{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:03:46Z","timestamp":1793199826153,"version":"4.5.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2021,4,13]]},"abstract":"<jats:p>Background: In Parkinson\u2019s disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice. Objective: To critically evaluate PD subtyping systems. Methods: We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists. Results: We included 38 studies. The majority were cross-sectional (n\u200a=\u200a26, 68.4%), used a data-driven approach (n\u200a=\u200a25, 65.8%), and non-clinical biomarkers were rarely used (n\u200a=\u200a5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown. Conclusion: Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed.<\/jats:p>","DOI":"10.3233\/jpd-202472","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T12:45:05Z","timestamp":1614948305000},"page":"395-404","source":"Crossref","is-referenced-by-count":137,"title":["Parkinson\u2019s Disease Subtypes: Critical Appraisal and Recommendations"],"prefix":"10.1177","volume":"11","author":[{"given":"Tiago A.","family":"Mestre","sequence":"first","affiliation":[{"name":"Parkinson\u2019s disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, The University of Ottawa Brain and Research Institute, Ottawa, ON, Canada"},{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed-Mohammad","family":"Fereshtehnejad","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christian-Albrechts-University, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas I.","family":"Bohnen","sequence":"additional","affiliation":[{"name":"Departments of Radiology & Neurology, University of Michigan, University of Michigan Udall Center, Ann Arbor VAMC, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Dujardin","sequence":"additional","affiliation":[{"name":"Movement Disorders Department, Center of Excellence for Neurodegenerative Diseases LiCEND, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Erro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, Neuroscience Section, University of Salerno, Baronissi (SA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"James J. and Joan A. Gardner Family Center for Parkinson\u2019s Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Halliday","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre and Central Clinical School, Faculty of Medicine and Health, University of Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus J.","family":"van Hilten","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele T.","family":"Hu","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Neurology Department, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beomseok","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert F.G.","family":"Leentjens","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Marinus","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Paracelsus-Elena-Klinik, Kassel and University Medical Center Goettingen, Department of Neurology, Kassel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Postuma","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasumi","family":"Rajalingam","sequence":"additional","affiliation":[{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayela","family":"Rodr\u00edguez-Violante","sequence":"additional","affiliation":[{"name":"National Institute of Neurology and Neurosurgery, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Simuni","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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