{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T08:36:33Z","timestamp":1785573393414,"version":"3.56.0"},"reference-count":74,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Michael J. Fox Foundation for Parkinson\u2019s Research and funding partners"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson\u2019s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-na\u00efve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson\u2019s Progression Markers Initiative (PPMI). The sample included 376 treatment-na\u00efve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society\u2014Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 \u2265 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [123I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-na\u00efve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores\u2014reflecting greater motor severity\u2014and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-na\u00efve group. No significant differences were found in CSF biomarkers (\u03b1-synuclein, amyloid-\u03b2, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions.<\/jats:p>","DOI":"10.3390\/jcm15031006","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:05:27Z","timestamp":1769504727000},"page":"1006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Speech Impairment in Early Parkinson\u2019s Disease Is Associated with Nigrostriatal Dopaminergic Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Sotirios","family":"Polychronis","sequence":"first","affiliation":[{"name":"Department of Speech & Language Therapy, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7495-6863","authenticated-orcid":false,"given":"Grigorios","family":"Nasios","sequence":"additional","affiliation":[{"name":"Department of Speech & Language Therapy, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-641X","authenticated-orcid":false,"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Thessaly, 41500 Larissa, Greece"},{"name":"Department of Neurology, University Hospital of Larissa, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4858-1679","authenticated-orcid":false,"given":"Rayo","family":"Akande","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd., Neuroscience and Rare Diseases, Roche Pharma Research and Early Development, 4058 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Pagano","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd., Neuroscience and Rare Diseases, Roche Pharma Research and Early Development, 4058 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0028-3932(99)00067-6","article-title":"Speech volume regulation in Parkinson\u2019s disease: Effects of implicit cues and explicit instructions","volume":"37","author":"Ho","year":"1999","journal-title":"Neuropsychologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1044\/jshd.4301.47","article-title":"Frequency and cooccurrence of vocal tract dysfunctions in the speech of a large sample of Parkinson patients","volume":"43","author":"Logemann","year":"1978","journal-title":"J. Speech Hear. 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