In people with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD), reduced capacity for locomotor adaptation is a fundamental but poorly understood mechanism that can be a sensitive biomarker of cognitive-motor impairments. It is also an important therapeutic target for exercise-based interventions to improve walking function. The overall goal of this study is to understand the effects of MCI and AD on locomotor adaptation and walking function.
In conjunction with cognitive impairments, older adults with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) show increased impairments in walking function throughout disease progression. The ability to walk without the risk of falling is necessary for independent community activity and participation for elderly individuals. However, the relationships between cognition, gait dysfunction, and fall risk in people with MCI and AD are poorly understood, warranting further study. The objective of this study is to test the researchers' central hypothesis that in people with MCI and AD, decreased capacity for locomotor adaptation can worsen disease progression, and lead to reduced motor-cognitive function, mobility, and quality of life. Community-based walking function requires complex motor coordination, sensory feedback, dynamic balance, adaptation to changing environmental stimuli, while also engaging in attentional tasks such as crossing a busy street or talking over the phone. Unfortunately, cognitive dysfunction, the hallmark of MCI and AD, directly impacts the cognitive-motor neural resources needed to carry out activities of daily living. People with MCI and AD walk slower, fall more, and have deficits in gait performance variables such as stride symmetry, and step regularity. Importantly, gait disturbances have often been shown to precede cognitive decline. In this study, the researchers propose to test their hypothesis that a decline in locomotor adaptation capacity may explain gait and mobility deficits in people with MCI and AD. Locomotor adaptation is a fundamentally important process that enables humans to flexibility respond to environmental demands, enabling normal community walking function. Split-belt adaptation is a standardized, robust, well studied paradigm for quantifying a person's capacity for locomotor adaptation, but had not yet been evaluated in people with MCI and AD. Split-belt walking task assesses locomotor adaptation, i.e. the ability to adjust stepping movements to changing environmental demands via trial-and-error processing. The split-belt task is systematically assessed during treadmill walking, where the speed of each leg can be controlled independently such that one belt and the corresponding leg run at a different speed (e.g., twice as fast or a 2:1 speed ratio) than the other leg. In previous work, both the magnitude and rate of split-belt adaptation as well as de-adaptation (during the after-effect) have provided objective measures of an individual's locomotor adaptation capacity. The researchers of this study hypothesize that decreased capacity for split-belt adaptation may be an important contributing factor and a potentially sensitive indicator of increased fall risk and cognitive decline in older individuals with MCI and AD. The researchers will examine locomotor adaptation capacity with three study aims: Aims 1 and 2 are observational, assessing walking function among persons with MCI and AD and age-matched controls. In Aim 3, a clinical trial is performed to evaluate the feasibility of a split-belt walking intervention on walking function in older adults with MCI and AD. Ten participants (5 with MCI and 5 with AD) will complete 5 split-belt treadmill walking exercise sessions over a 2-week period. The primary and secondary outcome measures for this study are measured in evaluation sessions before (Pre-training) and after 5 training sessions (Post-training).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Participants will complete 5 sessions of split-belt treadmill-based locomotor adaptation. The split-belt instrumented treadmill allows the two belt speeds to be operated independently, enabling different belt speeds for each leg. The split-belt walking assessment will consist of 3 phases: baseline phase in which the belts operated at the same speed (Pre-tied, 2-minutes), a phase in which the belts operated at different speeds (Split-belt, 15-minutes), and a final phase in which the belts operated at the same speed (Post-tied, 4-minutes).
