Elevated blood glucose linked to memory decline

Physical exercise could improve memory via glucose-lowering.

Maintaining blood glucose levels, even in the absence of diabetes, may be an important strategy for preserving age-related memory and cognitive health.

Results of a study conducted by researchers at Columbia University Medical Center demonstrated that elevations in blood glucose affect the dentate gyrus, part of the hippocampal formation and vital for memory.

“We can finally pinpoint which part of the hippocampus is affected by glucose — the dentate gyrus — and conclude that age-related dysregulation of glucose is at least one etiology of normal cognitive aging,” Scott A. Small, MD, associate professor of neurology at Columbia University Medical Center, told Endocrine Today.

“Showing that blood glucose selectively targets the dentate gyrus is not only our most conclusive finding, but it is the one most important for ‘normal’ aging, that is, hippocampal dysfunction that occurs in the absence of disease states, such as Alzheimer’s disease, infarcts and diabetes,” the researchers wrote in the Annals of Neurology.

Although it is widely known that the early stages of Alzheimer’s disease cause damage to the hippocampus, studies have suggested that it is also vulnerable to normal aging. Until now, the underlying causes of age-related hippocampal dysfunction have remained largely unknown.

With the goal of identifying the physiological processes that underlie cognitive aging and age-related memory decline, Small and colleagues enrolled 240 elderly individuals (mean age, 79.7 years) into the study; 60 participants had type 2 diabetes and 74 had brain infarcts. Using MRI, the researchers generated high-resolution functional maps of the hippocampal formation. They also examined measures that typically change during aging, such as rising blood glucose, BMI, cholesterol and insulin levels.

Examination revealed that decreasing activity in the dentate gyrus only correlated with levels of blood glucose. Additional animal studies in aging rhesus monkeys and mice further confirmed the relationship between glucose and dentate gyrus activity; the researchers found the same association in adults and animals. These findings suggest that exercising to maintain blood glucose levels is one strategy to stave off the normal cognitive decline that comes with age, according to the researchers.

“Our findings predict that any intervention that causes a decrease in blood glucose should increase dentate gyrus function and would, therefore, be cognitively beneficial. By improving glucose metabolism, physical exercise also reduces blood glucose. It is possible, therefore, that the cognitive-enhancing effects of physical exercise are mediated by the beneficial effect of lower glucose on the dentate gyrus,” they wrote.

Previous findings have demonstrated that glucose regulation worsens with age, leading to mild but significant increases in blood glucose that are detrimental to the hippocampal formation, according to Small.

In addition, “both cognitive aging and glucose dysregulation begin around the third decade of life and worsen progressively across the lifespan,” he said.

“While more research is needed into the complex interaction of late-life disease and how it may affect the hippocampus, this new study is part of an ongoing effort to identify specific areas where interventions might preserve cognitive health,” Marcelle Morrison-Bogorad, PhD, director of the National Institute on Aging Division of Neuroscience, said in a press release.

This study was funded by the National Institute on Aging, American Diabetes Association and McKnight Brain Research Foundation. – by Katie Kalvaitis

Ann Neurol. 2008;64:698-707.

This is an interesting study that extends prior observations regarding risk factors for vascular disease being highly associated with dementia. Thus, mild hyperglycemia, or prediabetes, is seen here to be associated with central nervous system dysfunction, much as has already been described for peripheral neuropathy, nephropathy and retinopathy. These observations form the basis, in part, for the recommendations of the American Association of Clinical Endocrinologists Consensus Committee on the Diagnosis and Management of Pre-Diabetes that prediabetes be identified and treated early to possibly prevent such complications. This may therefore be extended to early dementia as well.

– Alan J. Garber, MD, PhD

Endocrine Today Chief Medical Editor

This was a complex study that seems to show some cognitive effects of increasing glucose levels. It suggests that tight control of diabetes is helpful and beneficial in terms of trying to alleviate the cognitive difficulties as people get older.

– Philip Levy, MD

Endocrine Today Editorial Board member