Cognitive impairment is an acknowledged feature of Parkinson’s disease (PD) and often coexists with the classic motor symptoms since their onset. Cognitive symptoms of PD typically affect the executive functions.

PD-MCI is of utmost clinical relevance, as it impacts the patients´ quality of life and is the major predictor for conversion to PD-dementia. To date, there are no routinely recommended interventions to address MCI in PD and prevent it from evolving. Recent evidence supports the benefit of aerobic exercise on motor symptoms of PD and its possible disease-modifying role, through functional and structural brain changes. Less is known about the impact of aerobic exercise on cognition in the PD population.

 Studies have proven aerobic exercise as a promising strategy to alter the trajectory of cognitive decline in subjects with MCI and in healthy elderly people. In particular, executive function were ameliorated by exercise intervention. A recent preclinical study also demonstrated a reduced spread of toxic a-synuclein species to vulnerable brain areas in PD. Nonetheless, the feasibility and efficacy of an unsupervised monitored exercise program on cognition for PD-MCI subjects has not been explored yet.

In this project, we will test the hypothesis that extensive home-based exercise may improve cognition in MCI-PD patients through a reduction of neuroinflammation and a-syn spreading via the activation of BDNF-related pathways. Motor, non-motor and cognitive evaluations, associated with measures of a-syn species, inflammation-related molecules and neurofilaments light chain in blood samples will be performed in a multicentre cohort, before and after the prescription of moderate/vigorous aerobic home-based exercise for 12 months and in a sedentary control population.

 Adherence to the protocol will also be evaluated. This will shed light on the impact of physical activity prescription in the care of PD patients, addressing one of the most unmet need in PD.