October 02, 2018
A systematic review and meta-analysis of more than 500,000 adults showed that those who reported regularly participating in moderate to vigorous activity had a 21% reduced risk of developing PD compared with those who reported no such activity. The significant benefits, however, only applied to men, not women.
There was strength in numbers, the investigators note. Individually, only one of the eight prospective studies showed a statistically significant correlation, but when combined, they yielded the stronger signal.
Although medical treatments for PD remain limited, "fortunately, emerging evidence supports" the idea that lifestyle factors could affect the risk of developing PD, principal investigator Fudi Wang, MD, PhD, School of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, told Medscape Medical News.
The meta-analysis suggests a protective effect of physical activity on PD risk that is largely dependent on the intensity, Wang added.
"Specifically, only moderate/vigorous activities — for example, swimming, jogging, and bicycling — were found to be significantly associated with the decreased risk for PD," he said.
The study was published online September 21 in JAMA Network Open.
'Inconsistencies' in Previous Research
Multiple past studies have supported lifestyle modifications for reducing risk for PD, including increased exercise.
However, previous research "varied with respect to sample size, ethnicity, and other characteristics, thereby leading to inconsistencies with respect to their interpretation," the current researchers write.
To address these disparities in the evidence, they searched the literature through February 2018 and included only prospective studies with risk estimates with 95% confidence intervals (CIs).
To address the heterogeneity with which physical activity levels were reported, they converted findings into a standard metabolic equivalent of task-hours (MET) units per week.
The meta-analysis included six studies from the United States and one each from Finland and Sweden, with a total of 544,336 participants who were followed an average of 12 years. Of these individuals, 2192 developed PD.
The researchers also conducted subgroup analyses on factors that included sex, geographic location, follow-up, sample size, and study quality.
Each increase of 10 MET-hours per week in moderate to vigorous physical activity decreased the risk for PD in men by 17% (relative risk [RR], 0.83; 95% CI, 0.76 - 0.90). This suggests "a very powerful effect," Wang said.
In addition, participants in this highest category of activity had a 29% lower risk compared with those who reported no moderate to vigorous activity (RR, 0.71; 95% CI, 0.58 - 0.87; I2 = 30.7%).
Light physical activity did not significantly correlate with PD risk (RR, 0.86; 95% CI, 0.60 - 1.23; I2 = 37.5%).
Interestingly, with regard to participants' sex, the association between moderate to vigorous physical activity and lower PD risk was stronger among men (RR, 0.68; 95% CI, 0.57 - 0.82).
"The meta-analysis was underpowered to observe a dose-response association for women," Wang said.
Research published since the systematic review also supports a difference by sex. For example, increased exercise reduced risk for PD in men in the Health Professionals Follow-up Study but not in women in the Nurses' Health Study.
"Men and women may have different biological responses to physical activity," the investigators note.
Physicians should encourage their patients to engage in a regular exercise program, Wang said. "However, although the elderly might benefit from moderate or vigorous physical activity, caution is also advised."
Professional guidance about proper moderate to vigorous activity is needed to ensure safe and effective recommendations, he added.
"To our knowledge, this meta-analysis is the largest and most comprehensive evaluation of the dose-response relationship between physical activity and the risk of PD in the general population," the researchers write.
Although the exact mechanism remains unknown, other investigators have proposed physiologic explanations behind the benefits associated with increased physical activity.
For example, exercise could promote the expression of neuroprotective growth factors, including brain-derived neurotrophic factor and glial-derived neurotrophic factor. In addition, physical activity also could reduce damage to dopaminergic neurons within motor circuits.
Although the researchers accounted for multiple factors, potential confounders not included in the study could have affected the results, they note. The self-reporting of physical activity levels in most of the studies included in the meta-analysis could represent another limitation.
"Large prospective cohort studies are needed to further evaluate the association between physical activity and PD risk and to investigate potential causal factors attributed to the observed gender differential effect," Wang said.
In addition, he noted that epidemiologic research that breaks down physical activity benefits by detailed types of exercise is warranted.
In an accompanying editorial, Lorene M. Nelson, PhD, Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, California, writes that the meta-analysis "provided compelling evidence that physical activity, particularly moderate to vigorous physical activity, was associated with a significantly reduced risk of developing PD."
Regarding the lack of a dose-response association observed among women, "it would be premature to conclude that moderate to vigorous physical activity is not a protective factor for women because only four of the eight studies included women and all but one of those studies had fewer than 150 women with PD," Nelson writes.
"Further opportunities to carry out prospective investigations that include women should be sought," she adds.
Although she applauds the researchers for use of the MET-hours per week measure for physical activity, she suggests that a metric such as number of minutes per week spent in moderate or vigorous exercise "would be helpful."
On the basis of the results, "it seems clear that protection against PD can be added to the list of likely benefits of physical activity," Nelson writes.
The study was funded by research grants from the National Key R&D Program of China, the Natural Science Foundation of China, and the Zhejiang Provincial Natural Science Foundation. Dr Wang and Dr Nelson report no relevant financial relationships.