While the influence of peripheral motor and sensory function on mobility is well known, a relatively unexplored area is how subclinical central nervous system dysfunction in older adults affects mobility. Damage to frontal-subcortical (F-SC) white matter tracts, identified as white matter hyperintensities (WMH) on MRI, has been identified as one of the factors associated with mobility impairments in older adults. These pathways are an integral component of F-SC circuits that modulate motor output for postural tasks. The primary F-SC circuit associated with motor control is the skeletomotor circuit, which is responsible for selection and initiation of movement, and encoding of direction, velocity and duration of movement. Another F-SC circuit that may affect mobility and balance function is the dorsolateral-prefrontal circuit, which plays a major role in executive function processes, including selective attention. Importantly, elements of executive function are recognized for their role in balance control, especially in older adults. The goal of this research is to investigate the relationship between damage to F-SC white matter tracts and mobility dysfunction in more detail. Community-ambulating older adults aged 70-85 years across a wide spectrum of mobility impairment will be tested. The damage to white matter tracts will be quantified by applying automated algorithms to compute the volume of white matter hyperintensities and fractional anisotropy in specific fiber tracts important for motor control. Mobility impairment will be assessed using both experimental and clinical measures. The experimental protocols will use choice reaction step tasks to assess the function of the skeletomotor and dorsolateral-prefrontal F-SC circuits. The choice reaction step tasks require subjects to step as quickly as possible to one of two potential step locations based on a salient visual cue under conditions with and without executive function involvement. The primary response measure from these tests is the amount of time to initiate the step. To complement the experimental tests, subjects will undergo a clinical balance assessment that uses tests of varying complexity (e.g. Short Physical Performance Battery, Multiple Tasks Test). In addition, clinical tests of executive function will be performed. Multiple linear regression models will be used to relate the measures of tract-specific white matter damage to the experimental and clinical measures, while controlling for confounding variables such as age medication use, and peripheral sensory function.

Public Health Relevance

stural dysequilibrium in older adults can markedly affect function and quality of life and increases the risk of injury and death due to falls. The contribution of subclinical central nervous system disease to balance dysfunction and falls is less understood. This research will help to identify a potential pathologic cause (i.e. damage to white matter) that contributes to age-related mobility impairment, and help to identify an area that should be a target of future interventions for improving mobility in older adults.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Aging Systems and Geriatrics Study Section (ASG)
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Chen, Wen G
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University of Pittsburgh
Other Health Professions
Schools of Allied Health Profes
United States
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