Changes in walking patterns could be an important new screening tool for Alzheimer’s in individuals with Down syndrome

[uw-reusable-content id=’29797′] At A Glance

• Individuals with Down syndrome have a 90% lifetime risk of developing Alzheimer’s disease.
• Gait impairments occur as part of Alzheimer’s disease in the general population.
• Individuals with Down syndrome also experience gait changes during Alzheimer’s disease progression.
• Gait changes present an important opportunity to develop inexpensive and time-efficient screening tools for Alzheimer’s in Down syndrome.
• Changes in gait may give caregivers important indicators that it is time to seek the attention of a clinician.

Changes in a person’s gait, a broad term that refers generally to how a person walks and moves about, may be an early indicator of Alzheimer’s disease in individuals with Down syndrome, a new longitudinal study shows. These results, published in the journal Alzheimer’s and Dementia, by the lab of Waisman investigator Sigan Hartley, PhD, UW-Madison professor of human development and family studies and 100 Women Distinguished Chair in Human Ecology, open the possibility of using gait as an inexpensive and time-efficient screening tool for the development of Alzheimer’s disease in Down syndrome. Down syndrome, also called Trisomy 21, is a genetic condition resulting from a third and extra copy of the 21^st chromosome. Typically, individuals with Down syndrome experience intellectual disability, developmental delays, and are at-risk for various medical conditions including Alzheimer’s disease (AD). Individuals with Down Syndrome have a 90% lifetime risk of developing AD, which is thought to be primarily driven by the triplicated 21^st chromosome. Given this high risk, there has been an uptick in research on how to screen for early symptoms of the disease in people with Down syndrome. “Over the past 20 or so years, research has found an association between changes in gait – things like shuffling when walking – and Alzheimer’s disease in the general population,” says Ashlyn Barry, graduate student in Hartley’s lab and first author on the paper. “We were really interested to see if gait impairments were also part of Alzheimer’s disease symptoms in people with Down syndrome.” In the general population, gait often begins to deteriorate early on in Alzheimer’s disease and then worsens over time. Hartley and Barry set out to determine if this held true in the Down syndrome community. Across the span of 32 months, Barry and Hartley measured changes in gait alongside several markers of AD development in 218 adults with Down syndrome. The participants are all part of the Alzheimer Biomarkers Consortium – Down Syndrome (ABC-DS) which is a large multisite research initiative that is funded by the National Institutes of Health (NIH) and focused on finding biomarkers of pathology related to AD in people with Down syndrome with the goal of informing screening practices and interventions. At UW-Madison, ABC-DS is run by Hartley and Waisman investigator Brad Christian, PhD, professor of medical physics and psychiatry. Barry and Hartley found consistent patterns of gait impairment as AD markers changed. Increases in the number of plaques in the brain, changes in brain volume, general cognitive decline, and clinical AD status were all associated with worse gait performance over time. Additionally, they observed that changes in gait could often be seen before the onset of observable changes in AD symptoms.

“This information can help us say, hey, if you start seeing change in how someone walks – more shuffling, uneven stride lengths, swaying – it might be time to get screened for AD.” -Ashlyn Barry, graduate student

Establishing changes with gait as part of AD in individuals with Down syndrome can open the door for developing inexpensive and less time-intensive screening tools. “This is very important from a clinical standpoint because typical screening tools for Alzheimer’s disease symptoms generally include lengthy cognitive testing. This is costly and takes a lot of time and requires experts,” Barry says. “However, if instead, we could ask about problems in gait or do quick observations of gait, it has the potential to be a cost-effective and time-effective screening tool.” Understanding the relationship between gait changes and AD development can also give clinicians and researchers another tool to help empower families with. “This information can help us say, ‘Hey, if you start seeing change in how someone walks – more shuffling, uneven stride lengths, swaying – it might be time to get screened for AD,” Barry says. Having visible signs of early dementia can be especially important for individuals with Down syndrome that may have limited verbal skills. “Many of our cognitive tests are not great for individuals with Down syndrome who have limited speech,” Barry says. “So, establishing valid tools of observable functional declines is important for ensuring we can screen for AD in the broad population of individuals with Down syndrome who greatly vary in their cognitive and verbal abilities.” This study has already opened doors to further questions for Barry and Hartley about gait and AD in Down syndrome. “This paper was our first step in understanding how gait changes in AD,” Barry says. “We now want to delve deeper to better understand these changes. Is it trunk sway or step cadence or something else that changes first?” They are both also interested understanding the potential for exercise and physical activity to protect against gait changes. “We hope that long term,” Barry says, “our work with AD in Down syndrome can lead to better screening tools of AD, inform safety planning, and inform AD prevention efforts for individuals with Down syndrome.” [uw-reusable-content id=’21214′]