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

Abstract

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.

Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson’s Disease: A Systematic Review and Meta-Analysis

“…In 2023, Li and colleagues [ 45 ] reported results of their meta-analysis pooling data on the exercise-induced effects on BDNF concentration from five comparisons in four RCTs with 192 participants with PD [ 52 , 53 , 54 , 55 ]. Overall, their meta-analytic procedure led to a statistically significant result of the effects of exercise versus control on BDNF concentration (see Supplementary S1 ).…”

“…In 2020, Johansson et al [ 44 ] included three studies without control groups in their meta-analysis of exercise effects on BDNF levels, showing no significant summary effect size. In 2023, Li et al [ 45 ] and Rotondo and colleagues [ 46 ] pooled data on exercise studies, showing positive effects on BDNF levels compared to controls. Due to the conflicting meta-analytic results and the lack of human PD trials detailing mechanisms of exercise on BDNF levels, the purpose of the present systematic review and meta-analysis is to give an updated overview of the mechanisms and effects of exercise therapy on BDNF levels in PD, in order to bring these insights into the clinical context of physical medicine and rehabilitation for people living with PD.…”

Changes of brain-derived neurotrophic factor (BDNF) levels after different exercise protocols: a systematic review of clinical studies in Parkinson’s disease

“…The effect of exercise on these clinical outcomes can be explained by a variety of mechanisms ( Xu et al, 2019 ), including the synthesis of several neurotrophic factors, as reported in a review of animal studies and in a systematic review in patients with PD ( da Silva et al, 2016 ; Li et al, 2023 ). Brain-Derived Neurotrophic Factor (BDNF) protects the brain against destruction of dopaminergic neurons and acts as a growth factor for dopaminergic neurons of the substantia nigra pars compacta ( Hyman et al, 1991 ).…”

“…Previous research, including recent systematic reviews on the effect of exercise on BDNF levels, limited the analysis to controlled trials only ( Hirsch et al, 2018 ; Li et al, 2023 ; Rotondo et al, 2023 ). Randomised trials provide evidence of efficacy of interventions in “ideal” settings, whereas non-randomised studies more accurately reflect usual clinical practice ( Sørensen et al, 2006 ).…”

“…This heterogeneity, coupled with a very limited number of trials, makes the evaluation of the effectiveness of exercise intervention extremely hard. Recent meta-analyses aimed at assessing whether exercise determined an improvement of BDNF levels ( Hirsch et al, 2018 ; Li et al, 2023 ; Rotondo et al, 2023 ), but a quantitative estimate of the effect of exercise intensity and volume is still lacking. Since it is not known which characteristics of exercise determine the largest benefits for patients with PD, this study aimed at assessing to what extent intensity, volume and type of exercise are associated with changes in BDNF levels in patients with PD.…”