Impulsive and compulsive behaviors in Parkinson's disease.
ABSTRACT: BACKGROUND: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson's disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs). CONTENTS: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs. RESULTS: The prevalence of ICBs in PD patients is approximately 3-4% for DDS, 0.34-4.2% for punding, and 6-14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs. CONCLUSION: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.
Project description:The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation.We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was adopted to rate ICB severity.Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score.Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity.
Project description:Impulsive and compulsive behaviors (ICBs) are frequent in Parkinson's disease (PD), but data from population-based cohorts is lacking.To determine the frequency and associated demographic, clinical, neuropsychiatric and cognitive features of ICBs in a population-based PD cohort.This cross-sectional study included 125 patients with PD and 159 age- and gender-matched normal controls recruited from the Norwegian ParkWest study. Participants underwent comprehensive neurological, neuropsychiatric and neuropsychological assessments. ICBs were assessed using the Questionnaire for Impulsive-Compulsive Disorders in PD short form. Multiple logistic regression analyses were performed to compare the odds of ICBs between groups and to identify independent correlates of ICBs in PD.30.4% of patients reported at least one ICB, with an odds ratio (OR) of 3.2 (95% confidence interval [CI] 1.8-5.9) compared with controls. Multiple ICBs were experienced by 8.8% of patients vs 1.3% of controls (OR 7.6, 95% CI 1.7-34.8). Compared to controls, the ORs of having an ICB were 7.4 (95% CI 2.6-20.9) in patients taking DA without levodopa, 4.6 (95% CI 2.3-9.3) in those treated with both DA and levodopa, and 1.2 (95% CI 0.5-3.2) in patients using levodopa but not DA. In multivariate models, ICB status in patients was independently associated with DA treatment and depressive symptoms, but not with other dopaminergic medications, motor function, or cognitive performance.Patients with PD treated with DA, but not other dopaminergic medications, have increased odds of having ICBs compared with age- and gender-matched controls. This has implications for individualized patient management and follow-up.
Project description:As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
Project description:Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome).The Parkinson's Impulse-Control Scale (PICS), the first PD-specific, semistructured interview to cover the full range of PD-related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92).The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%-95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (?) values for clinician-clinician rating of severity (? = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive-behavioral therapy and medication adjustment (t = 5.47; P < 0.001).The PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required.
Project description:Impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence, and risk factors of patients with PD. Results of behavioral studies assessing the neuropsychological profile of patients with PD emphasize that the ICBs, which are behavioral addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis, are discussed, and therapeutic guidelines for the management of ICBs in PD are given.
Project description:The longitudinal course of ICBs in patients with Parkinson's disease (PwP) relative to controls has not been explored as of yet. The aim of this study is to determine the frequency, evolution and associated cognitive and clinical features of impulsive and compulsive behaviors (ICBs) over 4 years of prospective follow-up in a population-based cohort with early Parkinson's disease (PD). We recruited 124 cognitively intact participants with early PD and 156 matched controls from the Norwegian ParkWest study. ICBs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Cognitive changes were examined in PwP with and without ICBs who completed the 4-year follow-up. Generalized linear mixed modelling and mixed linear regression were used to analyze clinical factors and cognitive changes associated with ICBs in PwP over time. ICBs were more common in PwP than controls at all visits, with an age-adjusted odds ratio (OR) varying between 2.5 (95% CI 1.1-5.6; p?=?0.022) and 5.1 (95% CI 2.4-11.0; p?<?0.001). The 4-year cumulative frequency of ICBs in PwP was 46.8% and 23.3% developed incident ICBs during the study period, but the presence of ICBs was non-persistent in nearly 30%. ICBs were independently associated with younger age (OR 0.95, 95% CI 0.91-0.99: p?=?0.008) and use of dopamine agonist (OR 4.1, 95% CI 1.56-10.69). Cognitive changes over time did not differ between patients with and without ICBs. In conclusion, ICBs are common in PwP, but are often non-persistent and not associated with greater cognitive impairment over time.
Project description:The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47?±?9.09 years, 59.87% men) and 179 CS (mean age 60.84?±?8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p?<?0.001; CBs 7.18% vs. 1.67%, p?=?0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p?<?0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p?<?0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p?<?0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.
Project description:Links between impulsive-compulsive behaviors (ICBs) in treated Parkinson's disease (PD), behavioral addictions, and substance abuse have been postulated, but no direct comparisons have been carried out so far. We directly compared patients with PD with and without ICBs with illicit drug abusers, pathological gamblers, and age-matched healthy controls using the beads task, a test of reflection impulsivity, and a working memory task. We found that all patients with PD made more impulsive and irrational choices than the control group. PD patients who had an ICB showed similar behavior to illicit substance abusers, whereas patients without ICBs more closely resembled pathological gamblers. In contrast, we found no difference in working memory performance within the PD groups. However, PD patients without ICBs remembered distractors significantly less than all other patients during working memory tests. We were able to correctly classify 96% of the PD patients with respect to whether or not they had an ICB by analyzing three trials of the 80/20 loss condition of the beads task with a negative prediction value of 92.3%, and we propose that this task may prove to be a powerful screening tool to detect an ICB in PD. Our results also suggest that intact cortical processing and less distractibility in PD patients without ICBs may protect them from developing behavioral addictions.
Project description:Impulse control disorders (ICDs) are debilitating side effects of dopamine replacement therapy (DRT) in Parkinson's disease (PD) that severely affect the quality of life of patients. While DRT, the pattern and extent of neurodegeneration, and prodromic factors of vulnerability (e.g. impulsivity) have all been hypothesized to play a role in the development of ICDs, their respective, and potentially interacting, contributions remain to be established. High impulsive (HI), Intermediate (Int) or low impulsive (LI) rats were identified based on their performance in both a differential reinforcement of low rate of responding (DRL) and a fixed consecutive number (FCN) schedules, that operationalize two independent facets of impulsivity, waiting and action inhibition (motor impulsivity). We investigated whether high impulsivity trait influenced the progressive development of a parkinsonian state induced by viral-mediated overexpression of ?-synuclein, and whether impulsivity trait and nigrostriatal neurodegeneration independently or jointly influenced the effects of DRT on impulse control. ?-synuclein-induced nigrostriatal neurodegeneration increased both waiting and motor impulsivity. The D2/D3 dopamine receptor agonist pramipexole exacerbated motor impulsivity more than waiting. However, the pramipexole-induced increase in waiting impulsivity observed in both sham and lesioned rats, was more pronounced in HI lesioned rats, which displayed a restricted ?-synuclein-induced dopaminergic neurodegeneration. Thus, a PD-like nigrostriatal lesion increases both motor and waiting impulsivity, but its interaction with a pre-existing impulsivity trait, which, at the cellular level, confers resilience to dopaminergic neurodegeneration, worsens the detrimental effects of D2/D3 dopamine receptor agonists on inhibitory control.
Project description:Punding, one of dopamine replacement treatment related complications, refers to aimless and stereotyped behaviors. To identify possible neural correlates of punding behavior in patients with Parkinson's disease (PD), we investigated the patterns of cognitive profiles and cortical thinning.Of the 186 subjects with PD screened during the study period, we prospectively enrolled 10 PD patients with punding and 43 without punding on the basis of a structured interview. We performed comprehensive neuropsychological tests and voxel-based and regions-of-interest (ROIs)-based cortical thickness analysis between PD patients with and without punding.The prevalence of punding in patients with PD was 5.4%. Punding behaviors were closely related to previous occupations or hobbies and showed a temporal relationship to changes of levodopa-equivalent dose (LED). Significant predisposing factors were a long duration of PD and intake of medications of PD, high total daily LED, dyskinesia, and impulse control disorder. Punding severity was correlated with LED (p = 0.029). The neurocognitive assessment revealed that PD patients with punding showed more severe cognitive deficits in the color Stroop task than did those without punding (p = 0.022). Voxel-based analysis showed that PD-punders had significant cortical thinning in the dorsolateral prefrontal area relative to controls. Additionally, ROI-based analysis revealed that cortical thinning in PD-punders relative to PD-nonpunders was localized in the prefrontal cortices, extending into orbitofrontal area.We demonstrated that PD patients with punding performed poorly on cognitive tasks in frontal executive functions and showed severe cortical thinning in the dorsolateral prefrontal and orbitofrontal areas. These findings suggest that prefrontal modulation may be an essential component in the development of punding behavior in patients with PD.