Article

International validation of a behavioral scale in Parkinson's disease without dementia: NEUROPSYCHIATRIC ASSESSMENT IN PD

August 2007
Movement Disorders 30(5)

DOI:10.1002/mds.26150

Source
PubMed

Authors:

Pablo Martinez-Martin

Instituto de Salud Carlos III

Bruno Pereira

Centre Hospitalier Universitaire de Clermont-Ferrand

Ingrid de Chazeron

Centre Hospitalier Universitaire de Clermont-Ferrand

Show all 18 authorsHide

The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

The Neuropsychiatric Fluctuations Scale for Parkinson's Disease: A Pilot Study

Article

Full-text available

Feb 2018

Background Non‐motor fluctuations represent a main source of disability in Parkinson's disease (PD). Among them, neuropsychiatric fluctuations are the most frequent and are often under‐recognized by patients and physicians, partly because specific tools for assessment of neuropsychiatric fluctuations are lacking. Objective To develop a scale for detecting and evaluating the presence and the severity of neuropsychological symptoms during the ON and OFF phases of non‐motor fluctuations. Methods Neuropsychiatric symptoms reported by PD patients in the OFF‐ and the ON‐medication conditions were collected using different neuropsychiatric scales (BDI‐II, BAI, Young, VAS, etc.). Subsequently, tree phases of a pilot study was performed for cognitive pretesting, identification of ambiguous or redundant items (item reduction), and to obtain preliminary data of acceptability of the new scale. In all the three phases, the scale was applied in both the OFF and ON condition during a levodopa challenge. Results Twenty items were selected for the final version of the neuropsychiatric fluctuation scale (NFS): ten items measured the ON neuropsychological symptoms and ten items the OFF neuropsychological manifestations. Each item rated from 0‐3, providing respective subscores from 0 to 30. Conclusions Once validated, our NFS can be used to identify and quantify neuropsychiatric fluctuations during motor fluctuations. The main novelty is that it could be used in acute settings. As such, the NFS can assess the neuropsychiatric state of the patient at the time of examination. The next step will be to validate the NFS to be used in current practice.

Psychostimulant effect of dopaminergic treatment and addictions in Parkinson's disease: Psychostimulant Effect of Dopaminergic Treatment

Article

Jul 2017

Background: Dopamine replacement therapy in PD has been associated with both behavioral addictions and dopamine addiction. Objectives: To investigate potential association between l-dopa induced neuropsychiatric fluctuations and addictions in PD. Methods: A cohort of 102 patients with PD suffering from motor complications of l-dopa treatment was prospectively analyzed. We evaluated dopamine addiction, behavioral addictions, and neuropsychiatric fluctuations using the Ardouin scale of behavior in PD. Results: Patients with (n = 51) or without (n = 51) neuropsychiatric fluctuations did not differ in age, disease duration, medication, or UPDRS III motor score during on and off drug condition. Patients with neuropsychiatric fluctuations had a higher H & Y stage in off-drug condition. A multivariate model showed that dopamine addiction (odds ratio: 8.9; P = 0.02) and behavioral addictions (odds ratio: 3.76; P = 0.033) were more frequent in the presence of neuropsychiatric fluctuations. Behavioral addictions and dopamine addiction were more frequent in the presence than in the absence of on-drug euphoria (46% vs. 13.9%; P < 0.001 and 27% vs 6.2 %; P = 0.003), while conversely, no association emerged between dopamine or behavioral addictions and presence of off-drug dysphoria. Patients with neuropsychiatric fluctuations had a poorer quality of life and a more frequent history of anxiety disorder. Conclusions: The psychostimulant effects of dopamine treatment during on-drug euphoria, rather than avoidance of off-drug dysphoria, appear to drive both behavioral addictions and abuse of medication. © 2017 International Parkinson and Movement Disorder Society.

Impact of Mood and Behavioral Disorders on Quality of Life in Parkinson's disease

Article

Mar 2016

Background: Mood symptoms negatively affect quality of life of Parkinson's disease (PD); however little is known about the impact of behavioral disorders such as impulse control disorders, and non-motor fluctuations on quality of life. Objective: To assess the impact of mood and behavioral disorders on quality of life in PD. Methods: 136 (84% male) PD were included (mean age: 61±8y; mean duration of disease: 8.8±5.4y). Mood symptoms, behavioral disorders and non-motor fluctuations were detected and quantified using the recently validated "Ardouin Scale of Behavior in Parkinson's Disease". Motor symptoms were assessed using UPDRS and quality of life with the "39-item Parkinson's Disease Questionnaire". Results: Both motor and non-motor factors significantly affected the quality of life of PD patients. Multivariate regression of the relationship between items of the quality of life questionnaire and the Ardouin Scale showed that alteration of patients' quality of life was strongly correlated with the presence of mood symptoms (such as depression, anxiety ...) and with non-motor fluctuations (especially in the OFF period). A significant correlation was also found between the number of symptoms and their severity, and the quality of life deterioration. Some behavioral disorders (compulsive buying / eating behavior) also negatively affected patient's quality of life to a lesser extent. Alternatively, excess in motivation and hobbyism behaviors had a positive impact on mobility and emotional well-being dimensions respectively of quality of life. Conclusions: This study shows the main impact of mood symptoms and non-motor fluctuations on worsening quality of life in PD.

Profile of Neuropsychiatric Symptoms in Parkinson's Disease: Surgical Candidates Compared to Controls

Article

Full-text available

Feb 2016

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson's disease (PD) and motor complications of dopaminergic treatment. Whether STN-DBS should be considered when PD patients experience neuropsychiatric symptoms is controversial. Lack of systematic behavioral evaluation at baseline hampers the understanding of postoperative neuropsychiatric outcomes. Objective: This study compares the behavioral profile of a surgical population to that in general PD. Methods: Single center data from 234 PD surgical candidates were compared to data from 260 non-demented PD patients consulting in 13 PD expert centers at different stages of disease. The latter were considered representative of the general PD population. Neuropsychiatric symptoms were assessed using the Ardouin Scale of Behavior in PD, a guided interview quantifying changes in severity of 21 neuropsychiatric symptoms, classified into psychic non-motor fluctuations, hypo- and hyperdopaminergic behaviors. Multivariate analyses were performed to study differences in behavioral items between the two groups. Results: Surgical candidates were younger, had longer disease duration and used significantly higher doses of dopaminergic drugs. After adjustment for covariates, dopaminergic addiction (OR 10.83; p = 0.002), nocturnal hyperactivity (OR 1.87; p = 0.04), excessive hobbyism (OR 2.37; p = 0.008), "excess in motivation" (OR 4.02; p < 0.001), psychic OFF (2.87; p < 0.001) and psychic ON (2.10; p = 0.001) fluctuations were more frequent in the surgical candidates. Depressed mood prevailed in the general PD population (OR 0.53; p = 0.045). Conclusion: Behavioral complications of dopaminergic treatment are frequent in PD patients candidates for STN-DBS. They cannot be considered as contraindications for STN-DBS but must be taken into account in postoperative management.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD

Article

Full-text available

Dec 2020

Management of apathy, depression and anxiety in Parkinson’s disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo ( p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

Human Behavioral Assessments in Current Research of Parkinson’s Disease

Article

Jun 2016

Parkinson's disease (PD) is traditionally classified as a movement disorder because patients mainly complain about motor symptoms. Recently, non-motor symptoms of PD have been recognized by clinicians and scientists as early signs of PD, and they are detrimental factors in the quality of life in advanced PD patients. It is crucial to comprehensively understand the essence of behavioral assessments, from the simplest measurement of certain symptoms to complex neuropsychological tasks. We have recently reviewed behavioral assessments in PD research with animal models (Asakawa et al., 2016). As a companion volume, this article will systematically review the behavioral assessments of motor and non-motor PD symptoms of human patients in current research. The major aims of this article are: (1) promoting a comparative understanding of various behavioral assessments in terms of the principle and measuring indexes; (2) addressing the major strengths and weaknesses of these behavioral assessments for a better selection of tasks/tests in order to avoid biased conclusions due to inappropriate assessments; and (3) presenting new concepts regarding the development of wearable devices and mobile internet in future assessments. In conclusion we emphasize the importance of improving the assessments for non-motor symptoms because of their complex and unique mechanisms in human PD brains.

