Impulse Control Disorders In Parkinson's Disease Research Articles

Trait Impulsivity as a Feature of Parkinson's Disease Treatment and Progression.

Heightened trait impulsivity in both subclinical and pathological senses is becoming increasingly recognised in Parkinson's disease (PD). Impulsive behaviours and impulse control disorders (ICDs) are a consequence of perturbation to the rewards pathway leading individuals to conduct activities in a repetitive, excessive, and maladaptive fashion. Commonly linked to PD, heightened trait impulsivity has been found to primarily manifest in the forms of hypersexuality, pathological gambling, compulsive shopping, and binge eating, all of which may significantly impact social and financial standing. Subsequent burden to quality of life for both individuals with PD and caregivers are common. Although risk factors and indicators for ICDs in PD are currently lacking, it is recognised that the condition is often precipitated by dopamine replacement therapies, primarily dopamine agonist administration. While this nonmotor symptom is being increasingly diagnosed in PD populations, it remains relatively elusive in comparison to its motor counterparts. Through discussion of impulsivity characteristics, neuroanatomy, and neurochemistry, in addition to reviewing existing research on the potential contributing factors to impulsivity in PD, this review highlights impulsivity as a significant and detrimental PD symptom. Thus, emphasising the imperative need to establish efficacious diagnostic tools and treatments.

Morphometric alterations of the mesocorticolimbic network in Parkinson's disease with impulse control disorders.

Impulse control disorders (ICDs) are a group of non-motor symptoms of Parkinson disease (PD) leading to significant psychosocial detrimental outcome. The mesocorticolimbic network plays a distinctive role in reward learning and executive decision making and has been suggested to be involved in ICDs in PD. To study morphometric changes of the mesocorticolimbic network in PD with ICD. A total of 18 patients of PD with ICD (PD + ICD), 19 patients of PD without ICD (PD - ICD) and 19 healthy controls (HC) were included in the study. ICDs were diagnosed using Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). MRI was done using a 3T scanner and assessment of cortical thickness and subcortical volumes were done using FreeSurfer. Brain regions known to be part of the mesocorticolimbic network were extracted and included for statistical analysis. There was no difference between PD + ICD and PD - ICD with regard to duration of illness or total dopaminergic medication. In comparison to HC, patients with PD + ICD demonstrated atrophy of the left frontal pole, and this atrophy neared significance in comparison to PD - ICD. The QUIP-RS had a negative correlation with left caudate volume in PD + ICD. The PD + ICD group showed distinct morphometric changes in regions involved in the mesocorticolimbic system which may contribute to the presence of ICD.

White matter hyperintensities associated with impulse control disorders in Parkinson’s Disease

Impulse control disorders (ICDs) in Parkinson's disease (PD) are increasingly recognized as clinically significant non-motor features that potentially impair the quality of life. White matter hyperintensities (WMHs), detected by magnetic resonance imaging, are frequently observed in PD and can be associated with both motor- and certain non-motor symptoms. Given the limited number of non-motor features studied in this context, our aim was to reveal the potential association between the severity of WMHs and ICDs in PD. Fluid-attenuated inversion recovery magnetic resonance images were retrospectively evaluated in 70 patients with PD (48 males; 59.3 ± 10.1 years). The severity of WMHs was assessed by Fazekas scores and by the volume and number of supratentorial WMHs. ICDs were evaluated using the modified Minnesota Impulsive Disorders Interview. Significant interaction between age and the severity of WMHs was present for ICDs. In our younger patients (< 60.5 years), severity of WMHs was positively associated with ICDs (p = 0.004, p = 0.021, p < 0.001 and p < 0.001, respectively for periventricular white matter and total Fazekas scores and the volume and number of WMHs). Our study supports the hypothesis that WMHs of presumed vascular origin may contribute to ICDs in PD. Future prospective studies are needed to assess the prognostic relevance of this finding.

Association between metabolic syndrome components and impulse control disorders in Parkinson's disease.

