Objective: To identify clinical, imaging, and biochemical measures, obtained early in the disease course that predict clinical and dopamine transporter (DAT) imaging progression in PD.

Background: Improved prognostic information in PD would be useful both clinically and in research. Baseline characteristics that are associated with disease progression could be used to select study participants, making possible smaller and/or shorter clinical trials.

Methods: Data from the Parkinson’s Progression Markers Initiative (PPMI) study were used for this analysis. At enrollment, PPMI participants had disease duration ≤2 years, abnormal DAT SPECT, and were untreated with PD medications. Linear mixed-effects models were used to identify predictors of change in MDS-UPDRS total score. Baseline predictors included clinical (motor scales, non-motor questionnaires, orthostatic systolic blood pressure (SBP), BMI), CSF (abeta1-42, alpha-synuclein, total tau, phospho-tau), and DAT SPECT binding measures (mean putamen, mean striatum). Analyses were adjusted for sex and baseline values for age, MDS-UPDRS score, and disease duration.

Results: Among 423 PD participants enrolled in PPMI (mean age 61.7 years, 65.48% male, mean disease duration 6.71 months), mean follow-up duration was 4.25 years. Predictors of change in MDS-UPDRS total score included: male gender (β=1.903; 95%CI 0.069,3.738; p=0.042), orthostatic SBP change (β =-0.076; 95% CI -0.144,-0.008; p=0.030), CSF abeta1-42 (β=-0.003 (95% CI -0.006,-0.001; p=0.021), and mean putamen DAT binding (β=-4.828; 95% CI -7.950,-1.707; p=0.003). Predictors of change in mean striatum DAT binding included: modified Schwab and England (β=0.071; 95% CI 0.004, 0.480; p=0.242), RBD symptoms (β=-1.003; 95%CI -1.527, -0.479; p=0.0002) and orthostatic SBP (β=0.115; 95%CI 0.007, 0.224; p=0.036).

Conclusions: In the PPMI PD cohort, several baseline demographic and clinical variables were associated with greater progression of MDS-UPDRS. Among biomarkers, significant associations were identified between mean putamen DAT binding and CSF abeta1-42 and change in MDS-UPDRS. A few motor and non-motor clinical features were associated with reduced DAT binding over time. While these factors may help stratify patients for clinical trial participation, discovery of novel markers with greater predictive capacity is still needed to optimize trial efficiency.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-predictors-of-clinical-and-imaging-progression-in-parkinsons-disease-results-from-the-ppmi-study/