Exercise Targeting Cognitive Impairment in Parkinson's Disease

Not Applicable

• Conditions: Parkinson's Disease
• Interventions: Other: Aerobic Exercise; Other: Social Contact; Other: Skill-Based Exercise

• Registration Number: NCT02267785
• Lead Sponsor: University of Southern California

Brief Summary

The aim of this application is to compare and elucidate the effects of skill-based versus aerobic exercise versus control on mild cognitive impairment (MCI) of the executive function (EF) subtype in Parkinson's disease (PD); we hypothesize that skill-based exercise will result in the greatest improvement in EF and lead to modification of underlying neural substrates.

Detailed Description

Mild cognitive impairment (MCI), particularly of the executive function (EF) subtype, is common in Parkinson's disease (PD) and transitions to dementia, increased fall risk, and poor quality of life. EF is a set of processes that include mental flexibility and attention that are needed to learn and optimize performance of complex cognitive and motor skills. Such skills include the ability to generalize task performance under different conditions (context processing) and to perform two tasks simultaneously termed dual-task (DT) performance. Deficits in EF lead to problems in daily functioning and loss of independence and create psychosocial and economic burdens on patients and caregivers and stakeholders including health care providers. There is currently no effective treatment in PD to address EF deficits. Our animal and clinical studies in PD demonstrate that skilled exercise facilitates neuroplasticity of the basal ganglia (BG), a brain region sub-serving EF and supports the hypothesis that exercise will reverse EF deficits in PD. Furthermore, recent studies in healthy aging support that skill-based exercise that specifically promotes motor skill fitness (MSF), compared with aerobic exercise that promotes cardiovascular fitness (CF), has a greater impact on EF and related BG circuits. The aim of this application is to compare and elucidate the effects of skill-based versus aerobic exercise versus control on MCI of the EF subtype in PD; we hypothesize that skill-based exercise will result in the greatest improvement in EF and lead to modification of underlying neural substrates.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2014-10-14
• Study First Submitted QC: 2014-10-14
• Study First Posted: 2014-10-17
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-30
• Last Update Posted: 2019-05-31
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• willing and able to provide informed consent
• confirmed diagnosis of idiopathic PD based on the United Kingdom Brain Bank criteria
• Mild cognitive impairment (Level II criteria Movement Disorder Task Force)
• medically eligible for MRI imaging
• able to provide a written medical clearance from their primary physician to participate in exercise
• stable PD medications for 3 months

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Exclusion Criteria

• a Hoehn & Yahr staging greater than 2.5 at screening
• severe cardiac disease (New York Heart Association classification IIIV)
• history of an abnormal stress test
• clinically significant medical or psychiatric illness
• electrically, magnetically, or mechanically activated implant (such as cardiac pacemakers or intracerebral vascular clip)
• metal in any part of the body including metal injury to the eye
• past history of brain lesions (such as stroke)
• seizures or unexplained spells of loss of consciousness
• family history of epilepsy
• physical therapy within 6 months of the study
• symptomatic orthostatic hypotension at the screening visit
• orthopedic and other movement-influencing diseases such as arthritis or total hip joint replacement
• requirement for central nervous system active therapies (e.g. hypnotics, antidepressants, anxiolytics)
• moderate or severe depression or apathy using the Geriatric depression scale and Apathy scale
• taking anticholinesterase inhibitors
• taking anticholinergic medication
• PD dementia
• Colorblindness

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerobic Exercise	Aerobic Exercise	Participants assigned to this arm will complete the Aerobic Exercise Intervention
Social Contact Group	Social Contact	Participants assigned to this arm will complete the Social Contact Intervention
Skill-Based Exercise	Skill-Based Exercise	Participants assigned to this arm will complete the Skill-Based Exercise Intervention

Primary Outcome Measures

Name	Time	Method
Change in Context Dependent Motor Learning (CDML)	at Baseline, after 12 week intervention, and at 12 week follow up visit	All subjects from each group will undergo a finger sequence motor learning task to determine exercise effects on EF as evaluated through improvement in the transfer of a learned motor task from one contextual setting to another.
Change in Tower of London Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Tower of London test will be used to evaluate executive function
Change in Wisconsin Card Sorting Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Wisconsin Card Sorting test will be used to evaluate executive function
Change in Dual Task Performance and Functional Magnetic Resonance Imaging (fMRI)	at Baseline, after 12 week intervention	A subset of subjects (60 representing 20 per group) will be invited to undergo fMRI studies at University of California, Los Angeles. Patients will perform a learned single finger-sequencing task (a condition of the CDML) with an additional secondary dual task (DT) component during an fMRI scan.
Change in D-KEFS Verbal Fluency Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The D-KEFS Verbal Fluency test will be used to evaluate executive function

