Journal article
Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression
Journal of Parkinson's disease, Vol.13(6), pp.899-916
09/08/2023
DOI: 10.3233/JPD-223433
PMCID: PMC10578214
PMID: 37458046
Abstract
Background: Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge. Objective: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods: Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression. Results: Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0033). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639). Conclusion: Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.
Details
- Title: Subtitle
- Parkinson’s Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson’s Disease Progression
- Creators
- Michael C. Brumm - University of IowaAndrew Siderowf - University of PennsylvaniaTanya Simuni - Northwestern UniversityElliot Burghardt - University of IowaSeung Ho Choi - University of IowaChelsea Caspell-Garcia - University of IowaLana M. Chahine - University of PittsburghBrit Mollenhauer - Paracelsus Elena Klinik KasselTatiana Foroud - Indiana UniversityDouglas Galasko - University of California San DiegoKalpana Merchant - Northwestern UniversityVanessa Arnedo - Michael J. Fox FoundationSamantha J. Hutten - Michael J. Fox FoundationAlyssa N. O’Grady - Michael J. Fox FoundationKathleen L. Poston - Stanford UniversityCaroline M. Tanner - University of California, San FranciscoDaniel Weintraub - University of PennsylvaniaKarl Kieburtz - University of Rochester Medical CenterKenneth Marek - Institute for Neurodegenerative DisordersChristopher S. Coffey - University of IowaParkinson’s Progression Markers Initiative
- Resource Type
- Journal article
- Publication Details
- Journal of Parkinson's disease, Vol.13(6), pp.899-916
- DOI
- 10.3233/JPD-223433
- PMID
- 37458046
- PMCID
- PMC10578214
- NLM abbreviation
- J Parkinsons Dis
- ISSN
- 1877-7171
- eISSN
- 1877-718X
- Language
- English
- Electronic publication date
- 07/12/2023
- Date published
- 09/08/2023
- Academic Unit
- Biostatistics
- Record Identifier
- 9984445525402771
Metrics
17 Record Views