normal blood sugar levels)," he noted, "had a smaller hippocampus, and scored worse on tests for recent memory. We have thus demonstrated that impaired glucose regulation is associated, as people age, with memory dysfunction and shrinkage of the hippocampus. It raises the intriguing possibility," Convit suggested, "that improving glucose tolerance could reverse some age-associated problems in cognition."

Brain Demoted In Role Of Glucose Fuel

"The brain uses glucose almost exclusively as a fuel source," Convit explained. "It was once generally believed that the brain occupied a privileged position; it could get all 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 transport glucose from the blood to the tissues - including the brain - is reduced in diabetes."

Convit speculates that during periods of increased metabolic demand - such as while trying to remember something - glucose levels drop deeper in the parts of the brain doing the work in individuals with impaired glucose tolerance, leading to the memory problems reported in his paper. "Since the hippocampus is especially vulnerable to injury," he pointed out, "the inadequate sugar supply may cause it to atrophy over time.

"Researchers have yet to determine," Convit went on, "whether a less severe form of blood sugar increase, known as impaired glucose tolerance' (IGT), also affects memory function. Because the prevalence of IGT rises with age, we searched for a possible association between IGT and memory deficiency in our cohort of healthy aging adults."

The NYU study subjects received glucose intravenously, and the investigators assessed how quickly the sugar moved from the blood to the tissues - a measure of glucose tolerance. They had previously tested the subjects' overall cognitive function, and ability to recall short paragraphs they had read. Individuals who scored lowest on these recall exams also exhibited the poorest glucose tolerance. Additionally, magnetic resonance imaging brain scans indicated that those with poor glucose tolerance had a significantly smaller hippocampus.

"Twenty-five percent of individuals over 65 years of age have sufficient cognitive problems, short of dementia, to affect the quality of their lives," Convit observed. "The ability to learn consciously and recall new information, which is known as recent or declarative memory, is one of the areas most affected during aging. However, our knowledge about the medical factors that predispose a person to age-associated cognitive problems remains undeveloped. The prevalence of memory problems and IGT rise with age. In addition to genetic predisposition, obesity and low levels of physical activity have been identified as risk factors for IGT in adults and children.

"Our study might help create the view that metabolic substrate delivery may influence brain structure and function, and that better lifetime management of blood sugar could improve memory in old age, perhaps even reduce the risk of hippocampal damage and possibly Alzheimer's disease."

Diabetics Have Unsuspected Memory Problems

"For every person with Alzheimer's disease," Convit continued, "there are some eight people with severe memory problems, but who don't go on to develop dementia. Our work seeks to understand what other medical factors influence memory in aging. In fact, the medical literature demonstrates that diabetics experience memory and learning problems that cannot be explained away by other conditions, such as cardiovascular disease, which is often linked with diabetes.

"Our results were independent of age or overall cognitive performance," Convit pointed out, "and suggest that delivery of glucose may influence hippocampal structure or function. These observations, like other new medical findings, need to be confirmed by other investigators," he observed. "If our results are confirmed, then they may have significant therapeutic implications, given that diabetes and obesity are reaching epidemic proportions in the U.S., and there are a large number of middle-aged and elderly individuals with impaired glucose metabolism and memory dysfunction.

"In this study we proposed that among nondiabetic normal elderly, poorer glucose tolerance would be associated with decreased recent memory performance and smaller hippocampal volumes.

"Our study," Convit concluded, "raises the intriguing possibility that behavioral interventions, through diet and exercise, which help control blood sugar levels, as well as pharmacological interventions, such as new markets for insulin-sensitizing drugs, may be able to reverse some of the memory loss that accompanies aging."