Exercise as Medicine for Parkinson’s Disease

For decades, exercise was viewed largely as an adjunct to medical treatment for Parkinson’s disease (PD): good for mobility, cardiovascular health, and quality of life but not necessarily central to treatment.That view is changing. A growing body of evidence suggests that exercise may do more than improve symptoms. Studies have linked exercise to changes in brain structure and connectivity, while emerging clinical evidence raises the possibility that it could have disease-modifying effects. “Exercise should be prescribed with the seriousness of medication and the precision of rehabilitation,” said Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, Florida. “Across different programs, demonstrated benefits include better motor function, walking, balance, strength, fitness, and quality of life. It belongs alongside medication, not at the bottom of a lifestyle handout,” he added. What Does the Evidence Show? In a longitudinal cohort study, higher levels of physical activity were associated with slower cognitive and motor progression in PD, with the slowest progression seen among those with the highest levels of physical activity.In a separate longitudinal study, regular physical activity was associated with slower loss of cortical thickness and brain volume in temporoparietal and limbic regions, along with more favorable cognitive outcomes. In the Park-in-Shape trial, aerobic exercise, compared with stretching, increased functional connectivity of the anterior putamen and right frontoparietal network, reduced global brain atrophy, improved cognitive control, and attenuated off-state motor signs in patients with PD. A 2024 review concluded that evidence for symptomatic benefit from exercise in PD is convincing, whereas evidence for disease modification is less robust, although highly plausible. “Exercise has established functional benefits; protection against neuronal loss remains under investigation. We do not need to oversell neuroprotection to take functional improvement seriously,” said Lakhan. Does Exercise Type Matter? Aerobic exercise has perhaps the most compelling evidence, particularly treadmill walking and cycling. The phase 2 SPARX trial helped establish that high-intensity treadmill exercise was safe and feasible in patients with early, untreated PD. Patients assigned to high-intensity treadmill exercise targeting 80%-85% of maximum heart rate had less worsening in motor scores over 6 months than those receiving usual care, although the trial was designed primarily to assess feasibility, safety, and nonfutility rather than efficacy. In the CYCLE-II randomized trial, patients with mild-to-moderate PD assigned to home-based cycling for 45 minutes three times weekly at a cadence of at least 75 rpm had significantly less worsening in motor symptoms at 12 months than peers assigned to usual care.“We’re not measuring inside the brain in terms of the pathophysiology per se. But clinically, there’s a slowing of the clinical symptoms, which obviously that’s probably what patients care most about anyway,” said principal investigator Jay Alberts, PhD, from the Cleveland Clinic Neurological Institute. Benefits are not limited to aerobic exercise. Resistance training can improve strength and physical function, while tai chi and dance-based exercise may improve balance and motor symptoms in people with mild-to-moderate PD.How Much Is Enough? The 2026 Parkinson’s Foundation and American College of Sports Medicine recommendations call for about 150 minutes of moderate-to-vigorous exercise weekly, incorporating aerobic activity, strength, balance and agility, and flexibility. The framework includes aerobic sessions of at least 30 minutes 3 days weekly, strength and balance work 2-3 days weekly, and stretching 2-3 days weekly. Exercise should be tailored to disease stage, medication status, ability, and safety considerations. Lakhan emphasized that telling patients simply to “move more” is not enough. “If exercise is medicine, ‘move more’ is not a complete prescription,” he said. The prescription should specify “the activity, intensity, progression, and necessary supervision. The endpoint is not exhaustion; it is function.”Alberts suggested using the “talk test”: The effort should be high enough that someone can answer simple questions but not comfortably carry on a detailed conversation. “You’re not exhausted,” he said. “You’re not working at an exhausted level.” What’s Happening in the Brain? Exactly how exercise affects PD remains unsettled. One hypothesis is that exercise may trigger release of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), which may support neuronal health. Human studies have documented exercise-related increases in BDNF, whereas evidence involving GDNF remains largely preclinical. Alberts said “very