Movement Improves Brain Health and Cognition in Parkinson's Disease

NCT07299279 | Recruiting

• 1 other identifier: 7536
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (4)

• Motor performance

  · Unified Parkinson's Disease Rating Scale - MDS (MDS-UPDRS) to evaluate various aspects of PD, including non-motor and motor experiences of daily living and motor complications (0-272, the higher, the worse)

  From enrollment (time 0) to the end of exercise (after 12 months)

• non motor assessment

  · MDS - Non-Motor Symptoms Rating Scale (MDS-NMS) which measures the severity and frequency of non-motor symptoms (0-360, the higher, the worse)

  From enrollment (time 0) to the end of exercise (after 12 months)

• disease stage

  · Hoehn and Yahr stage (H\&Y), to assess disease stage (1-4, the higher the worse)

  From enrollment (time 0) to the end of exercise (after 12 months)

• Cognitive evaluation

  . Montreal Cognitive assessment (0-30, the lower the worse)

  From enrollment (time 0) to the end of exercise (after 12 months)

Secondary Outcomes (1)

• Biochemical analysis of biomarkers

  From enrollment (time 0) to the end of exercise (after 12 months)

Study Arms (2)

Exercise group (EG)

EXPERIMENTAL

The EG will be prescribed aerobic exercise for \>\_ 75 minutes/week of vigorous aerobic exercise (60%-85% of HR MAX) or \>\_150 minutes/week of moderate aerobic exercise (40%-60% of HR MAX) in at least two weekly sessions, for 12 months.

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

Sedentary group (SG)

NO INTERVENTION

The SG will be told to continue their routine daily activities and will be followed up regularly at the outpatient clinic.

Interventions

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 BEHAVIORAL

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.

Exercise group (EG)

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged between 30 and 80 years, with a clinical diagnosis of Parkinson's disease (PD) according to the Movement Disorder Society (MDS) diagnostic criteria and a Hoehn \& Yahr (H\&Y) stage between 1 and 3, as well as a diagnosis of mild cognitive impairment (MCI) according to MDS-PD-MCI level II criteria, will be consecutively enrolled during routine clinical practice at the hospitals of the Principal Investigator (PI) and Partner

You may not qualify if:

• Pregnant patients, patients with medical conditions that prevent vigorous physical exercise, those with oncological or autoimmune comorbidities, or those taking immunomodulatory or anti-inflammatory medications will be excluded from the study

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, Rome, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Exercise; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Paolo Calabresi

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Calabresi, Prof

CONTACT

+390630154303; paolo.calabresi@policlinicogemelli.it

Flavia Torlizzi

CONTACT

+390630155701; flavia.torlizzi@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: December 23, 2025
• Study Start: June 9, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: December 23, 2025

Record last verified: 2025-05

Locations

IT (1)