'Robust Evidence' That Exercise Cuts Parkinson Risk in Women

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'Robust Evidence' That Exercise Cuts Parkinson Risk in Women

Physical activity has been tied to a significantly decreased risk of Parkinson's disease (PD) in women, results of a large, long-term prospective study show.

Investigators found that among almost 99,000 women participating in the ongoing E3N study, those who exercised the most frequently had up to a 25% lower risk for PD than their less-active counterparts.

The results highlight the importance of exercising early in mid-life to prevent PD later on, study investigator Alexis Elbaz, MD, PhD, research director, French Institute of Health and Medical Research (Inserm), Paris, France, told Medscape Medical News.

This is especially critical since there is no cure nor disease-modifying treatments. The medications that are available are aimed at symptom reduction.

"Finding ways to prevent or delay the onset of Parkinson's is really important, and physical activity seems to be one of the possible strategies to reduce the risk," Elbaz said.

The study was published online May 17 in Neurology.

Direct Protective Effect?

Results from previous research examining the relationship physical activity and PD has been inconsistent. One meta-analysis showed a statistically significant association among men but a nonsignificant link in women.

The investigators note that some of the findings from previous studies may have been affected by reverse causation. As nonmotor symptoms like constipation and subtle motor signs such as tremor and balance issues can present years before a PD diagnosis, patients may reduce their physical activity because of such symptoms.

To address eliminate this potential confounder, the researchers used "lag" analyses, where data on physical activity levels in the years close to a PD diagnosis are omitted.

The study relied on data from the E3N, an ongoing cohort study of 98,995 women, born between 1925 and 1950 and recruited in 1990, who were affiliated with a French national health insurance plan that primarily covers teachers. Participants completed a questionnaire on lifestyle and medical history at baseline and follow-up questionnaires every 2-3 years.

In six of the questionnaires, participants provided details about various recreational, sports and household activities — for example, walking, climbing stairs, gardening, and cleaning. The authors attributed metabolic equivalent of task (MET) values to each activity and multiplied METs by their frequency and duration to obtain a physical activity score.

Definite and probable PD cases were determined through self-reported physician diagnoses, anti-parkinsonian drug claims, and medical records, with diagnoses verified by an expert panel.

Researchers investigated the relationship between physical activity and PD onset in a nested-case control study that included 25,075 women (1196 PD cases and 23,879 controls) with a mean age of 71.9 years. They found physical activity was significantly lower in cases than in controls throughout follow-up.

The difference between cases and controls began to increase at 10 years before diagnosis (P-interaction = .003). "When we looked at the trajectories of physical activity in PD patients and in controls, we saw that in the 10 years before the diagnosis, physical activity declined at a steeper rate in controls. We think this is because those subtle prodromal symptoms cause people to exercise less," said Elbaz.

In the main analysis, which had a 10-year lag, 1074 women developed incident PD during a mean follow-up of 17.2 years. Those in the highest quartile of physical activity had a 25% lower risk for PD vs those in the lowest quartile (adjusted hazard ratio [HR], 0.75, 95% CI, 0.63 - 0.89).

The risk for PD decreased with increasing levels of physical activity in a linear fashion, noted Elbaz. "So doing even a little bit of physical activity is better than doing nothing at all."

Analyses that included 15-year and 20-year lag times had similar findings.

Sensitivity analyses that adjusted for the Mediterranean diet and caffeine and dairy intake also yielded comparable results. This was also true for analyses that adjusted for comorbidities such as body mass index, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease, all of which can affect PD risk.

"This gives weight to the idea that diabetes or cardiovascular diseases do not explain the relationship between physical activity and PD, which means the most likely hypothesis is that physical activity has a direct protective effect on the brain," said Elbaz.

Studies have shown that physical activity affects brain plasticity and can reduce oxidative stress in the brain — a key mechanism involved in PD, he added.

Physical activity is a low-risk, inexpensive, and accessible intervention. But the study was not designed to determine the types of physical activity that are most protective against PD.

The study's main limitation is that it used self-reported physical activity rather than objective measures such as accelerometers. In addition, the participants were not necessarily representative of the general population.

Robust Evidence

In an accompanying editorial, Lana M. Chahine, MD, associate professor in the Department of Neurology at the University of Pittsburgh, and Sirwan K. L. Darweesh, MD, PhD, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson and Movement Disorders, Nijmegen, the Netherlands, note the study "provides robust evidence" that physical activity reduces risk for PD in women.

"These results show that the field is moving in the right direction and provide a clear rationale for exercise trials to prevent or delay the onset of manifest PD in at-risk individuals" they write.

The study highlights "gaps" in knowledge that merit closer attention and that "further insight is warranted on how much the effects on PD vary by type, intensity, frequency, and duration of physical activity," the editorialists note.

Another gap is how the accuracy of assessment of physical activity can be improved beyond self-report. "Wearable sensor technology now offers the potential to assess physical activity remotely and objectively in prevention trials," they add.

Other areas that need exploring relate to mechanisms by which physical activity reduces PD risk, and to what extent effects of physical activity vary between individuals, Chahine and Darweesh note.

Commenting for Medscape Medical News, Michael S. Okun, MD, executive director of the Fixel Institute for Neurological Diseases at University of Florida Health, and medical advisor for the Parkinson's Foundation, said the findings are "significant and important."

Based on only a handful of previous studies, it was assumed that physical activity was associated with reduced Parkinson's diagnosis only in men, said Okun.

"The current dataset was larger and included longer-term outcomes, and it informs the field that exercise may be important for reducing the risk of Parkinson's disease in men as well as in women."

The investigators, the editorialists, and Okun report no relevant financial relationships.

Neurology. Published online May 17, 2023. Full text, Editorial