While pharmacological treatment is helpful in the early stages of the disease, increased attention has been given to rehabilitation that may lead to clinical improvements in motor and non-motor impairments.~Recently synthesized evidence suggests that physical exercise may lead to neuroplastic changes at the functional, structural and molecular levels.~Accessible and measurable biomarkers are needed to monitor the disease progression and the neurobiological changes resulting from pharmacological and rehabilitative treatments, also can be a useful and valuable tool to test rehabilitation effectiveness.~The present project will start from the reliable clinical assessment of rehabilitation effectiveness of an intensive multidisciplinary rehabilitation program, to verify the ability of a new panel of measurable biomarkers to assess neurobiological and functional changes in pwPD.~The purpose of this study is to determine the effects of an intensive multidisciplinary, aerobic, motor-cognitive rehabilitation treatment on accessible and measurable molecular biomarkers (primary outcome); balance and gait performance; aerobic capacity; motor and non-motor symptoms; cognitive functions; neuroimaging biomarker (secondary outcomes) in comparison to an active control group receiving a home-based self-treatment program. Thereafter, the investigators aim to relate the effects seen in motor and non-motor behavior to changes in biomolecular and neuroimaging markers.~To achieve this purpose, the study is designed as a Randomized Controlled Trial (RCT) and participants will be recruited at Fondazione Don C. Gnocchi-ONLUS, IRCCS S. Maria Nascente. Seventy-two subjects with a diagnosis of PD in accordance of MDS criteria will be randomly allocated to the experimental (EXP) or control group (CTR).
Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms such as rigidity, bradykinesia, resting tremor, cognitive and autonomic dysfunctions, gait and balance difficulties.~The impairment of gait, balance and cognitive performances is partially responsive to dopaminergic medications. This emphasizes the importance of non-pharmacological interventions for people with PD (pwPD).~Intensive multidisciplinary motor and cognitive rehabilitation has been proposed as a complementary and effective treatment for managing pwPD.~Several structural and physiological mechanisms have been suggested to underpin exercise-induced neuroplastic changes in PD, such as enhanced synaptic strength and preservation of dopamine neurons. To date, studies on brain changes induced by motor and cognitive exercises in pwPD have been small-scaled and uncontrolled.~Identifying accessible and measurable biomarkers for monitoring the events induced by intensive motor and cognitive rehabilitation program would help in testing the treatment effectiveness and would allow personalization of rehabilitation strategies by predicting patients' responsiveness.~Based on validated clinical assessments of intensive multidisciplinary rehabilitation treatment, the project will test the ability of a new set of biomarkers to evaluate rehabilitative outcomes in a cohort of people with PD.