Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures.

BACKGROUND: Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials. OBJECTIVES: To examine whether baseline measures and their 1-year change predict longer-term progression in early PD. METHODS: Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models. RESULTS: Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (ß= 0.351; 95% CI = 0.146, 0.555), male gender (ß= 3.090; 95% CI = 0.310, 5.869), and baseline (ß= -0.199; 95% CI = -0.315, -0.082) and 1-year change (ß= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (ß= -0.6229; 95% CI = -1.2910, 0.0452), baseline (ß= 7.232; 95% CI = 2.268, 12.195) and 1-year change (ß= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (ß= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance. CONCLUSIONS: Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI).

OBJECTIVE: To determine the feasibility, safety and tolerability of lumbar punctures (LPs) in research participants with early Parkinson disease (PD), subjects without evidence of dopaminergic deficiency (SWEDDs) and healthy volunteers (HC). BACKGROUND: Cerebrospinal fluid (CSF) analysis is becoming an essential part of the biomarkers discovery effort in PD with still limited data on safety and feasibility of serial LPs in PD participants. DESIGN/METHODS: Parkinson's Progression Marker Initiative (PPMI) is a longitudinal observation study designed to identify PD progression biomarkers. All PPMI participants undergo LP at baseline, 6, 12 months and yearly thereafter. CSF collection is performed by a trained investigator using predominantly atraumatic needles. Adverse events (AEs) are monitored by phone one week after LP completion. We analyzed safety data from baseline LPs. RESULTS: PPMI enrolled 683 participants (423 PD/196 HC/64 SWEDDs) from 23 study sites. CSF was collected at baseline in 97.5% of participants, of whom 5.4% underwent collection under fluoroscopy. 23% participants reported any related AEs, 68% of all AE were mild while 5.6% were severe. The most common AEs were headaches (13%) and low back pain (6.5%) and both occurred more commonly in HC and SWEDDs compared to PD participants. Factors associated with higher incidence of AEs across the cohorts included female gender, younger age and use of traumatic needles with larger diameter. AEs largely did not impact compliance with the future LPs. CONCLUSIONS: LPs are safe and feasible in PD research participants. Specific LP techniques (needle type and gauge) may reduce the overall incidence of AEs.