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Timing of device-aided therapy initiation in Parkinson's disease: reference estimates for healthcare planning and biological heterogeneity

Lookup NU author(s): Dr David Ledingham, Charlotte Stewart, Dr Sahana Sathyanarayana, Victoria Foster, Robyn IredaleORCiD, Debra Galley, Professor Mark Baker, Professor Nicola PaveseORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© 2026 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/ Introduction: Device-aided therapies including deep brain stimulation and continuous infusion therapies are effective for medication-refractory Parkinson's disease, yet longitudinal data on when patients undergo these interventions remain limited. We aimed to estimate cumulative incidence and identify predictors of device-aided therapy timing using survival analysis. Methods: We analysed 1454 participants with Parkinson's disease from the Parkinson's Progression Markers Initiative (PPMI), including 1079 with sporadic disease. Kaplan-Meier analysis estimated cumulative incidence of device-aided therapy from diagnosis. Multivariable Cox proportional hazards models identified baseline predictors in sporadic Parkinson's disease, with a separate model examining genetic and biomarker effects across cohorts. Results: During follow-up (median 3.0 years), 144 participants (9.9%) underwent device-aided therapy, predominantly deep brain stimulation (87.5%). In sporadic Parkinson's disease, cumulative incidence was 2.6% at 5 years and 15.3% at 10 years, with 10% reaching device-aided therapy by 8.6 years. Younger age at diagnosis (HR 0.92 per year, p < 0.001), higher tremor subscore (HR 1.16, p < 0.001), and higher postural instability/gait difficulty subscore (HR 1.68, p = 0.016) independently predicted earlier initiation. LRRK2 (HR 3.41) and GBA (HR 2.73) carriers had significantly earlier device-aided therapy compared to sporadic disease. Notably, no sporadic participant with negative CSF alpha-synuclein seed amplification assay (SAA) underwent device-aided therapy during follow-up. Site-level variation was not significant after adjusting for patient characteristics. Conclusions: This study provides Kaplan-Meier-derived reference estimates for device-aided therapy in sporadic Parkinson's disease. Younger age, motor phenotype and genetic status were associated with earlier therapy initiation. The absence of device-aided therapy among SAA-negative sporadic participants warrants further investigation.

Publication metadata

Author(s): Ledingham D, Stewart CB, Sathyanarayana S, Foster V, Iredale R, Galley D, Baker MR, Pavese N

Publication type: Article

Publication status: Published

Journal: Clinical Parkinsonism and Related Disorders

Year: 2026

Volume: 14

Online publication date: 04/06/2026

Acceptance date: 27/05/2026

Date deposited: 23/06/2026

ISSN (electronic): 2590-1125

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.prdoa.2026.100458

DOI: 10.1016/j.prdoa.2026.100458

Data Access Statement: The datasets generated and/or analysed during the current study are available in the Zenodo repository, DOI - https://doi.org/10.5281/zenodo.18525492

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