Does vigorous exercise have a neuroprotective effect in Parkinson’s Disease?

I’ve started this topic to collect references to studies that explore the neuroprotective benefits of vigorous exercise to slow the progression of Parkinson’s Disease.

Let’s start with a few quotes from the National Parkinson Foundation …

Research has shown that exercise can improve gait, balance, tremor, flexibility, grip strength and motor coordination.

There is a strong consensus among physicians and physical therapists that improved mobility decreases the risk of falls and some other complications of Parkinson’s.

Beyond this, we know that people who exercise vigorously, for example by doing things like running or riding a bicycle, have fewer changes in their brains caused by aging.

However, when it comes to exercise and PD, greater intensity equals greater benefits. Experts recommend that people with Parkinson’s, particularly young onset or those in the early stages, exercise with intensity for as long as possible as often as possible. Your doctor might recommend an hour a day three or four times a week, but most researchers think that the more you do, the more you benefit.

Scientists at University of Pittsburgh found that in animal models, exercise induces and increases the beneficial neurotrophic factors, particularly GDNF (glial-derived neurotrophic factor), which reduces the vulnerability of dopamine neurons to damage.

At the molecular level, at least two things are happening to make dopamine use more efficient:

1. Dopamine travels across a space between two adjacent brain cells called a synapse. This process is called signaling and it is essential for normal functioning. To end the signal, a protein complex called the dopamine transporter normally retrieves dopamine from the synapse. The first thing Fisher et al. found is that animals that had exercised possessed less of the dopamine transporter, meaning that dopamine stayed in their synapses longer, and their dopamine signals lasted longer.

2. Secondly, they found that the cells receiving the dopamine signal had more places for the dopamine to bind in animals that exercised, and so could receive a stronger signal. This binding site is called the D2 receptor.
They also studied the D2 receptor in a subset of the human subjects who were within one year of diagnosis and not on any medications, using the imaging technique known as positron emission tomography(PET). They found that in humans, too, exercise increased the number of D2 receptors.

The full article is at
http://www.parkinson.org/understanding-parkinsons/treatment/Exercise/Neuroprotective-Benefits-of-Exercise

The University of Pittsburgh study is at https://www.researchgate.net/profile/Richard_Smeyne/publication/258827563_Exercise_Is_it_a_neuroprotective_and_if_so_how_does_it_work/links/0f317537226ceb3e01000000.pdf

“Exercise and neuroplasticity in persons living with Parkinson’s disease” Mark A. Hirsch and Becky G. Farley in the European Journal of Physical and Rehabilitation Medicine (2009) provides more detailed references to back up the NPF recommendations. Read it at https://www.ncbi.nlm.nih.gov/pubmed/19532109

J. Eric Ahlskog of The Mayo Clinic provides an excellent review of exercise related clinical trials in “Does vigorous exercise have a neuroprotective effect in Parkinson disease?” which can be found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136051/

Several interesting quotes in that report:

“Vigorous exercise” may be variously defined, but for our purposes consider this to represent aerobic physical activity sufficient to increase heart rate and the need for oxygen. For this to be meaningful, it should be sustained (e.g., perhaps for at least 20–30 minutes at a time) and repeated/ongoing. Ultimately, such sustained and ongoing physical activity should translate into what physiologists term cardiovascular fitness, documented by relatively high oxygen uptake at peak exercise (VO2).
Cardiovascular fitness (measured by peak VO2) has been associated with better cognitive and motor scores in patients with PD.
Vigorous exercise improved corticomotor excitability in a PD cohort, suggesting potential neuroplasticity in one other investigation. (http://www.ncbi.nlm.nih.gov/pubmed/18534554)
This overall body of evidence suggests that vigorous exercise should be accorded a central place in our treatment of PD. … Second, clinicians must facilitate exercise by appropriately aggressive use of PD drugs. … A reasonable goal when prescribing PD medications is to maximize patients’ capabilities to engage in physical activities and potentially achieve the best level of physical fitness possible.

The report concludes with an interesting hypothesis:

Perhaps we have already seen evidence of the benefits of physical activity for PD in the mortality statistics published shortly after levodopa was introduced 4 decades ago. All 8 independent studies comparing longevity immediately before to just after levodopa availability documented substantially improved lifespans. Although this might reflect some neuroprotective effect of levodopa, per se, it is more likely reflective of mobilizing a generation of sedentary patients with PD. There may be a lesson in this early experience from the beginning of the levodopa era: mobilization and physical activity should not be underestimated in the treatment of PD.

While vigorous exercise appears to be neuroprotective, it appears to also be important not to forget resistance training and balance training. An interesting review titled “An Evidence-Based Exercise Regimen for Patients with Mild to Moderate Parkinson’s Disease” at http://www.mdpi.com/2076-3425/3/1/87/pdf recommends:

specific modalities of exercise such as cardiovascular training, resistance training, and balance training are able to relieve patients of debilitating motor and non-motor symptoms and allow for increased functional ability to complete ADLs. The most beneficial exercise regimen likely combines these three modes of exercise to reduce both motor and non-motor symptoms.

Utilizing the evidence available enumerated, we have formulated an exercise regimen tailored to treat the specific symptoms of PD:

(1) Cardiovascular exercise such as high intensity treadmill training or assisted cycling has been shown to reduce bradykinesia as well as improve gait function and ambulation [28–30]. Based on these data, and given the lack of evidence suggesting differences between various types of cardiovascular training, we recommend moderate to high intensity cardiovascular exercise in the form of treadmill training or assisted cycling for up to 30 min per session every other day.

(2) To increase muscle strength, we recommend moderate volume (3 sets each) high load resistance training 2–3 times per week. It has been suggested that this volume and modality may optimally increase muscle strength without causing excessive fatigue [75,79]. While both concentric contractions and eccentric contractions to will increase strength gains, we recommend an emphasis on eccentric movements to minimize metabolic demand.

(3) Balance training in the form of Tai Chi should be used to improve postural control and walking ability. A large-scale trial demonstrated that patients performing Tai Chi show improvements in maximum excursion and directional control that were not seen in balance training or strength training [51]. Given that patients can complete Tai Chi at home without the use of clinical equipment, coupled with the benefits to balance and postural control that were not observed with traditional balance training alone, we recommend Tai Chi for 1 h at least twice weekly.

While these recommendations are OK…I’d argue that a vigorous program that incorporates all 3 aspects is a better solution, although it may not be available locally to all PD patients.

I find it a little odd that Tai Chi is singled out, as there are certainly other valid balance training approaches. Balance training integrated with vigorous exercise is core to the Kickboxing For Parkinson’s class that I attend 4 times a week, and is a core part of the sessions with my personal trainer. In fact, let’s see how many times I can use the word core in the same paragraph. It may not be obvious to the non-exerciser, but core muscle exercises are not all about trying to develop a six-pack, long term they are about balance and stability.

Similarly, weight and resistance training are integrated into these vigorous exercise sessions. However, excessive fatigue is an issue, and it is a very good idea to also engage in moderate high load/resistance training sessions.

I suppose a similar argument could be made for low to moderate intensity balance and core training. I’ve never tried Tai Chi, so I may be missing something good.

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