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Non\u2010hierarchical cluster analysis using motor and non\u2010motor data was applied to stratify PD patients into two subtypes: 77 early\/mild and 70 early\/severe. Graph theory analysis and connectomics were used to assess global and local topological network properties and regional functional connectivity at baseline. Stepwise multivariate regression analysis investigated whether baseline functional imaging data were predictors of clinical progression over 2\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, widespread functional connectivity abnormalities were detected in the basal ganglia, sensorimotor, frontal, and occipital networks in PD patients compared to controls. Decreased regional functional connectivity involving mostly striato\u2010frontal, temporal, occipital, and limbic connections differentiated early\/mild from early\/severe PD patients. Connectivity changes were found to be independent predictors of cognitive progression at 2\u2010year follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings revealed that functional reorganization of the brain connectome occurs early in PD and underlies crucial involvement of striatal projections. Connectomic measures may be helpful to identify a specific PD patient subtype, characterized by severe motor and non\u2010motor clinical burden as well as widespread functional connectivity abnormalities. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28541","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T13:09:12Z","timestamp":1614431352000},"page":"1603-1616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Functional Connectomics and Disease Progression in Drug\u2010Na\u00efve Parkinson's Disease Patients"],"prefix":"10.1002","volume":"36","author":[{"given":"Rosa","family":"De Micco","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"},{"name":"MRI Research Center University of Campania \u201cLuigi 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