Response inhibition in Parkinson's disease: a meta-analysis of dopaminergic medication and disease duration effects

Abstract

Parkinson's disease is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. Dopamine-replacement therapy ameliorates some of the hallmark motor symptoms of Parkinson's disease, but whether these medications improve deficits in response inhibition, a critical executive function for behavioral control, has been questioned. Several studies of Parkinson's disease patients "on" and "off" (12-h withdrawal) dopaminergic medications suggested that dopamine-replacement therapy did not provide significant response inhibition benefits. However, these studies tended to include patients with moderate-to-advanced Parkinson's disease, when the efficacy of dopaminergic drugs is reduced compared to early-stage Parkinson's disease. In contrast, a few recent studies in early-stage Parkinson's disease report that dopaminergic drugs do improve response inhibition deficits. Based on these findings, we hypothesized that Parkinson's disease duration interacts with medication status to produce changes in cognitive function. To investigate this issue, we conducted a meta-analysis of studies comparing patients with Parkinson's disease and healthy controls on tests of response inhibition (50 comparisons from 42 studies). The findings supported the hypothesis; medication benefited response inhibition in patients with shorter disease duration, whereas "off" medication, moderate deficits were present that were relatively unaffected by disease duration. These findings support the role of dopamine in response inhibition and suggest the need to consider disease duration in research of the efficacy of dopamine-replacement therapy on cognitive function in Parkinson's disease.

Conflict of interest statement

The authors declare that they have no competing financial interests.

Figures

Fig. 1

a Flow chart of meta-analysis procedure. bLeft: simplified schematic for each task used in the meta-analysis. Right: outcome measure used for each task; we chose the measure that was most commonly reported across studies for each task

Fig. 2

Forest plot of effect sizes for all studies that compared performance on a response inhibition task between a PD group and a matched healthy control group. a Studies sorted by medication status. b Studies sorted by task. Effect sizes to the left of the vertical dashed line indicate that performance of the PD group was poorer than controls. Note: Avg., Average; SST, Stop-Signal Task; GNG, Go-NoGo; A-S, Anti-Saccade

Fig. 3

Regression plot of response inhibition deficits on average disease duration for the “off” medication (blue) and “on” medication (red) samples. Effect sizes less than 0 indicate that PD patients demonstrated poorer response inhibition performance than healthy controls. Each bubble represents a comparison from one study, weighted by within-study variance. Smaller bubbles represent studies with higher variance than others and thus, have less influence on the regression. The regression line of best fit for each sample is also shown. The difference in slopes was significant (z test; p = .04), indicating that “off” medication, deficits were moderate and relatively unaffected by disease duration, whereas “on” medication, deficits were significantly associated by disease duration. *p < .05; ***p = .001