Current evidence on management of impulse control disorders (ICDs) in Parkinson's disease (PD) remains scarce, and exploring modifiable risk factors is crucial. We evaluated the profiles of ICDs in PD patients and aimed to determine the associations between ICDs, metabolic syndrome components and other clinical features. We enrolled patients diagnosed with PD in this study and conducted comprehensive clinical assessments. We recruited 39 PD patients with ICDs and 66 PD patients without ICDs. Out of the 39 patients with ICDs, 19 (48.7%) had one impulse control disorder, while 20 (51.3%) had two or more. The most commonly reported symptom of ICDs was compulsive eating (48.7%). Significant differences were observed between the PD patients with and without ICDs in terms of their HbA1c levels, history of diabetes mellitus, dopamine agonist use, levodopa equivalent dose of dopamine agonists (LED DA), and Hamilton Depression Rating Scale (HAMD) scores. HbA1c levels were significantly higher in the PD patients with compulsive eating. Stepwise logistic regression analyses were performed with the dependent variables of ICDs (yes/no) and compulsive eating (yes/no). Among the 105 PD patients, those with ICDs exhibited higher levels of HbA1c, HAMD score and LED DA than those without ICDs (p < 0.01). Among 39 PD patients with ICDs, those with compulsive eating exhibited higher levels of HbA1c (OR = 2.148, 95% CI = 1.004-4.594, p < 0.05). Among 105 PD patients, those with compulsive eating exhibited higher levels of HbA1c, LED DA and HAMD score (p < 0.05). This study provides insights into the profiles of ICDs in PD patients and their associations with various clinical features. Compulsive eating was the most common ICDs symptom reported. Notably, HbA1c levels were found to be higher in patients with compulsive eating, indicating that poor blood glucose control may be a potential risk factor for ICDs in PD. However, it should be noted that the higher HbA1c levels could also be a consequence of compulsive eating rather than a causal factor for ICDs in PD. Further research is needed to confirm the modifiable risk factors for ICDs in PD.

Rapid Eye Movement Sleep Behavior Disorder in Parkinson's Disease: A Survey-Based Study.

To characterize Parkinson's disease (PD) symptoms based on the presence, onset time, and severity of rapid eye movement sleep behavior disorder (RBD) and their association with impulse control disorders (ICD). RBD is a frequent non-motor symptom in PD, usually described as prodromal. The severity of RBD according to the start time and its relationship with ICD in PD needs further clarification. A survey-based study was performed to determine the presence of RBD symptoms, their severity, and the temporal relationship with the PD onset. The survey included RBD1Q, the Mayo Sleep, and the RBDQ-HK questionnaires and questions about clinical characteristics, including ICD. Only PD patients with care partners spending night hours in the same room were included. 410 PD patients were included: 206 with RBD (50.2%) and 204 non-RBD (49.8%). The PD-RBD patients were younger and their daily levodopa dose was higher than the non-RBD group. Most of these patients developed RBD symptoms after the onset of clinical PD were younger at motor symptom onset and had higher scores in the hallucinations and psychosis subsection of MDS-UPDRS-I. RBD group had a more severe non-motor phenotype, including more ICD than those without RBD, mainly due to higher compulsive eating. In our study, most patients recognized RBD symptoms after the onset of the PD motor symptoms and the clinical features of PD with and without RBD were distinctive, supporting the hypothesis that PD-RBD might represent a variant pattern of neurodegeneration.

Neural correlates of risky decision making in Parkinson's disease patients with impulse control disorders.

Some patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by deficient voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of impulsive, risky decision making in PD patients with ICDs by disentangling potential dysfunctions in decision and outcome mechanisms. We collected fMRI data from 20 patients with ICDs and 28 without ICDs performing an information gathering task. Patients viewed sequences of bead colors drawn from hidden urns and were instructed to infer the majority bead color in each urn. With each new bead, they could choose to either seek more evidence by drawing another bead (draw choice) or make an urn-inference (urn choice followed by feedback). We manipulated risk via the probability of bead color splits (80/20 vs. 60/40) and potential loss following an incorrect inference ($10 vs. $0). Patients also completed the Barratt Impulsiveness Scale (BIS) to assess impulsivity. Patients with ICDs showed greater urn choice-specific activation in the right middle frontal gyrus, overlapping the dorsal premotor cortex. Across all patients, fewer draw choices (i.e., more impulsivity) were associated with greater activation during both decision making and outcome processing in a variety of frontal and parietal areas, cerebellum, and bilateral striatum. Our findings demonstrate that ICDs in PD are associated with differences in neural processing of risk-related information and outcomes, implicating both reward and sensorimotor dopaminergic pathways.

