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In the Clinic-Parkinson's Disease
Early PD Patients May Benefit from Exercising at a High Intensity

ARTICLE IN BRIEF

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HIGH-INTENSITY treadmill exercise was found feasible and attenuated worsening on the motor scores in testing.

A phase 2 study in patients with early Parkinson's disease found that high-intensity treadmill exercise resulted in clinically meaningful motor skill improvements.

High-intensity treadmill exercise may help slow the progression of Parkinson's disease (PD) early on, according to a randomized study that analyzed the feasibility and safety of prescribing regular, vigorous workouts to patients who did not yet need medication.

Study participants who exercised on the treadmill about three times a week at 80 to 85 percent of their maximum heart rate had less worsening of motor function at six months, as measured by a standardized score, compared to control patients who did not undertake the exercise regimen. Participants who did moderately intense treadmill workouts (reaching 60 to 65 percent of their maximum heart rate) did not fare sufficiently better than the controls.

The study, which was published in the December 11, 2017 online edition of JAMANeurology, also demonstrated that most of the PD patients were willing and able to stick with the demanding exercise routine.

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DR. MARGARET SCHENKMAN said it is not clear whether the same results would be obtained if participants did not have the initial on-site training. Also, the study only included patients early in the disease process, so it cant be assumed that dose effect would be similar for patients with more advanced disease.

The phase 2 multicenter trial was not designed to reach any definitive conclusions, but the researchers said the preliminary results were encouraging enough to pursue a phase 3 trial using a high amount of treadmill exercise to analyze clinical response rates. Another question for study is whether exercise might delay the need for dopaminergic medication and how quality-of-life factors change.

“A larger efficacy trial is warranted to determine whether exercising at 80 percent to 85 percent maximum heart rate produces meaningful clinical benefits in de novo Parkinson disease,” the study authors wrote. “Meanwhile, clinicians may safely prescribe exercise at this intensity for this population.”

Lead author Margaret Schenkman, PhD, PT, professor and associate dean of physical therapy education at the University of Colorado School of Medicine, said some published reports suggest that exercise may improve motor symptoms in PD patients, and animal research indicates that endurance exercise may promote neurogenesis and provide a neuroprotective effect. But research had yet to firmly answer a question that neurologists may want to know: “What dose [amount] should I prescribe to my patient?”

“We wanted to begin by trying to nail down the right dose for future studies moving forward,” Dr. Schenkman told Neurology Today.

STUDY DESIGN, FINDINGS

The SPARX study (Study in Parkinson Disease of Exercise) was conducted at the University of Colorado, Northwestern University, Rush University, and the University of Pittsburgh. It compared patients randomized to high-intensity treadmill exercise or moderately intense treadmill exercise to a group of control patients who were placed on a wait list. The 128 patients, enrolled from 2012 to 2015, were aged 40 to 80, were within five years of diagnosis, and were not exercising at moderate intensity more than three times a week. Participants were not taking dopaminergic medication at the start of the trial and were not expected to need it within six months.

The high-intensity group (43 people) was prescribed treadmill exercise four days a week at 80 to 85 percent of their maximum heart rate. The moderate-intensity group (45) was instructed to exercise four times a week at 60 to 65 percent of their maximum heart rate. The controls (40) went about their usual routines.

The researchers looked at several feasibility measures, including adherence to a prescribed heart rate, exercise frequency of three days a week, and safety.

The clinical outcome for the study was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score from baseline to the six-month mark. Secondary outcomes included changes in UPDRS total and subscores and the Movement Disorders Society UPDRS (MDS-UPDRS) subscores, as well as maximal aerobic power.

The participants wore heart rate monitors to measure the intensity of exercise. The high-intensity group exercised on average 2.8 days per week and the moderately-intense group exercised 3.2 days weekly. Overall attrition was 8.6 percent.

The mean change in UPDRS score in the high-intensity group was 0.3 compared to 3.2 in the control group, indicating that intense exercise may be beneficial. The mean change in UPDRS score in the moderate-intensity group was 2.0, not good enough to warrant further investigate that dose of exercise, the researchers said.

Adverse events resulting from endurance exercise occurred as expected and were typical for people beginning an exercise program. There were no serious adverse events related to workouts. All participants wore pedometers to count their daily steps, but there were no differences in total steps among the three groups, suggesting that the prescribed exercise may have prompted people to move less during the rest of the day to compensate.

