Exercise and Neuroprotection in Human Parkinson’s: The Long and Winding Road

“It is exercise alone that supports the spirits, and keeps the mind in vigor.” Marcus Tullius Cicero

“Lack of activity destroys the good condition of every human being.” Plato

Introduction: I have been convinced for a while that exercise is medicine. This blog post summarizes two publications:

Crotty, Grace F., and Michael A. Schwarzschild. “Chasing protection in Parkinson’s disease: does exercise reduce risk and progression?.” Frontiers in Aging Neuroscience 12 (2020): 186. https://doi.org/10.3389/fnagi.2020.00186

Johansson, Martin E., Ian GM Cameron, Nicolien M. Van der Kolk, Nienke M. de Vries, Eva Klimars, Ivan Toni, Bastiaan R. Bloem, and Rick C. Helmich. “Aerobic Exercise Alters Brain Function and Structure in Parkinson’s Disease: A Randomized Controlled Trial.” Annals of Neurology 91, no. 2 (2022): 203-216. https://doi.org/10.1002/ana.26291

“I don’t care how old I live! I just want to be living while I am living!” Jack LaLanne

PART 1- Reviewing the Review Paper on Exercise and Parkinson’s:
Crotty and Schwarzschild (2020) is an excellent overview of the field that begins with the difference between exercise and physical activity and nicely follows the history of exercise and Parkinson’s. Next, the paper focuses on the epidemiological evidence that exercise can be a disease modifier and reviews the randomized controlled trials of exercise and Parkinson’s.

“Good things come to those who initiate.” Susan RoAne

Randomized Control Trials (RCTs) of Parkinson’s and Exercise: One noteworthy section is devoted to reviewing previous RCTs comparing the impact of exercise on the progression of Parkinson’s. After reading this section a few times, it is clear that many RCTs have been performed. Still, they are difficult to compare due to variability in study design, the actual type of exercise used, the patient selection process, and outcome measurement. Nevertheless, much positive evidence has been published reinforcing the positive benefit of exercise for Parkinson’s symptoms and quality of life. It also seems evident that the more intense the aerobic exercise routine, the better the benefit to the person-with-Parkinson’s (PwP).

The comments about dysautonomia seemed especially relevant. Unfortunately, Parkinson’s alters the autonomic nervous system, which regulates our bodies’ cardiovascular, gastrointestinal, genitourinary, and thermoregulatory functions. There has only been a single RCT performed in studying the autonomic nervous system in Parkinson’s, where cardiac autonomic functionality was studied. I agree with the authors that more studies on how exercise could positively regulate the autonomic nervous system in Parkinson’s are clearly in need of further research.

“It’s not what you do some of the time that counts, it’s what you do all of the time that counts.” Jack LaLanne

Concluding Thoughts: Crotty and Schwarzschild close “Chasing Protection in Parkinson’s Disease: Does Exercise Reduce Risk and Progression?” with the following comments: “There is increased recognition of the potential for long-term benefits of exercise in individuals with PD. In this review article, we summarized the supportive epidemiological, basic science, and randomized control trial data on exercise in PD. However, many outstanding questions remain, including whether exercise is truly neuroprotective and disease-modifying versus symptomatically but reversibly beneficial, and if so, what exercise should we recommend. Rigorously designed, large-scale studies are warranted….”

The authors nicely balanced the paper, including papers that were not statistically different between exercise and control groups. Instead of being an exhaustive review, they tend to stress more recent studies. This is also a well-written and thoughtfully organized paper. In the exercise and Parkinson’s field reviews, Crotty and Schwarzschild (2020) rank with a few other favorite papers* of mine (these are llsted at the bottom of the blog post).

“Most people, when they reach a certain age, let down and talk about what they used to do. Well, who gives a damn about what you used to do? It’s what you’re doing now.” Jack LaLanne

PART 2- Reviewing How Aerobic Exercise Alters Brain Structure and Function in Parkinson’s:
Clearly, from the work discussed above, there is substantial evidence of the benefit of aerobic exercise for improving motor symptom progression in Parkinson’s. This publication by Johansson et al. (2022) studied the impact of aerobic exercise on the structure and function of the brain of PwP. It combines exercise physiology with Resting-State Functional Magnetic Resonance Imaging (MRI). And their results were both educational and exciting. Pretend you are Alice in Wonderland and “falling down the rabbit hole.”

