ObjectivesThe aim of the present systematic review and meta-analysis was to synthesize evidence associated with the functional and clinical effectiveness of rhythmic cueing, dance, or resistance training (RT) on motor and non-motor parameters in Parkinson's Disease patients, and to provide a comparative perspective not offered by existing systematic reviews.MethodologyEligibility criteria for selecting studies retained no restrictions in methodological design and included interventions of rhythmic cueing, dance, RT, and measurements of motor and non-motor parameters. Animal studies, reviews, editorials, conferences, magazines, and gray literature articles were excluded. Two independent investigators searched Cochrane Library, Medline, PubMed, and SPORTDiscus from the date of their inception until 1 June 2021. The ROBINS-I tool was employed for the non-randomized controlled trials, and the updated for Risk of Bias 2 tool of Cochrane Library used for randomized controlled trials. For meta-analyses, the RevMan 5.4.13 software was used. For incompatible meta-analysis studies, a narrative data synthesis was conducted.ResultsA total of 49 studies included in the systematic review involving 3767 PD participants. Meta-analyses revealed that rhythmic cueing training assists gait velocity (p = 0.01), stride length (p = 0.01), and motor symptoms (p = 0.03). Similarly, dance training benefits stride length (p = 0.05), lower extremity function-TUG (p = 0.01), and motor symptoms (p = 0.01), whilst RT improves lower extremity function-TUG (p = 0.01), quality of life (p = 0.01), knee flexion (p = 0.02), and leg press (p = 0.01). Subgroup analyses have shown non-significant differences in gait velocity (p = 0.26), stride length (p = 0.80), functional mobility-TUG (p = 0.74), motor symptoms-UPDRS-III (p = 0.46), and quality of life-PDQ39 (p = 0.44).ConclusionRhythmic cueing, dance, or RT positively affect the examined outcomes, with rhythmic cueing to be associated with three outcomes (Gait, Stride, and UPDRS-III), dance with three outcomes (TUG, Stride, and UPDRS-III), and RT with two outcomes (TUG and PDQ-39). Subgroup analyses confirmed the beneficial effects of these forms of exercise. Clinicians should entertain the idea of more holistic exercise protocols aiming at improving PD manifestations.International Prospective Register of systematic reviews (PROSPERO) (registration number: CRD42020212380).

Depression represents one of the most common non-motor disorders in Parkinson’s disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind–body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.