{"doi":"10.1101/2025.05.16.25327469","title":"Characterizing Parkinson’s Disease Clinical and Biomarker Interactions in REM Sleep Behavior Disorder","abstract":"Background: REM Sleep Behavior Disorder (RBD), marked by dream enactment due to loss of REM-related muscle atonia, is a prominent prodromal indicator of synucleinopathies, particularly Parkinson's Disease (PD). Objectives: This study aimed to investigate the interplay among key PD biomarkers- α-synuclein seed amplification assay (SAA), hyposmia, and dopamine transporter (DaT) SPECT imaging - in individuals with RBD. Additionally, we evaluated how phenoconversion events and Movement Disorder Society (MDS)-Prodromal PD probability scores relate to clinical symptoms and biomarker profiles in an incident RBD population. Methods: Participants with polysomnographically-confirmed RBD underwent comprehensive clinical and biomarker assessments. They were grouped along three non-exclusive biomarker-based axes (hyposmic vs. normosmic, SAA positive vs. SAA negative, and DaT positive vs. intermediate vs. negative) and two clinical outcome-based axes (high vs. intermediate/low MDS-Prodromal PD probability; phenoconverters vs. non-phenoconverters). Within each category, performance on various clinical assessments, the presence of other biomarkers, and clinical outcomes were evaluated. Results: Hyposmia was associated with reductions in striatal DaT binding and α-syn SAA positivity. MDS Prodromal PD Probability Scores, which incorporate DaT and olfactory function, predicted SAA positivity and phenoconversion. DaT positivity was much more common (80%) among phenoconverters (RBD-PC), than non-phenoconverters (10%). No significant motor or non-motor symptom differences were observed between the two groups at baseline, likely due to the small sample size. Conclusions: α-syn SAA positivity, DaT positivity, and hyposmia are highly associated with each other. MDS Prodromal PD Probability scores may be useful predictors of near-term progression, and thus as stratification factors in clinical research study design.","journal":"medRxiv","year":2025,"id":566177,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"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":1314623,"name":"Samantha B. Esposito","orcid":null,"position":1,"is_corresponding":false},{"id":1470304,"name":"Erika Renkl","orcid":null,"position":2,"is_corresponding":false},{"id":1470305,"name":"Amine Benyakoub","orcid":null,"position":3,"is_corresponding":false},{"id":1469995,"name":"Kara Mead","orcid":"0000-0002-1166-1125","position":4,"is_corresponding":false},{"id":1470306,"name":"Camalene V. Chrysostoum","orcid":null,"position":5,"is_corresponding":false},{"id":1469996,"name":"Sapna Patel","orcid":"0000-0002-8069-9012","position":6,"is_corresponding":false},{"id":246442,"name":"John Seibyl","orcid":"0000-0002-4917-5413","position":7,"is_corresponding":false},{"id":1469997,"name":"Yuan Huang","orcid":"0000-0002-7005-1319","position":8,"is_corresponding":false},{"id":1469998,"name":"Brendan Koo","orcid":"0000-0003-1229-0247","position":9,"is_corresponding":false},{"id":51715,"name":"Jesse M. Cedarbaum","orcid":"0000-0002-5146-8784","position":10,"is_corresponding":false},{"id":1469994,"name":"Vijaya L. Reddy","orcid":"0009-0003-0954-4549","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":"40463563","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":[]}