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Lookup NU author(s): Dr David Ledingham, Dr Sahana Sathyanarayana, Charlotte StewartORCiD, Robyn Iredale, Victoria Foster, Debra Galley, Professor Mark BakerORCiD, Professor Nicola PaveseORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Objective: To characterise the progression of motor symptoms and identify eligibility for device-aided therapies in Parkinson's disease, using both the 5-2-1 criteria and a refined clinical definition, while examining differences across genetic subgroups. Methods: We analysed 1205 individuals with sporadic and genetic Parkinson's disease from the Parkinson's Progression Markers Initiative (mean follow-up: 5.6 ± 4.3 years). Kaplan–Meier analysis estimated time to meeting the 5-2-1 criteria (five or more daily levodopa doses, two or more hours of OFF time, or one or more hours of troublesome dyskinesia) and a stricter definition of eligibility for device-aided therapy based on disabling, medication-refractory symptoms and/or tremor. In the sporadic Parkinson's disease subgroup (n = 943), we assessed therapy initiation and clinical suitability, including potential contraindications. Genetic subgroup analyses explored differences in progression, eligibility timing and treatment uptake. Results: Among individuals with sporadic Parkinson's disease, 257 (27.3%) met the 5-2-1 criteria, with 25%, 50% and 75% doing so by 5.3, 8.2 and 10.7 years, respectively. A total of 176 (18.6%) met stricter eligibility criteria, with 50% doing so by 12 years. Only 25% of those meeting the 5-2-1 criteria initiated device-aided therapy within 6.8 years. Most had no contraindications. Deep brain stimulation was the most used therapy. GBA and SNCA carriers met criteria earlier. LRRK2 carriers were more likely to initiate therapy, while PRKN carriers were less likely to meet eligibility thresholds. Interpretation: Eligibility for device-aided therapy is common but underutilised. These findings highlight missed opportunities and support earlier, genotype-informed treatment planning in Parkinson's disease.
Author(s): Ledingham D, Sathyanarayana S, Stewart CB, Iredale R, Foster V, Galley D, Baker M, Pavese N
Publication type: Article
Publication status: Published
Journal: Annals of Clinical and Translational Neurology
Year: 2025
Pages: epub ahead of print
Online publication date: 12/12/2025
Acceptance date: 13/08/2025
Date deposited: 22/12/2025
ISSN (print): 2328-9503
ISSN (electronic): 2328-9503
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/acn3.70188
DOI: 10.1002/acn3.70188
Data Access Statement: The datasets generated and/or analysed during the current study are freely available following written request from https://www.ppmi-info. org/access-data-specimens/download-data.
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