image: Gelsy Torres-Oviedo oversees a student demonstration of the split-belt treadmill in her lab.
Credit: Swanson School of Engineering
In the United States, Alzheimer's Disease and Related Dementias (ADRD) affects as many as five million people and nearly 40% of the population aged 85 and older. Even with such prevalence, ADRD is difficult to diagnose early — but an interdisciplinary group of researchers at the University of Pittsburgh is looking to change that.
Gelsy Torres-Oviedo, associate professor of bioengineering at Pitt’s Swanson School of Engineering received a five-year, $5.3 million R01 award from the National Institutes of Health (NIH) National Institute on Aging (NIA) with interdisciplinary co-investigators Helmet Karim, assistant professor of psychiatry and bioengineering; Andrea Rosso, associate professor of epidemiology; Gong Tang, professor of biostatistics; and Andrea Weinstein, assistant professor of psychiatry.
Their project, “Neural Mechanisms Underlying Cognitive Contributions to Walking as an Early Marker for Risk of Alzheimer’s Disease and Related Dementias,” will study the correlation between walking and mild cognitive impairment (MCI). The team hopes to unveil neural mechanisms underlying the relation between mobility and cognitive decline to enhance early ADRD risk prediction.
“Assessing someone who is at risk of developing dementia is difficult, it's not very clear cut, and the existing tests are often not enough to identify whether someone is at risk of cognitive decline.” Torres-Oviedo said. “But mobility could be a potent predictor, and just having someone perform a walking task could eventually help clinicians better classify those who are at risk for dementia.”
The study will begin by screening research participants for MCI, a condition defined by mild levels of cognitive decline such as memory loss and trouble with language and judgment, but does not typically interfere with daily life. Not all people with MCI develop ADRD, but according to Andrea Weinstein, it’s a useful research diagnosis because people with MCI have a greater risk of developing dementia.
“When you wait until someone has been diagnosed with dementia to start treating them, they're already fairly far along in the disease, so a lot of research has moved toward intervening at the MCI stage instead.” Weinstein said. “We want to look at locomotor learning in people with MCI and assess whether we can kind of see their neural efficiency and ability to adapt to new walking patterns.”
To study this, participants with and without MCI will perform a walking task on the Sensorimotor Learning Laboratory’s split-belt treadmill, which moves each leg at different speeds to challenge participants to adjust their gait. After a few recurring visits, Torres-Oviedo can then analyze the muscle activity and leg movements to track how both groups of individuals adapt to these changes over time.
“When you're walking in a new environment like the treadmill, you’ll feel off balance at first, but the motor system eventually adjusts and learns how to walk under these circumstances,” Torres-Oviedo said. “Healthy older adults show a greater locomotor learning index—they learn a new motor memory and retrieve it the next time they’re in the lab. But for people with mild cognitive impairment, this ability is diminished.”
The group hypothesizes that the diminished locomotor ability in individuals with MCI could be related to dysfunction in the basal ganglia, a cluster of structures at the center of the brain that impacts mobility and cognition.
“This link in the brain between cognition and motor performance is incredibly important,” Weinstein said. “The basal ganglia has interconnected loops throughout the brain that are involved not just in motor systems, but also in cognitive control. We’ve been working together for a long time to emphasize thinking about cognition and motor performance together, because they're all resulting from the central nervous system.”
Looking ahead, solidifying and understanding this link between mobility and MCI could eventually help clinicians more efficiently identify individuals at risk for ADRD and even help aging individuals without dementia maintain their independence, according to epidemiologist and collaborator Andrea Rosso.
“Ultimately, I really want to help people maintain independence— like making sure they can get out the door and grocery shop or be with their family.” Rosso said. “Understanding what mechanisms are behind reduced mobility and why it may be more common among people who are at risk of dementia can help us create interventions that will help them. Whether that's directly targeting brain health, or even using physical therapy, we want to help reduce fall risk and maintain their mobility.”