By Amanda Gardner
WEDNESDAY, August 25 (Health.com) — People at risk for are also more likely to have brain abnormalities associated with Alzheimer's disease, according to a new study from Japan. The study is the latest evidence of a diabetes-dementia link.
The researchers found that men and women in their 60s with higher-than-average levels of blood sugar (glucose) or insulin—two signs of type 2 diabetes—are between three and six times more likely to have certain protein deposits in their brains a decade or more later, according to the study, which appears in the journal Neurology.
The deposits, known as plaques, don’t always lead to Alzheimer’s disease, but they do raise the risk of the memory-robbing condition.
If future research confirms that high glucose and insulin can in fact cause some cases of Alzheimer's, it may open the door to preventative drugs that target the insulin system, says William Thies, PhD, chief medical and scientific officer at the Alzheimer's Association, a nonprofit research and advocacy group.
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"That's ultimately why people are so interested in this relationship," says Thies, who was not involved in the new research.
Alzheimer's disease affects as many as 5 million people in the U.S., and the cause is largely unknown (although genes play a role).
About 24 million people in the U.S. have diabetes, and about 90% of those have type 2. Type 2 diabetes is caused by insulin resistance, a condition in which the body loses its sensitivity to the hormone insulin. The result is greater production of insulin—as the body struggles to overcome resistance—and high blood sugar, because the insulin that's produced can’t move the blood sugar into the liver and muscles.
Obesity and a lack of exercise raise the risk of type 2 diabetes, and several studies have shown that people with type 2 are at increased risk of dementia and faster cognitive decline as they age.
In the study, researchers autopsied the brains of 135 Japanese people from a single town who died between 1998 and 2003. (The average age at death was just under 80.) Ten to 15 years earlier, the researchers had given the study participants a glucose tolerance test, a common test for diabetes. They also measured other health factors such as blood pressure, cholesterol, and body mass index.
The individuals with the highest levels of blood glucose, insulin, and insulin resistance were more likely to have brain plaques, a distinguishing feature of Alzheimer's, compared to those with healthier levels. Although only 15% of the subjects developed Alzheimer's-type dementia, 65% had brain plaques. Another marker of the disease, brain fiber tangles, did not appear to be linked to glucose or insulin.
The relationship was strongest among the 20% of participants who carried the ApoE4 gene variant, a known risk factor for Alzheimer's. Compared to those without the gene variant who had low glucose, the people who had both high glucose and the ApoE4 variant had a 38-fold higher risk of plaques, for instance.
It's far from certain that insulin resistance actually causes Alzheimer's, however. The study wasn't able to rule out the possibility that an unidentified factor may contribute independently to both brain plaques and insulin resistance.
Still, a link between insulin resistance and Alzheimer's is plausible. Insulin resistance causes insulin levels to rise, which may interfere with enzymes that slow down the production of the protein found in brain plaques, says Ian Murray, PhD, an assistant professor of neuroscience at the Texas A&M Health Science Center College of Medicine, in College Station.
"The brakes are turned off," Murray says.
The study had some important shortcomings. It was relatively small, for one, and the researchers did not track whether the participants were being treated for diabetes. And the rates of diabetes, insulin resistance, and obesity in the study were low overall, which makes comparisons to the U.S. difficult.
"It is likely that the levels [of insulin resistance] will be much higher in a Western society, where obesity and diabetes are more prevalent," Murray says.