“If you’re not doing what is best for your body, you are the one who lose.” Julius Erving

The Parkinson’s Brain: The brain, on a functional level, is amazing due to its breadth of actions, including thoughts and decisions; memories and emotions; movements (motor function), balance and coordination; perception of various sensations, including pain; automatic behavior such as breathing, heart rate, sleep, and temperature control; regulation of organ function; and speech and language functions. The brain structurally is more complex than given that the brain is composed of the cerebrum, cerebellum, and brainstem. Nerve tissue, nerve cells, and the like are interconnected, and action in one part of the brain likely influences other parts of the brain.

Parkinson’s is due to a progressive reduction of dopaminergic neuronal cells in the substantia nigra, which depletes dopamine in the striatum. Early in the progression of Parkinson’s, the posterior putamen is most affected by dopamine depletion; however, the anterior putamen is spared any difficulty. The brain reacts to this change by altering the corticostriatal connection to use more of the anterior putamen, and this change is referred to as adaptive neuroplasticity. One aspect of this study addressed whether aerobic exercise could prevent disorder progression by enhancing (or sustaining) this adaptive neuroplasticity. Another aspect of this work was directly focused on the influence of aerobic exercise on the substantia nigra. The final part of this study focused on the impact of aerobic exercise on cognition.

“Better to wear out than rust out.” Jack LaLanne

Dopamine and the Basal Ganglia: The nuclei of the basal ganglia are involved in motor control and contribute to motor learning, executive functions, behavior, and emotions:
•The basal ganglia contain input, output, and intrinsic nuclei.
•Input nuclei receive information and include the caudate nucleus, putamen, and the accumbens nucleus.
•Output nuclei transmit information to the thalamus, consisting of the internal segment of the globus pallidus and the substantia nigra pars reticulata.
•Intrinsic nuclei relay information, including the external segment of the globus pallidus, subthalamic nucleus, and the substantia nigra pars compacta. The intrinsic nuclei are found between the input and output nuclei in the relay of information.
•The release of dopamine at the input nuclei allows the basal ganglia system to function. A simplified view of the basal ganglia is shown below.

“To give anything less than your best, is to sacrifice the gift.” Steve Prefontaine

Design and Results of the Aerobic Exercise Study:
•They recruited 57 participants from their earlier study, “Park-in-Shape” trials.
•The participants remained blinded to the study’s goal; they were told that the study would compare the effects of 2 home-based exercise programs.
•The actual program compared cycling on a stationary bike to stretching and relaxation exercises. They rode stationary bikes at home thrice weekly for 30-45 min over 6 months. They were asked to cycle to 50-80% of their heart rate reserve. It sounds like they followed a HIIT (High-intensity interval training)-type bike workout. The control group performed various stretching routines that were varied every 2-4 weeks to prevent loss of motivation.
•Resting-State Functional MRI was used to acquire images and quantify changes in the brain, especially the corticostriatal sensorimotor connectivity from the posterior to anterior
putamen. It is beyond my mind’s capacity to understand, let alone try to explain, the MRI study here.
•Effect of aerobic exercise, compared to stretching, resulted in a larger posterior-to-anterior shift in corticostriatal sensorimotor connectivity.
•The aerobic exercise group had significantly lower changes in global percentage-based volume compared to stretching alone. They found no effect of exercise to gray matter volume.
•The results of the behavioral study showed that the exercise group had improved (oculomotor) cognitive control compared to the stretching control group of PwP.

“The body achieves what the mind believes.” Jim Evans

Discussion or What Do Their Results Suggest? The hypothesis being tested here was would regular aerobic exercise be neuroprotective in Parkinson’s brain and whether exercise could positively affect cognitive function. They report that the exercise group resulted in a posterior to anterior shift in corticostriatal sensorimotor connectivity, which suggests that aerobic exercise promoted adaptive neuroplasticity. Next, they found that aerobic exercise reduced brain atrophy and measured global brain volume. Cognitive control was also improved by aerobic exercise. However, their study found no change in substantia nigra integrity or gray matter volume.

