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Does diabetes lurk behind Alzheimer's?



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Like most people his age, 56-year-old Howard Gruetzner had put on a few pounds over the years. That wasn't a disaster; he figured he could lose the weight with a better diet.

Then Gruetzner developed type 2 diabetes. That still wasn't so bad, he thought. After all, people can lead a relatively normal life as long as they treat the illness.

But Gruetzner got a jolt a couple of years ago when he heard some of the first reports to link type 2 diabetes and Alzheimer's, an incurable brain-wasting disease that causes forgetfulness, changes in behavior and confusion.

"I began to pay a lot more attention to my diabetes," Gruetzner says.

With good reason. Gruetzner's family history of Alzheimer's, coupled with his diabetes, might very well magnify his risk of coming down with the fatal disease.

When it comes to keeping the brain healthy, putting on extra weight could be far riskier than most people have imagined. Scientific findings, some released within the past two years, indicate that weight gain and type 2 diabetes might trigger degenerative changes in the brain and very possibly Alzheimer's, says Marilyn Albert, an Alzheimer's expert at Johns Hopkins University in Baltimore.

Up to 16 million people will get Alzheimer's by 2050, experts believe. That projection could increase if the rates of obesity and diabetes don't start to come down, says Zoe Arvanitakis, a neurologist at Rush University Medical Center in Chicago. "There are more and more people with type 2 diabetes. We're going to see more and more people with dementia, including Alzheimer's."

Many factors cause Alzheimer's, so losing weight doesn't offer any guarantee of a senility-free old age. But people who lose weight or control their diabetes might be able to keep aging brain cells in top shape as long as possible, experts say.

Then, if Alzheimer's does set in later in life, the process might be slower than usual, and people might die of another cause before they develop any sign of Alzheimer's, says Gregory Cole, a researcher at the University of California at Los Angeles. "If you're going to get the disease when you are 80, and you delay it by 10 years, you have a pretty good chance of not getting it at all," Cole says.

The evidence linking diabetes and Alzheimer's includes a Chicago study of 842 older Catholic nuns, priests and brothers. None had any sign of Alzheimer's at the start, but during the nine-year study, 151 developed Alzheimer's.

People who had type 2 diabetes had a 65% increased risk of getting Alzheimer's, according to a statistical analysis. The findings were published in the Archives of Neurology last year.

Here's the scenario suggested by the study: Weight gain triggers insulin resistance, a condition in which cells don't respond to the hormone insulin. Normally, insulin helps transport sugar into cells, where it is used for fuel.

But when insulin resistance develops, cells don't get enough sugar. As time goes by, insulin resistance can lead to type 2 diabetes, and the lack of sugar might cause brain cells to malfunction or die, Cole says. Dying brain cells may set the stage for Alzheimer's.

Of mice and insulin

The whole process may be kicked off by a high-fat diet. "If you look at our fat intake, it's terrible," Cole says. "We eat too much fat."

Food that's easy to grab and eat, especially fast food, contains lots of saturated fat that can clog blood vessels.

Cole's research found that mice fed a fatty lab chow developed insulin resistance. That condition, in turn, fueled a problem thought to be central to Alzheimer's: a build-up of a poisonous short protein called beta amyloid.

Beta amyloid clumps together, damaging brain cells and connections. It is thought to play a central role in memory loss and other symptoms of the disease. Cole published his findings in December in the Journal of Neuroscience.

Research published this month in the Archives of Neurology suggests that high blood levels of insulin, a key factor in insulin resistance, might lead to increased production of beta amyloid in the human brain. Other work suggests that diabetes increases the risk of clogged blood vessels. Those clogged vessels can restrict blood flowing to the brain, and that could lead to Alzheimer's, Albert says.

The findings highlight the risks of excess weight, but they also suggest novel ways to deal with Alzheimer's, which typically strikes after age 60 and can take eight years or longer to ravage the brain.

"If we treat insulin resistance, we might be reducing the accumulation of beta amyloid and the risk of Alzheimer's," Cole says.

The research also holds out the hope that treating insulin resistance actually might provide a benefit for people who already have Alzheimer's, says Suzanne Craft, a researcher at the University of Washington in Seattle.

She gave 30 people with memory problems, including Alzheimer's, either a drug used to combat insulin resistance or a placebo. She found that people who received four milligrams a day of Avandia performed about 20% better on tests of memory and attention.

Then Craft gave insulin, a mainstay of diabetes care, to 26 people with memory problems, including Alzheimer's. The treatment produced a boost for a subgroup of people who had a genetic risk factor for Alzheimer's.

That group of 14 people had a "robust improvement in memory," Craft said in June at the Alzheimer's Association International Conference on Prevention of Dementia held in Washington, D.C.

Steven DeKosky, an Alzheimer's expert at the University of Pittsburgh, cautions that studies linking diabetes and insulin resistance to Alzheimer's are too preliminary to provide any proof that diabetes drugs might help boost memory for people with Alzheimer's.

Some researchers doubt that such drugs will be able to reverse the widespread damage already inflicted by the disease at the time of diagnosis. "Drugs are unlikely to fix everything," Cole says.

A better way to fix Alzheimer's is to prevent it or at least to slow down the damage, he says. To do that, scientists must learn more about human behavior: the habits that have pushed more people to the brink of obesity and beyond.

"Everything in our society conspires against us," Craft says.

People drive everywhere instead of walking, and increased commute times on snarled roadways often mean people don't have time to prepare lower-fat meals, she says.

Instead, they grab a burger and fries at a fast-food outlet.

"It's hard to turn down high-fat food, which is all around us," Cole says.

'Losing your mind at the end'

And so the pattern begins: Poor eating habits and a sedentary lifestyle contribute to weight gain and set the stage for insulin resistance, diabetes and a disease that many people fear more than death itself.

"Losing your mind at the end is the worst of all possible things," says Suzanne de la Monte, a neuropathologist at Brown Medical School in Providence, who also has done studies linking insulin abnormalities to Alzheimer's.

Gruetzner knows all about the risk. As the regional director for the Alzheimer's Association in Waco, Texas, he talks to families all the time about the disease. But when his mother got a diagnosis in 2002, the risk hit close to home.

He has watched as the disease has destroyed his mother's mind, slowly taking away her ability to think. The 78-year-old former elementary school teacher can't remember how to do simple math problems anymore.

Gruetzner can't change his family background or his age, which is approaching the risk zone. But he does what he can to lower his chances of getting the disease. He keeps his blood sugar levels under control. He has upped his activity level by walking more. He has given up high-fat favorite foods such as chicken-fried steak.

But Gruetzner admits having a hard time with late-night snacks.

"I do enjoy eating," he says. "So I have to watch it."

Gruetzner says he plans to redouble his efforts to lose weight. He knows the link between Alzheimer's and diabetes isn't rock-solid, but he figures losing the extra 15 pounds couldn't hurt.

And if the research pans out, then Gruetzner figures he has everything to gain: "I've seen how destructive this disease becomes."

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© Copyright 2004 USA TODAY, a division of Gannett Co. Inc.

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