Direct dopaminergic responsiveness of activity performance

Objective: To assess the direct dopaminergic responsiveness of motor and process aspects of activity performance in people with parkinsonian disorders, and to compare this to the symptomatic motor response. 

Background: Parkinsonian disorders are associated with limitations in daily activity performance. However, while the dopaminergic responsiveness of motor symptoms is well established, the direct dopaminergic responsiveness of aspects of activity performance appears unaddressed since assessments of activity performance typically are retrospective. This is a limitation since impairment (symptoms and signs) is a separate construct from activity limitations, and the latter is not only related to the former. 

Methods: Twenty-seven people with parkinsonian disorders (18 men; mean age and disease duration, 68 and 8 years, respectively) underwent a clinical dopaminergic drug response test (median (range) L-dopa dose, 150 (100-300) mg) following 12 hours of dopaminergic drug withdrawal. Participants were tested according to the Unified PD Rating Scale (UPDRS) motor examination and the Assessment of Motor and Process Skills (AMPS) scale in the defined ”off” and best ”on” states. Similar to the UPDRS motor examination, AMPS ratings are based on direct observations of activity performance. Average ”off”, ”on” and change scores were compared, and magnitudes of responsiveness were estimated using Cohen’s d_zeffect size (ES). Correlations between outcomes were also computed. 

Results: Motor symptoms (mean UPDRS motor scores) improved from 36.2 in the defined “off” to 22.5 in the best “on” state, representing an ES of 0.74. Mean AMPS motor scores improved from 1.46 (defined “off”) to 2.34 (best “on”) and mean process scores improved from 1.37 to 1.85, representing ESs of 1.13 (motor) and 0.79 (process). Absolute correlations between UPDRS motor scores and AMPS motor/process scores ranged between 0.40-0.61 for defined “off”, best “on” and change scores.

Conclusions: The dopaminergic responsiveness was more pronounced for activity performance than for motor symptoms, although motor symptom responsiveness was similar to that of process aspects of activity performance. Correlations suggest that symptomatic motor response is a relatively weak predictor of daily activity performance. These observations argue for the need to specifically address activity performance outcomes in clinical studies.