Objective: To systematically compare long-term course of Parkinson’s disease (PD) by the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and investigate possible predictive parameters of different clinical progression in the single-center DeNovo Parkinson [DeNoPa] cohort and the multicenter Parkinson´s Progression Markers Initiative [PPMI] cohort. Due to the Heterogeneity of PD, cohorts need to be compared and merged to increase numbers.

Background: Not much is known about long-term progression of PD and the factors influencing a rapid/pronounced deterioration vs. a benign/slower progression based on UPDRS. Data from validated and comparable long-term cohorts and controlled clinical trials can provide important information about progression in PD for planning research studies.

Method: De novo PD subjects and healthy controls (HC) from DeNoPa (HC 110, PD 159) and PPMI (HC 195, PD 415) were investigated at baseline and up to 72 months of follow-up. Further, to model longitudinal time change of the single items a cumulative link mixed model was fitted, using a random intercept model and adjustment for time and levodopa equivalent daily dose (LEDD). All items that showed a significant odds ratio (OR) for TIME or LEDD > 1.25 or < 0.75 were extracted. A linear mixed effect model estimated the annual rate of change adjusted for age and LEDD.

Results: No significant differences between the demographic data was found between PPMI and DeNoPa except multi-ethnicity in PPMI indicating comparability of cohorts; Annual rates of progression of the MDS-UPDRS sum scores in DeNoPa were: UPDRS-I 0.54 (points/year); UPDRS-II 1.22; UPDRS-III 2.12; UPDRS-IV 0.36; UPDRS total score 4.15); in PPMI (UPDRS-I 0.78; UPDRS-II 1.01 Point/Year; UPDRS-III 2.43; UPDRS-IV 0.50; UPDRS total score 4.145) and thus quite similar.
Age contribution was significant for all sum scores except of UPDRS-IV in PPMI. LEDD in DeNoPa was only significantly associated with the UPDRS-III sum score, whereas in PPMI with UPDRS-III and total score.

Conclusion: Both cohorts showed similar demographics and progression rates. Some (UPDRS-III, UPDRS total score) significantly depended on LEDD, but single items are independent. Age plays a relevant role in affecting MDS-UPDRS items with patients with higher age at onset showed a faster increase of the total scores in the course. Thus, the two cohorts are comparable and can be validated against each other.

References: 1: Mollenhauer B, Zimmermann J, Sixel-Döring F, Focke NK, Wicke T, Ebentheuer J, Schaumburg M, Lang E, Friede T, Trenkwalder C; DeNoPa Study Group. Baseline predictors for progression 4 years after Parkinson’s disease diagnosis in the De Novo Parkinson Cohort (DeNoPa). Mov Disord. 2019 Jan;34(1):67-77. doi: 10.1002/mds.27492. Epub 2018 Nov 23. PubMed PMID: 30468694. 2: Mollenhauer B, Zimmermann J, Sixel-Döring F, Focke NK, Wicke T, Ebentheuer J, Schaumburg M, Lang E, Trautmann E, Zetterberg H, Taylor P, Friede T, Trenkwalder C; DeNoPa Study Group. Monitoring of 30 marker candidates in early Parkinson disease as progression markers. Neurology. 2016 Jul 12;87(2):168-77. doi: 10.1212/WNL.0000000000002651. Epub 2016 May 6. PubMed PMID: 27164658; PubMed Central PMCID: PMC4940068.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-course-and-confounding-factors-of-mds-updrs-in-a-longitudinal-single-center-denopa-and-a-multicenter-cohort-ppmi/