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease

Article

Full-text available

Oct 2022

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson’s disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson’s disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson’s disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality.The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody.As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference.R2∗ values significantly increased in Parkinson’s disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND

The Objective Buttocks Assessment Scale (OBAS): a new and complete method to assess the gluteal region

Article

Full-text available

Sep 2022

Introduction: New treatment methods to improve and enhance buttocks appearance require globally accepted scales for aesthetic research and patient evaluation. The purpose of our study was to develop a set of grading scales for objective assessment of the gluteal region and assess their reliability and validity. Materials and methods: Twelve photonumeric grading scales were created. Eleven aesthetic experts rated photographs of 650 women in 2 validation sessions. Responses were analyzed to assess inter-rater and intra-rater reliability. The Rasch model was used as part of the validation process. Results: All the scales exceeded criteria for acceptability, reliability and validity. Overall inter-rater reliability and intra-rater reliability were both "almost perfect" (p=0.15 and p=0.16 respectively). Conclusion: Consistent outcomes between raters and by individual raters at 2 time points confirm the reliability of the Objective Buttocks Assessment Scale in female patients and suggest it will be a valuable tool for use in research and clinical practice.

Fatigue in de novo Parkinson’s Disease: Expanding the Neuropsychiatric Triad?

Article

Mar 2022

Background: Fatigue is a frequent and troublesome symptom present from the early stages of Parkinson's disease (PD). Objective: To examine the relationship between fatigue and the neuropsychiatric triad, which includes apathy, depression, and anxiety, in de novo PD. Methods: We performed a cross-sectional study including 197 patients with de novo PD and assessed fatigue using the Parkinson's Disease Fatigue Scale (PDFS-16). We evaluated motor status using the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and evaluated neuropsychiatric status using the Ardouin Scale of Behavior in Parkinson's Disease (ASBPD). We carried out univariate and multivariate analyses to model association between motor signs, non-motor signs, and fatigue risk. Results: Frequency of fatigue (28.9%) was of the same order of magnitude as that of apathy. PD patients with fatigue reported a lower quality of life than patients without fatigue (p < 0.0001). The ASBPD showed that patients with fatigue had higher scores for depressed mood (p < 0.0001), anxiety (p < 0.0001), and apathy (p < 0.0001). In the univariate analysis, fatigue score was positively correlated with apathy, depression, anxiety, and the neuropsychiatric triad as a whole, and to a lesser extent with female sex, hyperemotivity, and the UPDRS part III score. In the multivariate analysis, after adjusting for sex and motor status, the fatigue score remained significantly correlated with apathy (OR = 11.17 [4.33-28.78], p < 0.0001) and depression (OR = 4.28 [1.39-13.12], p = 0.01), but not with anxiety (OR = 0.94 [0.34-2.58], p = 0.9). Conclusion: We propose that the neuropsychiatric triad could be expanded to include fatigue.

Preoperative REM Sleep Behavior Disorder and Subthalamic Deep Brain Stimulation Outcome in Parkinson Disease 1 Year After Surgery

Article

Oct 2021
NEUROLOGY

Objective: To determine whether Parkinson's disease (PD) patients eligible to subthalamic deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) pre-operatively could be more at risk of poorer motor, non-motor and quality of life outcomes 12 months after surgery, compared to those without RBD. Methods: We analyzed the preoperative clinical profile of 448 PD from a French multicentric prospective study (PREDISTIM), according to the presence or absence of probable RBD, based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 PD patients with 12 months follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile and quality of life outcomes in patients with (preopRBD+) or without probable RBD preoperatively (preopRBD-). Results: At preoperative evaluation, preopRBD+ were older (61±7.2 vs. 59.5±7.7 years; p=0.02), had less motor impairment (MDS-UPDRS III Off: 38.7±16.2 vs. 43.4±7.1; p=0.03) but more non-motor symptoms on daily living activities (MDS-UPDRS I: 12.6±5.5 vs. 10.7±5.3; p<0.001), more psycho-behavioral manifestations (ASBPD total: 7.7±5.1 vs. 5.1±0.4; p=0.003) and worse quality of life (PDQ39: 33±12 vs. 29±12; p=0.03), as compared to preopRBD-. Both preopRBD+ and preopRBD- had significant MDS-UPDRS IV score decrease (-37% and -33% respectively), MDS-UPDRS III "MedOff/StimOn" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between group difference. There was no between group difference for cognitive and global quality of life outcomes. Conclusions: In PD patients eligible to STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery. Registration number: ClinicalTrials.gov: NCT02360683. Classification of evidence: This study provides Class II evidence that, in PD patients eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes one year post surgery.

Impulse control disorders and related behaviors in Parkinson's disease: risk factors, clinical and genetic aspects, and management

Article

May 2021

Purpose of review: To review recent findings and research directions on impulse control disorders and related behaviors (ICDRBs) in Parkinson's disease (PD). Recent findings: Longitudinal studies found that prevalence increases during PD progression, incident ICDRBs being around 10% per year in patients treated with dopaminergic therapies. Screening tools and severity scales already developed have been validated and are available in several countries and languages. The main clinical risk factors include young age, male gender, type, doses and duration of dopaminergic therapy, PD motor severity and dyskinesia, depression, anxiety, apathy, sleep disorders, and impulsivity traits. Genetic factors are suspected by a high estimated heritability, but individual genes and variants remain to be replicated. Management of ICDRBs is centered on dopamine agonist decrease, with the risk to develop withdrawal symptoms. Cognitive behavioral therapy and subthalamic nucleus deep brain stimulation also improve ICDRBs. In the perspective of precision medicine, new individual prediction models of these disorders have been proposed, but they need further independent replication. Summary: Regular monitoring of ICDRB during the course of PD is needed, particularly in the subject at high risk of developing these complications. Precision medicine will require the appropriate use of machine learning to be reached in the clinical setting.

Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease

Article

Full-text available

Aug 2020
BRAIN

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

Management of psychiatric disorders in Parkinson’s disease: Neurotherapeutics - Movement Disorders Therapeutics

Article

Jun 2020

Daniel Weintraub

Affective disorders (depression and anxiety), psychosis, impulse control disorders, and apathy are common and sometimes disabling psychiatric conditions in Parkinson disease (PD). Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their high frequency, there remains incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically co- or multimorbid, and there is great intra- and interindividual variability in presentation [1]. The neuropathophysiological changes that occur in PD, as well as the association between PD treatment and particular psychiatric disorders, suggest a neurobiological contribution to many psychiatric symptoms. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated, and although psychotropic medication use is common, randomized controlled trials demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors, and most importantly, establishing efficacious and well-tolerated treatment strategies.

Scales to assess impulsive and compulsive behaviors in Parkinson's disease: Critique and recommendations

Article

May 2019

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated “recommended” if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's disease (QUIP) and QUIP‐Rating Scale (QUIP‐RS) are recommended, and for severity rating across the range of ICBs the QUIP‐RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease–Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society

Wait and you shall see: sexual delay discounting in hypersexual Parkinson’s disease

Article

Jan 2019

Wait and you shall see: sexual delay discounting in hypersexual Parkinson's disease

Article

Jan 2019
BRAIN

Patients with Parkinson’s disease may develop impulse control disorders under dopaminergic treatments. Impulse control disorders include a wide spectrum of behaviours, such as hypersexuality, pathological gambling or compulsive shopping. Yet, the neural systems engaged in specific impulse control disorders remain poorly characterized. Here, using model-based functional MRI, we aimed to determine the brain systems involved during delay-discounting of erotic rewards in hypersexual patients with Parkinson’s disease (PD+HS), patients with Parkinson’s disease without hypersexuality (PD − HS) and controls. Patients with Parkinson’s disease were evaluated ON and OFF levodopa (counterbalanced). Participants had to decide between two options: (i) wait for 1.5 s to briefly view an erotic image; or (ii) wait longer to see the erotic image for a longer period of time. At the time of decision-making, we investigated which brain regions were engaged with the subjective valuation of the delayed erotic reward. At the time of the rewarded outcome, we searched for the brain regions responding more robustly after waiting longer to view the erotic image. PD+HS patients showed reduced discounting of erotic delayed rewards, compared to both patients with Parkinson’s disease and controls, suggesting that they accepted waiting longer to view erotic images for a longer period of time. Thus, when using erotic stimuli that motivate PD+HS, these patients were less impulsive for the immediate reward. At the brain system level, this effect was paralleled by the fact that PD+HS, as compared to controls and PD − HS, showed a negative correlation between subjective value of the delayed reward and activity of medial prefrontal cortex and ventral striatum. Consistent with the incentive salience hypothesis combining learned cue–reward associations with current relevant physiological state, dopaminergic treatment in PD+HS boosted excessive ‘wanting’ of rewards and heightened activity in the anterior medial prefrontal cortex and the posterior cingulate cortex, as reflected by higher correlation with subjective value of the option associated to the delayed reward when ON medication as compared to the OFF medication state. At the time of outcome, the anterior medial prefrontal/rostral anterior cingulate cortex showed an interaction between group (PD+HS versus PD − HS) and medication (ON versus OFF), suggesting that dopaminergic treatment boosted activity of this brain region in PD+HS when viewing erotic images after waiting for longer periods of time. Our findings point to reduced delay discounting of erotic rewards in PD+HS, both at the behavioural and brain system levels, and abnormal reinforcing effect of levodopa when PD+HS patients are confronted with erotic stimuli. Close

Psychiatric Manifestation in Patients with Parkinson's Disease

Article

Full-text available

Nov 2018

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Although its major manifestation is motor symptoms, resulting from the loss of dopaminergic neurons in the substantia nigra, psychiatric symptoms, such as depression, anxiety, hallucination, delusion, apathy and anhedonia, impulsive and compulsive behaviors, and cognitive dysfunction, may also manifest in most patients with PD. Given that the quality of life — and the need for institutionalization — is so highly dependent on the psychiatric well-being of patients with PD, psychiatric symptoms are of high clinical significance. We reviewed the prevalence, risk factors, pathophysiology, and treatment of psychiatric symptoms to get a better understanding of PD for improved management.

Wait and you shall see: sexual delay discounting in hypersexual Parkinson’s disease

Preprint

Oct 2018

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Impulse control disorders in Parkinson's disease patients with RLS: a cross sectional-study

Article

Aug 2018

Impulse control disorders in Parkinson’s disease patients with RLS: a cross sectional-study

Article

Mar 2018
SLEEP MED

Background Although dopamine replacement therapy is the main risk factor for the occurrence of Impulse Control Disorders (ICDs) in Parkinson's disease (PD), non-pharmacological risk factors for have also been identified in that population and sleep disorders could be part of them. Our objective is to determine whether Restless Legs Syndrome (RLS), that has been associated with more impulsive choices in general population regardless of dopaminergic therapy, could be associated with a specific psycho-behavioral profile and ICDs in PD. Methods eighty consecutive PD patients were screened for the presence of RLS in a cross-sectional study. Sleep features were evaluated during one video-polysomnography. The frequency of ICDs, according to standard criteria, together with a broad range of psycho-behavioral features using the Ardouin Scale of Behavior in PD, were compared in patients with RLS (PD-RLS, n=30) versus without RLS (PD-nRLS, n=50). Results PD patients with RLS reported significantly more ICDs than those without RLS (50% versus 26%, p=0.03), especially compulsive eating disorders, and a different psycho-behavioral profile with more hyperdopaminergic behaviors. There was no between group difference for total and dopamine agonists levodopa equivalent doses. However, age and durations of both disease and dopaminergic treatment were greater in the RLS group. Multivariate and propensity score analyses controlling for age, gender, total sleep time, disease severity, dose and duration of treatment, anxiety and depression showed that RLS was an independent predictor of ICDs in PD (OR=5.91 [1.63;22.1] and OR=2.89 [1.63;6.67] respectively). Conclusion RLS per se could be a risk factor for impulsive behaviors in PD.

Weight gain after subthalamic nucleus deep brain stimulation in Parkinson’s disease is influenced by dyskinesias’ reduction and electrodes’ position

Article

Full-text available

Sep 2017

Parkinson’s disease is a common neurodegenerative disease that can be treated with pharmacological or surgical therapy. Subthalamic nucleus (STN) deep brain stimulation is a commonly used surgical option. A reported side effect of STN-DBS is weight gain: the aim of our study was to find those factors that determine weight gain, through one year-long observation of 32 patients that underwent surgery in our centre. During the follow-up, we considered: anthropometric features, hormonal levels, motor outcome, neuropsychological and quality of life outcomes, therapeutic parameters and electrodes position. The majority (84%) of our patients gained weight (6.7 kg in 12 months); more than a half of the cohort became overweight. At 12th month, weight gain showed a correlation with dyskinesias reduction, electrodes voltage and distance on the lateral axis. In the multivariate regression analysis, the determinants of weight gain were dyskinesias reduction and electrodes position. In this study, we identified dyskinesias reduction and distance between the active electrodes and the third ventricle as determining factors of weight gain after STN-DBS implantation in PD patients. The first finding could be linked to a decrease in energy consumption, while the second one could be due to a lower stimulation of the lateral hypothalamic area, known for its important role in metabolism and body weight control. Weight gain is a common finding after STN-DBS implantation, and it should be carefully monitored given the potential harmful consequences of overweight.

