{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:18:23Z","timestamp":1791389903697,"version":"4.3.3"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Exercise has been proposed as the \u201cUniversal Prescription for Parkinson\u2019s Disease\u201d; 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 Behavior recommend older adults (&amp;gt; 65+ years) to achieve weekly minimal activity levels, indicating the intensity of aerobic exercise as the metabolic equivalent of task and duration as minutes\/week (150\u2013300\u2009min\/week at a moderate intensity of 3\u20135.9 MET- or 75\u2013150\u2009min\/week of a vigorous intensity of \u22656 MET). Translating these recommendations to PD patients, the study aimed to assess the dose\u2013response 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 the two rehabilitation settings will be evaluated based on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life, and cortical activity and brain connectivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>METEX-PD is a pilot, prospective, observational, cohort study. The study will enroll consecutively thirty (<jats:italic>N<\/jats:italic>\u2009=\u200930) participants with mild-to-moderate Parkinson\u2019s disease diagnosis to be assigned to a non-intensive or intensive rehabilitation group. The non-intensive rehabilitation group will achieve a range of 180\u2013270 METs-min\/week (90\u2009min\/week of low-intensity aerobic exercise, 2\u20133 METs), while the intensive rehabilitation group will exercise at 1350\u20131980 METs-min\/week (225\u2009min\/week of high-intensity aerobic exercise, 6\u20138.8 METs). The METEX-PD trial will last 12\u2009weeks, including 4\u2009weeks of aerobic training program and two follow-ups. Assessments will be performed at baseline (T0), at the end of the exercise program (T1\u2014end of the program), and 4- and 8\u2009weeks 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>METEX-PD trial will enable us to estimate the change in BDNF levels and other peripheral biomarkers under precise exercise-induced energy expenditure. The primary results of the METEX-PD study will allow the development of a larger multicenter randomized controlled trial to investigate the molecular pathways inducing the change in selected neurotrophic factors, such as BDNF, IGF-1, or irisin, and the downstream mechanisms of neuroplasticity in PD patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1412311","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T04:49:28Z","timestamp":1719982168000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Dose\u2013response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson\u2019s disease: a prospective, observational, cohort study"],"prefix":"10.3389","volume":"15","author":[{"given":"Rossella","family":"Rotondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Padua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Annino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Guescini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Donati-Zeppa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Goffredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilberto","family":"Stocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Stocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"De Pandis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"CD013856","DOI":"10.1002\/14651858.CD013856.pub3","article-title":"Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis","volume":"4","author":"Ernst","year":"2024","journal-title":"Cochrane Database Syst Rev"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.3233\/JPD-202100","article-title":"The universal prescription for Parkinson's disease: exercise","volume":"10","author":"Alberts","year":"2020","journal-title":"J Parkinsons Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1249\/MSS.0b013e318213fefb","article-title":"American College of Sports Medicine position stand. 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