Their results indicate that aerobic exercise resulted in functional and structural neuroplasty focused on motor and cognitive brain networks in Parkinson’s. They also imply that aerobic exercise may benefit brain networks outside the motor region, which would be additional ‘icing on the cake’ for PwP. Their results suggest that aerobic exercise, using structural brain changes, stimulated protective and restorative forms of neuroplasticity in sensorimotor networks. 

The remaining part of the Discussion is a tour de force interpretation of their collective results. They go further by describing their results showing the effect of exercise in Parkinson’s on the corticostriatal sensorimotor network, brain atrophy, cognitive control, and the overall benefit of exercise and fitness on brain health and cognition.

“If you always put limit on everything you do, physical or anything else. It will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them.” Bruce Lee

Concluding Thoughts: Johansson et al. (2022) have provided convincing evidence that exercise is a medicine for treating Parkinson’s. Their results suggest that sustained aerobic exercise stabilizes motor progression and improves cognitive performance in PwP. Thus, aerobic exercise promotes functional and structural neuroplasticity in the corticostriatal sensorimotor and cognitive control networks. As Alice climbs out of the rabbit hole, leaves Wonderland, and returns to reality, the results validate aerobic exercise as an essential part of the arsenal for treating Parkinson’s.

“Because you are alive, everything is possible.” Thích Nhất Hạnh

The Long and Winding Road: “The Long and Winding Road” was the last number-one hit single for the Beatles (it was on their 1970 album, Let It Be). The song was released a month after the Beatles broke up. Paul McCartney wrote the song, but it is credited to Lennon-McCartney. McCartney said this about the song: “I was a bit flipped out and tripped out at that time. It’s a sad song because it’s all about the unattainable, the door you never quite reach. This is the road that you never get to the end of.” 

Relating to Parkinson’s, the long and winding road could be considered a metaphor for the journey and the life challenges ahead. Yes, the road ahead is long, but clues are being provided that can help improve the quality of life for PwP. And yes, include aerobic exercise to shorten the length of that long road. Exercise is a medicine for Parkinson’s.

Some Favorite Articles on Exercise and Parkinson’s*:
Hirsch, M. A., and B. G. Farley. “Exercise and neuroplasticity in persons living with Parkinson’s disease.” Eur J Phys Rehabil Med 45, no. 2 (2009): 215-29.

Speelman, Arlene D., Bart P. Van De Warrenburg, Marlies Van Nimwegen, Giselle M. Petzinger, Marten Munneke, and Bastiaan R. Bloem. “How might physical activity benefit patients with Parkinson disease?.” Nature Reviews Neurology 7, no. 9 (2011): 528-534.

Petzinger, Giselle M., Beth E. Fisher, Sarah McEwen, Jeff A. Beeler, John P. Walsh, and Michael W. Jakowec. “Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease.” The Lancet Neurology 12, no. 7 (2013): 716-726.

Ahlskog, J. Eric. “Aerobic exercise: evidence for a direct brain effect to slow parkinson disease progression.” In Mayo Clinic Proceedings, vol. 93, no. 3, pp. 360-372. Elsevier, 2018.

*Please note that there are 100s of reviews and publications on exercise and Parkinson’s that are probably just as convincing and valuable to someone else as these above are to me. The above just spoke a louder volume to me as I read them. I am sure if you sent me your own favorite Parkinson’s exercise reviews, I would find your list very relevant as well. The key to such studies and reviews is filling the gaps with new knowledge and information.

“Physical fitness takes commitment to exercise just as it requires good nutrition. But it doesn’t have to be painful. Just the opposite: Vigorous exercise actually is stimulating. It boosts your energy levels, invigorates your mind, and just feels good afterward. The hardest part, of course, is getting started.”Jack LaLanne

Cover Photo Image by bertvthul from Pixabay