12:14pm Monday 18 November 2019

Insulin Resistance May Prime the Brain for Alzheimer's Disease

While the relationship between type 2 diabetes and Alzheimer’s disease has been known, the new imaging study suggests a mechanism by which insulin resistance damages the brain.

Insulin resistance is a growing problem in most developed countries; the American Diabetes Association says more than half of adults older than 64 have pre-diabetes, in addition to the 29 million with full-blown diabetes.

The researchers studied 150 cognitively normal late middle-aged adults, who underwent a fasting blood draw to determine their insulin levels; cognitive tests; and a PET scan, which showed which parts of the brain are actively metabolizing sugar.

Lead author Dr. Barbara Bendlin, an associate professor of medicine at the University of Wisconsin School of Medicine and Public Health, found an association between higher levels of insulin resistance and lower metabolism of glucose in several areas of the brain, including, importantly, in the left medial temporal lobe, where memories are made. People with lower glucose metabolism in that part of the brain performed worse on tests of immediate and delayed memory.

Co-lead author Dr. Auriel Willette, of Iowa State University, explains that the brain may not have enough fuel to make new memories.

“One effect of insulin resistance or type 2 diabetes is that certain brain regions end up using less and less blood sugar over time,” he says. “Blood sugar is the main fuel of the brain. Less fuel may be one of the reasons why brain cells in the medial temporal lobe have difficulty helping us form new memories.” 

The participants in the study are part of the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study and included 103 people at a higher risk of Alzheimer’s because they had a parent with the disease. About 40 percent of them also had a gene, APOE, that is associated with Alzheimer’s and seven of the participants had type 2 diabetes. Their average age was 61.

Bendlin says the study adds to a growing body of knowledge that insulin resistance at mid-life results in measurable brain changes. It also suggests that improving health through diet and exercise in mid-life may help prevent Alzheimer’s disease by reducing insulin resistance.

“Mid-life may be a time when the trajectories of brain and cognitive aging can be modified,” she says. Bendlin is associated with the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Alzheimer’s Institute, which runs the WRAP study.

The study was published in the journal JAMA Neurology.

University of Wisconsin School of Medicine and Public Health

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