Investigating Exercise-Induced Neuroplasticity and Its Mechanisms in Parkinson s Disease: Targeting Executive Function and Brain Circuitry
Abstract
Background and Rationale: Parkinson s disease (PD) is a chronic progressive degenerative brain disorder that disrupts connections in the brain responsible for normal cognition (thinking) and movement (walking and balance). In PD, thinking problems are common and often involve aspects of executive function that are important for processing information and flexibility (adapting behaviors to new situations), as well as planning and working memory. Thinking problems worsen over time and cause significant disability. Currently, there are no effective treatments for thinking problems in PD. Studies in the field of aging suggest that regular exercise may hold great promise for improving executive function in PD by enhancing neuroplasticity, which is defined as the ability of the brain to modify and improve brain connections lost in disorders, such as PD. Understanding how exercise helps neuroplasticity may provide important insight towards new treatments and may slow disease progression. Objectives/Study Question: For this study we will examine three aspects of exercise shown to be beneficial in thinking problems related to aging and how they may work to facilitate neuroplasticity and improve executive function and brain connections in PD. Aims: Studies in this application will look at several parameters of exercise including: (i) intensity, (ii) level of cardiovascular and motor fitness and (ii) exercise type (skilled vs. aerobic) and their impact on executive function and neuroplasticity. The first two questions will be examined in individuals with PD, and the last question will be addressed in an animal model of PD. First, we will examine whether strenuous exercise (exercise intensity), improves executive function and brain connections. Second, we will examine whether the level of fitness an individual gains through exercise is associated with improvement in thinking and brain connections. Studies in the aging field have suggested that motor fitness (agility, speed, and coordination) more than cardiovascular fitness (ability to transport and use oxygen) promotes improvement in executive function. Our clinical study will be complemented by an exercise study in a rodent model of PD where we will directly tease apart the specific benefits of skilled exercise vs. aerobic exercise using two different customized motorized running wheels. We will examine the benefits of these different forms of exercise on thinking, blood flow, and changes in genes and proteins that strengthen connections between brain regions. In these animal studies we predict that we will see significant changes in brain regions responsible for executive function called the prefrontal cerebral cortex that project to regions of the brain, including the basal ganglia, which will lead to improved behavior. Taken together, these studies will examine whether strenuous exercise, motor fitness, and skilled exercise will lead to a lower decline in executive function over time than non-strenuous exercise, cardiovascular fitness, and aerobic exercise, respectively. Study Approach: Studies have shown the benefits of a short course of exercise intervention on motor performance, such as walking and balance in PD. However, there are no studies that have examined the long-term effects of exercise on executive function. For this study we will utilize a naturalistic, observational approach to monitor exercise intensity and fitness levels of individuals with PD over an 18-month period and evaluate changes in thinking using brain imaging. In order to determine the biggest impact of exercise effects on thinking we will be enrolling patients who can walk independently and do not have dementia. Exercise intensity and fitness measurements will be evaluated regularly throughout the study using self-report exercise logs and wearing a portable device that monitors activity. The clinical study will be complemented by an exercise study in a rodent model of PD where we will directly tea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810666
Entities
People
- Daniel P Holschneider
Organizations
- United States Army
- University of Southern California