“We found that high-intensity treadmill exercise is feasible and attenuates worsening on the UPDRS motor score consistent with the clinically meaningful threshold of 3.5,” the study authors wrote. In addition, the between-group difference for the MDS-UPDRS motor subscores was comparable to the 3.2-point improvement that would be considered minimally clinically important for an individual.

The study was funded by grants from the National Institute of Neurological Disorders and Stroke, the University of Pittsburgh, the University of Colorado, and the Parkinson's Disease Foundation. The study authors declared no conflicts of interest.

STUDY LIMITATIONS

Some patients started on PD medication during the study, as expected. They were told to hold off on it within 12 hours of UPDRS testing, but not all participants remembered to do so. (The researchers factored that into their analysis.)

Whether the results could be replicated in a real-world setting is another question. Treadmill workouts took place in a highly controlled setting for the first two weeks so that participants learned how to monitor intensity. After that, most exercised at home or at a community center, Dr. Schenkman said. It is not clear whether the same results would be obtained if participants did not have the initial on-site training. Also, the study only included patients early in the disease process, so it can't be assumed that the dose effect would be similar for patients with more advanced disease.

Cynthia Comella, MD, FAAN, a study coauthor and professor of neurology in the department of neuroscience at Rush University Medical Center, said the study, while not definitive, does provide a rationale for doctors to tell their PD patients “to exercise at least three times a week at about 80 to 85 percent of their maximal heart rate.”

She said giving a specific exercise prescription to patients is probably better than making a general suggestion to simply exercise.

Dr. Comella said patients may find an exercise prescription to be appealing on a couple of levels. “First, this is not just another pill,” she said. “Secondly, you are exerting control over your future.”

“We should no longer think of exercise as something you do. Exercise is now considered a treatment for Parkinson's disease,” Dr. Comella said.

Study author Brian D. Berman, MD, MS, associate professor of neurology, psychiatry and radiology at University of Colorado, agreed, but said many questions remain to be answered. Among them, he said, are questions about the mechanism by which high-intensity exercise might help with PD, whether it is helpful because it is aerobic and keeps people fit, and whether exercise will help preserve gait and balance.

The new study used treadmills, he noted, but questions remain about the effectiveness of other forms of exercise, such as strength training (for which there is some positive research for PD) or walking or hiking outdoors.

Dr. Berman said a phase 3 study on high-intensity exercise, which is in the planning stage, would be designed to provide added information regarding disease progression and symptom relief, as well as information on quality-of-life issues, such as sleep and everyday function.

EXPERT COMMENTARY

Commenting on the study, C. Warren Olanow, professor of neurology and neuroscience at Mount Sinai School of Medicine, said: “Exercise is something we all recommend for our patients, but whether it actually influences the disease process or the symptoms remains open to question.”

He said it isn't easy to study the effects of exercise on Parkinson's disease because it “has been very difficult to control for exercise and to eliminate bias in evaluating results.” But he said the new study “is a good attempt to do this, although the results are very modest and the issue is far from resolved.”

“Still, there does not seem to be any good reason not to recommend exercise for patients if only to keep them limber and fit,” Dr. Olanow said in an email.

John G. Nutt, MD, FAAN, professor of neurology at Oregon Health & Science University, said the study findings pointing to an exercise benefit echo what he sees with his PD patients.

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DR. BRIAN D. BERMAN said among questions to be answered are which high-intensity exercise might help with PD, whether it is helpful because it is aerobic and keeps people fit, and whether exercise will help preserve gait and balance.

“I think there are many clinicians who are convinced that exercise does help,” Dr. Nutt said, even as the research continues to evolve. He said there is no reason to prescribe medication to a PD patient who is not yet experiencing any problematic symptoms, but prescribing exercise provides a way for them to take some action against their disease. He said that while the best type and intensity of exercise are being further studied, it makes sense to encourage patients to pursue activities that keep them moving, flexible and agile. Exercise that focuses on strength and balance is good also, he said.

“This is Portland, where there is a fairly tight Parkinson community and a lot of emphasis on exercise,” he said. He noted, for example, that he tells people about a popular boxing program for people with PD.

No matter what the direct medical benefits of exercise may be on PD patients, “it gets them out of their homes and with a group of people,” which can be a good thing unto itself, Dr. Nutt said.

The commentators declared no conflicts of interest.

LINK UP FOR MORE INFORMATION:

•. Schenkman M, Moore CG, Kohrt WN, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: A phase 2 randomized clinical trial https://jamanetwork.com/journals/jamaneurology/article-abstract/2664948. JAMA Neurol 2017; Epub 2017 Dec 11.