Intense Exercise Helps Early Parkinson’s Patients Retain Motor Skills, Phase 2 Trial Shows

IN NEWS

High-intensity exercise is not only safe and feasible, but it can also delay disease progression in early stage Parkinson’s patients, results of a Phase 2 trial report.

The study, “Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease,” was published in the journal JAMA Neurology.

SPARX, or a Study in Parkinson Disease of Exercise (NCT01506479), was a Phase 2 multicenter trial led by researchers at the University of Colorado’s UC Health. It addressed if high-intensity exercise was safe for people in very early stages of the disease, and what physical intensity might be of most benefit to them.

It enrolled 128 people with early Parkinson’s disease, between 40 and 80 years old and diagnosed within five years. None were   taking any Parkinson’s medications.

Participants were randomly assigned to one of three groups — moderate exercise, vigorous exercise, or usual care — for six months.

Disease progression was assessed at the study’s start and again after six months using the Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Score: the higher the score, the greater a patient’s motor disability.

Exercise intensity was measured using heart rate monitors at all workout sessions.

People in the moderate group engaged in treadmill exercises four times a week, bringing their heart rate up to 60 to 65 percent of maximum capacity. Those in the vigorous group also exercised on a treadmill with the same frequently, but brought their heart rates to 80 to 85 percent of maximum.

At six months, the UPDRS score for the high-intensity exercise group had barely changed, indicating these patients’ motor skills did not worsen.

But these scores rose on average by 8 percent among patients in the moderate exercise group, and by 15 percent in those given usual care, indicating a worsening in movement and motor skills in these people. 

No serious side effects were reported in any group, and adverse events were considered “anticipated,” the researchers wrote, including falls, pain, muscle and joint disorders. 

These results show that high-intensity exercise can preserve movement abilities in early stage Parkinson’s patients and can do so safely if exercise programs are guided by specialists.

They also warrant further investigation in a Phase 3 trial evaluating more fully the benefits of regular high-intensity exercise in Parkinson’s patients, the team said.

“The study shows that neurologists can rest assured that it’s safe and feasible for their patients to exercise at a high intensity. That’s huge. We can get people started right away on exercise habits, when that is easier to do,” Margaret Schenkman, director of the Physical Therapy Program at the UC School of Medicine, and principal investigator for the SPARX study, said in a UC Health news release.

Previous studies have shown that exercise can help Parkinson’s patients maintain balance, mobility, and the ability to perform daily routines while preserving a better quality of life.

But studies to date have only tested moderate exercise programs, and most have not addressed whether exercise intensity might affect disease severity or its progression.

Research subjects needed: Aging and Parkinson's disease

We are recruiting older adults and people with Parkinson's disease into three active research protocols at UD.  The Exercise Neuroscience Lab does research related to functional longevity in people with Parkinson's disease and older adults.  

I supervise three wonderful graduate students in this laboratory.  Each of them is on schedule to defend their Thesis or Dissertation and graduate in the spring or early summer.  To say it is crunch time for them is an understatement. 

Each student has urgent needs to recruit subjects for single days of testing.  This would be one visit to the lab at the STAR campus and testing should take less than 2 hours.  You do not need to participate in the exercise program to be in this research.  

We are looking for people with PD who can walk without assistance (use of a cane is ok) and adults who are 55 years of age or older.   

If you can participate in the next month or two, you will be helping to ensure that these talented graduate students can successfully move onto the next phase of their training or careers and you will be making an important contribution to this science.

Two of our recruiting flyers are linked below.  If you contact Rebecca Daniels (details below) she will answer any of your questions and help determine whether you qualify for any of the ongoing studies.

Recruiting Flyer: Older adults

Recruiting Flyer: Parkinson's disease
  
Contact Rebecca Daniels at rdaniels@udel.edu or 978-885-0943 for more information.

This research is generously supported by Shake It Off, Inc. and if you live in the area, you should check out the Philly Rabbit Run on Saturday March 31, 2018.

Thank you,

Christopher A. Knight, PhD
University of Delaware

Running reversed MPTP-Parkinson's in mice.

Featured Paper: 
https://www.ncbi.nlm.nih.gov/pubmed/27816415

In the MPTP-mouse model of Parkinson's disease, eight weeks of running improved balance, reduced the amount of a bad protein in the brain, reduced neuroinflammation and slowed cell death.