Measurement of Nonmotor Symptoms in Clinical Practice

Chapter

Full-text available

Jun 2017
INT REV NEUROBIOL

Nonmotor symptoms constitute a prominent part of Parkinson's disease manifestations. They are present since the first phases of the disease, increase their number and severity with disease progression, and importantly impact on patients' health and quality of life, caregivers' burden, and social resources.Research on Parkinson's disease has traditionally focused on the motor aspects of the disease, but an increasing interest in the nonmotor manifestations has risen in the past decade. The availability of assessment instruments for detecting and measuring these symptoms has allowed understanding of their importance and course over time, as well as estimation of therapeutic effects on them.In this chapter, a review of the basic characteristics of nonmotor symptom assessments used in clinical practice and research are presented.

Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease

Article

Feb 2017

Parkinson's disease is a complex neurodegenerative disorder characterized by motor and non-motor symptoms, with neuropsychiatric manifestations among the most frequent non-motor symptoms. Health-related quality of life is a patient-reported outcome that reflects the impact of the disease on physical, mental, and social wellbeing, and on other aspects of patient’ life. Although older studies on health-related quality of life in Parkinson's disease mainly investigated the role of the motor impairment, recent research focused on non-motor symptoms has highlighted the critical role that behavioural disturbances due to neuropsychiatric symptoms play in determining health related quality of life. A considerable number of studies have demonstrated the importance of depression as a determinant of health-related quality of life in this population, but less evidence is available regarding the role of other neuropsychiatric symptoms such as anxiety, apathy, psychosis, and impulse control disorders. This narrative review analyses recent literature on this topic, focusing on studies in which neuropsychiatric symptoms were investigated as potential determinants of quality of life using regression techniques, including discussion of the assessment tools used.

Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease

Article

Jan 2017
J NEUROL SCI

The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations: A Review On Nonmotor Fluctuations

Article

Jul 2016

Only a few years after the introduction of levodopa, the first descriptions of motor fluctuations and dyskinesia related to dopaminergic therapy appeared. In PD, attention turned to their management, that had dampened the euphoria of the "levodopa miracle." It soon became clear that neuropsychiatric, autonomic, and sensory features also tend to develop fluctuations after chronic exposure to l-dopa. The diversity of fluctuating nonmotor symptoms, their largely subjective nature, coupled with a frequent lack of insight led to difficulties in identification and quantification. This may explain why, despite the high impact of nonmotor symptoms on patient autonomy and quality of life, evaluation of nonmotor fluctuations is not part of clinical routine. In view of the lack of specific validated assessment tools, detailed anamnesis should ideally be coupled with an evaluation in both ON and OFF drug conditions. The mechanisms of nonmotor fluctuations are not well understood. It is thought that they share dopaminergic presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms with the classical motor complications, but involve different neural pathways. Although symptoms fluctuate with dopaminergic treatment, serotonine and norepinephrine denervation, as well as interactions between neurotransmitter systems, probably contribute to their diversity. The lack of validated tools for assessment of these phenomena explains the almost complete absence of treatment studies. Management, largely resulting from expert opinion, includes psychiatric follow-up, nondopaminergic drugs, and advanced dopaminergic treatment, including drug delivery pumps and DBS. This review aims to provide a starting point for the understanding, diagnosis, and management of nonmotor fluctuations. © 2016 International Parkinson and Movement Disorder Society.

Quality of life in Parkinson’s disease improved by apomorphine pump: the OPTIPUMP cohort study

Article

Full-text available

Jun 2016
J NEUROL

To report on OPTIPUMP, a cohort study, investigating the impact in real-life clinical settings of continuous subcutaneous apomorphine infusion (CSAI) on the quality of life (HRQoL) of patients with Parkinson's disease. OPTIPUMP was a prospective, open-label, observational cohort study involving 30 investigational sites in France. CSAI was proposed as part of routine clinical care to patients aged ≥18 years, in absence of dementia, with a PD diagnosis and based on the presence of motor fluctuations not controlled by oral treatments. The impact of APO-pump on quality of life was evaluated as the difference in PDQ-39 scores between the initiation treatment and the follow-up visit after 6 months' treatment. All adverse events were recorded. Hyper- and hypodopaminergic behavioral tolerance was assessed on the Ardouin Scale of Behavior in Parkinson's Disease. Between September 2011 and January 2013, we enrolled 142 patients: 42 patients were withdrawn due to pump removal (33), death (4), lost of follow-up (4), no available data (1). 100 completed the study. At 6 months, their HRQoL had significantly improved (p = 0.011), as had their total UPDRS score (p < 0.001). Regarding the safety profile, Ardouin scale scores indicated that their hyperdopaminergic behaviors had not increased. CSAI had a favorable impact on HRQoL, with benefits outweighing risks. The analysis of the withdrawn patients highlights the heterogeneity of the use of the pump having an impact on its efficacy and tolerability.

Translational research on cognitive and behavioural disorders in neurological and psychiatric diseases

Article

Feb 2016
THERAPIE

The important medical and social burden of nervous system diseases contrasts with the currently limited therapeutic armamentarium and with the difficulty encountered in developing new therapeutic options. These failures can be explained by the conjunction of various phenomena related to the limitations of animal models, the narrow focus of research on precise pathophysiological mechanisms, and methodological issues in clinical trials. It is perhaps the paradigm itself of the way research is conducted that may be the real reason for our incapacity to find effective strategies. The purpose of this workshop was to define overall lines of research that could lead to the development of effective novel therapeutic solutions. Research has long focused on diseases per se rather than on cognitive and behavioural dimensions common to several diseases. Their expression is often partial and variable, but can today be well-characterised using neurophysiological or imaging methods. This dimensional or syndromic vision should enable a new insight to the question, taking a transnosographic approach to re-position research and to propose: translational models exploring the same functions in animal models and in humans; identification of homogeneous groups of patients defined according to the clinical, anatomico-functional and molecular characteristics; and preclinical and clinical developments enriched by the use of cognitive-behavioural, biological neurological, and imaging biomarkers. For this mutation to be successful, it must be accompanied by synchronised action from the public authorities and by ad hoc measures from the regulatory agencies.

What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson’s disease?

Article

Full-text available

Mar 2016

In addition to classical motor symptoms, Parkinson’s disease (PD) patients display incapacitating neuropsychiatric manifestations, such as apathy, anhedonia, depression and anxiety. These hitherto generally neglected non-motor symptoms, have gained increasing interest in medical and scientific communities over the last decade because of the extent of their negative impact on PD patients’ quality of life. Although recent clinical and functional imaging studies have provided useful information, the pathophysiology of apathy and associated affective impairments remains elusive. Our aim in this review is to summarize and discuss recent advances in the development of rodent models of PD-related neuropsychiatric symptoms using neurotoxin lesion-based approaches. The data collected suggest that bilateral and partial lesions of the nigrostriatal system aimed at inducing reliable neuropsychiatric-like deficits while avoiding severe motor impairments that may interfere with behavioral evaluation, is a more selective and efficient strategy than medial forebrain bundle lesions. Moreover, of all the different classes of pharmacological agents, D2/D3 receptor agonists such as pramipexole appear to be the most efficient treatment for the wide range of behavioral deficits induced by dopaminergic lesions. Lesion-based rodent models, therefore, appear to be relevant tools for studying the pathophysiology of the non-motor symptoms of PD. Data accumulated so far confirm the causative role of dopaminergic depletion, especially in the nigrostriatal system, in the development of behavioral impairments related to apathy, depression and anxiety. They also put forward D2/D3 receptors as potential targets for the treatment of such neuropsychiatric symptoms in PD.

