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High-intensity exercise can reverse neurodegeneration in Parkinson's Disease

High-intensity exercise induces brain-protective effects that have the potential to not just slow down but possibly reverse the neurodegeneration associated with Parkinson's disease, a new pilot study suggests.

Prior research has shown that many forms of exercise are linked to improved symptoms of Parkinson's disease. But there has been no evidence that hitting the gym could create changes at the brain level. Now, a small proof-of-concept study involving 10 patients showed that high-intensity aerobic exercise preserved dopamine-producing neurons, the brain cells that are most vulnerable to destruction in patients with the disease.


In fact, after six months of exercise, the neurons actually had grown healthier and produced stronger dopamine signals. Dopamine is a chemical that helps brain cells communicate with one another.


"This is the first time imaging has been used to confirm that the biology of the brain in those suffering with Parkinson's disease is changed by intense exercise," says Evan D. Morris, Ph.D., professor of radiology and biomedical imaging at Yale School of Medicine and co-principal investigator of the paper.


What causes Parkinson's disease?

Parkinson's disease is a neurodegenerative disorder caused by the misfolding of alpha synuclein protein that is naturally present in our cells. The misfolded protein accumulates within neurons and damages them.


The dopamine-producing cells that are most affected reside in the part of the brain known as the substantia nigra, an area near the base of the brain. As these cells die off, the lack of dopamine creates the physical symptoms of the disease, particularly motor symptoms such as tremors and slowed movement. It's a gradual progression, and at the time of diagnosis, typically patients have already lost over half of their dopamine-producing neurons.


The most common available medication, levodopa, replaces the missing dopamine. While the drug is effective in alleviating motor symptoms, it does not prevent the ongoing neurodegeneration and can cause undesirable side effects with long-term use such as uncontrolled excessive movements [dyskinesia]. There is currently no cure for the disease.


Exercise plays a vital role in treating Parkinson's disease

Previously, two well-designed clinical trials have shown that engaging in high-intensity exercise—in which participants reach around 80% to 85% of their age-appropriate maximum heart rate—three times a week for six months is correlated with less severe motor symptoms. These trials suggested that exercise really is disease-modifying in a clinical sense.


High-intensity exercise reverses neurodegeneration

Following the six-month program, brain imaging showed a significant increase in both the neuromelanin and DAT signals in the substantia nigra. This suggests that high-intensity exercise not only slowed down the neurodegenerative process, but also helped the dopaminergic system grow healthier.

"Where we would have ordinarily expected to see a decline in the DAT and neuromelanin signals, we saw an increase," says Bart de Laat, Ph.D., associate professor adjunct in psychiatry and the study's first author. "We had hoped to see that the neurodegeneration would not progress as quickly or stop temporarily, but instead we saw an increase in 9 out of 10 people. That was remarkable."


The study highlights the importance of including an exercise regimen as part of one's Parkinson's treatment plan.

The medications we have available are only for symptomatic treatment. They do not change the disease course. But exercise seems to go one step beyond and protect the brain at the neuronal level.


While this is an exciting finding, additional research will be needed to fully understand the neuroprotective effects of exercise. Parkinson's disease is the fastest-growing neurological disease. By 2040, researchers estimate that over 12 million people worldwide will be living with the condition. The new study holds promise that exercise can help mitigate the enormous personal and economic costs the disease poses.


References:

Bart de Laat et al, Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson's disease, npj Parkinson's Disease (2024). DOI: 10.1038/s41531-024-00641-1

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