Does Exercise Attenuate Disease Progression in People With Parkinson's Disease? A Systematic Review With Meta-Analyses

Introduction Exercise has many benefits for people with Parkinson's disease (PD) and has been suggested to modify PD progression, but robust evidence supporting this is lacking. Objective This systematic review (PROSPERO registration: CRD42020169999) investigated whether exercise may have neuroplastic effects indicative of attenuating PD progression. Methods Six databases were searched for randomized controlled trials (RCTs) that compared the effect of exercise to control (no or sham exercise) or to another form of exercise, on indicators of PD progression (eg, brain-derived neurotrophic factor [BDNF], brain activation, "off" Unified Parkinson's Disease Rating Scale [UPDRS] scores). Trial quality was assessed using the Physiotherapy Evidence Database Scale. Random-effects meta-analyses were performed where at least 3 comparable trials reported the same outcome; remaining results were synthesized narratively. Results Forty-nine exercise trials involving 2104 PD participants were included. Compared to control, exercise improved "off" UPDRS motor scores (Hedge's g -0.39, 95% CI: -0.65 to -0.13, P = .003) and BDNF concentration (Hedge's g 0.54, 95% CI: 0.10-0.98, P = .02), with low to very low certainty of evidence, respectively. Narrative synthesis for the remaining outcomes suggested that compared to control, exercise may have neuroplastic effects. The exercise versus exercise comparisons were too heterogenous to enable pooling of results. Discussion This review provides limited evidence that exercise may have an attenuating effect on potential markers of PD progression. Further large RCTs are warranted to explore differential effects by exercise type, dose and PD stage, and should report on a core set of outcomes indicative of PD progression.