Secondary Outcome Measures

Name	Time	Method
Change in Exercise Control Beliefs (BEL)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The BEL, 6-item scale was developed to assess beliefs about control over exercise behavior.
Change in Geriatric Anxiety Inventory	at Baseline, after 12 week intervention, and at 12 week follow up visit
Change in Parkinson Disease Questionnaire-39 (PDQ-39)	at Baseline, after 12 week intervention, and at 12 week follow up visit	Parkinson Disease Questionnaire-39 (PDQ-39) will be used to indicate overall quality of life and frequency with which patients experience difficulties; high scores for the PDQ-39 reflect poorer quality of life.
Change in Activity Specific Balance Confidence (ABC) Scale	at Baseline, after 12 week intervention, and at 12 week follow up visit	Activity Specific Balance Confidence (ABC) Scale is a 16-item self-report in which patients rate their balance confidence in performing several activities; high scores indicate greater balance confidence.
Change in Confidence in ability to maintain an exercise program (CONF)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The CONF scale includes nine items, which assesses how sure subjects are that they would do exercise under different conditions or constraints, including when they are tired.
Change in Self-efficacy for Exercise Scale (EFFIC)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The EFFIC scale is a self-efficacy barriers to exercise measure, a 13-item instrument that focuses on self-efficacy expectations related to the ability to continue exercising in the face of barriers to exercise.
Change in Body Mass Index	at Baseline, after 12 week intervention, and at 12 week follow up visit
Change in Body Fat Percentage	at Baseline, after 12 week intervention, and at 12 week follow up visit
Change in Adaptive Digit Ordering Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Adaptive Digit Ordering Test will be used to evaluate attention and working memory
Change in Apathy Scale	at Baseline, after 12 week intervention, and at 12 week follow up visit
Change in Hooper Visual Organization Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Hooper Visual Organization Test will be used to evaluate visuospatial function
Change in Benton's Judgment of Line Orientation	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Benton's Judgment of Line Orientation test will be used to evaluate visuospatial function
Change in California Verbal Learning Test- 2nd Edition (CVLT-II)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The CVLT-II will be used to evaluate memory function
Change in WAIS-IV Similarities Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The WAIS-IV Similarities test will be used to evaluate language function
Change in Evaluation of PD Motor Symptoms with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The MDS-UPDRS is the established gold standard that is currently used for the vast majority of clinical settings and for scientific trials. This scale was developed in 1987 and is the most widely used tool in PD.
Change in Frontal Systems Behavior Scale (FrSBe)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The FrSBe assesses changes in behavior dysfunction and disturbances associated with frontal-subcortical damage, which is the circuitry involved with executive functioning
Change in Motor Skill Fitness	at Baseline, after 12 week intervention, and at 12 week follow up visit	An individual's Motor skill fitness will be a composite score of their Physical Performance Test (PPT) and their Timed Up and Go (TUG).
Change in Cardiovascular Fitness	at Baseline, after 12 week intervention, and at 12 week follow up visit	Subjects will participate in testing designed to determine their level of cardiovascular fitness by estimating maximal oxygen uptake (V02max) known as the Balke treadmill submaximal fitness test and has been optimized for use in samples of elderly adults.
Change in Lifetime Total Physical Activity Questionnaire (LTPAQ)	at Baseline	The LPAQ measures the time spent in physical activity over the lifetime of the subject
Change in Global Physical Activity Questionnaire (GPAQ)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The GPAQ measures the time spent in physical activity during a normal week
Change in D-KEFS Color Word Interference Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The D-KEFS Color Word Interference Test will be used to evaluate attention, working memory and executive function
Change in Mattis Dementia Rating Scale	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Mattis Dementia Rating Scale will be used to differentiate between study subjects with mild cognitive impairment and dementia
Change in Geriatric Depression Scale	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Geriatric Depression Scale will be used to evaluate study subjects for depression
Change in Revised Activities of Daily Living Scale	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Revised Activities of Daily Living Scale will be used to evaluate independent living skills
Change in the Frontal Systems Behavior Scale (FrSBe)	at Baseline, after 12 week intervention, and at 12 week follow up visit	The FrSBe will be used to evaluate frontal systems behavior
Change in Boston Naming Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The Boston Naming Test will be used to evaluate language function
Change in WMS-II Visual Reproduction Test	at Baseline, after 12 week intervention, and at 12 week follow up visit	The WMS-II Visual Reproduction Test will be used to evaluate memory function

Trial Locations

Locations (1)

University of Southern California; 🇺🇸 Los Angeles, California, United States