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Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess early brain involvement in PAF using neuromelanin\u2010sensitive magnetic resonance imaging (NM\u2010MRI) and fluorodopa\u2010positron emission tomography (FDOPA\u2010PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM\u2010MRI contrast in the LC and SN compared with controls and low\u2010LR patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants with PAF (<jats:italic>n<\/jats:italic>\u2009=\u200923) were categorized as high\u2010LR (<jats:italic>n<\/jats:italic>\u2009=\u200913) or low\u2010LR (<jats:italic>n<\/jats:italic>\u2009=\u200910) for conversion to central synucleinopathy. Additional participants included PD (<jats:italic>n<\/jats:italic>\u2009=\u200922), DLB (<jats:italic>n<\/jats:italic>\u2009=\u20098), and age\u2010 and sex\u2010matched healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u200923). NM\u2010MRI at 3\u2009T was used to quantify contrast ratios in the LC and SN, while FDOPA\u2010PET measured presynaptic dopamine synthesis. Linear regression analyses, adjusted for age and sex, were used to compare NM\u2010MRI contrast across groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High\u2010LR PAF patients showed reduced contrast in the LC and SN compared with controls and low\u2010LR PAF patients, with values similar to PD and DLB. The NM\u2010MRI contrast in the SN correlated with dopamine uptake in the striatum. Longitudinal imaging in PAF patients (<jats:italic>n<\/jats:italic>\u2009=\u20096) demonstrated reduced NM\u2010MRI and PET values in individuals who developed central synucleinopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NM\u2010MRI and FDOPA\u2010PET may serve as potential biomarkers for early brain involvement and predicting progression to central synucleinopathies in PAF and could help identify patients for early intervention. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30119","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T07:09:41Z","timestamp":1737184181000},"page":"716-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Central Involvement in Pure Autonomic Failure: Insights from Neuromelanin\u2010Sensitive Magnetic Resonance Imaging and <sup>18<\/sup>F\u2010Fluorodopa\u2010Positron Emission Tomography"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-7071","authenticated-orcid":false,"given":"Paula","family":"Trujillo","sequence":"first","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn R.","family":"O'Rourke","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia C.","family":"Roman","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander 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