Movement Improves Brain Health and Cognition in Parkinson's Disease

Summary

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 can be differentiated from other neurodegenerative diseases by the affected domains: typically, the executive functions are primarily affected, to a greater extent than the mnesic ones. PD-MCI is of utmost clinical relevance, as it impacts the patients' quality of life and as the major predictor for conversion to PDD. To date, there are no routinely recommended interventions to address MCI in PD and prevent it from evolving into dementia. 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. In the last decade, studies have proven aerobic exercise as a promising strategy to alter the trajectory of cognitive decline in subjects with cognitive impairment and in elderly people. In particular, executive functions were ameliorated by exercise intervention to a greater extent. A recent preclinical study also demonstrated a reduced spread of toxic alpha-synuclein (a-syn) species to vulnerable brain areas, along with the restoration of the striatal synaptic plasticity. 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 homebased exercise may improve cognition in MCI-PD 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 multicenter 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 people with PD, addressing one of the most unmet needs in PD, since no disease-modifying treatments are available for cognitive deficits to date.

Conditions

• Parkinson Disease

Interventions

BEHAVIORAL

Aerobic exercise for >_75 minutes/week of vigorous aerobic exercise or >_ 150 minutes/week of moderate aerobic exercise in at least two weekly sessions, for 12 m

Participants will use a commercially available wearable device with a heart rate monitor to prove adherence to the program and record the intensity of all exercise sessions.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Principal Investigators

• Paolo Calabresi · Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-09

Primary Completion

2028-04-30

Completion

2028-04-30

Countries

• Italy

Study Locations