Objective estimation of patient age through a new composite scale for facial aging assessment: The face - Objective assessment scale

Article

Full-text available

Feb 2016
J CRANIO MAXILL SURG

Most patients requesting aesthetic rejuvenation treatment expect to look healthier and younger. Some scales for ageing assessment have been proposed, but none is focused on patient age prediction. The aim of this study was to develop and validate a new facial rating scale assessing facial ageing sign severity. One thousand Caucasian patients were included and assessed. The Rasch model was used as part of the validation process. A score was attributed to each patient, based on the scales we developed. The correlation between the real age and scores obtained, the inter-rater reliability and test-retest reliability were analysed. The objective was to develop a tool enabling the assigning of a patient to a specific age range based on the calculated score. All scales exceeded criteria for acceptability, reliability and validity. The real age strongly correlated with the total facial score in both sex groups. The test-retest reliability confirmed this strong correlation. We developed a facial ageing scale which could be a useful tool to assess patients before and after rejuvenation treatment and an important new metrics to be used in facial rejuvenation and regenerative clinical research.

Psychiatric Conditions in Parkinson Disease: A Comparison With Classical Psychiatric Disorders

Article

Sep 2015

Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD.

OPTIPUMP study: impact of apomorphine pump therapy at 6 months on 145 parkinsonian patients' quality of life. A multicentre French observational prospective study

Conference Paper

Full-text available

May 2014

[Continuous subcutaneous infusion of apomorphine in Parkinson's disease: Retrospective analysis of a series of 81 patients.]

Article

Mar 2014
REV NEUROL-FRANCE

Continuous subcutaneous infusion of apomorphine (CAI) has shown efficacy in the treatment of motor fluctuations but its place in the therapeutic arsenal remains poorly defined in terms of indication, acceptability and long-term tolerance. Indeed, few studies have been carried out with a follow-up greater than 12 months. The main objective was to assess the quality of life of Parkinson's disease (PD) patients treated with CAI. We also evaluate the effectiveness on the motor fluctuations, the long-term tolerance of this treatment with its causes of discontinuation and the treatment regimens used. We conducted a retrospective study of 81 PD patients treated with CAI between April 2003 and June 2012. Data were collected from medical records. A repeated measures analysis of variance by the linear mixed model was used (significance level: 5%). In August 2012, 27/81 patients were still treated with CAI with a mean duration of 28 months, 46/81 discontinued CAI (9 precociously), and 8 were lost to view. We didn't show improvement in the quality of life nor efficacy of CAI on the UPDRS IV score (P=0.54) and dyskinesia score (P=0.95). The CGI score patient also reflects this result with a majority response suggesting no significant change with CAI. We observed relative good cognitive and psychiatric tolerance. Adverse events were frequent but often benign. The average (±SD) rate of apomorphine was 3.15±1.71mg/h and the oral dopaminergic treatment was decreased by 37.8%. The results are consistent with the literature except for the lack of efficiency on motor fluctuations which may be due to the use of too small doses of apomorphine. This seems to be a leading cause of discontinuation of CAI, especially when it is associated with side effects or important constraints. For better efficiency on motor fluctuations, we recommend the use of apomorphine at higher doses to obtain an optimal continuous dopaminergic stimulation.

The Objective Stretch Marks Photonumeric Assessment Scale: A New and Complete Method to Assess Striae Distensae

Article

Full-text available

Nov 2022
PLAST RECONSTR SURG

Background: Striae distensae evaluation criteria have been recently described, but none is focused on objective striae assessment. With the purpose of better and objectively estimating the severity of striae distensae, the Objective Stretch Marks Assessment Scale has been developed by the authors' team. Methods: Seven hundred White patients were included in the study and assessed. To assess the severity of striae distensae, abdomen, breasts, hips, gluteal area, back area, thighs, calves, and upper limbs photonumeric grading scales were developed. The Rasch model was used as part of the validation process. A score was attributed to each patient, based on the scales we developed. The interrater reliability and test-retest reliability were analyzed. Results: Eight photonumeric scales for striae distensae treatment outcomes assessment were developed. All scales exceeded criteria for acceptability, reliability and validity. The interrater and intrarater reliabilities were good, with a substantial or virtually perfect interrater reliability for the total score (P = 0.16). Conclusions: The authors' results allowed them to validate the Objective Stretch Marks Assessment Scale as a reliable and reproducible tool to assess striae distensae treatment outcomes. This scale could be also considered as an important new metric that can be used in clinical research.

Objective evaluation of face-lift outcomes through a new composite photo-numerical scale: The face and neck lift Objective Photo-Numerical Assessment Scale

Article

Full-text available

Oct 2022
PLAST RECONSTR SURG

Background: Success or failure of plastic surgery procedures relies on cosmetic results. Understanding the objective perception of favourable aesthetic results is critical to ensure patient satisfaction. The aim of this study was to develop and to validate a new facial rating scale that could objectively assess face and neck lift outcomes: The face and neck li ft Objective Photo-Numerical Assessment Scale. Material and methods: One thousand Caucasian patients were included in our study and assessed. To validate our scale the inter-rater reliability and the test-retest reliability were analysed. The Rasch model was used as part of the scale validation process. Results: Eleven scales for face and neck lift outcomes assessment were developed. All scales exceeded criteria for acceptability, reliability and validity. The inter and intra-rater reliabilities were good with a substantial or virtually perfect inter-rater reliability for the total score (p=0.15). Conclusion: Our results allowed us to validate the face and neck lift Objective Photo-Numerical Assessment Scale as a reliable and reproducible tool to assess face and neck lift outcomes. This scale could be also considered as an important new metrics to be used in facial rejuvenation surgery clinical research.

Limbic Serotonergic Plasticity Contributes to the Compensation of Apathy in Early Parkinson's Disease

Article

Mar 2022

Background: De novo Parkinson's disease (PD) patients with apathy exhibit prominent limbic serotonergic dysfunction and microstructural disarray. Whether this distinctive lesion profile at diagnosis entails different prognosis remains unknown. Objectives: To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in PD patients with or without apathy at diagnosis. Methods: Thirteen de novo apathetic and 13 nonapathetic PD patients were recruited in a longitudinal double-tracer positron emission tomography cohort study. We quantified the progression of presynaptic dopaminergic and serotonergic pathology using [11 C]PE2I for dopamine transporter and [11 C]DASB for serotonin transporter at baseline and 3 to 5 years later, using linear mixed-effect models and mediation analysis to compare the longitudinal evolution between groups for clinical impairment and region-of-interest-based analysis. Results: After the initiation of dopamine replacement therapy, apathy, depression, and anxiety improved at follow-up in patients with apathy at diagnosis (n = 10) to the level of patients without apathy (n = 11). Patients had similar progression of motor impairment, whereas mild impulsive behaviors developed in both groups. Striato-pallidal and mesocorticolimbic presynaptic dopaminergic loss progressed similarly in both groups, as did serotonergic pathology in the putamen, caudate nucleus, and pallidum. Contrastingly, serotonergic innervation selectively increased in the ventral striatum and anterior cingulate cortex in apathetic patients, contributing to the reversal of apathy besides dopamine replacement therapy. Conclusion: Patients suffering from apathy at diagnosis exhibit compensatory changes in limbic serotonergic innervation within 5 years of diagnosis, with promising evidence that serotonergic plasticity contributes to the reversal of apathy. The relationship between serotonergic plasticity and dopaminergic treatments warrants further longitudinal investigations. © 2022 International Parkinson and Movement Disorder Society.

Medical management after subthalamic stimulation in Parkinson’s disease: a phenotype perspective

Article

Full-text available

Apr 2020

Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment that improves motor fluctuations, dyskinesia, and tremor in Parkinson’s disease (PD). After the surgery, a careful electrode programming strategy and medical management are crucial, because an imbalance between them can compromise the quality of life over time. Clinical management is not straightforward and depends on several perioperative motor and non-motor symptoms. In this study, we review the literature data on acute medical management after STN DBS in PD and propose a clinical algorithm on medical management focused on the patient’s phenotypic profile at the perioperative period. Overall, across the trials, the levodopa equivalent daily dose is reduced by 30 to 50% one year after surgery. In patients taking high doses of dopaminergic drugs or with high risk of impulse control disorders, an initial reduction in dopamine agonists after STN DBS is recommended to avoid the hyperdopaminergic syndrome, particularly hypomania. On the other hand, a rapid reduction of dopaminergic agonists of more than 70% during the first months can lead to dopaminergic agonist withdrawal syndrome, characterized by apathy, pain, and autonomic features. In a subset of patients with severe dyskinesia before surgery, an initial reduction in levodopa seems to be a more reasonable approach. Finally, when the patient’s phenotype before the surgery is the severe parkinsonism (wearing-off) with or without tremor, reduction of the medication after surgery can be more conservative. Individualized medical management following DBS contributes to the ultimate therapy success.

Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease: OPRM1 AND ICDS IN PARKINSON'S DISEASE

Article

Nov 2018

Background: Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD. Methods: We performed a multicenter case‐control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of >300 mg levodopa‐equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset. Results: The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P < 0.001) and had a higher family history of pathological gambling (12% vs 5%, P = 0.03). No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32‐0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40‐base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24‐2.68; P = 0.0021; Bonferroni adjusted P = 0.105). Conclusions: Our results are suggestive of a novel association of the opioid receptor gene OPRM1 with impulse control disorders and related behaviors in PD and confirm a previous association with DAT1. Although replication in independent studies is needed, our results bring potential new insights to the understanding of molecular mechanisms of impulse control disorders. © 2018 International Parkinson and Movement Disorder Society

Sleep and REM sleep behaviour disorder in Parkinson’s disease with impulse control disorder

Article

Oct 2017

Introduction Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson’s disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs. Methods Eighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case–control study. Forty patients (22 men; mean age: 62.6±9.7 years, Hoehn & Yahr: 2.1±0.6) with one or more current ICDs were age-matched and sex-matched with 40 patients with no history of ICDs (22 men, mean age: 64.9±7.8 years, Hoehn & Yahr: 2.2±0.6). They underwent a detailed sleep interview followed by a full-night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis included a clinical complaint of enacted dreams and/or documented behaviour during rapid eye movement (REM) sleep, with the presence of quantified REM sleep without atonia (RSWA). Results Patients with ICDs had a higher arousal index and higher RSWA than those without ICDs (51.9%±28.2%vs 32.2±27.1%, p=0.004). In addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was still associated with ICDs in a multivariate regression analysis including age of onset, PD duration and severity, treatment duration, levodopa-equivalent and dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI 1.3 to 18.5), p=0.02). Conclusions This large, controlled series of patients with PD with ICDs assessed by v-PSG confirms the association between ICDs and RBD. Increased surveillance of symptoms of ICDs should be recommended in patients with PD with RBD.

Emotional manifestations of PD: Neurobiological basis

Article

Full-text available

Apr 2016
MOVEMENT DISORD

Neuropsychiatric symptoms are common and disabling in PD. Their neurobiological bases are complex, partly because of the disease itself and partly because of the dopaminergic treatment. The aim of this review is to focus on the emotional manifestations stemming from the neurodegenerative process itself. We focus on depression, anxiety, apathy, and fatigue, which can all be part of the clinical spectrum of premotor disease and may be improved or masked by medications targeting parkinsonian motor signs or psychiatric symptoms as the disease progresses. Findings from clinical, neuroimaging, and animal studies are reviewed, showing a major contribution of the dopaminergic system to the pathophysiology of these disabling symptoms. Degeneration of noradrenergic and serotonergic projection systems also has an impact on psychiatric symptoms of PD. The available literature is reviewed, but at present there is a lack of studies that would allow disentangling the separate contribution of each of the monoaminergic systems. The use of a pragmatic classification of all these symptoms under the umbrella of hypodopaminergic behavioral syndrome seems clinically useful, as it emphasizes the crucial, although not exclusive, nature of their dopaminergic neurobiological basis, which has important implications in the clinical management of PD. © 2016 International Parkinson and Movement Disorder Society.

Recherche translationnelle sur les troubles cognitifs et comportementaux dans les maladies neurologiques et psychiatriques

Article

Feb 2016
THERAPIE

Résumé L’importance du fardeau médico-social des maladies du système nerveux contraste avec les limites de l’arsenal thérapeutique disponible et les difficultés pour le développement de nouvelles approches thérapeutiques. Ces échecs sont expliqués par une conjonction de phénomènes liés aux limites des modèles animaux, une trop forte focalisation sur des mécanismes physiopathologiques précis, ou des défauts méthodologiques des essais cliniques. C’est peut-être aussi le paradigme même de la manière dont la recherche est menée qui pourrait être responsable de l’incapacité à aboutir à des stratégies efficaces. L’objectif de cet atelier était de définir les grandes orientations à donner pour aboutir au développement efficace de nouvelles solutions thérapeutiques. La recherche s’est longtemps focalisée sur les maladies au lieu de se consacrer aux dimensions cognitivo-comportementales, dont on sait maintenant qu’elles peuvent être communes à différentes pathologies. Leur expression est souvent partielle et variable, mais il est aujourd’hui possible de les caractériser au plan neurophysiologique ou en imagerie. Cette approche dimensionnelle ou syndromique devrait permettre d’aborder la question de manière transnosographique en décloisonnant la recherche pour proposer : des modèles translationnels explorant les mêmes fonctions chez l’animal ou chez l’homme ; l’identification de groupes homogènes de patients définis selon leurs dimensions cliniques, anatomofonctionnels et moléculaires ; des développements précliniques et cliniques enrichis par l’utilisation de biomarqueurs cognitivo-comportementaux, biologiques, neurophysiologiques et d’imagerie. Pour que la mutation s’opère, elle devra être accompagnée par une synchronisation des actions des Tutelles, et par les mesures ad hoc des agences régulatrices.

Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors

Article

Full-text available

Apr 2015

Neuropsychiatric symptoms are common non-motor symptoms in Parkinson's disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states. Apathy belongs to the spectrum of hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy is a key symptom of PD which worsens with disease progression. Animal models, imaging and pharmacological studies concur in pointing out dopaminergic denervation in the aetiology of parkinsonian apathy with a cardinal role of decreased tonic D2/D3 receptor stimulation. ICDs are part of the hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine dysregulation syndrome (DDS), which are all related to non-physiological dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical observations in drug addiction and PD as well as data from studies in dopamine depleted rodents provide hints allowing to argue that both pulsatile D1 and D2 receptor stimulation and the severity of dopaminergic denervation are risk factors to develop punding behavior and DDS. Imaging studies have shown that the brain structures involved in drug addiction are also involved in hyperdopaminergic behaviours with increase of bottom-up appetitive drive and decrease in prefrontal top down behavioural control.

Insights into pathophysiology of punding reveal possible treatment strategies

Article

Full-text available

Jun 2010

Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, nongoal oriented, repetitive activity. Men tend to repetitively tinker with technical equipment such as radio sets, clocks, watches and car engines, the parts of which may be analyzed, arranged, sorted and cataloged but rarely put back together. Women, in contrast, incessantly sort through their handbags, tidy continuously, brush their hair or polish their nails. Punders are normally aware of the inapposite and obtuse nature of the behavior; however, despite the consequent self-injury, they do not stop such behavior. The most common causes of punding are dopaminergic replacement therapy in patients affected by Parkinson's disease (PD) and cocaine and amphetamine use in addicts. The vast majority of information about punding comes from PD cases. A critical review of these cases shows that almost all afflicted patients (90%) were on treatment with drugs acting mainly on dopamine receptors D1 and D2, whereas only three cases were reported in association with selective D2 and D3 agonists. Epidemiological considerations and available data from animal models suggest that punding, drug-induced stereotypies, addiction and dyskinesias all share a common pathophysiological process. Punding may be related to plastic changes in the ventral and dorsal striatal structures, including the nucleus accumbens, and linked to psychomotor stimulation and reward mechanisms. Possible management guidelines are proposed.

Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128: 1314-1322

Article

Full-text available

Jul 2005
BRAIN

The reason for the high frequency of depression and anxiety in Parkinson's disease is poorly understood. Degeneration of neurotransmitter systems other than dopamine might play a specific role in the occurrence of these affective disorders. We used [11C]RTI-32 PET, an in vivo marker of both dopamine and noradrenaline transporter binding, to localize differences between depressed and non-depressed patients. We studied eight and 12 Parkinson's disease patients with and without a history of depression matched for age, disease duration and doses of antiparkinsonian medication. The depressed Parkinson's disease cohort had lower [11C]RTI-32 binding than non-depressed Parkinson's disease cases in the locus coeruleus and in several regions of the limbic system including the anterior cingulate cortex, the thalamus, the amygdala and the ventral striatum. Exploratory analyses revealed that the severity of anxiety in the Parkinson's disease patients was inversely correlated with the [11C]RTI-32 binding in most of these regions and apathy was inversely correlated with [11C]RTI-32 binding in the ventral striatum. These results suggest that depression and anxiety in Parkinson's disease might be associated with a specific loss of dopamine and noradrenaline innervation in the limbic system.

The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: Validation in Parkinson's disease

Article

Full-text available

Jun 2006

Apathy is usually defined as reduced interest and participation in various activities. It is a frequent consequence of neurological and psychiatric disorders. Although various scoring methods have been proposed, there is a lack of validated, standardised instruments for detecting apathy and assessing its severity. To develop an apathy rating scale using a structured standardised interview capable of distinguishing between the condition's various features. The Lille Apathy Rating Scale (LARS) is based on a structured interview. It includes 33 items, divided into nine domains. Responses are scored on a dichotomous scale. The participants used to validate the scale consisted of 159 patients with probable Parkinson's disease and 58 healthy control subjects. The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and the Mattis Dementia Rating Scale were also administered. Principal component analysis showed that the LARS probed a single construct which forms the root of an oblique factor structure reflecting four dimensions: intellectual curiosity, self awareness, emotion, and action initiation. The main psychometric properties of the LARS (internal consistency, inter-rater and test-retest reliability) were satisfactory. Concurrent validity was evaluated by reference to the Marin scale and to judgements provided by expert clinicians. Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression. As a screening tool, the scale is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, also determine the severity of apathy within a four category classification.

Association of Dopamine Agonist Use With Impulse Control Disorders in Parkinson Disease

Article

Full-text available

Jul 2006
ARCH NEUROL-CHICAGO

To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson disease (PD). An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen-positive patients. Two university-affiliated movement disorders centers. A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications. Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview. Eighteen patients (6.6%) with PD met criteria for an ICD at some point during the course of PD, including 11 (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptoms prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001). Patients with PD treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. Because dopamine agonists are increasingly being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.

Quality criteria were proposed for measurement properties of health status questionnaires

Article

Full-text available

Feb 2007
J CLIN EPIDEMIOL

Recently, an increasing number of systematic reviews have been published in which the measurement properties of health status questionnaires are compared. For a meaningful comparison, quality criteria for measurement properties are needed. Our aim was to develop quality criteria for design, methods, and outcomes of studies on the development and evaluation of health status questionnaires. Quality criteria for content validity, internal consistency, criterion validity, construct validity, reproducibility, longitudinal validity, responsiveness, floor and ceiling effects, and interpretability were derived from existing guidelines and consensus within our research group. For each measurement property a criterion was defined for a positive, negative, or indeterminate rating, depending on the design, methods, and outcomes of the validation study. Our criteria make a substantial contribution toward defining explicit quality criteria for measurement properties of health status questionnaires. Our criteria can be used in systematic reviews of health status questionnaires, to detect shortcomings and gaps in knowledge of measurement properties, and to design validation studies. The future challenge will be to refine and complete the criteria and to reach broad consensus, especially on quality criteria for good measurement properties.

Dopamine dysregulation syndrome in Parkinson's disease - Case report

Article

Full-text available

Jan 2007

We report a 67-year-old man with Parkinson's disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.Relatamos sobre um homem de 67 anos de idade com doença de Parkinson por 9 anos e que desenvolveu uso compulsivo de levodopa. Esse fenômeno é a principal característica da síndrome de desregulação dopaminérgica. Outros sintomas apresentados pelo paciente foram flutuações do humor e atividade de escrita aumentada, comportamento este sugestivo de punding.

New onset heightened interest or drive for gambling, shopping, eating or sexual activity in patients with Parkinson's disease: The role of dopamine agonist treatment and age at motor symptoms onset

Article

Full-text available

Jul 2007
J PSYCHOPHARMACOL

Alterations of impulse control that have recently been associated with Parkinson's disease (PD) are serious behavioural disturbances with significant impact on PD patients and their families. A total of 193 consecutive PD patients with no history of psychiatric illness and 190 age/gender-matched healthy controls were queried on the presence of new onset heightened interest or drive for gambling, shopping, eating or sexual activity (GSES). Clinical data were retrieved from medical charts and interviews. logistic regressions models assessed risk factors for these specific troublesome behaviours. New or heightened interests or drives for GSES behaviours were reported by 27 patients (14% vs 0% for controls). Younger age at PD motor symptoms onset (OR = 0.99, p = 0.0172), male gender (OR = 1.10, p = 0.0576) and longer duration of treatment with dopamine agonists (DAs)(OR = 1.18, ≥6 years versus never treated, p = 0.0459) contributed additively to the risk of developing one or more of these behavioural features. New onset heightened interests or drives for GSES are not rare behavioural disturbances among patients with PD. Age, gender and duration of treatment with DAs have an independent and additive effect on the risk to develop such behavioural changes. Patients should be informed about potential treatment-associated behavioural changes.

