Studying Diabetes and the Brain
Gail Musen, Ph.D.
Thursday, May 26, 2011
People with diabetes are at a greater risk for developing Alzheimer’s disease and other neurological conditions, as well as more extensive damage from strokes caused by bleeding. Researchers at Joslin are taking significant steps to understand what drives these risks and to work toward preventive mechanisms.
Gail Musen, Ph.D., examines whether warning signs for Alzheimer’s disease can be detected among people with insulin resistance, who are at higher risk for developing the grim neurodegenerative disease. “This study will help us begin to identify how insulin resistance increases risk for Alzheimer’s, and to identify people who are at risk so that we can try early interventions to decrease that risk,” Dr. Musen says.
She explains that people developing Alzheimer’s may show unusual patterns in the brain’s “default network,” a set of areas of the brain that get busier when the brain is relatively quiet. Importantly, these brain changes can be detected when cognition is still entirely normal. Dr. Musen and her colleagues employ functional magnetic resonance imaging (fMRI) to examine brain activity in people with various levels of insulin resistance, both while they are mentally “at rest” and when performing memory tasks.
Joslin’s Edward Feener, Ph.D., is making key discoveries about strokes that involve intracerebral hemorrhage (bleeding in the brain). There are no effective treatments to control such bleeding, and diabetes and high blood glucose levels are associated with increased bleeding and worse clinical outcomes.
But studies in the Feener lab have pinpointed a new mechanism involving a protein called plasma kallikrein that interferes with the normal clotting process in the brain following blood vessel injury in people with diabetes.
Given the prevalence of strokes and the damage they inflict, “these were exciting results,” says Dr. Feener. The finding raises the possibility of developing drugs that act as preventive measures in people with diabetes or others at high risk for stroke.
In 2010, work at Joslin also produced a surprising finding about another aspect of brain function: diabetes can affect how much cholesterol the brain can make. The brain produces its own cholesterol and won’t function normally if it doesn’t churn out enough. Investigators in the lab of C. Ronald Kahn, M.D., found that brain cholesterol synthesis drops below normal levels in several mouse models of diabetes.
“This decrease in cholesterol could affect how nerves function for appetite regulation, behavior, memory and even pain and motor activity,” says Dr. Kahn. “Thus, this has broad implications for people with diabetes.”
Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the level of oxygenated blood in brain regions. This image from Dr. Gail Musen’s research shows brain activity at rest for subjects with (left) and without diabetes (right). The patients with diabetes show less activation in these regions during rest—a pattern also found in other groups of people who are at increased risk for Alzheimer’s disease.
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