Study	Neuropotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice. (Jang et al., 2017).
Research  model	Parkinson's disease mouse.  Mice were injected with a toxin called MPTP to cause Parkinson's disease.  Three groups of mice were studied: 1. no MPTP injection; 2. MPTP injection; 3. MPTP injection plus exercise.
Exercise	Endurance exercise (EE): Running five days per week for 1 hour for 8 weeks.
Findings	Eight weeks of EE restored motor performance.  alpaha-synuclein levels were suppressed to non PD levels. EE reversed PD neuro-inflammation which leads to cell death.
Action	Gradually add endurance exercise to your exercise program.   Shake it Off and Step Up.

Click the links throughout this post to learn more about some related topics.

What is MPTP?  In the late 1970s a young chemistry student was trying to make synthetic opioids for illicit use.  He accidentally made MPTP which causes permanent Parkinson's symptoms.  Currently, MPTP injected animals provide the best research model to study Parkinson's disease.

Mobility tests:  How do you test the motor ability of mice?  See this Rotarod test video.  The cellular and molecular measures in this paper are very interesting.  However, the story would have been less complete if the researchers did not also study motor function.  In this paper (Figure 1B) the Parkinson's mice that exercised for 8-weeks (ME group) stayed balanced on the rod just as long as the non-PD mice.  

What is alpha-Synuclein?  This is a protein that accumulates in excess in the Parkinson's brain. In this paper (see Figure 1D) this protein was restored to the normal levels in the Parkinson's mice who did 8-weeks of endurance exercise (ME).

Neuroinflammation is seen in multiple neurodegenerative diseases.  This is a link to a scientifically 'heavy' paper.  In the abstract, you will find a long list of neurodegenerative diseases that involve neuroinflammation.  The scientific progress we make with Parkinson's disease benefits other conditions like Alzheimer's disease and visa versa.   Neuroinflammation is part of the pathway to cell death or apoptosis.  In Figure 3F of our selected paper, the bar graph shows the normal amount of neuronal apoptotic cells in the PD mice that exercised.  The PD mice that did not exercise had about 300% more cells that were dying.

Exercise Prescription: Running for an hour, five times per week, for eight weeks might seem out of reach.  But you shouldn't ignore the amazing potential of some amount of endurance exercise in your life.  Five days of running was used in this study because it is a standard in this type of research. No information in this study suggests that five days of running is the minimal effective dose. You are likely to benefit even if you do less than this amount. We know for sure that you will not get these benefits if you don't exercise.  If you already do endurance exercise several days per week - fantastic!  Keep it up and be sure to also pursue other aspects of fitness like functional strength and balance.

Type: If running is not enjoyable or possible, consider other types of exercise like hiking, cycling, swimming or stationary exercise equipment (Ellipticals, rowing machines…). 

The First Step for Beginning Exercise

Historically, fast, high intensity or high power exercise strategies have not been recommended for older adults and patients.  These exercises have been avoided mainly to minimize cardiovascular and musculoskeletal risks.  We are beginning to understand the benefits of high power and high intensity exercise in various patient groups but we still need to apply such exercise strategies with caution.  In 2015, the American College of Sports Medicine (ACSM) updated its approach to Pre-Participation Health Screening to minimize the risks of exercise without creating unnecessary barriers to exercise participation.  Click here if you are interested in best-practices for screening.

Before you begin an exercise program, take a fitness test, or substantially increase your level of activity, make sure to answer the following questions. This physical activity readiness questionnaire (PAR-Q) will help determine if you’re ready to begin an exercise routine or program.

• Has your doctor ever said that you have a heart condition or that you should participate in physical activity only as recommended by a doctor?
• Do you feel pain in your chest during physical activity?
• In the past month, have you had chest pain when you were not doing physical activity?
• Do you lose your balance from dizziness? Do you ever lose consciousness?
• Do you have a bone or joint problem that could be made worse by a change in your physical activity?
• Is your doctor currently prescribing drugs for your blood pressure or a heart condition?
• Do you know of any reason you should not participate in physical activity?

If you answered yes to one or more questions, if you are over 40 years of age and have recently been inactive, or if you are concerned about your health, consult a physician before taking a fitness test or substantially increasing your physical activity. If you answered no to each question, then it’s likely that you can safely begin exercising, according to these guidelines provided by the ACSM.

What are the Side Effects of exercise?

Some people with PD have momentary drops in their blood pressure.  Be careful when you rise from the bike after exercise.  Take it slow.  Other than this, exercise sometimes comes with some reversible fatigue and some soreness.  If you keep taking this wonderful medicine called exercise, these side effects will likely diminish.  Then there are all the good side-effects of exercise: improved heart health, reduced depression and anxiety, improved bone health and more.  The side effects of exercise, if you want to think of them that way, are mostly good.

The Shake It Off Story

A parable is told of a farmer who owned an old mule. The mule fell into the farmer's well. The farmer heard the mule 'braying'. After carefully assessing the situation, the farmer sympathized with the mule, but decided that neither the mule nor the well was worth the trouble of saving. Instead, he called his neighbors together and enlisted them to help haul dirt to bury the old mule in the well and put him out of his misery. Initially, the old mule was hysterical! But as the farmer and his neighbors continued shoveling and the dirt hit the mule’s back, the mule shook the dirt off. Suddenly dawned on the mule that every time a shovel load of dirt landed on his back he should shake it off and step up on the dirt pile! This he did, blow after blow. "Shake it off and step up...shake it off and step up!" the mule repeated to encourage himself. No matter how painful the blows, or distressing the situation seemed the old mule fought "panic" and just kept right on SHAKING IT OFF AND STEPPING UP! It wasn't long before the old mule, battered and exhausted, stepped triumphantly over the wall of that well! What seemed like a situation that would bury him, actually blessed him...all because of the manner in which he handled his adversity. IT'S NOT WHAT HAPPENS TO US IN LIFE-IT'S HOW WE REACT TO WHAT HAPPENS TO US IN LIFE. "Taking care of my body today through exercise gives me hope for tomorrow." ~Jodi Cianci

Speed-Based Interval Training for PD

Featured Paper: https://www.ncbi.nlm.nih.gov/pubmed/28812404

This is our first post to the Shake It Off  blog where we will review scientific papers about exercise for people with Parkinson’s disease (PD). The research in this post was supported by ShakeIt Off and their generous friends.  If you ran in the Philly Rabbit Run on Easter weekend, or if you rode in the Shake Off theHills Challenge in the Fall, or if you donate time or money in other ways, you made this research possible. Thank you!  

This is also an exciting post to write because the research was conducted in my (CA Knight, PhD) research laboratory at the University of Delaware with two enjoyable colleagues who have since moved on to continue their scholarly work at other institutions.

Title	Effects of a low-resistance, interval bicycling intervention in Parkinson's Disease. Uygur M, Bellumori M, and Knight CA
Research model	Human: 14 volunteer subjects from local support groups.  Tested before and after 6-week exercise program.  Testing and exercise were performed while subjects were following their normal routines for symptom management (e.g. on medication).
Exercise	Speed-based interval training on a stationary bike.  Two 30-minute sessions per week for six weeks. See more at this link: SpeedGeezer Training
Findings	The exercise program was well-tolerated by all participants.  Significant improvements were observed in many variables: Fast pedaling cadence during exercise, the UPDRS-III score as well as the bradykinesia sub-score, timed tests of whole body mobility, reaction time and the nine-hole peg test.

What is SpeedGeezer?

You won’t find the word “SpeedGeezer” in the related paper but this is what we affectionately call the exercise program.  We originally designed SpeedGeezer to help older adults to fight age-related slowing.  For a related paper see: High-Speed CyclingIntervention Improves Rate-Dependent Mobility in Older Adults

While conducting the first studies, we became interested in Parkinson's disease (PD) and the symptom of bradykinesia (slow movement).  We wanted to learn how speed-based exercise could be used to improve the function of the nervous system in people with PD.  We also sought to provide scientific evidence to support an exercise approach that is practical and accessible  to this population.  These were some of our considerations in the design of SpeedGeezer:

1. Targeting people in the early stages of PD.  Good science requires focused work that is well-supported by the expertise of the research team.  Among people with PD, our intentional focus is on individuals who have good enough mobility and cognition to get to an exercise facility or exercise safely at home and perform their exercise without mechanical assistance (voluntarily).  Some of you might be familiar with devices such as the Theracycle which have motors to help you pedal. This type of equipment might be appropriate for people in later stages of disease progression.  Other exceptional research teams have demonstrated benefits of this active-assisted exercise in PD but our focus is on exercise that is not-assisted by the equipment.  Our present findings support the benefits of voluntary speed-based exercise. 
2. Training the Brain. Even though we chose bicycle exercise for this study, we believe that other fast movements will work too.  This exercise program uses fast bicycling with the legs in order to train the brain.  PD is a brain problem, not a legs problem.  During speedwork exercise, the brain has to deliver well-timed busts of electrical excitation to all the working muscles.    You can find more details on SpeedGeezer Training at this link, and substitute a different movement of your choice if necessary.  One former research participant used a treadmill to do the SpeedGeezer exercise routine at home.
3. Avoid Soreness in New Exercisers: Some people with PD are new to exercise or have not exercised in a long time.  Even among people who exercise regularly, fast or powerful movements are less commonly practiced.  This is why we insist on using the lowest (easiest) resistance settings on the bike.  Pedaling fast without resistance might seem awkward or annoying but it requires you to improve the smoothness of your pedaling motion.  If you find yourself 'shaking the bike apart' you should a) slow down, b) focus on smoothness and then c) try to speed up again.  Improving your coordination may provide other benefits through the processes of motor learning.  The exercise session might still seem challenging, but it is designed to minimize the risk of muscle soreness and joint pain.  When you graduate from SpeedGeezer, you can increase your pedaling resistance in a sensible progression. 
4. Minimize Fall Risk: A stationary recumbent bicycle with an open step-through area has minimal fall risk. See 'What kind of bike?' for more detail on bike selection.
5. Availability of Equipment: We want to train people with equipment that they can find and use after their involvement in our research ends.  These bikes are easy to find in exercise facilities, can be purchased for the home, and do not require technical assistance for use.
6. Intervals help manage cardiovascular risk: Some people with PD also have other health conditions that need to be managed during exercise.  The rest periods between the intervals of fast pedaling allow heart rate and blood pressure to recover towards resting levels.  We can increase the duration of rest periods between intervals or reduce the number of intervals to keep a person exercising at a safe intensity. 
7. Intervals provide practice with motor-switching: We believe that practicing the pattern of SLOW-FAST-SLOW-FAST… in the exercise program will help fight some of the other motor difficulties such as freezing of gait (FOG, see this paper).  We did not test this hypothesis in the present study but we have seen some subjects improve their ability to switch from slow pedaling to fast pedaling throughout the SpeedGeezer program.  This practice of motor switching would not happen if you pedaled fast continuously for 20 minutes.  Also, people can achieve higher peak pedaling speeds during short intervals.  If you want to mix things up and if your bike allows it, try switching to backwards pedaling.

Are we really training the brain or just the legs?  As a responsible scientist, I have to state that this study would provide stronger evidence if we had a control group of people with PD who did not exercise.  The fact that this group of people is becoming harder to find suggests that the message about the benefits of exercise is spreading!  Despite this limitation of the study, we are encouraged by the significant improvement in the 9-hole-peg test which is a timed test of hand dexterity.  In our ongoing research, we are interested in how fast exercise involving the legs can improve physical performance in the arms and hands as well as cognition.  If this pattern of transferred benefits emerges in multiple studies, we will have greater confidence that this exercise is affecting the brain.  However, the benefits of physical activity on cognition are already well supported by science: PubMed Search.

Is the speed-based interval training studied here the same as High Intensity Interval Training (HIIT)?    Read more at this post…

The First Step for Beginning Exercise

Historically, fast, high intensity or high power exercise strategies have not been recommended for older adults and patients.  These exercises have been avoided mainly to minimize cardiovascular and musculoskeletal risks.  We are beginning to understand the tremendous benefits of high power and high intensity exercise in various patient groups but we still need to apply such exercise strategies with caution.  In 2015, the American College of Sports Medicine (ACSM) updated its approach to Pre-Participation Health Screening to minimize the risks of exercise without creating unnecessary barriers to exercise participation.  Click here if you are interested in best-practices for screening.

Before you begin an exercise program, take a fitness test, or substantially increase your level of activity, make sure to answer the following questions. This physical activity readiness questionnaire (PAR-Q) will help determine if you’re ready to begin an exercise routine or program.

• Has your doctor ever said that you have a heart condition or that you should participate in physical activity only as recommended by a doctor?
• Do you feel pain in your chest during physical activity?
• In the past month, have you had chest pain when you were not doing physical activity?
• Do you lose your balance from dizziness? Do you ever lose consciousness?
• Do you have a bone or joint problem that could be made worse by a change in your physical activity?
• Is your doctor currently prescribing drugs for your blood pressure or a heart condition?
• Do you know of any reason you should not participate in physical activity?

If you answered yes to one or more questions, if you are over 40 years of age and have recently been inactive, or if you are concerned about your health, consult a physician before taking a fitness test or substantially increasing your physical activity. If you answered no to each question, then it’s likely that you can safely begin exercising, according to these guidelines provided by the ACSM.

What are the Side Effects of exercise?

Some people with PD have momentary drops in their blood pressure.  Be careful when you rise from the bike after exercise.  Take it slow.  Other than this, exercise sometimes comes with some reversible fatigue and some soreness.  If you keep taking this wonderful medicine called exercise, these side effects will likely diminish.  Then there are all the good side-effects of exercise: improved heart health, reduced depression and anxiety, improved bone health and more.  The side effects of exercise, if you want to think of them that way, are mostly good.