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BACKGROUND/OBJECTIVE: To synchronize data collection, the National Institute of Neurological Disorders and Stroke recommended Common Data Elements (CDEs) for use in Parkinson’s disease (PD) research. This study delineated the progression patterns of these CDEs in a cohort of PD patients. METHODS: One hundred-twenty-five PD patients participated in the PD Biomarker Program (PDBP) at Penn State. CDEs, including MDS-Unified PD Rating Scales (UPDRS)-total, questionnaire-based non-motor (-I) and motor (-II), and rater-based motor (-III) subscales; Montreal Cognitive Assessment (MoCA); Hamilton Depression Rating Scale (HDRS); University of Pennsylvania Smell Identification Test (UPSIT); and PD Questionnaire (PDQ-39) were obtained at baseline and three annual follow-ups. Annual change was delineated for PD or subgroups [early=PDE, disease duration (DD)5 y] using mixed effects model analyses. RESULTS: UPDRS-total, -II, and PDQ-39 scores increased significantly, and UPSIT decreased, whereas UPDRS-I, -III, MoCA, and HDRS did not change, over 36 months in the overall PD cohort. In the PDE subgroup, UPDRS-II increased and UPSIT decreased significantly, whereas MoCA and UPSIT decreased significantly in the PDM subgroup. In the PDL subgroup, UPDRS-II and PDQ-39 increased significantly. Other metrics within each individual subgroup did not change. Sensitivity analyses using subjects with complete data confirmed these findings. CONCLUSIONS: Among CDEs, UPDRS-total, –II, PDQ-39, and UPSIT all are sensitive metrics to track PD progression. Subgroup analyses revealed that these CDEs have distinct stage-dependent sensitivities, with UPSIT for DD5 y, UPDRS-II for early (DD 5).

Postural instability is a major disabling feature in Parkinson’s disease (PD). We quantified the organization of leg and trunk muscles into synergies stabilizing the center of pressure (COP) coordinate within the uncontrolled manifold hypothesis in levodopa-naive patients with PD and age-matched control subjects. The main hypothesis was that changes in the synergic control of posture are present early in the PD process even before levodopa exposure. Eleven levodopa-naive patients with PD and 11 healthy controls performed whole-body cyclical voluntary sway tasks and a self-initiated load-release task during standing on a force plate. Surface electromyographic activity in 13 muscles on the right side of the body was analyzed to identify muscle groups with parallel scaling of activation levels (M-modes). Data were collected both before (“off-drug”) and approximately 60 min after the first dose of 25/100 carbidopa/levodopa (“on-drug”). COP-stabilizing synergies were quantified for the load-release task. Levodopa-naive patients with PD showed no COP-stabilizing synergy “off-drug”, whereas controls showed posture-stabilizing multi-M-mode synergy. “On-drug”, patients with PD demonstrated a significant increase in the synergy index. There were no significant drug effects on the M-mode composition, anticipatory postural adjustments, indices of motor equivalence, or indices of COP variability. The results suggest that levodopa-naive patients with PD already show impaired posture-stabilizing multi-muscle synergies that may be used as promising behavioral biomarkers for emerging postural disorders in PD. Moreover, levodopa modified synergy metrics differently in these levodopa-naive patients compared to a previous study of patients on chronic antiparkinsonian medications (Falaki et al. in J Electromyogr Kinesiol 33:20–26, 2017a), suggesting different neurocircuitry involvement.

We explored the origin of the impaired control of action stability in Parkinson’s disease (PD) by testing levodopa-naive PD patients to disambiguate effects of PD from possible effects of long-term exposure to levodopa. Thirteen levodopa-naive PD patients and 13 controls performed single- and multi-finger force production tasks, including producing a self-paced quick force pulse into a target. A subgroup of patients (n = 10) was re-tested about 1 h after the first dose of levodopa. Compared to controls, PD patients showed lower maximal forces and synergy indices stabilizing total force (reflecting the higher inter-trial variance component affecting total force). In addition, PD patients showed a trend toward shorter anticipatory synergy adjustments (a drop in the synergy index in preparation to a quick action) and larger non-motor equivalent finger force deviations. Lower maximal force, higher unintentional force production (enslaving) and higher inter-trial variance indices occurred in PD patients after one dosage of levodopa. We conclude that impairment in synergies is present in levodopa-naive patients, mainly in indices reflecting stability (synergy index), but not agility (anticipatory synergy adjustments). A single dose of levodopa, however, did not improve synergy indices, as it did in PD patients on chronic anti-PD medication, suggesting a different mechanism of action. The results suggest that indices of force-stabilizing synergies may be used as an early behavioral sign of PD, although it may not be sensitive to acute drug effects in drug-naive patients.