Locomotion adaptation deficits in older adults with mild cognitive impairment and Alzheimers disease

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PROJECT ABSTRACT Community walking function requires complex motor coordination, sensory feedback, dynamic balance, adaptation to changing environmental stimuli, while also attending to tasks such as crossing a street or talking over the phone. Unfortunately, cognitive dysfunction, the hallmark of mild cognitive impairments (MCI) and Alzheimer’s Disease (AD), directly impacts the cognitive-motor neural resources available to carry out such activities of daily living. The rigor of previous research shows that compared to healthy older adults (HOA), people with MCI and AD walk slower, fall more, and have deficits in gait performance. Notably, gait disturbances and changes in gait variability often precede cognitive decline. Thus, our overall goal is to understand the effects of MCI and AD on gait function and locomotor flexibility, and the inter-relationships with cognitive impairments. Locomotor adaptation is a fundamentally important process that enables humans to flexibility respond to environmental demands, enabling normal community walking function. Split-belt walking is a standardized, robust, well studied paradigm for quantifying capacity for locomotor adaptation, with potential implications for walking function and fall prevention. Despite a large body of literature on split-belt adaptation in individuals of multiple ages and neuro-pathologies, surprisingly, split-belt adaptation has not been assessed in MCI and AD. A previous study showed reduction in the rate of split-belt adaptation when able-bodied participants were distracted by a cognitive task, suggesting that adaptation processes interact with cognitive functions. Another study showed multiple sessions of split-belt walking improved mobility outcomes post- stroke, suggesting its potential as an exercise intervention. However, there is a knowledge gap regarding if and how split-belt adaptation relates to cognitive deficits and walking function in individuals with MCI and AD. The current R21 will build upon MPI Kesar and Nocera’s new published study that provides the first preliminary evidence that split-belt adaptation is significantly impaired in people with MCI and AD compared to HOA. Our premise is that in people with MCI and AD, reduced capacity for locomotor adaptation is a fundamental but poorly understood mechanism that can be a sensitive biomarker of cognitive-motor impairments, and an important therapeutic target for exercise-based interventions. Here, we propose the first comparison of split- belt adaptation, in conjunction with comprehensive assessments of gait and cognitive function, in MCI, AD, and HOA. We propose a unique combination of cross-sectional between-group comparisons (Aim 1) and repeated- measures longitudinal time-point comparisons of disease progression (Aim 2). Aim 3 is a preliminary feasibility study to guide future clinical trials on split-belt aerobic walking exercise interventions in MCI and AD. Further, in parallel with locomotor adaptation (not previously studied), we will also evaluate walking function (gait speed, gait endurance, mobility outcomes), gait performance (step length, gait variability, stride time), and cognition in the same participant cohort, generating an innovative, rich, multi-modal dataset.