Parkinson's disease (PD) is an age-related neurodegenerative disease that is characterized by the loss of dopamine-producing neurons in the substantia nigra, a basal ganglia sub-structure. This loss of dopamine functioning leads to the classic PD motor symptoms such as muscular rigidity, tremor, and slowed movements. However, individuals with PD also exhibit cognitive symptoms in the areas of memory, visuospatial ability, and executive function. Executive functions are a set of cognitive processes that include cognitive flexibility, inhibiting inappropriate and selecting appropriate actions, maintaining and manipulating information in working memory, and selectively attending to relevant information. Current medications primarily target the motor symptoms of PD, thus underscoring the need to develop treatments for the cognitive symptoms reported by PD patients. Aerobic exercise is a potent method to treat cognition in neurologically healthy older adults. Fortunately, the strongest effects of aerobic exercise are seen in the same cognitive symptoms seen in PD patients (i.e., executive function). The primary aim of this proposal is to determine the feasibility of recruiting, enrolling, and maintaining adherence in a 12-week aerobic exercise intervention in individuals diagnosed with PD. Further sub-aims include examining whether 12 weeks of exercise in PD patients can 1) improve cognitive function and 2) enhance functional connectivity in brain networks that are affected by PD. This study will enroll 30 participants with mild to moderate PD and randomly assign them to either an aerobic exercise (treadmill walking or cycling) or non-aerobic stretching exercise group. Both exercise groups will receive 1 hour of instruction in a small group setting (3-4 people), 3 times per week for 12 weeks. Cognitive ability will be assessed using the Wisconsin Card Sorting Test to measure selective attention and set-shifting and a task- switching paradigm to measure cognitive flexibility. Functional connectivity will be measured using resting state functional magnetic resonance imaging. Functional correlations between sub-regions in the basal ganglia and thalamus with the prefrontal cortex will be assessed in relation to participation in 12 weeks of exercise. Assessments of cognitive ability, physical function, and neural functional connectivity will be collected prior to and immediately following the exercise intervention. Detailed records of compliance will be kept to determine adherence to the exercise protocol. The proposed study will bridge research and practice in a multidisciplinary fashion by gathering information about recruitment and adherence in an exercise intervention, cognitive function, brain connectivity, and quality of life for individuals diagnosed with PD.

Public Health Relevance

Parkinson's disease (PD) is neurodegenerative disease that is the 14th leading cause of death in the United States. PD symptoms are primarily motor problems such as resting tremor and slowed movements, but individuals with PD also suffer from cognitive problems that are not effectively treated by current medications. This study investigates whether 12-weeks of physical exercise is a feasible approach to improve cognitive and brain health in people with PD, with the ultimate goal of improving overall quality-of-life.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Sieber, Beth-Anne
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University of Pittsburgh
Schools of Arts and Sciences
United States
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Nagamatsu, Lindsay S; Weinstein, Andrea M; Erickson, Kirk I et al. (2016) Exercise Mode Moderates the Relationship Between Mobility and Basal Ganglia Volume in Healthy Older Adults. J Am Geriatr Soc 64:102-8
Erickson, Kirk I; Leckie, Regina L; Weinstein, Andrea M et al. (2015) Education mitigates age-related decline in N-Acetylaspartate levels. Brain Behav 5:e00311