Obesity Today, Alzheimer's Disease Tomorrow?

Today's obesity epidemic may be tomorrow's Alzheimer's disease epidemic, a new study shows.

People with diabetes are at particularly high risk of Alzheimer's disease. But now there's strong evidence that people with high insulin levels — long before they get diabetes — already are on the road to Alzheimer's disease.

As the body becomes more and more overweight, it becomes more and more resistant to the blood-sugar-lowering effects of insulin. To counter this insulin resistance, the body keeps making more insulin. If it continues, this escalating cycle of insulin resistance and insulin production end in type 2 diabetes.

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Insulin Triggers Amyloid Buildup

High insulin levels are known to cause blood vessels to become inflamed. Inflamed tissues send off chemical warning signals. These warning signals set off an avalanche of tissue-damaging effects.

But insulin doesn't just cause inflammation in the lower body. It also causes inflammation in the brain, find University of Washington researcher Suzanne Craft, PhD, and colleagues.

One dangerous effect of this insulin-caused brain inflammation is increased brain levels of beta-amyloid. Beta-amyloid is the twisted protein that's the main ingredient in the sticky plaques that clog the brains of people with Alzheimer's disease.

"What was striking was the magnitude of the effect," Craft tells WebMD. "Inflammation can be a result of amyloid elevations but can also create an environment in which amyloid is made more readily. Inflammation can be both the result and cause of amyloid production."

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Brave Volunteers

Craft's research team signed up 16 very brave volunteers. These men and women, ranging in age from 55 to 81, let research doctors give them two-hour infusions of both insulin and sugar. This kept their blood sugar at normal levels while creating the same kind of high insulin levels seen in people with insulin resistance. The volunteers then let the researchers give them a spinal tap so they could analyze their spinal fluid.

Just this brief rise in insulin levels had what Craft calls "striking" effects:

—It set off inflammation in the brain.

—The spinal fluid had increased levels of a compound called F2-isoprostane. Alzheimer's patients have unusually high brain levels of F2-isoprostane.

—Brain levels of beta-amyloid increased.

Except for the spinal tap, many Americans already are undergoing the same experiment as the study volunteers did. And they are doing it for a lot longer than two hours.

Because they are overweight and inactive — and because they may have genetic risk factors — many people have high insulin levels. It's not good for their hearts. And it's not good for their brains, says Samuel Gandy, MD, PhD. Gandy, chairman of the Alzheimer's Association's medical and scientific advisory committee, is director of the Farber neuroscience institute at Thomas Jefferson University, Philadelphia.

"I think this reinforces the idea that it's wise to maintain your brain," Gandy tells WebMD. "Controlling blood sugar and body weight — all those things we know are good for your heart health are also really good at preventing Alzheimer's disease. So there are more and more reasons not to be slouchy about getting these things under control."

Craft and colleagues report their findings in the October issue of Archives of Neurology.

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By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: Fishel, M.A. Archives of Neurology, October 2005; vol 62: early online edition. Suzanne Craft, PhD, University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, Seattle. Samuel Gandy, MD, PhD, chairman, medical and scientific advisory committee, Alzheimer's Association; and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia.