Ask an Expert: Dr. Michael Jakowec Discusses the Powerful Benefits of Exercise for Parkinson’s

Dr. Michael Jakowec, PhD, is Associate Professor in the Department of Neurology at the University of Southern California. He focuses on how molecules and drugs affect the brain, especially in Parkinson's disease (PD). His lab uses different methods, like studying animal behavior, looking at structures in the brain, and working with cells, to understand how exercise and other treatments can change how the brain works in PD. Recently, his research has been looking at how energy in the brain and other cells besides nerve cells can help the brain heal itself. Alongside his research, he has been teaching undergraduate students about how drugs affect the brain for 20 years.

Why is exercise consistently regarded as one of the most effective non-medical interventions for individuals with Parkinson’s disease?

Our brains evolved to control our body's movements, from basic tasks like picking up objects to more complex challenges like longdistance navigation. Practicing these skills makes them automatic, allowing our consciousness to focus on other activities, such as socializing. To maintain our motor skills, we must continuously engage them, and that is what physical activity does for us. Exercise strengthens learned behaviours and facilitates the acquisition of new skills. A feature of the brain is that we lose connections if we do not use them, which is why the common term “use it or lose it” applies to maintaining proper brain function.

While we are gathering research evidence that exercise is one of the most important factors impacting the progression of Parkinson’s disease (PD), it is not the cure. There is evidence that the loss of dopamine in PD occurs years before motor symptoms become most evident. Is this a more effective period to prescribe interventions such as exercise and possibly neuroprotective compounds? The lack of a reliable biomarker to detect changes in the brain long before motor symptoms emerge is a major challenge for researchers.

In terms of treating Parkinson’s disease, exercise is now considered a component of the standard of care. Twenty years ago, when we began lab and clinical research to study the impact of exercise on the brain, exercise was not considered important. In fact, patients were told exercise could increase the risk of falls and injury and thus should be avoided. Now we know that everyone with PD should exercise, since it has tremendous impact on symptomatic progression and quality of life.

Can exercise prevent people from getting Parkinson’s or delay its onset, and if so, how?

Over decades, epidemiological studies in large populations across a lifespan have suggested that being physically active has tremendous benefits on delaying or reducing the onset of Parkinson’s disease and other brain disorders impacting cognition. One hypothesis about why exercise protects the brain and may alter disease progression is that physical activity over a lifespan can build resilience and generate reserve to resist brain disease and promote repair. Diet, stress, and a healthy gut microbiota may also contribute to strengthening brain health. Building resilience may delay the onset of Parkinson’s disease in some individuals, but there are many individuals who have high degrees of physical activity but still get the disease. We do not know why. The health of our brains is impacted by a combination of lifestyle, genetics, and environmental factors. Together these parameters highlight a complex series of interactions. However, research continues to support that lifestyle, especially exercise and diet, is critical to brain health and healthy aging.

It is never too late to embrace the benefits of exercise and healthy diet for individuals with Parkinson’s disease. Exercise shows benefits at any age and at any stage of the disorder. Diet and exercise can also can have tremendous benefits for PD symptoms.

Research shows that exercise does not make the brain produce more dopamine but does allow it to more effectively use what dopamine it already has. Can you please elaborate and explain why this is?

It was once assumed that exercise simply increases the amount of dopamine in the brain and that this leads to its benefits. This is not necessarily the case. In fact, our studies and the research of several other groups around the world have shown that exercise alters how the brain uses the remaining dopamine. Changes in the release of dopamine from existing neuronal fibers in the basal ganglia, along with changes in its uptake, result in an increase in the time dopamine spends in the synapse acting as a signal between neurons. In addition, we also observe increases in the expression of dopamine D2 receptors in the brain; these play a critical role in cognition, especially cognitive flexibility, as well as many other aspects of learning. Exercise appears to strengthen some of the molecular features necessary for thinking and cognition, all of which are central to our ability to move.

Can you speak to the difference between neurogenesis and neuroplasticity, and how they differ in the context of exercise and PD?

Neurogenesis refers to the birth of new neurons in the brain, whereas neuroplasticity refers to changes in the brain, mainly concerning the number and strength of connections between brain cells.

We know that exercise increases neurogenesis, as seen in the birth of new neurons. However, this does not appear to occur throughout the brain, but is limited to specific regions, such as the hippocampus, an area of the brain responsible for memory and learning. There is little evidence that neurogenesis is enhanced by exercise in other regions, such as the basal ganglia and frontal cortex, which are regions critical for motor and cognitive behaviours, and are also affected by Parkinson’s.

Interestingly, our studies reveal that exercise doesn’t boost overall brain blood flow, but is increased in specific regions involved in the exercise. For example, forms of exercise that engage a high degree of cognition and motor behaviours, such as pickleball, increase blood flow in these regions of the brain, especially the basal ganglia and frontal cortex. The result is an increase in the promotion of connections within these regions. In other words, exercise can be targeted to promote repair of specific brain regions.

Can you explain what synaptogenesis is, and how exercise promotes it? How does synaptogenesis help people with PD?

Synaptogenesis is a general term that describes changes in the connection between neurons, specifically at synapses, the primary physical connection that exists between neurons. The communication between neurons is made possible by neurotransmitters, such as dopamine. Exercise impacts the number and strength of these connections, as observed in both animal and human models of Parkinson’s disease, where we can see the loss of synaptic connections, especially in the basal ganglia (where movement is controlled) and in the frontal cortex (where cognition and thinking reside). Within these regions of the brain are morphological or structural changes with synaptic loss, and this loss of connections is reflected in the reduced number of dendritic spines, the site of communication between neurons. Importantly, we and others have shown that exercise can reverse this loss and increase the number of synapses, as well as the strength, between neurons.

Recent studies, including those from our lab, have begun to show that synaptogenesis involves more than just changes between neurons. In fact, astrocytes and microglia, nonneuronal glial cells that support and protect neurons, exhibit biochemical changes due to exercise, reversing deficits seen in disease. This is a new frontier in finding novel treatments for Parkinson’s disease.

How exercise increases brain-derived neurotrophic factor (BDNF), a chemical in the brain that is associated with cognitive improvement and neurogenesis, has been an exciting area of research for many years. How do increased levels of BDNF impact individuals with PD?

Decades ago, researchers showed that exercise increases the expression of neurotrophic factors, which are chemicals that feed and nurture neurons in the brain, including BDNF. While this is beneficial, the full molecular mechanism remains unclear. If proven helpful, we may need to discover and test new drugs that increase the expression of BDNF in humans, especially in those with Parkinson’s disease.

Studies in our lab have shown an interesting relationship between exercise and BDNF. Neurotrophic factors like BDNF were thought to repair the brain. However, the brain requires guidance, as it may not recognize its own impairment and can persist in responding to its current state, potentially leading to behavioural deficits. The benefits of BDNF and repair of the brain (through synaptogenesis, for example) are seen when the brain is undertaking new behaviours like exercise. In other words, the brain will establish new connections for motor behaviours when it is driven to do so, and exercise is one means to drive these beneficial changes.

Are there any potential risks to consider when prescribing exercise for people with Parkinson’s disease?

Any exercise, in any amount, of any type is beneficial, no matter how much or how intense. We do know that there are important parameters of exercise we try to achieve to get the most benefits. For example, studies in our group have shown that achieving 150 minutes per week of moderate to vigorous exercise leads to a high degree of benefit. A moderate level of exercise is achieved when you start to break a sweat and your ability to carry out a conversation with a partner is reduced, but not eliminated. This target of 150 minutes per week can be accomplished in very short bouts of exercise of less than 10 minutes. Another important parameter is intensity. Make your exercise as intense as possible.

What is the best form of exercise for people with PD who want to maintain or improve their cognitive function?

Studies from our group have highlighted some critical factors impacting the relationship between exercise and cognition. In simple terms, make your exercise a learning modality and make it intense. Try to learn a new skill. Pickleball and trail hiking are two popular means to achieve these goals. Additionally, one of the most important aspects of exercise and physical activity is the tremendous benefits of socializing, such as doing exercise with a partner or in a group. In fact, studies have shown that the social aspects of group exercise are as important as the exercise itself for brain health.

Anything else you would like to add?

We need to find a cure. While we are learning a great deal from studying the mechanisms by which exercise alters the brain in Parkinson’s disease, we have not yet stopped the disease from progressing, though exercise appears to alter disease progression. We need to know the cause of Parkinson’s disease, when it starts, and to develop biomarkers to detect and monitor disease progression.

We need to continue to better understand the role of lifestyle, especially the impact of diet, stress, immune, and gut on brain disorders like Parkinson’s disease. Diet is critical to enhance brain health, maintain the energetic state of the brain, and repair circuits compromised in motor and cognitive behaviours.

In the meantime, make exercise a central part of your daily routine.

This content was published in the Winter 2023 edition of our quarterly magazine, Viewpoints. The content was accurate as of this publication date.