{"doi":"10.1002/mds.30119","title":"Central Involvement in Pure Autonomic Failure: Insights from Neuromelanin‐Sensitive Magnetic Resonance Imaging and <sup>18</sup>F‐Fluorodopa‐Positron Emission Tomography","abstract":"BACKGROUND: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies. OBJECTIVES: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients. METHODS: Participants with PAF (n = 23) were categorized as high-LR (n = 13) or low-LR (n = 10) for conversion to central synucleinopathy. Additional participants included PD (n = 22), DLB (n = 8), and age- and sex-matched healthy controls (n = 23). NM-MRI at 3 T was used to quantify contrast ratios in the LC and SN, while FDOPA-PET measured presynaptic dopamine synthesis. Linear regression analyses, adjusted for age and sex, were used to compare NM-MRI contrast across groups. RESULTS: High-LR PAF patients showed reduced contrast in the LC and SN compared with controls and low-LR PAF patients, with values similar to PD and DLB. The NM-MRI contrast in the SN correlated with dopamine uptake in the striatum. Longitudinal imaging in PAF patients (n = 6) demonstrated reduced NM-MRI and PET values in individuals who developed central synucleinopathies. CONCLUSIONS: NM-MRI and FDOPA-PET 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. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2025,"id":520370,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9698,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1390324,"name":"Kaitlyn R. O'Rourke","orcid":null,"position":1,"is_corresponding":false},{"id":767376,"name":"Olivia C. Roman","orcid":null,"position":2,"is_corresponding":false},{"id":757197,"name":"Alexander K. Song","orcid":"0000-0003-1590-4144","position":3,"is_corresponding":false},{"id":544219,"name":"Kilian Hett","orcid":"0000-0001-8831-4247","position":4,"is_corresponding":false},{"id":1389927,"name":"Amy Cooper","orcid":"0000-0003-3354-0364","position":5,"is_corresponding":false},{"id":657913,"name":"Bonnie K. Black","orcid":null,"position":6,"is_corresponding":false},{"id":326159,"name":"Manus J. Donahue","orcid":"0000-0002-4123-9275","position":7,"is_corresponding":false},{"id":333770,"name":"Cyndya A. Shibao","orcid":"0000-0002-4518-6801","position":8,"is_corresponding":false},{"id":333771,"name":"Italo Biaggioni","orcid":"0000-0001-7667-7083","position":9,"is_corresponding":false},{"id":388676,"name":"Daniel O. Claassen","orcid":"0000-0002-9853-4902","position":10,"is_corresponding":false},{"id":750930,"name":"Paula Trujillo","orcid":"0000-0001-9753-7071","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:49:28.470782Z","pmid":"39825743","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}