AUTHOR=Rotondo Rossella , Padua Elvira , Annino Giuseppe , Guescini Michele , Donati-Zeppa Sabrina , Goffredo Michela , Stocchi Vilberto , Stocchi Fabrizio , De Pandis Maria Francesca 

TITLE=Dose–response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson’s disease: a prospective, observational, cohort study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1412311

DOI=10.3389/fneur.2024.1412311

ISSN=1664-2295

ABSTRACT=Background: Exercise has been proposed as the “Universal Prescription for Parkinson’s Disease”, however the specificity of exercise dose in terms of frequency, intensity, duration and type to be prescribed remains to be elucidated. 
The 2018 US updated guidelines and WHO Guidelines on Physical Activity and Sedentary Behaviour recommends for older adults to achieve weekly minimal activity levels, indicating the intensity of aerobic exercise as Metabolic Equivalent of Task and duration as minutes/week.  
Translating these recommendations to PD patients, study aims to assess the dose-response effects of standardized volume of structured exercise, measured as METs-minutes/week (weekly energy expenditure) of two different rehabilitation settings to quantify the change in neurotrophic factors.
The exercise-induced benefits between two rehabilitation settings will be evaluate on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life and in cortical activity and brain connectivity.
Methods: METEX-PD is a pilot, prospective, observational, cohort study. The study will enroll consecutively thirty (N=30) participants with mild-to-moderate Parkinson’s Disease diagnosis to be assigned to non-Intensive (EG) or Intensive rehabilitation (IG) group.
The non-Intensive Rehabilitation Group will achieve a range of 180-270 METs-min/week (90 min/week of low intensity aerobic exercise, 2-3 METs), while Intensive Rehabilitation Group will exercise at 1350-1980 METs-min/week (225min/week of high intensity aerobic exercise, 6-8.8 METs).
The METEX-PD trial will last 12 weeks, including a 4-weeks of aerobic training program and two follow-ups. Assessments will be performed at baseline (T0), at the end of the exercise program (T1- End of program) and 4- and 8-weeks after the end of the training program (FU-1 and FU-2).
The primary outcome is the change from baseline in peripheral blood BDNF levels. Secondary outcomes are differences in peripheral biomarkers, functional-motor assessments, clinical-functional evaluations and brain imaging.
Conclusion: METEX-PD trial will let us to estimate the change in BDNF levels and other peripheral biomarkers under precise exercise-induced energy expenditure. 
The primary results of METEX study will allow to develop a larger multi-center randomized controlled trial to investigate the molecular pathways inducing the change in neurotrophic factors, such as BDNF, IGF-1 or Irisin, and the downstream mechanisms of neuroplasticity in PD patients.