Imaging Dopaminergic Neurotransmission in Neurodegenerative Disorders.

Imaging of dopaminergic transmission in neurodegenerative disorders such as Parkinson disease (PD) or dementia with Lewy bodies plays a major role in clinical practice and in clinical research. We here review the role of imaging of the nigrostriatal pathway, as well as of striatal receptors and dopamine release, in common neurodegenerative disorders in clinical practice and research. Imaging of the nigrostriatal pathway has a high diagnostic accuracy to detect nigrostriatal degeneration in disorders characterized by nigrostriatal degeneration, such as PD and dementia with Lewy bodies, and disorders of more clinical importance, namely in patients with clinically uncertain parkinsonism. Imaging of striatal dopamine D2/3 receptors is not recommended for the differential diagnosis of parkinsonian disorders in clinical practice anymore. Regarding research, recently the European Medicines Agency has qualified dopamine transporter imaging as an enrichment biomarker for clinical trials in early PD, which underlines the high diagnostic accuracy of this imaging tool and will be implemented in future trials. Also, imaging of the presynaptic dopaminergic system plays a major role in, for example, examining the extent of nigrostriatal degeneration in preclinical and premotor phases of neurodegenerative disorders and to examine subtypes of PD. Also, imaging of postsynaptic dopamine D2/3 receptors plays a role in studying, for example, the neuronal substrate of impulse control disorders in PD, as well as in measuring endogenous dopamine release to examine, for example, motor complications in the treatment of PD. Finally, novel MRI sequences as neuromelanin-sensitive MRI are promising new tools to study nigrostriatal degeneration invivo.

Imaging Cognitive Impairment and Impulse Control Disorders in Parkinson's Disease

Dementia and mild forms of cognitive impairment as well as neuropsychiatric symptoms (i. e., impulse control disorders) are frequent and disabling non-motor symptoms of Parkinson's disease (PD). The identification of changes in neuroimaging studies for the early diagnosis and monitoring of the cognitive and neuropsychiatric symptoms associated with Parkinson's disease, as well as their pathophysiological understanding, are critical for the development of an optimal therapeutic approach. In the current literature review, we present an update on the latest structural and functional neuroimaging findings, including high magnetic field resonance and radionuclide imaging, assessing cognitive dysfunction and impulse control disorders in PD.

Impulse control disorders are associated with lower ventral striatum dopamine D3 receptor availability in Parkinson's disease: A [11C]-PHNO PET study

IntroductionReduced postsynaptic D3 dopaminergic receptor availability has been reported in the ventral striatum of pathological gamblers without Parkinson's disease (PD) and in patients with PD and impulse control disorders (ICD). However, a direct relationship between ventral striatum D3 dopaminergic receptors and the severity of ICD in PD patients has not yet been proven using a validated tool for ICD in PD, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease-Rating Scale (QUIP-RS). In this pilot study, we investigated the relationship between ventral striatum D3 dopamine receptor availability and severity of impulse control disorder (ICD) in Parkinson's disease (PD). MethodsTwelve patients were assessed with PET and the high affinity dopamine D3 receptor radioligand [11C]-PHNO. Severity of ICD was assessed with the QUIP-RS. ResultsWe found that lower ventral striatum D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of ICD, as measured by the QUIP-RS score (rho = −0.625, p = 0.03). ConclusionThese findings suggest that the occurrence and severity of ICD in Parkinson's disease may be linked to reductions in ventral striatum dopamine D3 receptor availability. Further studies in larger cohort of patients need to be performed in order to confirm our findings and clarify whether lower ventral striatum D3 receptor may reflect a pharmacological downregulation to higher dopamine release in ventral striatum of patients with ICD or a patients' predisposition to ICD.

