Nigrostriatal dopamine transporter availability, and its metabolic and clinical correlates in Parkinson’s disease patients with impulse control disorders
Previous studies in patients with Parkinson’s disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD.
In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed.
PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus.
ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.
KeywordsParkinson’s disease Impulse control disorders Dopamine transporter Cerebral metabolism Cognition
M.C.R.-O. and I.N.-G. designed and organized the study; I.N.-G, R.D.-A. and M.C.R.-O. collected the data; M.C.R.-O. supervised the study; A.B.-P., F.M.-D. and I.N.-G. performed the statistical analysis; I.N.-G and M.C.R.-O. interpreted the results of the analysis with substantial contribution from all the authors; I.N.-G. and F.M.-D. drafted the manuscript, to which all the authors contributed with revisions.
This study was funded by the Carlos III Institute of Health (PI11/02109) and by the ERA-Neuron program (PIM2010ERN-00733). In addition, Dr. Navalpotro-Gomez held a Rio Hortega 2016 grant (CM16/00033) from the Carlos III Institute of Health.
Compliance with ethical standards
Conflict of interest
I.N.-G. received honoraria for travel and accommodation to attend scientific meetings from Zambon. R.D.-A., F.M.-D., H.J.-U, B.G. and A.Q.-V. have no disclosures to declare. A.M.-B received honoraria for travel and accommodation from Zambon and Bial. M.C.R.-O. received honoraria for lectures, travel and accommodation to attend scientific meetings from Abbvie, Zambon, Bial and Boston Scientific, and she received financial support for her research from national and local government funding agencies in Spain (Institute of Health Carlos III, Basque Country Local Government, and CIBERNED). M.D.-A. received honoraria for travel and accommodation to attend scientific meetings from UCB and Zambon. None of these bodies influenced the content of the manuscript or the decision to publish in any way.
All the procedures carried out involving human participants were in accordance with the ethical standards of the Gipuzkoa Clinical Research Ethics Committee, and with the principles of the 1964 Declaration of Helsinki and its later amendments, or comparable ethical standards.
Informed consent was obtained from all the participants prior to their inclusion in the study.
- 6.Son HJ, Jeong YJ, Yoon HJ, Kim JW, Choi GE, Park JH, et al.Parkinson disease-related cortical and striatal cognitive patterns in dual time F-18 FP CIT: evidence for neural correlates between the caudate and the frontal lobe. Q J Nucl Med Mol Imaging. 2017. https://doi.org/10.23736/S1824-4785.17.02976-4.
- 33.Varrone A, Dickson JC, Tossici-Bolt L, Sera T, Asenbaum S, Booij J, et al. European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis. Eur J Nucl Med Mol Imaging. 2013;40:213–27.CrossRefGoogle Scholar
- 50.Biars JW, Johnson NL, Nespeca M, Busch RM, Kubu CS, Floden DP. Iowa gambling task performance in Parkinson disease patients with impulse control disorders. Arch Clin Neuropsychol. 2019;34(3):310–8. https://doi.org/10.1093/arclin/acy036.
- 55.Weintraub D, Newberg AB, Cary MS, Siderowf AD, Moberg PJ, Kleiner-Fisman G, et al. Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson’s disease. J Nucl Med. 2005;46:227–32.Google Scholar