Emory Rehabilitation Hospital
Atlanta, Georgia, United States
RECRUITINGChange in Adaptation Magnitude Assessed as Peak Step Length Symmetry
Locomotor adaptation is the ability to adjust stepping movements to changing environmental demands via trial-and-error processing. Step length symmetry data from the split-belt phase will be used to evaluate each individual's locomotor adaptation magnitude capacity by assessing the peak step length symmetry in the early adaptation period.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Adaptation Rate Assessed as the Number of Steps to Reach Step Symmetry
The adaptation rate is assessed as the number of steps required to reach a plateau in step symmetry during late adaptation.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in 10-Meter Overground Walk Test
Gait speed is assessed with the 10-Meter Overground Walk Test. The 10-Meter Overground Walk Test is used to assess walking speed over a short distance. A 10 meter (m) walkway over solid flooring will be measured and marked at start (0 m), 2 m, 8 m, and finish (10 m). Participants will be asked to complete three trials of the 10 m walk at their comfortable self-selected walking speed. The time for the three trials for each speed will be averaged and gait speed converted to meters/second.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in 6-Minute Walk Test
Gait endurance is assessed with the 6-minute walk test. The 6-Minute Walk Test is a sub-maximal exercise test used to assess walking endurance. A walkway of a minimum 12 m over solid flooring will be measured and marked with a turn-around marked at either end of the walkway. The turn-around points will be approximately 49 inches (124 cm) wide with clear markings. A chair will be placed at one end of the walkway to allow for seated rest breaks if necessary. Prior to administering the test, the participant will be seated in the chair resting. The participant will then be asked to walk as far as possible in 6 minutes along the walkway using scripted instruction (see below). The distance (in meters) will be calculated by multiplying the number of total laps by 12 meters and adding the distance of the partial lap completed at the time the test ended.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Montreal Cognitive Assessment (MoCA) Score
MoCA is an instrument to screen for mild cognitive dysfunction, assessing the cognitive domains of attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total scores range from 0 to 30 with higher scores indicating better cognitive function. A normal score is considered to be 26 or higher.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in NIH-EXAMINER n-back Task Accuracy
The NIH-EXAMINER assesses spatial working memory with the n-back tasks. The 1-back involves maintaining and updating one location at a time while two locations at a time are maintained and updated with the 2-back. During the n-back tasks, participants view a series of stimuli and press a button when a particular stimulus has been previously shown. The 1-back consists of one block of 30 trials, ten of which match the location of the previous square, and 20 that are in a different location. The 2-back consists of one block of 90 trials, 30 of which match the location of the square two before, and 60 that are in a different location. The score is calculated as the percentage of correct responses.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in De-adaptation Magnitude Assessed as Peak Step Length Symmetry
Step length symmetry data from the split-belt phase will be used to evaluate each individual's locomotor de-adaptation magnitude capacity by assessing the peak step length symmetry after treadmill belt speeds return to normal.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in De-adaptation Rate Assessed as the Number of Steps to Reach Step Symmetry
The de-adaptation rate is assessed as the number of steps required to reach a plateau in step symmetry after treadmill belt speeds return to normal.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Timed Up and Go (TUG) Test
The Timed Up and Go test assesses mobility, balance, walking ability, and fall risk in older adults. The participant will be asked to be seated in a standard height chair (seat height 46 cm, arm height 67 cm), placing his/her back against the chair and resting his/her arms on the chair's arms. The participant will be asked to get up from the chair, walk to a line 3 m from the edge of the chair, turn around at the line, walk back to the chair, and sit down. The test will be timed using a stopwatch from when the investigator says "Go" to when the participant's buttocks touches the chair upon return. Time of the test will be recorded for single and dual-task conditions.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Falls History
Falls incidence and risk is assessed as self-reported history of falls.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Stride Duration
Gait performance is assessed as gait cycle duration, which is the time in milliseconds (ms) for the same foot to contact the floor in consecutive footsteps.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Double-support Duration
Gait performance is assessed as double-support duration. Double-support is the time when both feet are contacting the ground and it increases as walking speed decreases.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Executive Index Score (EIS)
Cognition is assessed with the Executive Index Score (EIS) which is based on performance on Trail-Making Test Part B, Clock Drawing, Digit Span, Letter A Tapping, Serial 7 Subtraction, Letter Fluency and Abstraction items. The EIS is calculated by adding raw scores for the included tasks. Total scores range from 0 to 13 and higher scores indicate better cognitive function.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Trail Making Test Part B Score
In Part A of the Trail Making Test (TMT) participants are presented with a sheet of paper with 25 circles numbered 1 through 25. Participants are asked to draw lines connecting the circles in ascending order of the numbers. The task is scored as the amount of time it takes in seconds for the circles to be correctly connected. The average time to complete the task is 29 seconds. Times greater than 78 seconds indicate cognitive impairment.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Step Length
Gait performance is assessed with step length. Step length is the distance between heel of one foot to the heel print of the other foot, measured in feet.
Time frame: Baseline (Pre-training), Week 2 (Post-training)
Change in Step Length Variability
Gait performance is assessed with the variability of step length.
Time frame: Baseline (Pre-training), Week 2 (Post-training)