Effectiveness of physical exercise and advanced rehabilitation technologies on cognitive and motor impairments in people with Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative disease with early prominent degeneration of dopaminergic neurons in the substantia nigrapars compacta (SN). The loss of dopamine compromises the connection between the striatum and the SN; this connection is necessary for motor control. The resultant dopamine deficiency within the basal ganglia leads to a movement disorder characterized by classical motor symptoms. In addition, PD is also associated with numerous non-motor symptoms, some of which precede the motor dysfunction by more than a decade. The gold standard pharmacological treatment of PD is symptomatic treatment with drugs that increase dopamine concentrations or directly stimulate dopamine receptors. The lifelong management of people with PD needs a multidisciplinary approach, which includes coordination of pharmacological and non-pharmacological interventions. The use of prescribed physical exercise as a non-invasive tool to improve PD symptomsis well recognized. What needs further research and development is an evidence-basedanalysis for the type, intensity, frequency, duration etc. of exercise bouts. Therefore, the overall aim of this thesis was to investigate the effectiveness of physical exercise and robot assisted gait training (RAGT) on motor and cognitive impairments in patientswith PD. In particular, we evaluated the association between physical exercise and dementia risk factors in people with PD. Further, we investigated the effectiveness of RAGT on motor impairments, postural instability, gait parameters and freezing of gait. In our first study, we evaluated the association between levels of physical activity and well-known risk factors for PD/dementia, such as mood disorders and amyloid-β42 cerebrospinal fluid (CSF) content. International Physical Activity Questionnaires—Short Form (IPAQ–SF) was used to measure the level of physical activity in 128 cognitively intact patients with PD and correlated with the Hamilton-Depression (HAM-D) and the Hamilton-Anxiety (HAM-A) scores. Moreover, in a homogenous subgroup of 40 people of PD, it was further correlated with a panel of CSF biomarkers, including amyloid-β42, total α-synuclein, total, and II phosphorylated tau. The results of this study demonstrated that both the HAM-A and HAM-D scores, as well as the Aβ42 CSF content, improved in parallel with the increase of the total week amount of physical activity. In the second study, a systematic review and meta-analysis was carried out on the effectiveness of robot-assisted gait training (RAGT) on motor impairments in patients with PD. A systematic literature search was performed in six databases according to PRISMA guidelines. Seven randomized controlled trials (RCTs) that assessed the effects of RAGT on motor impairments in PD were included. The meta-analysis showed significant improvement on Unified Parkinson Disease Rating Scale Part III after intervention and after 1-month follow-up. Stride length and gait speed showed significant improvements after RAGT. Balance, as measured by Berg Balance Scale improved significantly after intervention and at 1-month follow-up. The pooled analysis did not detect any significant changes regarding stride time, cadence and functional balance scales. The RAGT showed better outcomes than conventional interventions on some motor aspects in PD. However, RAGT did not seem superior to control interventions. Finally, in order to assess the effectiveness of RAGT on freezing of gait in people with PD, the third study was performed to evaluate, summarize and discuss the available literature concerning the effect of RAGT on people with PD and freezing of gait (FOG). A total of 4 studies were evaluated after a comprehensive literature search was conducted utilizing MEDLINE, Embase, Scopus, Web of Science, PEDro (Physiotherapy Evidence Database), and the Cochrane Review. All the 4 studies noted positive outcomes by using RAGT on FOG. No adverse events or side effects occurred during and/or after the interventions. While the current literature generally offers support for the use of RAGT for FOG treatment, there is a paucity of strong evidence to support its widespread use. The increasing availability of RAGT technology offers the potential for engaging therapy in FOG rehabilitation, but its utility remains uncertain given the limited studies available at this time