Locomotion Adaptation Deficits in Older Adults With Mild Cognitive Impairment and Alzheimers Disease

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).

Eligibility Criteria:
Inclusion Criteria:

* AD and MCI will be defined through formal diagnosis provided by a board-certified Neurologist. Amnestic MCI will be defined using the AD Neuroimaging Initiative (ADNI) criteria. All MCI participants in ADNI are required to have an amnestic subtype defined as:

  * Subjective memory concern or a memory problem noted by their partner
  * Abnormal memory function documented by a specified education adjusted cutoff score on the delayed paragraph recall of the Anna Thompson story of the Logical Memory subtest from the Wechsler Memory Scale-Revised
  * Mini-Mental State Exam (MMSE) score between 20 and 26 (inclusive). Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI. (iv) Single or multi-domain amnestic MCI (both subtypes are at high risk for progression to AD)
  * Clinical Dementia Rating (CDR) = 0.5 (Memory Box score must be at least 0.5)
  * General functional performance sufficiently preserved
* Evidence of impaired executive function based on Montreal Cognitive Assessment (MoCA) score 13-17
* Able to walk 10 or more feet without an assistive device
* Completed six grades of education or has a good work history (sufficient to exclude intellectual disabilities)
* Not hospitalized within the last 60 days

Exclusion Criteria:

* Acute medical illness requiring hospitalization
* Uncontrolled congestive heart failure
* History of stroke
* Inability to perform study procedures
* Medical or physical conditions that would preclude participation or walking (e.g., severe arthritis or mobility problems, uncontrolled hypertension or diabetes, renal failure, history of angina with activity)
* On medications that could adversely affect cognition, eg: antipsychotics, opioids, stimulants, chemotherapy, anti-parkinsonian drugs (eg Levodopa), neurologic prescriptions to treat Multiple sclerosis and/or Parkinson's
* Psychotic disorders
* Confounding neurologic conditions (e.g., active central nervous system (CNS) opportunistic infections, seizure disorders, head injury with loss of consciousness \>30 minutes, intracranial neoplasms, stroke with neurological or neuropsychiatric sequelae)
* Substance Use Disorder, Major Depressive and Generalized Anxiety Disorders within six months of evaluation