Greatest mortality reduction seen for those who maintained PA before and after diagnosis

Physical activity (PA) was associated with a reduction in all-cause mortality in people with Parkinson’s disease (PD), an observational study found, although those who maintained their activity through their diagnosis saw the greatest benefit.

Adjusted analysis showed a lower mortality rate among PD patients who were active at all intensities, with HRs of 0.80 (95% CI 0.69-0.93) for vigorous intensity PA, 0.66 (95% CI 0.55-0.78) for moderate intensity PA, and 0.81 (95% CI 0.73-0.90) for light intensity PA, reported Kyungdo Han, PhD, of Soongsil University in Seoul, Republic of Korea, and co-authors in JAMA Neurology.

In the analysis of 10,699 patients with PD, they found an inverse association between PA and all-cause mortality, which was seen in both men and women, the researchers noted: “Those who maintained PA before and after receiving their PD diagnosis showed the greatest mortality reduction, while PA after the PD diagnosis was also associated with reduced mortality.”

Investigators analyzed data from the Korean National Health Insurance System data and included people diagnosed with PD from January 2010 through December 2013. Only people who attended health checkups within two years before and after receiving the PD diagnosis were included.

All had evaluations including a physical examination and a physical activity questionnaire with 7-day recall at the time of health check-up. Activity was dichotomized as physically active or inactive based on activity type and frequency, and activity intensity was categorized as light, moderate, or vigorous.

Mean age was 69.2 and 54% were women. Follow-up was through December 2017 with mean follow-up of 4.5 years. There were 1,823 deaths (17% mortality rate) during up to eight years of follow-up.

The inverse dose-response association was seen between the total PA volume in metabolic minutes (MET-minutes) per week and mortality. Adjusted regression analysis showed progressively decreasing risk of mortality from the first quartile (<90 MET-minutes per week) to the fourth quartile (≥820 MET-minutes per week). Compared with the first quartile, mortality HRs for the second through fourth quartiles were 0.81 (95% CI 0.71-0.92), 0.76 (95% CI 0.67-0.85), and 0.61 (95% CI 0.53-0.70), respectively.

PA before and after the PD diagnosis conferred the greatest reductions in mortality rate with respect to inactivity (vigorous: HR 0.66, 95% CI 0.50-0.88, moderate: HR 0.49 95% CI 0.32-0.75, light: 0.76, 95% CI 0.66-0.89).

People who started PA after their PD diagnosis still had a lower mortality rate than those who remained inactive (vigorous: 0.82, 95% CI 0.70-0.97, moderate: HR 0.69, 95% CI 0.57-0.83, light: HR 0.86, 95% CI 0.78-0.98). People who were active before, but not after, their PD diagnosis did not have a reduced mortality rate compared with inactive people, however.

In an accompanying editorial, Bastiaan Bloem, MD, PhD, of Radboud University Medical Center in Nijmegen, the Netherlands, and co-authors pointed out several limitations of the study, including possible reverse causality—physical activity levels may have been determined by underlying conditions that affected mortality rates—and selection bias from including only people with two health checkups.

“We were also somewhat concerned that the two types of categorizations (active versus inactive, with three intensity levels) were arbitrary,” Bloem and colleagues wrote. In addition, “physical activity questionnaires are generally unreliable because of recall bias and because people find it difficult to quantify their exact activity level,” they added.

Despite these drawbacks, the study may have two potentially important implications, the editorialists noted.

“The first is that the sheer amount (volume) of physical activity seems to matter,” they wrote. “Should this be demonstrated in further studies, then this would practically mean that people with PD should not necessarily be encouraged to reach high-intensity exercise levels, but that achieving a higher volume of physical activities (e.g., by simply taking longer daily walks) would also confer symptomatic improvement.”

The findings also “provide cautious evidence for a disease-modifying potential of high-volume exercise,” Bloem and co-authors added. “Observational studies in humans have shown that regular physical activity is associated with a reduced PD risk, suggesting that the disease-modifying properties of physical activity may extend to the prodromal phase of PD.”

The ongoing STEPWISE trial of smartphone-based exercise is studying the dose-response association between exercise volume and disease progression, the editorialists pointed out. This approach may also benefit prodromal PD research in the future, as well as deliver treatment, they observed: “Remotely administered and gamification-enhanced exercise volume interventions could be used to delay the onset of clinically manifest PD in people at high risk of the disease.”

In Parkinson’s disease, effects of physical activity on basal ganglia circuits may result from activity-induced neuroplasticity amid changes in multiple neurotransmitters, including dopamine and glutamate.

A 2010 study of 213,701 participants in the NIH-AARP Diet and Health Study cohort reported that higher levels of moderate to vigorous activity at age 35-39 or in the past 10 years were associated with lower PD risk—HR 0.62 and 0.65, respectively—in a dose-response relationship. A 2020 review concluded that although favorable associations between physical activity and PD progression showed a potentially protective effect on neurodegeneration, they also may simply reflect a symptomatic benefit as seen with dopaminergic therapy.

“Activity modification to increase and maintain PA would be beneficial for PD management, and future prospective randomized clinical trials to elucidate causal associations between PA and mortality in PD are warranted,” Han and co-authors noted.

  1. Physical activity (PA) was associated with all-cause mortality in people with Parkinson’s disease (PD), an observational study found.

  2. Possible reverse causality and selection bias may be limitations of the study.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This work was supported by a National Research Foundation of Korea grant funded by the Korea government.

Han had no disclosures to report.

Bloem reported grants from Netherlands Organization for Health, Michael J. Fox Foundation, Nothing Impossible, Parkinson Vereniging, Parkinson’s Foundation, Hersenstichting Nederland, Verily Life Sciences, Horizon 2020, Topsector Life Sciences and Health, AbbVie, UCB, and Zambon and personal fees from Critical Path Institute, Kyowa Kirin, UCB, Zambon, AbbVie, Bial, Biogen, GE Healthcare, Oruen, and Roche.

Cat ID: 130

Topic ID: 82,130,730,130,37,192,925