Objective: To investigate inhibitory control under dopamine (DA) in Parkinson’s disease (PD).

Background: The pattern of degeneration in PD as well as side effects of dopaminergic treatment depend on the patients’ age. Impaired inhibitory control under DA can have serious implications¹ and is more frequently observed in young onset PD patients (YOPD)².

Methods: Our study included 10 YOPD and 17 late onset PD patients (LOPD) who differed strongly with respect to age (48.9y±3.2y vs. 68.0y±6.0y, p<0.001) but not disease duration (4.6y±3.8y vs. 5.0y±4.0y, p=0.941). All patients underwent a Go/NoGo paradigm comprising a global and specific Go and a global and specific NoGo condition both ON and OFF dopaminergic medication. The ratio of DA transporter (DAT) availability in the associative relative to the sensorimotor part of the striatum according to [123I]FP-CIT SPECT was employed to compare patterns of nigrostriatal degeneration between YOPD and LOPD (n=8/10). Computational modeling identified mechanisms through which therapy and degeneration affect Go/NoGo performance.

Results: Patients made more errors ON compared to OFF in the global NoGo (2.7%±3.3% vs. 1.5%±3.4%, p=0.033) independent of their age. Reaction times did not differ. The DA effect on the ON-OFF difference of global NoGo error rates correlated with disease duration (r=0.489, p=0.010). The YOPD group made more errors in the specific NoGo ON-OFF (Z=-2.398, p=0.015) compared to the LOPD group [figure 1]. The associative-to-sensorimotor DAT ratio showed a negative correlation with age (r=-0.748; p<0.001). Thus, YOPD patients had a higher associative-to-sensorimotor DAT ratio compared to LOPD patients (Z=-3.626, p<0.001). Neuro-computational modeling of the basal ganglia suggested that the effect of age on specific NoGo performance could be explained by DA overdosing in the relatively intact associative striatum in YOPD.

Conclusions: Overall, patients performed worse ON DA in the global NoGo suggesting dopaminergic treatment to impair inhibition. The negative impact of DA on global NoGo performance increased with disease duration but did not differ with respect to age. DA had a detrimental effect on specific NoGo performance, too, but only in YOPD which also showed less degeneration in the associative compared to the sensorimotor striatum. Our findings suggest that worsened performance under DA in YOPD is due to overdosing in the relatively intact associative striatum.

References: 1. Maloney E, Djamshidian A, O’Sullivan S. Phenomenology and epidemiology of impulsive-compulsive behaviours in Parkinson’s disease, atypical Parkinsonian disorders and non-Parkinsonian populations. J Neurol Sci 2017; 374: 47–52. 2. Fereshtehnejad S-M, Postuma R. Subtypes of Parkinson’s Disease: What Do They Tell Us About Disease Progression? Curr Neurol Neurosci 2017; 17: 34.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/opposite-effects-of-dopamine-on-specific-nogo-perfomance-in-young-and-late-onset-parkinsons-disease-and-the-relationship-to-nigrostriatal-degeneration/