French women who were more physically active had a lower incidence of Parkinson's disease as they aged, prospective data showed.
Women in the highest quartile of physical activity at age 49 and older had 25% less risk of subsequent Parkinson's disease compared with those in the lowest quartile (adjusted HR 0.75, 95% CI 0.63-0.89, P<0.001), reported Alexis Elbaz, MD, PhD, of the Inserm Research Center in Paris, and co-authors in Neurology.
Lag analyses suggested it was unlikely that reverse causation drove this association. Ten years before diagnosis, physical activity declined at a faster rate in women with Parkinson's than in women without the disease, likely due to prodromal symptoms.
Promising drug candidates may one day prevent or delay the onset of clinically manifest Parkinson's disease, but many are still in early development stages, noted Lana Chahine, MD, MS, of the University of Pittsburgh in Pennsylvania, and Sirwan Darweesh, MD, PhD, of Radboud University Medical Center in Nijmegen, The Netherlands.
"By contrast, a promising, readily applicable, and low-risk approach consists of regularly engaging in exercise," Chahine and Darweesh wrote in an accompanying editorial.
The Park-in-Shape and SPARX trials of Parkinson's patients showed that exercise could stabilize motor symptoms, but this may have been a symptomatic effect, they pointed out. A meta-analysis of observational data found a link between higher physical activity and lower incident Parkinson's, but this may have been influenced by reverse causation.
"An approach to minimize reverse causation in observational studies consists of lag analysis, in which data on physical activity levels in the years proximate to the diagnosis of Parkinson's disease (i.e., the 'lag') are omitted," the editorialists wrote. "This approach was not commonly used in previous studies."
Furthermore, women have been underrepresented in Parkinson's research about exercise, Chahine and Darweesh observed.
Elbaz and colleagues used a lag analysis approach to examine the relationship between physical activity and Parkinson's in E3N, an ongoing prospective cohort study of 98,995 French women born between 1925-1950, recruited in 1990, and affiliated with a national health insurance plan that covered mostly teachers.
Participants self-reported physical activity in six questionnaires over the follow-up period. Activity was evaluated as time-varying metabolic equivalent task (MET)-hours per week. Vigorous activities had a value greater than 6 METs, while moderate activities were 3 to 6 METs, depending on intensity.
Parkinson's was self-reported and ascertained through medical records or by an algorithm using drug claims. Other self-reported data included comorbidities, smoking, diet, and reproductive health.
Mean baseline age was 49 and mean baseline physical activity level was 45 MET-hours/week. The top quartile had a mean level of 71 MET-hours a week; the bottom quartile had 27.
The researchers incorporated increasing lags -- 5, 10, 15, and 20 years -- between activity assessment and Parkinson's incidence in their analyses. They also evaluated trajectories of activity in a nested case-control study of 1,196 Parkinson's cases and 23,879 age-matched controls.
The main survival analysis included a 10-year lag; over a mean follow-up of 17.2 years, 1,074 women developed incident Parkinson's. Adjusting for potential confounders showed 25% less risk of Parkinson's in the highest quartile of physical activity compared with the lowest. A 15-year lag produced similar results.
Physical activity decreased with age in both cases and controls, but the decline was steeper in cases, suggesting that activity levels dropped in women with prodromal Parkinson's. Differences in activity levels emerged 29 years before Parkinson's was diagnosed.
The findings highlight four knowledge gaps, the editorialists noted: which activity components may have protective effects; how activity monitoring could be improved with wearable sensors; mechanisms and potential mediators of activity; and how much results may vary from person to person.
"The E3N cohort is restricted to women in France with (mostly) a professional background in teaching," they wrote. "Future studies are warranted in samples that are diverse in demographic and socioeconomic background. Such knowledge could inform the design of tailored exercise regimens for subgroups at risk of Parkinson's disease."
The study was supported by General Mutual of National Education, the Gustave Roussy Institute, the French League Against Cancer, and the French National Research agency.
Elbaz has obtained research grants from the Michael J. Fox Foundation, Plan Ecophyto, and France Parkinson. Co-authors reported relationships with the French Ministry of Research, Orkyn Aguettant, Elivie, Allergan, Merz-Pharma, EVER Pharma, Fondation Desmarest, AMADYS, ADCY5.org, Agence Nationale de la Recherche, Societé Française de Médecine Esthétique, and the Dystonia Medical Research Foundation.
The editorialists reported no relevant disclosures.
Source Reference: Portugal B, et al "Association of physical activity and Parkinson disease in women: Long-term follow-up of the E3N Cohort Study" Neurology 2023; DOI:10.1212/WNL.0000000000207424.
Source Reference: Chahine LM, Darweesh SKL "Physical activity and the risk of Parkinson disease: Moving in the right direction" Neurology 2023; DOI:10.1212/WNL.0000000000207527.