Objective: To provide a reference of individual Parkinson’s disease (PD) progression by assessing multimodal milestones over 10 years (y) in patients of the DeNoPa cohort.

Background: The clinical course of PD is characterized by a marked interindividual heterogeneity regarding the progression of motor- and non-motor symptoms. The lack of a predictable disease course hampers the assessment of potentially disease-modifying drugs. Hence, studies in comprehensively characterized and uniform cohorts assessing the natural disease progression are urgently needed.

Method: For up to 10y, 116 PD patients from the DeNoPa cohort that were diagnosed with idiopathic PD shortly before baseline (BL) were examined longitudinally. Follow-up examinations (FU) were scheduled biannually comprising clinical and neuropsychological examinations. In total, 21 clinical milestones (MS) were assessed. Following a previous approach[1], these MS were selected within five clinical domains: walking and balance (MS within this domain, n=6), motor complications (n=3), autonomic symptoms (n=3), cognitive symptoms (n=4), and activities of daily living (n=5). Clinical thresholds for each MS were set to represent relevant impairment.

Results: In total, 75,9% of patients accomplished the 8y FU and 61,2% the 10y FU. A 60.2% of all patients reached at least one MS, and MS in the walking and balance domain were reached most often (46.10%), followed by MS in the cognitive domain (37.3%). The earliest MS were in the walking and balance domain, whilst motor complications (dyskinesia/wearing-off) emerged last, with no patient reaching a motor complications MS before the 6y FU. Correlations between different BL parameters showed that within some domains, older age at BL and higher body mass index (BMI) lead to a significantly higher risk to reach the MS. In contrast, levodopa medication (measured as time dependent variable) lead to a risk reduction.

Conclusion: Our results illustrate the heterogeneous progression of PD regarding different clinical MS in a longitudinal cohort. We showed that certain BL parameters are associated with a reduced or elevated risk to reach MS within different domains. Further studies in longitudinal cohorts are essential to delineate predictors of progression that will eventually facilitate patient stratification in clinical trials.

References: [1] M. Brumm, A. Siderowf, T. Simuni, C. Caspell-Garcia, L. Chahine, T. Foroud, V. Arnedo, A. Reimer, C. Tanner, K. Poston, D. Weintraub, S. Hutten, K. Kieburtz, K. Marek, C. Coffey. A Milestone-based approach to monitoring disease progression in Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a-milestone-based-approach-to-monitoring-disease-progression-in-parkinsons-disease/. Accessed March 14, 2023.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/measuring-the-heterogeneity-of-disease-progression-in-parkinsons-disease-with-multimodal-clinical-milestones-over-10-years-in-the-denopa-cohort/