Dopa responsiveness in Parkinson’s disease

Abstract

AbstractBackgroundDopaminergic responsiveness is a defining feature of Parkinson’s disease (PD). However, there is limited information on how this evolves over time.ObjectivesTo examine serial dopaminergic responses, if there are distinct patterns, and which factors predict these.MethodsWe analyzed data from theParkinson’s Progression Markers Initiativeon repeated dopaminergic challenge tests (≥ 24.5% defined as a definite response). Growth-mixture modeling evaluated for different response patterns and multinomial logistic regression tested for predictors of these clusters.ResultsThere were 1,525 dopaminergic challenge tests from 336 patients. At enrolment, mean age was 61.2 years (SD 9.6), 66.4% were male and disease duration was 0.5 years (SD 0.5). 1 to 2 years after diagnosis, 48.0% of tests showed a definite response, but this proportion increased with longer duration (51.1-74.3%). We identified 3 response groups: ‘Striking’ (n = 29, 8.7%); ‘Excellent’ (n = 110; 32.7%) and ‘Modest’ (n = 197, 58.6%). Significant differences were as follows: striking responders commenced treatment earlier (P = 0.02), were less likely to be on dopamine agonist monotherapy (P = 0.01), and had better cognition (P < 0.01) and activities of daily living (P = 0.01). Excellent responders had higher challenge doses (P = 0.03) and were more likely to be on combination therapy (P < 0.01).ConclusionThree distinct patterns of the dopaminergic response were observed. The proportion of PD cases with definite dopa responsiveness increased over time, so the initial treatment response may be an unreliable diagnostic aid.