Dopa Responsiveness in Parkinson's Disease

Abstract

Background: Dopaminergic responsiveness is a defining feature of Parkinson's disease (PD). However, there is limited information on how this evolves over time.

Objectives: To examine serial dopaminergic responses, if there are distinct patterns, and which factors predict these.

Methods: We analyzed data from the Parkinson's Progression Markers Initiative on 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.

Results: 1525 dopaminergic challenge tests were performed in 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 disease 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).

Conclusion: Three distinct patterns of the dopaminergic response were observed. As the proportion of PD cases with definite dopa responsiveness increased over time, the initial treatment response may be an unreliable diagnostic aid.

Keywords: Parkinson's disease; dopa response; levodopa.

Figure 1

Percentage change in MDS‐UPDRS part III scores in 1525 challenge tests in 336 cases of Parkinson's disease. At 1–2 years, 48.0% of challenge tests met the 24.5% threshold for a definite response, and a progressively greater proportion exceeded this threshold subsequently. Error bars are mean ± standard error, MDS‐UPDRS: Movement Disorder Society‐Unified Parkinson's Disease Rating Scale.

Figure 2

Trajectory of dopaminergic responsiveness over time according to data‐driven cluster categorization. Three groups were identified with differing dopa responsiveness. Most cases had increased responsiveness over time. MDS‐UPDRS, Movement Disorder Society‐Unified Parkinson's Disease Rating Scale.

Figure 3

Odds ratios from univariable modeling of the factors associated with dopa responsiveness. BMI, Body mass index; MoCA, Montreal Cognitive Assessment; MDS UPDRS III, Movement Disorder Society Unified Parkinson's Disease Rating Scale.

Figure 4

Odds ratios from multivariable modeling of the factors associated with dopa responsiveness. BMI, Body mass index; MoCA, Montreal Cognitive Assessment; MDS UPDRS III, Movement Disorder Society Unified Parkinson's Disease Rating Scale.

Figure 5

Motor scores in the off and on state in 336 cases of Parkinson's disease, categorized by test result. MDS UPDRS, Movement Disorder Society‐Unified Parkinson's Disease Rating Scale.