Controlling Blood Glucose May Fend Off Cognitive Decline

by Tom Valeo

March, 2009

Controlling levels of glucose in the blood through diet, exercise and perhaps medication may protect memory and cognitive function by preserving the hippocampus, the delicate brain structure essential for the creation of short-term memories.

Researchers did magnetic resonance imaging brain scans of 240 elderly subjects involved in an ongoing study by Richard Mayeux, co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center. They found that elevated glucose affected the dentate gyrus, a subregion of the hippocampus vital to memory formation. Therefore, maintaining normal glucose levels should benefit the dentate gyrus and slow agerelated cognitive decline, according to the authors of the study, which appears in the December Annals of Neurology. Exercise provides a safe, simple means of regulating glucose, they add.

“This paper clarified a study we did a couple of years ago where we found that physical exercise differentially improves the function of the dentate gyrus,” says Scott Small, the lead author. “One of the things exercise does is improve glucose utilization, so what we’re testing here is the hypothesis that exercise benefits the hippocampus.”

Elevated glucose is a promising suspect in cognitive decline not only because it appears to target the dentate gyrus, the brain region most affected the aging process, but also because it coincides with the aging process itself, Small adds.

“All of us beginning at about the age of 30 have greater difficulty handling glucose,” Small said. “We all become insulin resistant, so we have glucose spiking when we eat. I’m 47, so if I were to eat a large meal I’d experience a spike in glucose for about 3 hours—a spike that would be higher and last longer than in someone younger. As we age our brains are bathed in glucose, and that tracks with cognitive aging.”

People with diabetes, who experience chronically elevated levels of blood glucose, are known to be more susceptible to the memory problems associated with Alzheimer’s disease, and Small’s paper provides a plausible explanation for this correlation.

That’s why Mony de Leon, a professor of psychiatry at New York University and founder of the Center for Brain Health, finds these results intriguing. “The work is very interesting,” he says. “If diabetes injures the brain selectively, that could help explain the memory problems associated with diabetes.”

Caloric restriction, known to extend longevity in everything from yeast to primates, also appears to help the brain, presumably by keeping glucose levels in check, according to German researchers.

In a study published online Jan. 26 in the Proceedings of the National Academy of Sciences they reported that elderly people who reduced their caloric intake by 30 percent for three months scored 20 percent higher than controls on a test that involved remembering lists of words.

The study was small—it involved 50 elderly people divided into three groups—but lead author Agnes Floel, a neurologist at the University of Munster, says that she and her colleagues were so encouraged by the results that they plan to repeat the study with a larger number of subjects.

“We hope to at least double the number of participants,” she says. “Also, we hope to introduce a diet with more omega-3 fatty acids, and to do MRI scans of the head before and after intervention.”

Other researchers are investigating whether certain medications may help the body absorb glucose and prevent harmful elevations of glucose in the blood. Suzanne Craft, professor of psychiatry and behavioral sciences at the University of Washington and the Department of Veterans Affairs’ VA Puget Sound Health Care System, has conducted a six-month study in which healthy elderly patients who took rosiglitazone, a drug used to promote insulin uptake in diabetic patients, showed better memory and attention than those who took a placebo.

The results prompted the National Institutes of Health to fund a larger study to see if rosiglitazone can improve memory and attention in older adults with mild cognitive impairment. The study also will attempt to determine the effects of the drug on inflammation and cardiovascular disease.

Craft also is conducting a study funded by the National Institute on Aging that involves delivering insulin directly to the brain via a nasal spray, a method that does not affect glucose or insulin regulation in the rest of the body. This study is testing the hypothesis that insulin in the brain facilitates memory in people with memory problems.

And researchers at Northwestern University reported in the Feb. 10 Proceedings of the National Academy of Sciences that treating neurons with insulin in the lab protected them from attack by the soluble protein fragments that appear to be involved in causing Alzheimer’s disease.

Small and his colleagues suspect that a medication such as memantine, an Alzheimer’s drug that blocks glutamate receptors, might help block the destructive chemical cascade that follows a stroke and selectively damages region CA1 in the hippocampus.