Kathleen McLaughlin
The Bulletin

It’s well-known that the risk of dementia is increased in people with type 2 diabetes, but scientists don’t yet understand how the diseases are linked.

That’s because of apparent conflicts in evidence, where one set of research points to a lack of insulin as the problem while other studies conclude that too much insulin in the body is to blame.

A professor of business management took it upon herself to untangle the evidence and published her theory in the recent edition of the Journal of Alzheimer’s Disease. New York University professor Melissa Schilling feels so strongly that pre-diabetes plays a role in many cases of Alzheimer’s that she’s asking all neurologists to test their dementia patients for glucose tolerance.

Schilling also plans to petition the U.S. Food and Drug Administration to add a glycemic index to food labels. She thinks knowing how foods affect blood sugar would help people control it.

“If it helps one person keep their mother, it’s worth it,” Schilling said.

Schilling thinks that type 2 diabetes and Alzheimer’s are linked because of insulin-degrading enzyme, which also breaks down the amyloid protein that forms plaques on the brain in Alzheimer’s patients.

When insulin in the body increases, so does insulin-degrading enzyme, Schilling said, but that system can malfunction in different ways, all of which lead to Alzheimer’s disease.

People may have less insulin-degrading enzyme because of type 1 diabetes, or because of genetics, and that could make it easier to accumulate amyloid plaques, Schilling said. Or a person could produce more than the typical level of amyloids, which would again would overwhelm the enzyme’s ability to break them down.

Schilling believes that pre-diabetes and type 2 diabetes come into the picture by producing excess insulin and making the insulin-degrading enzyme too busy to go after the amyloid proteins.

She thinks researchers failed to see the common thread of insulin and insulin-degrading enzyme because most of the human studies on Alzheimer’s purposely exclude people with other health conditions, including diabetes.

While aspects of Schilling’s analysis require further study, she said the one thing the medical community could be doing now is checking patients for glucose-tolerance problems. “There’s no downside,” she said.

Dr. Paul Crane, a University of Washington researcher who tied dementia risk to blood-sugar levels, agreed. “As a general internist the idea that older people should be tested for glucose tolerance seems compelling,” he said. “Diabetes, of course, is a tip of that iceberg, and there are many benefits to identifying more modest levels of metabolic derangements.”

Crane was the lead author of a study, published in the New England Journal of Medicine in 2013, that observed blood-glucose levels and dementia in 2,067 people participating in the long-term Adult Changes in Thought study. Participants’ blood sugar had been measured multiple times without fasting and with fasting, and those readings were poured into a composite score. In follow-up more than six years later, people with higher blood sugar levels were more likely to have dementia — whether they had been diagnosed with diabetes or not. The risk increased with each incremental increase in blood sugar.

In general, medical research points to a link between cardiovascular health and brain health, said Sarah Holland, program director of the Alzheimer’s Association, Oregon Chapter.

The Alzheimer’s Association wants people to know that there are steps they can take to protect their overall health, Holland said. At the same time, there’s still no bio-marker or set of health indicators that says someone will develop Alzheimer’s, she said. “If you’re diabetic, you shouldn’t assume that you’re going to get Alzheimer’s disease.”

Schilling lost her grandmother to the disease several years ago, and more recently, a close friend died of multiple sclerosis. Schilling began reading extensively about neurodegenerative diseases, and she noticed a pattern of incongruent research findings. She began reviewing the basic research and developed a theory about how scientists were missing the big picture on insulin and insulin-degrading enzyme.

Schilling shared her theory with Dr. Wendy Qiu, a Boston University Alzheimer’s researcher who drew a similar conclusion about the role of insulin in the late 1990s.

Schilling said Qiu encouraged her to publish her theory. That meant reading about 1,000 articles and hiring a biochemistry graduate student as a tutor.

“Medical researchers get really, really specified,” said Schilling. “They get really wed to a particular research trajectory. I wasn’t constrained by any of those things.”

— Reporter: 541-617-7860, kmclaughlin@bendbulletin.com