Exploratory analysis of the genetics of impulse control disorders in Parkinson's disease using genetic risk scores

ObjectiveTo study the association between impulse control disorders (ICDs) in Parkinson's disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits). BackgroundIn absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD. MethodsWe searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson's Progression Markers Initiative database (N = 368, 33% female, age range = [33–84]) and the Drug Interaction With Genes in Parkinson's Disease study (N = 373, 40% female, age range = [29–85]). ResultsWe considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis. ConclusionAlbeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.

Integrating genetic and clinical data to predict impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) are frequent in Parkinson's disease (PD), with associated clinical and genetic risk factors. This study was aimed at analyzing the clinical features and the genetic background that underlie ICDs in PD. We included 353 patients with PD in this study (58.9% men, mean age 62.4±10.58years, mean age at disease onset 52.71±11.94years). We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease for ICDs screening. Motor, nonmotor, and treatment-related features were evaluated according to the presence of ICDs. Twenty-one variants related to dopaminergic, serotonergic, glutamatergic, and opioid neurotransmitter systems were assessed. Association studies between polymorphisms and ICDs were performed. The combination of clinical and genetic variables was analyzed with receiver operating characteristic curves to assess the predictability of experiencing ICDs. Impulse control disorders appeared in 25.1% of the cases. Patients with ICDs were younger and presented a higher rate of anxiety. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P<0.05). Genetic association studies showed that the DOPA decarboxylase gene (DDC), rs1451375, might modulate the risk of ICDs. Plotting the clinical-genetic model, the predictability of ICDs increased 11% (area under curve=0.80; z=3.22, P=0.001) when adding the genotype data for single nucleotide polymorphisms. Polymorphisms in DDC might act as risk markers for ICDs in PD. The predictability of experiencing ICDs increased by adding genetic factors to clinical features. It is therefore important to assess the patient's genetic background to identify individuals at risk for ICDs.

Relationship between impulse control disorders and preexisting type 2 diabetes mellitus in drug naïve Parkinson's Disease patients

Objective: To examine the possible impact of type 2 diabetes mellitus on impulse control disorders and other non-motor symptoms of de novo drug naïve PD patients. There is ample evidence to support the relationship between Parkinson's disease (PD) and type 2 diabetes mellitus, but the possible relationship between diabetes and impulse control disorders in PD has not yet been clarified.

Co-occurrence of apathy and impulse control disorders in Parkinson disease.

To empirically test whether apathy and impulse control disorders (ICDs) represent independent, opposite ends of a motivational spectrum. In this single-center, cross-sectional study, we obtained retrospective demographics and clinical data for 887 patients with idiopathic Parkinson disease (PD) seen at a tertiary care center. Mood and motivation disturbances were classified using recommended cutoff scores from self-reported measures of apathy, ICD, anxiety, and depression. Prevalence rates included 29.0% of patients with PD with depression, 40.7% with anxiety, 41.3% with apathy, 27.6% with ICDs, and 17.0% with both apathy and ICD. The majority (61.6%) of people reporting clinically significant ICDs also reported clinically significant apathy, and more than a third of patients with apathy (41.3%) also reported elevated ICD. Anxiety and depression were highest in patients with both apathy and ≥1 ICDs. Dopamine agonist use was higher in people with only ICD compared to people with only apathy. Mood significantly interacted with demographic variables to predict motivational disturbances. Motivational disturbances are common comorbid conditions in patients with PD. In addition, these complex behavioral syndromes interact with mood in clinically important ways that may influence the design of future clinical trials and the development of novel therapies. This study challenges the concept of apathy and ICD in PD as opposite ends of a spectrum.

Exome Sequencing Reveals Signal Transduction Genes Involved in Impulse Control Disorders in Parkinson's Disease.

