Big Bellies Linked to Alzheimer's Disease

By Rob Stein
Washington Post Staff Writer
Wednesday, March 26, 2008; 4:00 PM

People who have big bellies in their 40s are much more likely to get Alzheimer's disease and other forms of dementia in their 70s, according to new research that links the middle-age spread to fading minds for the first time.

The study of more than 6,000 people found the more fat they had in their guts in their early to mid-40s the greater their chances of becoming forgetful or confused or showing other signs of senility as they aged. Those who had the most impressive midsections faced more than twice the risk of the leanest.

Surprisingly, a sizable stomach seems to increase the risk even among those who are not obese, or even overweight, the researchers reported in a paper published online today by the journal Neurology.

"A large belly independent of total weight is a potent predictor of dementia," said Rachel A. Whitmer, a research scientist at the Kaiser Permanente Division of Research in Oakland, Calif., who led the new study.

The findings are alarming in light of America's growing girth, Whitmer and other experts said.

"If these findings are replicated and better understood, it looks like an unhealthy brain could be another consequence of this epidemic of obesity," Lenore Launer of the National Institute on Aging said.

The research is the latest evidence that fat in the abdomen is the most dangerous kind. Previous studies have linked the apple-shaped physique to a greater risk of diabetes, heart disease and even cancer. Researchers suspect that those fat cells are the worst because of their proximity to major organs. They ooze noxious chemicals, stoking inflammation, constricting blood vessels and triggering other processes that might also damage brain cells.

"There is a lot of work out there that suggests that the fat wrapped around your inner organs is much more metabolically active than other types of fat right under the skin," Whitmer said. "It's pumping out toxic substances. It's very potent toxic fat."

Whitmer and her colleagues analyzed data from 6,583 members of Kaiser Permanente of Northern California who had their belly fat carefully calculated as part of a broad health study between 1964 and 1973. The researchers examined whether there was a link between abdominal obesity between the ages of 40 and 45 and the chances of developing Alzheimer's and other forms of dementia by the time they hit their 70s between 1994 and 2006.

The risk for dementia, the researchers found, increased steadily with the amount of fat in the abdomen, even after accounting for alternative explanations, such as other diseases, bad habits and lower education. They found no such association for fat in the thigh.

The researchers used a complicated method for measuring fat known as sagittal abdominal diameter (SAD). Those with a SAD score above 25 had the biggest bellies and the greatest risk. That is roughly equivalent to a waist of at least 39 inches.

Previous studies have shown people who are overweight are at increased risk for dementia. But when the researchers examined the relationship between body mass index (BMI), which is most common way to determine whether someone is overweight or obese, they found that those with big bellies were still nearly twice as likely to develop dementia even if they had BMIs that were considered healthy. In fact, their risk was about the same as for those who were overweight or obese.

"What that tells you is the effect of the belly is over and above that of being overweight," Whitmer said. "One of the take-home messages is it's not just your weight but where you carry your weight in middle age that is a strong predictor of dementia."

Stomach fat might increase the risk for dementia in the same ways it promotes heart disease -- by boosting blood pressure and constricting blood flow, Jose A. Luchsinger of Columbia University said. But Luchsinger and others said it might also promote the accumulation of a substance found in brain of Alzheimer's patients known as amyloid.

"We think the buildup and clumping of this material is an important risk factor," said Sam Gandy of the Mount Sinai School of Medicine, who chairs the Alzheimer's Association's medical and scientific advisory council. Previous research has found that people who are obese have higher levels of amyloid in their blood, he said.

Some experts remained skeptical, saying this kind of study cannot rule out the possibility that whatever is making people gain weight in their bellies in their 40s also puts them at risk for dementia in their 70s.

"There could be a connection. I'm not saying there couldn't be," said Barbara Corkery, director of Boston University's obesity research center. "But it could be those two things are caused by the same root cause."

While acknowledging that more research was needed, Whitmer said the findings provide one more reason to try to maintain a healthy weight, noting that this type of fat is the most easily shed by dieting and exercise.

"It's not as stubborn as the fat under the skin," she said. "It's a modifiable risk factor."