Associations between Sleep Disorders and Impulsive-Compulsive Behaviors in Parkinson's Disease: A Prospective Cohort Study.

OBJECTIVE: To examine the associations of excessive daytime sleepiness (EDS) and probable rapid eye movement sleep behavior disorder (pRBD), respectively, with impulsive-compulsive behaviors (ICBs) over a 5-year follow-up in patients with early Parkinson's disease (PD). METHODS: The Parkinson's Progression Markers Initiative is a multicenter cohort study based on an ongoing and open-ended registry. Longitudinal associations of sleep disorders with ICB over 5-year follow-up visits were estimated using generalized linear mixed-effects models among PD participants. RESULTS: A total of 825 PD participants were enrolled at baseline. The study sample had a median baseline age of 63.1 (interquartile range: 55.6-69.3) years and comprised 496 (61.5%) men. Among them, 201 (24.9%) had ICB at baseline. In the generalized mixed-effects models, EDS (odds ratio [OR] = 1.09, 95% confidence interval [CI] 1.05, 1.12) and RBD (OR = 1.07, 95% CI 1.03, 1.12) were substantially associated with higher odds of developing ICB over time in PD patients, after multivariate adjustment including age, gender, family history, GDS score, STAI-Y score, MDS-UPDRS part III score, LEDD, and disease duration. Consistent results were observed when stratifying by age at baseline, gender, and PD family history. CONCLUSIONS: The study findings suggest a longitudinal association between EDS and pRBD with an increased risk of developing ICB in patients with PD. The findings emphasize the significance of evaluating and addressing sleep disorders in PD patients as a potential approach to managing ICB.

Case report: Dopamine Dysregulation Syndrome, mania, and compulsive buying in a patient with Parkinson's disease.

Neuropsychiatric symptoms and syndromes are among the most common non-motor symptoms of Parkinson's Disease but they are frequently unrecognized and untreated. Dopamine Dysregulation Syndrome is an uncommon complication of the treatment of Parkinson's disease, characterized by an addictive use of dopamine far more than the dosage required for treatment of objective motor impairment, leading to severe dyskinesia, euphoria, aggressivity, or psychosis. We present a paradigmatic case of Dopamine Dysregulation Syndrome, Mania, and Compulsive Buying in a 55-year-old male with Parkinson's Disease. We also reviewed the risk factors and the therapeutic management of Dopamine Dysregulation Syndrome in Parkinson's Disease.

Dyskinesia and impulsive compulsive behaviour in Parkinson's disease are not related: Insights from a study with a wearable sensor.

INTRODUCTION: Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. OBJECTIVES: To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device. METHODS: In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient's and clinician's based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson's KinetiGraph™(PKG). RESULTS: We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample. CONCLUSION: Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.

Punding in Parkinson's Disease: An Update.

Background: Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, non-goal oriented, repetitive activity affecting individuals with Parkinson's disease (PD) on dopamine replacement therapy (DRT). Objectives: In 2010, we published the first review focused on the pathophysiology of punding. This study aims to systematically review the literature of the past decade on punding in PD, particularly focusing on the clinical features, underlying pathophysiological mechanisms, and treatment. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and APA PsycInfo for articles published between July 1, 2010 and March 19, 2022. The search strategy included: (punding) AND (parkinson*). Results: Of 256 studies identified, 29 were eligible for inclusion with 19 original research articles and 10 case reports. This review confirmed that predictors of punding in PD are higher doses of DRT, younger age, male sex, and increasing disease severity. We also found an association between punding and psychiatric and/or cognitive symptoms. Neuroimaging studies have showed that punding in PD is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices and a breakdown of the connectivity among the crucial nodes of the reward circuit. Low-frequency repetitive transcranial magnetic stimulation on the dorsolateral prefrontal cortex has been shown to produce a transient beneficial effect in PD patients with punding. Conclusion: In conclusion, although the clinical features of punding have been established, in the past 12 years, we gained a better understanding of the pathophysiological mechanisms of punding, mainly thanks to magnetic resonance imaging techniques.

Neural correlates of impulsive compulsive behaviors in Parkinson's disease: A Japanese retrospective study.

BACKGROUND: Impulsive compulsive behaviors (ICBs) often disturb patients with Parkinson's Disease (PD), of which impulse control disorder (ICD) and dopamine dysregulation syndrome (DDS) are two major subsets. The nucleus accumbens (NAcc) is involved in ICB; however, it remains unclear how the NAcc affects cortical function and defines the different behavioral characteristics of ICD and DDS. OBJECTIVES: To identify the cortico-striatal network primarily involved in ICB and the differences in these networks between patients with ICD and DDS using structural and resting-state functional magnetic resonance imaging. METHODS: Patients with PD were recruited using data from a previous cohort study and divided into those with ICB (ICB group) and without ICB (non-ICB group) using the Japanese version of the Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease (J-QUIP). From these two groups, we extracted 37 pairs matched for age, sex, disease duration, and levodopa equivalent daily dose of dopamine agonists. Patients with ICB were further classified as having ICD or DDS based on the J-QUIP subscore. General linear models were used to compare gray matter volume and functional connectivity (FC) of the NAcc, caudate, and putamen between the ICB and non-ICB groups and between patients with ICD and those with DDS. RESULTS: We found no significant differences in gray matter volumebetween the ICB and non-ICB groups or between patients with ICD and those with DDS. Compared with the non-ICB group, the FC of the right NAcc in the ICB group was lower in the bilateral ventromedial prefrontal cortex and higher in the left middle occipital gyrus. Furthermore, patients with DDS showed higher FC between the right putamen and left superior temporal gyrus and higher FC between the left caudate and bilateral middle occipital gyrus than patients with ICD. In contrast, patients with ICD exhibited higher FC between the left NAcc and the right posterior cingulate cortex than patients with DDS. CONCLUSIONS: The functionally altered network between the right NAcc and ventromedial prefrontal cortex was associated with ICB in PD. In addition, the surrounding cortico-striatal networks may differentiate the behavioral characteristics of patients with ICD and those with DDS.

Association between REM sleep behavior disorder and impulsive-compulsive behaviors in Parkinson's disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Both REM sleep behavior disorder (RBD) and impulsive-compulsive behaviors (ICBs) are well-recognized non-motor features in patients with Parkinson's disease (PD). Studies have given contradictory results about the potential association between RBD and ICBs. METHODS: PubMed, Embase (via Ovid), and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases were systematically searched till August 20, 2019 to identify studies that explored the possible correlation between RBD and ICBs in patients with PD. Two authors independently screened records, extracted data and evaluated quality of included studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by employing a random or fixed-effects model. We performed subgroup and sensitivity analyses, and we assessed potential publication bias. RESULTS: A total of 134 references were screened and 10 studies involving 2781 PD patients were included. Overall, RBD was associated with a more than twofold higher risk of developing ICBs (OR 2.12, 95% CI 1.43-3.14, I2 = 56.7%, P < 0.01). Similar results were obtained in sensitivity analyses and in meta-analyses of subgroups stratified based on multivariable adjustment and methods for diagnosing RBD and ICBs. No significant risk of publication bias was found. CONCLUSION: RBD in PD is confirmed to be a risk factor for ICBs. Clinicians should be aware of this association to help them improve patient management.

Deterioration of postural deformity in Parkinson's disease patients with punding and hobbyism.

This study aimed to examine whether worsening of postural deformities is seen in Parkinson's disease (PD) patients who exhibit the behavioral disorders punding or hobbyism (P-H), which involve maintaining the same poor posture. The subjects were 80 patients with PD (aged 73.1 ±â€¯8.8 years; duration of disease, 6.4 ±â€¯5.5 years). Using the Japanese-language version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (J-QUIP), a group with P-H alone (P-H only group) and a group without impulsive-compulsive behaviors (non-ICB group) were compared with respect to the angles of forward and lateral trunk flexion while standing at rest. The group with ICBs (ICB group) identified by the J-QUIP consisted of 36 patients (45.0%). Of these, 25 (31.3%) were in the P-H only group. The non-ICB group, who were negative on all items of the J-QUIP, consisted of 44 patients (55.0%). Significantly higher values were seen in the P-H only group compared with non-ICB group for the angle of forward flexion of the trunk (FFT angle, p = 0.04), Unified Parkinson's Disease Rating Scale (UPDRS) part II score (p = 0.002), and UPDRS total score (p = 0.007). The FFT angle was increased and activities of daily living decreased in PD patients with P-H.

Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors.

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n = 17) and without (n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [18F]fallypride, a high affinity D2-like receptor ligand that can measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BPND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D2/3 receptor BPND Group differences in regional D2/3 BPND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BPNDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.SIGNIFICANCE STATEMENT The biologic determinants of compulsive reward-based behaviors have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease patients with impulsive compulsive behaviors (ICBs). This is the first study to image a large cohort of ICB+ patients using positron emission tomography with [18F]fallypride, allowing quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in dopaminergic networks, including (1) D2-like receptor distinctions in the ventral striatum and putamen, and (2) a preservation of widespread dopaminergic projections emerging from the midbrain, which is associated with the severity of compulsive behaviors. This clearly illustrates the roles of D2/3 receptors and medication effects in maladaptive behaviors, and localizes them specifically to nigrostriatal and extrastriatal regions.

Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors.

BACKGROUND: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.

A Retrospective Evaluation of the Frequency of Impulsive Compulsive Behaviors in Parkinson's Disease Patients Treated with Continuous Waking Day Apomorphine Pumps.

BACKGROUND: Impulsive compulsive behaviors (ICBs) can have a deleterious impact on the lives of patients with PD with orally active dopamine agonist treatment recognized as the greatest risk factor. However, the relationship between subcutaneous administration of the dopamine agonist, apomorphine, and impulsive compulsive behaviors is unknown. METHODS: We conducted a retrospective analysis of 28 advanced PD patients treated with subcutaneous waking day apomorphine ambulatory minipumps at the National Hospital for Neurology and Neurosurgery (London, UK). RESULTS: Twelve of the patients had experienced impulsive compulsive behaviors before starting apomorphine. Reduction of oral dopamine agonist dose before apomorphine had led to complete resolution in 6 cases with no recurrence on long-term apomorphine maintenance therapy. Six patients still had active impulsive compulsive behaviors when apomorphine was started. Four of these improved, and in the other 2 there was no worsening. Of the 16 patients with no previous history of impulsive compulsive behaviors who started apomorphine, only 1, who was still receiving concurrent levodopa, developed impulsive compulsive behaviors. CONCLUSIONS: These data provide preliminary evidence that continuous apomorphine pump therapy has a lower proclivity to trigger or exacerbate impulsive compulsive behaviors than oral dopamine agonists. This is likely to be attributed to a more tonic stimulation of striatal dopamine receptors leading to desensitisation, but could also be attributed to a different pharmacological profile of apomorphine compared with orally active dopamine agonists. Apomorphine can be considered as a treatment option in patients who have developed disabling impulsive compulsive behaviors on oral agonist therapy whose motor handicap cannot be controlled adequately on l-dopa alone. Further prospective studies are needed to provide a definitive answer to this question.

Do Parkinson's Disease Patients Have Deficits in Sequential Sampling Tasks?

The aim of this study was to assess the neuropsychological behavior of Parkinson's disease (PD) patients with addictive behaviors. Characteristically, these patients have younger onset of PD, higher novelty-seeking personality traits, jump to conclusions, and often make irrational choices. We assessed whether PD patients with and without addictive behaviors have deficits in a sequential sampling task, often called the secretary problem. In this task, participants needed to pick the best out of multiple offers. Critically, once participants rejected a deal, this option became unavailable. Thus, decisions needed to be balanced not to stop too soon or sample for too long and miss the best deal. We tested 13 PD patients with and 13 patients without addictive behaviors. Results were compared to healthy volunteers. We found that all patients declined fewer options before committing to a deal. There was, however, no difference between the two patient groups. Furthermore, there was no difference in overall choice rank between patients and controls. These results suggest that, compared to controls, PD patients gather less evidence before committing to an offer, but have no deficits in recognizing the best deal out of many options, regardless of whether or not they have addictive behaviors.