Introduction: Impulse control disorders (ICDs) frequently complicate dopamine agonist (DA) therapy in Parkinson's disease (PD). There is growing evidence of a high heritability for ICDs in the general population and in PD. Variants on genes belonging to the reward pathway have been shown to account for part of this heritability. We aimed to identify new pathways associated with ICDs in PD.Methods: Thirty-six Parkinsonian patients on DA therapy with (n = 18) and without ICDs (n = 18) matched on age at PD's onset, and gender was selected to represent the most extreme phenotypes of their category. Exome sequencing was performed, and variants with a strong functional impact in brain-expressed genes were selected. Allele frequencies and their distribution in genes and pathways were analyzed with single variant and SKAT-O tests. The 10 most associated variants, genes, and pathways were retained for replication in the Parkinson's progression markers initiative (PPMI) cohort.Results: None of markers tested passed the significance threshold adjusted for multiple comparisons. However, the “Adenylate cyclase activating” pathway, one of the top associated pathways in the discovery data set (p = 1.6 × 10−3) was replicated in the PPMI cohort and was significantly associated with ICDs in a post hoc pooled analysis (combined p-value 3.3 × 10−5). Two of the 10 most associated variants belonged to genes implicated in cAMP and ERK signaling (rs34193571 in RasGRF2, p = 5 × 10−4; rs1877652 in PDE2A, p = 8 × 10−4) although non-significant after Bonferroni correction.Conclusion: Our results suggest that genes implicated in the signaling pathways linked to G protein-coupled receptors participate to genetic susceptibility to ICDs in PD.

The urge to move: From restless legs syndrome to impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are defined as a failure to resist an "urge" to behave in a way that may be debilitating for oneself or others. The suggested immobilization test (SIT) has been developed to assess the "urge" to move and support the diagnosis of restless legs syndrome (RLS) in the general population and in PD. A clinical association between RLS and ICDs has been shown in PD and in the general population. We hypothesized that there could be a semiological overlap between RLS and ICDs, and conducted SIT in PD patients with and without ICDs. Fifty PD patients with (n=17) and without (n=33) current ICDs were included. SIT, videopolysomnography, demographical treatment, and motor, psycho-behavioural and sleep characteristics, including RLS, were recorded. PD patients with ICDs reported increased subjective discomfort during SIT (SD-SIT) compared to those without ICDs (p=.024). Multivariable analysis confirmed ICDs as an independent factor associated with increased SD-SIT in PD, regardless of the presence of RLS, PD severity and dopamine agonist treatment dose. The discomfort measured by SIT might not only reflect the "urge" to move in RLS but also the ICDs in PD, suggesting that ICDs and RLS in PD could share a common phenomenology.

What drugs modify the risk of iatrogenic impulse-control disorders in Parkinson's disease? A preliminary pharmacoepidemiologic study.

Parkinson's disease (PD) patients treated with pramipexole (PPX) and ropinirole (ROP) exhibit a higher risk of developing impulse control disorders (ICDs), including gambling disorder, compulsive shopping, and hypersexuality. The management of ICDs in PD is challenging, due to the limited availability of effective therapeutic alternatives or counteractive strategies. Here, we used a pharmacoepidemiological approach to verify whether the risk for PPX/ROP-associated ICDs in PD patients was reduced by drugs that have been posited to exert therapeutic effects on idiopathic ICDs-including atypical antipsychotics (AAs), selective serotonin reuptake inhibitors (SSRIs), and glutamatergic modulators (GMs). To quantify the strength of the associations between PPX/ROP and other medications with respect to ICD risk, odds ratios (ORs) were calculated by multivariable logistic regression, adjusting for age, gender, marital status race, psychiatric comorbidities, and use of cabergoline and levodopa. A total of 935 patients were included in the analysis. Use of GMs, SSRIs, and AAs was not associated with a decreased ICD risk in PD patients treated with PPX/ROP; conversely, ICD risk was significantly increased in patients treated with either GMs (Adjusted Odds Ratio, ORa: 14.00 [3.58-54.44]) or SSRIs (ORa: 3.67 [1.07-12.59]). Results were inconclusive for AAs, as available data were insufficient to compute a reliable ORa. These results suggest that some of the key pharmacological strategies used to treat idiopathic ICD may not be effective for ICDs associated with PPX and ROP in PD patients. Future studies with larger cohorts are needed to confirm, validate, and extend these findings.

Depression as a Risk Factor for Impulse Control Disorders in Parkinson Disease.

