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Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations

BACKGROUND: In Parkinson’s 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. Th...

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Autores principales: Mestre, Tiago A., Fereshtehnejad, Seyed-Mohammad, Berg, Daniela, Bohnen, Nicolaas I., Dujardin, Kathy, Erro, Roberto, Espay, Alberto J., Halliday, Glenda, van Hilten, Jacobus J., Hu, Michele T., Jeon, Beomseok, Klein, Christine, Leentjens, Albert F.G., Marinus, Johan, Mollenhauer, Brit, Postuma, Ronald, Rajalingam, Rajasumi, Rodríguez-Violante, Mayela, Simuni, Tanya, Surmeier, D. James, Weintraub, Daniel, McDermott, Michael P., Lawton, Michael, Marras, Connie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150501/
https://www.ncbi.nlm.nih.gov/pubmed/33682731
http://dx.doi.org/10.3233/JPD-202472
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author Mestre, Tiago A.
Fereshtehnejad, Seyed-Mohammad
Berg, Daniela
Bohnen, Nicolaas I.
Dujardin, Kathy
Erro, Roberto
Espay, Alberto J.
Halliday, Glenda
van Hilten, Jacobus J.
Hu, Michele T.
Jeon, Beomseok
Klein, Christine
Leentjens, Albert F.G.
Marinus, Johan
Mollenhauer, Brit
Postuma, Ronald
Rajalingam, Rajasumi
Rodríguez-Violante, Mayela
Simuni, Tanya
Surmeier, D. James
Weintraub, Daniel
McDermott, Michael P.
Lawton, Michael
Marras, Connie
author_facet Mestre, Tiago A.
Fereshtehnejad, Seyed-Mohammad
Berg, Daniela
Bohnen, Nicolaas I.
Dujardin, Kathy
Erro, Roberto
Espay, Alberto J.
Halliday, Glenda
van Hilten, Jacobus J.
Hu, Michele T.
Jeon, Beomseok
Klein, Christine
Leentjens, Albert F.G.
Marinus, Johan
Mollenhauer, Brit
Postuma, Ronald
Rajalingam, Rajasumi
Rodríguez-Violante, Mayela
Simuni, Tanya
Surmeier, D. James
Weintraub, Daniel
McDermott, Michael P.
Lawton, Michael
Marras, Connie
author_sort Mestre, Tiago A.
collection PubMed
description BACKGROUND: In Parkinson’s 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 = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 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.
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spelling pubmed-81505012021-06-09 Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations Mestre, Tiago A. Fereshtehnejad, Seyed-Mohammad Berg, Daniela Bohnen, Nicolaas I. Dujardin, Kathy Erro, Roberto Espay, Alberto J. Halliday, Glenda van Hilten, Jacobus J. Hu, Michele T. Jeon, Beomseok Klein, Christine Leentjens, Albert F.G. Marinus, Johan Mollenhauer, Brit Postuma, Ronald Rajalingam, Rajasumi Rodríguez-Violante, Mayela Simuni, Tanya Surmeier, D. James Weintraub, Daniel McDermott, Michael P. Lawton, Michael Marras, Connie J Parkinsons Dis Systematic Review BACKGROUND: In Parkinson’s 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 = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 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. IOS Press 2021-04-13 /pmc/articles/PMC8150501/ /pubmed/33682731 http://dx.doi.org/10.3233/JPD-202472 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Systematic Review
Mestre, Tiago A.
Fereshtehnejad, Seyed-Mohammad
Berg, Daniela
Bohnen, Nicolaas I.
Dujardin, Kathy
Erro, Roberto
Espay, Alberto J.
Halliday, Glenda
van Hilten, Jacobus J.
Hu, Michele T.
Jeon, Beomseok
Klein, Christine
Leentjens, Albert F.G.
Marinus, Johan
Mollenhauer, Brit
Postuma, Ronald
Rajalingam, Rajasumi
Rodríguez-Violante, Mayela
Simuni, Tanya
Surmeier, D. James
Weintraub, Daniel
McDermott, Michael P.
Lawton, Michael
Marras, Connie
Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title_full Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title_fullStr Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title_full_unstemmed Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title_short Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations
title_sort parkinson’s disease subtypes: critical appraisal and recommendations
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150501/
https://www.ncbi.nlm.nih.gov/pubmed/33682731
http://dx.doi.org/10.3233/JPD-202472
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