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News Release

Joslin Researchers Find Markers That May Increase Risk of Cognitive Decline in Middle-Aged People with Type 2 Diabetes

Discovery could lead to early interventional therapy to delay cognitive disorders

Boston - (November 7, 2013) - Joslin researchers have discovered that middle-aged patients with type 2 diabetes are at increased risk for developing white matter abnormalities in the brain, which may raise risk for dementia or other cognitive disorders. The study will be published today online and in the upcoming print edition of Diabetes.

Gail Musen, Ph.D., is an Assistant Investigator in the Section on Clinical, Behavioral, and Outcomes Research and an Assistant Professor in Psychiatry at Harvard Medical School.


“Diabetes raises the risk about twofold for Alzheimer’s disease,” says senior author, Gail Musen, Ph.D., Assistant Investigator in the Section on Clinical, Behavioral, and Outcomes Research at Joslin Diabetes Center.

The researchers found a link between abnormalities in white matter and a decrease in functional connectivity in the brain’s default-mode network, a set of regions that typically shows abnormal behavior in people at genetic risk for Alzheimer’s disease. White matter fibers connect the different areas of the brain and abnormalities in white matter may be tied to the development of dementia and other cognitive disorders.

The study compared neurological data from eighteen patients with type 2 diabetes to nineteen volunteers without diabetes. The participants were between forty-five and sixty-five years of age.  The study subjects underwent a series of cognitive tests in which both groups scored within the normal range, indicating that none of the participants were displaying signs of dementia or other forms of cognitive decline.

Researchers used MRI to assess the strength of functional connectivity in the default-mode network, which are the regions of the brain most active when a person is in wakeful rest.  Diffusion tensor imaging was also used to study the white matter’s structural integrity.

When compared to the control group, type 2 patients showed decreased integrity in the white matter of two different areas in the brain-- the cingulum bundle, which is a fiber tract that connects regions in the default-mode network, and the uncinate fasciculus, which connects regions important for executive function and memory.

Even though both groups of subjects performed normally on the cognitive tests, the people with type 2 diabetes showed early physiological signs of reduced brain capacity.

Musen and her team believe that white matter abnormalities may contribute to the disrupted communication between regions in the default-mode network.

They hope that early detection of these neurophysiological abnormalities and decreased function will help with early identification of type 2 patients who are at the greatest risk for developing cognitive decline or possibly dementia. By starting cognitive training or some other therapy before the onset of cognitive decline, patients may be able to mitigate and possibly reverse cognitive deterioration.

Musen emphasizes that it is important to study both the structural and functional aspects of the brain in cognitive decline, explaining that, “We look at the correlation between the two because if a correlation exists, then it might suggest a common set of mechanisms underlying brain structure and function raising the possibility that similar treatments may be useful for improving both.”

Musen would like to employ amyloid imaging in type 2 diabetic patients to determine whether amyloid deposits are present in their brains. Amyloids are proteins that can build up in the brain, and beta amyloid is  one of the hallmark features of Alzheimer’s that can be detected in living brains. Such scans could help researchers determine if people with type 2 diabetes have elevated amounts of amyloid which may contribute to their increased risk for Alzheimer’s disease.

This study was funded in part by the National Institutes of Heath and the Herbert Graetz Fund.

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