To longitudinally evaluate the role of depression in the development of impulse control disorders (ICDs) in Parkinson disease (PD) patients. Using data from the Parkinson's Progression Markers Initiative, we included PD patients without ICDs at baseline according to the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Patients were prospectively evaluated first quarterly and then biannually. Development of an ICD was defined as an increase in QUIP scores during follow-up. Using survival proportional hazard models, we studied the effect of baseline depression on ICD risk. We also evaluated this effect controlling for dopamine agonist use as a time-dependent variable and for other potential confounders. Among 354 patients, 68 were depressed at baseline. The median follow-up was 4.08 years. Depression at baseline was associated with higher ICD risk (hazard ratio [HR] = 1.96, 95% confidence interval [CI] = 1.32-2.9, p < 0.001). This risk remained significant after controlling for dopamine agonist use (HR = 1.97, 95% CI = 1.33-2.9, p < 0.001), which was also independently linked to ICD development (HR = 1.87, 95% CI = 1.3-2.7, p < 0.001). Therefore, depressed patients faced an even higher ICD risk when receiving dopamine agonists. Controlling for multiple potential confounders did not alter these results. Depression predisposes to the development of ICDs in PD. This risk is magnified by dopamine agonists. Dopamine agonists should thus be used cautiously in depressed PD patients. ANN NEUROL 2019;86:762-769.

Impulse control disorders in Parkinson's disease: A systematic review on the psychometric properties of the existing measures.

BackgroundA significant percentage of patients suffering from Parkinson’s Disease (PD) experience Impulse Control Disorders (ICDs), contributing to reduced quality of life. As they can be managed by reducing the dopamine dosage, the detection of their presence is crucial for PD treatment plan. Nevertheless, they tend to be under-recognized in clinical practice, since routine screening is not common–despite existing instruments that may support clinicians. This work presents a systematic review on the psychometric properties of instruments measuring ICDs in PD, to test whether clinicians dispose of valid tools that may help them in clinical assessment.MethodA systematic literature search in three databases (EMBASE, MEDLINE, and PsycINFO) was conducted. Quality of the instruments’ psychometric properties was evaluated with Terwee et al.’s criteria, and methodological quality of the studies was evaluated with the COSMIN Checklist.ResultsTen studies examining seven instruments were selected. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) and the Ardouin Scale of Behavior in Parkinson’s Disease (ASBPD) resulted to be the best from a psychometric point of view.ConclusionsThough the gold standard for diagnosis remains a detailed diagnostic interview, this review will encourage clinicians to use validated tools to accurately assess ICDs.

Impact of Cognitive Profile on Impulse Control Disorders Presence and Severity in Parkinson's Disease.

Background: Impulse control disorders (ICDs) and related behaviors are frequent in Parkinson's disease (PD). Mild cognitive impairment (PD-MCI) and dementia (PDD), both characterized by heterogeneous cognitive phenotypes, are also commonly reported in PD. However, the frequency and severity of ICD within PD cognitive states is unknown.Methods: Three hundred and twenty-six PD patients completed a comprehensive neuropsychological assessment and were classified as PD-MCI, PDD, or without cognitive alterations (PD-NC). The Minnesota impulsive disorders interview was used to ascertain the presence (ICD+) or absence (ICD–) of ICD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale was used to assess ICD severity. A subsample of 286 patients evaluated with the same cognitive tasks was selected in order to investigate the characteristics of ICD in PD cognitive phenotypes.Results: ICDs were present in 55% of PD-NC, in 50% of PD-MCI, and in 42% of PDD patients. Frequencies of ICD+ with attentive (ICD+: 20% vs. ICD–: 4%; p = 0.031) and executive impairments (ICD+: 44% vs. ICD–: 30%; p = 0.027) were higher in the PD-MCI and PDD subgroups, respectively. As expected, no differences were observed in the PD-NC. PD-MCI with attentive impairments presented higher percentage of ICD+ with deficits in the Trail Making Test B-A but not in the Digit Span Sequencing task. In PDD, executive failures concerned Similarities task (ICD+: 67%; ICD–: 29%; p = 0.035), with no differences between ICD+ and ICD– in the Stroop task.Conclusions: Prevalence and severity of ICDs and related behaviors do not differ in PD with different cognitive states. However, ICD+ are more likely to show deficits, respectively in attentive and in executive domains, specifically in the Trail Making Test B-A task for the attention and working memory domain in PD-MCI and in the Similarities task for the executive function domain in PDD. Prospective studies should evaluate if these tests can be used as screening tool for ICDs in PD.

Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies.