Patient in bed having blood drawn.

Vascular dementia: Exercise, blood flow and the aging brain

MRI blood vessels of the brain

MRI image of the blood vessels of the brain.
Courtesy of Dr. Kejal Kantarci from the Department of Radiology at Mayo Clinic.

Exercise does the brain a world of good. But, how?

Answer that question and you might crack the code for the treatment and, most importantly, prevention of vascular dementia. It is the second most common form of dementia after Alzheimer’s disease, affecting about a third of people over age 70 and researchers funded by the NIH’s National, Heart, Lung, Blood Institute (NHLBI) are taking it on.

Vascular dementia used to be called post-stroke dementia, because strokes are its leading cause. When the vessels that supply blood to the brain are too clogged or damaged, the results are dire: a decline in cognitive function, memory loss, and an inability to think, plan, and make decisions. Mobility and balance get impaired, too.

Researchers already know, based on findings from the NHLBI-funded Framingham Heart Study and others, that the risk factors for stroke and vascular dementia are similar to those for heart disease and include, significantly, aging and lack of physical activity. They also know that as the body ages, so does the brain, as is often demonstrated by cognitive impairments. And previous studies showed that physical activity is associated with increased cerebral blood flow and better cognitive function.

With a new series of NHLBI-funded studies set to end in 2018, researchers want to build on this current body of knowledge in an effort to understand the “how” behind all these correlations. 

“We know that exercise improves cognitive function, but the mechanism is unknown,” said Zorina Galis, Ph.D., chief of the Vascular Biology and Hypertension Branch, in the NHLBI’s Division of Cardiovascular Sciences. Observational studies show a positive association, but do not explain how the improvement happens. This project tries to connect the dots by aiming to show that physical activity keeps the blood vessels healthy, leading to better blood flow to the brain and greater ability to support increased metabolic demands, which in turn, Galis explained, helps to maintain cognitive faculties as we age.

But, doesn’t exercise make everything better?

More physical activity always seems like good advice, said Jill Barnes, Ph.D., professor of Kinesiology at the University of Wisconsin-Madison, and the principal investigator, supported through an NHLBI career development award to apply her expertise to the area of cognitive function. However, recommending exercise in the case of Alzheimer’s disease and vascular dementia “could be reckless because we do not yet know what kind of physical activity is optimal for those patients and there are important safety concerns,” she said.

Doppler Ultrasound image of middle cerebral artery

Doppler ultrasound image of the middle cerebral artery. Courtesy of Kathleen Miller and Anna Howery from University of Wisconsin, Madison.

By understanding the inner workings of exercise in the brain, researchers will not only help devise prevention strategies and interventions much earlier; but “if we know the mechanism by which exercise improves blood flow to the brain, we may be able to mimic how that works even for people who cannot exercise safely,” said Barnes.

The basic hypothesis is three-fold: the efficiency of blood vessels decreases as we age; brain blood flow is directly linked to several potential biomarkers or indicators of risk for cognitive decline; since exercise improves vascular function, it should improve cerebral microvascular function and stave off vascular dementia.

To test the hypothesis, researchers are studying healthy young adults, sedentary older adults and older adults with an exercise regime.

Using neuropsychological testing and advanced magnetic resonance imaging (MRI), the study is looking at how blood vessels in various areas of the brain respond to a request to perform cognitive tasks, which typically requires more energy of the brain and an increased blood flow.

“In healthy adults, the brain is really good at self-regulating blood flow,” said Barnes. Data from previous studies suggest that the brains of adults who exercise regularly are better at regulating the blood flow than their sedentary counterparts.

In her current study, Barnes and her colleagues are altering the brain blood flow of the participants with chemical and cognitive challenges to see which areas of the brain are receiving a greater flow, and how much this flow is increasing.

“When we give a stimulus that increases blood flow, we see an elevated blood flow response in a healthy person. However, in people with Alzheimer’s disease you see very little response,” said Barnes. This is an indication of very damaged blood vessels, which inhibit critical executive functioning. It is what causes that familiar blank stare in people with dementia, rather than the concrete action those around them might expect.

But these changes in cognition and physical ability, common in vascular dementia and Alzheimer’s disease, don’t typically occur until far along in the aging process. For Barnes, a measure of the study’s success will be when researchers are able to identify the biomarkers, or signposts, in the body and the brain that are relevant to the development of cognitive impairment.

Knowing these indicators of decline could lead to earlier interventions for treatment and prevention of vascular dementia.