Two Michigan State University scientists are now using a 4-year, $2 million grant from the National Heart, Lung and Blood Institute to better understand the link between obesity and dementia.

Anne Dorrance, an associate professor, and William Jackson, a professor, who are both in the Department of Pharmacology and Toxicology, are exploring why people who are overweight develop dementia at a faster rate than their healthier peers.

To do this, Dorrance and Jackson have developed a model focused on lifelong obesity and will test if an existing FDA-approved drug might slow the cognitive decline associated with dementia.

“It seems that your weight when you’re 70 or 80 and dementia is developing is not important, but your weight as you go through middle age is,” Dorrance said. “If you are obese through middle age, something happens that sets your brain on a trajectory to develop dementia. We think that being overweight changes how the arteries in the brain contract and dilate. This, in turn, changes how much blood flow and, therefore, energy the brain receives."

The team is using a specially developed rat model to examine the changes in cerebral arteries that occur with obesity. In the obese model, the cerebral arteries don’t dilate in the same way as they do in a lean rat, which can mean a decreased blood flow, impaired neuron function, and memory development.

“One of the things we know about the obese population is that their cerebral blood flow is lower than non-obese patients and it appears that their ability to increase blood flow to active regions of the brain is impaired,” Dorrance said.

The question is why the dilation diminishes and how can it be treated?

“What we’re trying to understand with this grant is what makes the arteries not work correctly,” Jackson said.

The two are looking at a specific hormone produced by the adrenal gland called aldosterone. The hormone has been implicated in cardiovascular disease, especially in patients who have high blood pressure, or are hypertensive. Yet, obese people have higher circulating levels of aldosterone, regardless if they are hypertensive or not.

In previous work, Dorrance and Jackson have shown that by blocking the aldosterone receptor, they can improve the structure and the function of the brain’s blood vessels in hypertensive models.

“What we are hoping to show is that the same thing is true in the obese model—if we treat the obese rats with a drug that blocks the actions of aldosterone, we’ll get better dilation,” Dorrance said. “We’ll be able to look at behavioral and cognitive deficits and see whether the drug works.”

Jackson added that because the drugs they're testing are already FDA-approved and have been around for some time, they are no longer patented and are available as generics, which could significantly reduce costs for patients down the road.

Both researchers also indicated that although they expect that their findings may lead to therapies that can slow the progression of dementia, they don’t expect that the treatments will reverse any neuron damage that has already been done.

“While the adult human brain can generate new neurons, it has a relatively limited capacity in a lot of its regions,” Jackson said. "Our goal is to stop the damage before that happens.”