early data” from his group suggest that aerobic exercise may alter structure-function relationships within the basal ganglia in patients with PD. Other proposed mechanisms include enhanced neuroplasticity and effects on mitochondrial function, neuroinflammation, and cerebral blood flow, although much of the mechanistic evidence comes from preclinical studies. “Movement is not simply an output of the brain. It is also an input that can train the brain,” Lakhan noted. But he cautioned against equating neuroplasticity with neuroregeneration: “Helping the brain use what remains is different from proving that we have replaced what was lost.”Exercise benefits may also depend in part on continued participation. Alberts compared exercise with medication and deep brain stimulation: “It is not the panacea,” he said, but unlike many other treatments, exercise gives patients “an element of control.” Many patients, he added, find that “exercise actually is empowering.”Can Exercise Reduce PD Risk? An even more provocative question is whether physical activity might delay or prevent PD in people who have not yet developed clinically manifest disease. Observational data suggest that possibility, but causality remains uncertain.In the ongoing French E3N observational cohort, women with the highest levels of physical activity had a 25% lower incidence of PD than those with the lowest levels. A meta-analysis of 21 observational studies showed that higher levels of physical activity were associated with lower PD risk across populations, with evidence of an inverse dose-response relationship.Researchers are now moving the question into randomized trials. The Slow-SPEED program represents the first nonpharmacologic randomized PD prevention trials worldwide. The program includes three trials in Netherlands, the United Kingdom, and the United States testing remotely delivered, gamified physical activity programs over 18-36 months in people with prodromal risk factors: isolated REM sleep behavior disorder, hyposmia, or LRRK2/GBA1 genetic variants. The planned enrollment is 820 participants. The initial goal is to determine whether investigators can produce a sustained increase in physical activity and whether that is accompanied by changes in emerging prodromal features — not yet to prove that exercise prevents PD.Where Is the Research Headed? Two large NIH-funded trials could help answer the disease-modification question. The SPARX3 phase 3 trial is comparing moderate-intensity treadmill exercise at 60%-65% of maximum heart rate with high-intensity exercise at 80%-85% in 370 patients with recently diagnosed PD who had not started dopaminergic therapy, with change in motor scores at 12 months as the primary endpoint. Secondary outcomes include dopamine-transporter imaging and time to initiation of dopaminergic medication. The GEARS trial is designed to examine how genetics may influence the effects of exercise on PD progression. Participants will exercise on stationary bikes three times weekly for 12 months at 60%-80% of heart rate reserve, targeting a cadence of about 75 rpm. “The next frontier should be precision exercise: identify what matters to an individual patient, select the training, measure the response, and adjust the prescription,” Lakhan said. “We should measure success not only by how much someone moves, but by what that movement enables them to do.”Is It Time to Prescribe Exercise? For clinicians, a practical challenge is helping patients exercise safely despite freezing of gait, impaired balance, orthostatic hypotension, fatigue, depression, apathy, or cognitive impairment. Those barriers should shape, rather than eliminate, the prescription, Lakhan said. Exercise during medication “on” periods may be preferable for many patients, and physical therapy evaluation or supervision may be needed as disease advances. “The prescription should change with the patient, not disappear as the disease progresses,” he advised.Community programs may also improve adherence. Alberts noted that programs such as Pedaling for Parkinson’s provide structured exercise along with social connection in a disease that can be profoundly isolating. Group exercise, he said, can “bring people together with Parkinson’s” and help them “get out and build a community.”Asked whether exercise has reached the point where it should routinely be prescribed as part of PD treatment, Alberts did not hesitate: “Absolutely.”Lakhan agreed that exercise should be treated as an ongoing part of PD care rather than a finite intervention.“The end of supervised therapy should be a handoff, not a stop sign,” he said. He recommended building maintenance — and a plan for restarting after interruptions — into the original prescription. “The message should be consistency, not guilt.”Lakhan and Alberts had no relevant disclosures.