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Physical activity in patients with Parkinson’s disease (PD) is associated with increased longevity, new research suggests.

In a new analysis, how does prednisone help back aches “physical activity and all-cause mortality had a dose-response association in individuals with PD; although reverse causality might exist, modifications to increase and maintain physical activity may be beneficial for reducing mortality in PD,” the investigators, led by Seo Yeon Yoon, MD, PhD, Department of Physical Medicine & Rehabilitation, Korea University Guro Hospital, Seoul, South Korea, write.

The study, was published online November 1 in JAMA Neurology.

Large Study

Previous research has shown the beneficial effects of exercise on motor and cognitive function, as well as nonmotor symptoms such as mood and sleep in PD.

However, these studies were small with relatively short follow-up and few examined the association between physical activity and mortality in this patient population.

In the new study, researchers used data from the National Health Insurance Service, a single-payer system providing universal medical coverage for most citizens of South Korea.

They collected data on physical activity in the past week through self-reported questionnaires. They investigated three activity intensities — vigorous (running and fast biking for more than 20 minutes), moderate (fast walking and doubles tennis for more than 30 minutes), and light (walking to and from work or for leisure for more than 30 minutes).

Those who reported vigorous activity three or more times per week or moderate or light activity five or more times per week were considered physically active. Otherwise, they were considered physically inactive.

To quantify the total amount of physical activity, researchers calculated the metabolic equivalent of task (MET) minutes per week by summing the frequency, intensity, and duration of activity. They categorized the total amount into quartiles.

The study’s primary outcome was all-cause mortality by intensity, total amount, and maintenance of physical activity before and after a PD diagnosis.

The study included 10,699 individuals with new-onset PD who attended health checkups within 2 years before and after receiving a PD diagnosis. Of these, 46% were men and the mean age was 69.2 years.

Over 8 years of follow-up, the overall mortality rate was 17%. The median total physical activity was 270 MET-minutes per week for those who died compared with 450 MET-minutes for those who did not die.

Lower Death Rates

Results showed all activity levels were associated with significantly reduced mortality. After adjusting for confounding variables, including demographics, comorbidities, and body mass index, the hazard ratios (HRs) were: 0.80 (95% CI, 0.69 – 0.93) for vigorous activity, 0.66 (95% CI, 0.55 – 0.78) for moderate activity, and 0.81 (95% CI, 0.73 – 0.90) for light activity.

Moderate-intensity activity was more strongly associated with reduced mortality than vigorous activity, perhaps because the moderate group were active more days per week.

“This is somewhat in-line with a previous study, which suggested that duration of [physical activity] is more important than the intensity of [physical activity] in European older adults,” the investigators note.

Kaplan-Meier curves of all-cause mortality showed a significantly lower mortality rate among physically active vs inactive individuals (P < .001).

For MET-minutes per week, the analysis showed progressively decreasing mortality risk from the first quartile (< 90 MET-minutes per week) to the fourth quartile (≥ 820 MET-minutes per week) (HR, 0.61 [95% CI, 0.53 – 0.70]; P < .001).

There was an inverse association between mortality and amount of physical activity in both men and women. Previous studies demonstrated benefits only in men, possibly because they included relatively few women, the researchers note.

The study also showed maintaining physical activity was associated with lower mortality. Those who were physically active both before and after a PD diagnosis had the greatest reduction in mortality.

The study only included individuals who had had a checkup within 2 years before and after a PD diagnosis, so it’s possible that the study population was relatively healthy. Other potential limitations included recall bias regarding physical activity and noninclusion of PD severity, dietary habits, and antiparkinsonian medications.

In addition, given that it was an observational study, the investigators note that there could be a reverse causality between physical activity and mortality.

Important Implications

In an accompanying editorial, Nienke M. de Vries, PhD, Center of Expertise for Parkinson & Movement Disorders, Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands, and colleagues note that the study has “potentially important implications.”

The “sheer amount” of physical activity “seems to matter” in terms of reduced mortality, although “it remains to be determined whether this also translates into tangible health benefits during life for persons with PD,” they write.

If demonstrated in future studies, it might mean achieving a higher volume of physical activity — for example, by simply taking longer daily walks — would confer symptomatic improvement, they note.

The findings also provide “cautious evidence for a disease-modifying potential” of high-volume exercise, although to differentiate between true causal effects of exercise on PD progression requires phase 3 randomized clinical trials, the editorialists add.

“To pave the way for such trials, pilot studies should first address remaining knowledge gaps, such as how to mitigate the difficulty of engaging participants in exercise regimens for prolonged periods and identify the optimal dose of the exercise volume.”

Among the “drawbacks” of the study is that the physical activity level may in itself have been determined by underlying conditions — for example, osteoarthritis and obesity in people with a more severe PD phenotype who may be less physically active — that affected mortality, said the editorial writers.

They expressed concern that the two categorizations (active vs inactive, with three intensity levels) were “arbitrary,” and the choice for specific cutoff values “may have affected the results.”

In addition, they note that physical activity questionnaires “are generally unreliable” because of recall bias and because people find it difficult to quantify their exact activity level.

The study was supported by a National Research Foundation of Korea grant funded by the South Korean government. Yoon reported grant funding from the National Research Foundation of Korea (funded by the South Korean government). De Vries reported a personal grant and research grant from the Dutch Organization for Health Research and Development. Editorial author Sirwan K. L. Darweesh, MD, PhD, was supported in part by a Parkinson’s Foundation postdoctoral fellowship.

JAMA Neurol. Published online November 1, 2021. Abstract, Editorial

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