Does diabetes make the mind go to pieces?

Does diabetes make the mind go to pieces?
January 28, 2009
By Mary Brophy Marcus, USA TODAY

Sweet sugar. That's the Greek translation of the word glucose, the substance our bodies make to use for energy. Glucose and the glucose-regulating hormone insulin have long been studied by scientists looking for a cure for diabetes. Now the substances are increasingly coming under the study of brain scientists because it appears they might just be golden keys to brain health as we age.

A number of studies have suggested that people with diabetes — when the body either does not make enough insulin or cannot process it — are more prone to cognitive decline and Alzheimer's. Studies are getting closer to understanding the link between the two conditions and which parts of the brain are most affected by glucose and insulin.

A study in the January issue of Diabetes involving thousands of Swedish twins reports that developing diabetes before age 65 corresponds to a 125% increased risk for Alzheimer's.

A glucose-hungry brain may be more prone to cognitive decline, and other medical investigations indicate that the mind's ability to analyze problems and the speed at which it processes information may suffer if blood glucose is abnormal or if insulin is too high.

The National Institute on Aging is funding several diabetes clinical trials to see whether treating certain aspects of diabetes will affect cognitive health and Alzheimer's.

"There's an amazing interest in glucose and insulin as a risk factor for cognitive function and memory loss and also interest in using some of the tools we use for diabetes to treat Alzheimer's," says Stephen Clement, a diabetes researcher and associate professor of endocrinology at Georgetown University Hospital.

Younger, older diabetics not at risk

A study in the American Psychological Association's January issue of Neuropsychology confirmed that even people who keep diabetes in check are more likely than those without the condition to experience mental decline over time. The researchers from the University of Alberta in Canada went on to determine which specific brain functions declined. They followed 465 people between the ages of 53 and 90, measuring their cognitive abilities at three years using a battery of tests. Of the group, 41 patients had type 2 diabetes. The researchers found that executive function — complex, analytical thinking — and speed of processing were hurt in the people with diabetes, and not in the non-diabetic group.

The ongoing study also revealed that the younger and older diabetes group showed no difference in impaired performance, suggesting that cognitive decline occurs early in the disease, then remains stable, says author Roger Dixon, professor of psychology at the University of Alberta.

Another study, published in December in the journal Neuron, suggests that slow, chronic starvation of the brain — when it doesn't get enough sugar — may set off a biochemical process that causes sticky Alzheimer's plaques to form. Author Robert Vassar, a professor of cell and molecular biology at Northwestern University's Feinberg School of Medicine, discovered that a key brain protein called elF2alpha is altered when the brain is energy-poor. The protein appears to increase the production of an enzyme that flips the switch that produces the plaques.

"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," Vassar says. He suggests getting exercise, reducing cholesterol and managing hypertension: "If people start early enough, maybe they can dodge the bullet."

Contrary to scientific belief

The National Institute on Aging is funding research exploring the effect of insulin nose spray on memory. Preliminary data show people with Alzheimer's improved their verbal memory. Similar research is being done at the University of Washington-Seattle.

Spraying insulin into the nose allows it to bypass the bloodstream and go straight to the brain, avoiding a drop in blood sugar that can come when insulin is injected into the arm, says Clement, who is not involved in the studies.

Why insulin is working in the brain runs against what science knows about biochemistry in the brain, Clement says. "Insulin isn't necessary for glucose uptake in the brain, so it must have other functions there, such as helping neuron function," he says. Neurons are brain cells that process and send messages.

The research of Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York, says he and colleagues have identified a peptide called human IMN, which, when infused into the brains of mice — into the hypothalamus — alters the way insulin works in the body.

"It sends signals through the nerves — nothing to do with the blood. We see that it goes to the liver and tells the liver to stop producing glucose and essentially cures diabetes," he says.

"All of a sudden, the brain has now started to be central in metabolism," Barzilai says.