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  1. van Wegen, Erwin E. H. PhD
  2. Hirsch, Mark A. PhD
  3. Huiskamp, Marijn MSc
  4. Kwakkel, Gert PT, PhD


Despite advances in pharmacologic management, deficits in gait and gait-related activities remain persistent in Parkinson disease (PD), resulting in reduced safety and ADL independence. Alternative rehabilitative allied health approaches to the management of these problems, such as physical therapy or exercise training, are, therefore, important. We summarize literature on neuroprotective and neurorestorative effects of physical exercise. Next, we discuss data on the importance of exercise training with external rhythmic cues and summarize literature, demonstrating usefulness of goal-based exercise training with external cues on gait and gait-related activities in PD. The underlying mechanisms of cueing-induced neuroplasticity in PD are still unclear. It is also unclear whether cueing training can elicit neuroplastic effects comparable with those of regular exercise. Throughout this article, we maintain the following data-driven observations: (1) physical exercise can decrease the risk of later-developing PD, and evidence from animal studies suggests that neuronal cell death in the substantia nigra can be prevented through an exercise-induced increase in neurotrophic factors; (2) physical exercise has the potential to mitigate the effects of PD through an enhanced efficiency of dopamine transmission; (3) all modalities of cueing training can improve gait and gait-related activities in PD; (4) although no direct evidence for neuroprotective or neurorestorative effects of cueing training can be found, we predict that compensatory mechanisms play a role in cueing training, since externally triggered movements are thought to bypass the affected basal ganglia circuitry and activate the premotor cortex, cerebellum, and parietal cortex; and (5) learning-related improvements in motor function as a result of cueing training are likely to be accompanied by neuronal adaptations. The immediate effects of cueing training may relate to compensatory neuronal pathways that are not directly involved during regular exercise. We pose that external cueing facilitates the conditions for goal-based exercise training to improve gait and gait-related activities of patients with PD. The improved motor performance may result in increased exercise capacity and daily physical activity and as such indirectly affect neuroprotective and neurorestorative mechanisms comparable with regular exercise.