Recent Developments in Parkinson's Disease

Article

May 1987

Howard I. Hurtig

An Overview of Analytic Rotation in Exploratory Factor Analysis

Article

Jan 2001

Michael W. Browne

The use of analytic rotation in exploratory factor analysis will be examined. Particular attention will be given to situations where there is a complex factor pattern and standard methods yield poor solutions. Some little known but interesting rotation criteria will be discussed and methods for weighting variables will be examined. Illustrations will be provided using Thurstone's 26 variable box data and other examples.

S.14.02 Addicted to dopamine – the dopamine dysregulation syndrome in Parkinson's disease

Article

Sep 2009
EUR NEUROPSYCHOPHARM

Andrew H Evans

Clinical Correlates of Apathy in Patients Recently Diagnosed with Parkinson’s Disease: The ANIMO Study

Article

Jan 2012

Objective: Little is known about apathy in the early stages of Parkinson's disease (PD). We determined the clinical correlates of apathy in a large representative sample of patients recently diagnosed with PD (ANIMO study). Methods: PD patients, diagnosed within 2 years of inclusion, were recruited in 102 outpatient clinics situated in 82 populations throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale (LARS). Clinical comparisons and correlations were performed using nonparametric tests. Regression analyses were used to test the association of clinical variables with apathy. Results: We recruited 557 PD patients (60.3% men) with a mean age of 68.8 ± 9.7 years, and UPDRS motor score of 21.1 ± 10.8. Apathy only was diagnosed in 186 (33.4%), and apathy and depression in 215 patients (38.6%). Patients with higher comorbidity (OR = 1.10, 95% CI 1.01-1.20, p = 0.001), motor impairment (OR = 1.07, 95% CI 1.03-1.10, p < 0.0001), and lower education (OR = 2.16, 95% CI 1.21-3.85, p = 0.009) had higher odds of having apathy, in contrast to patients living in a rural environment (OR = 0.35, 95% CI 0.32-0.85, p = 0.01), and left predominant PD motor laterality (OR = 0.34, 95% CI 0.13-0.88, p = 0.01). LARS scores were significantly correlated with UPDRS motor scores (r(s) = 0.44, p < 0.001), predominantly with axial score (r(s) = 0.43, p < 0.001). Conclusions: In PD, apathy is a very common and disabling nonmotor symptom separable from depression. Patients living in a rural environment, with lower comorbidity and motor impairment, higher education background, and left predominant PD motor laterality are at lower risk of suffering from apathy.

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Article

Mar 2013
BRAIN

Apathy is one of the most common symptoms encountered in Parkinson's disease, and is defined as a lack of motivation accompanied by reduced goal-directed cognition, behaviour and emotional involvement. In a previous study we have described a delayed withdrawal syndrome after successful motor improvement related to subthalamic stimulation allowing for a major decrease in dopaminergic treatment. This withdrawal syndrome correlated with a diffuse mesolimbic dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being related to mesolimbic dopaminergic denervation, we performed a randomized controlled study using piribedil, a relatively selective D2/D3 dopamine agonist to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week prospective, placebo-controlled, randomized, double-blinded trial was conducted in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy Scale score > 14) following subthalamic nucleus stimulation. Patients received either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks. The primary end point was the improvement of apathy under treatment, as assessed by the reduction of the Starkstein Apathy Scale score in both treatment groups. Secondary end points included alleviation in depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints consisted in changes of the Robert Inventory score and Hamilton depression scales. An intention to treat analysis of covariance analysis was performed to compare treatment effects (P < 0.05). The number of premature study dropouts was seven in the placebo and five in the piribedil groups, mostly related to intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With piribedil, modifications in the Beck depression and anxiety scores were -19.8% and -22.8%, respectively versus +1.4% and -8.3% with placebo, without reaching significance level. Piribedil led to a trend towards improvement in quality of life (-16.2% versus +6.7% on placebo; P = 0.08) and anhedonia (-49% versus -5.6% on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score, improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005). Depression, measured by the Hamilton score, improved in the piribedil group (P = 0.05). No significant side effects were observed. The present study provides a class II evidence of the efficacy of the dopamine agonist piribedil in the treatment of apathy in Parkinson's disease.

Impulse Control and Related Disorders in Parkinson's Disease

Article

Oct 2012
NEURODEGENER DIS

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized complication of dopamine replacement therapy in Parkinson's disease (PD). Other impulsive-compulsive behaviors have been linked to dopaminergic medications; these include punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), particularly at higher dosages; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Risk factors for ICDs may include male sex; younger age; younger age at PD onset; a pre-PD history of ICD(s); personal or family history of substance abuse; bipolar disorder; gambling problems; and impulsive personality traits. The primary treatment of ICDs in PD is discontinuation of DA therapy. Not all patients can tolerate this, however, due to worsening motor symptoms and/or DA withdrawal syndrome (a severe, stereotyped drug withdrawal syndrome similar to that of other psychostimulants). While psychiatric medications are frequently used to treat ICDs in the general population, there is no empirical evidence to suggest that they are effective in PD. Given the paucity of treatment options and potentially serious consequences of ICDs in PD, it is critical for patients to be monitored closely for their development. As empirically validated treatments for ICDs emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Pathologic gambling in Parkinson's disease: A behavioral manifestation of pharmacologic treatment?

Article

Sep 2000
MOVEMENT DISORD

We describe 12 patients with Parkinson's disease and pathologic gambling. This association has apparently never been reported. The patients were selected from a Parkinson's disease unit of 250 patients. They met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for pathologic gambling. All patients underwent a neurologic, psychiatric, and psychologic examination, specifically noting the presence or absence of psychopathology in the spectrum of impulse control disorder and the nature of the gambling. Ten patients started gambling after the onset of Parkinson's disease and treatment with levodopa. The pathologic behavior was exclusively present or was markedly increased in “on” periods in 11 patients. All patients had motor fluctuations at the time of the study. Slot machines were the preferred source of gambling for 10 patients, similar to the Spanish gambling population. That the gambling behavior appears more often in the “on” periods of motor fluctuations and that it begins after the onset of Parkinson's disease in most patients and worsens with levodopa therapy suggest that it could be related to the dopaminergic tone in patients with Parkinson's disease and motor fluctuations (that is, it could represent a behavioral manifestation of pharmacologic treatment).

Identification of motor and nonmotor wearing‐off in Parkinson's disease: Comparison of a patient questionnaire versus a clinician assessment

Article

Jun 2005
MOVEMENT DISORD

This study compares the sensitivity of a Patient Questionnaire versus information gathered by clinicians at a routine clinic visit in recognizing symptoms of wearing-off in early Parkinson's disease (PD). This Patient Questionnaire, containing 32 items representing a wide spectrum of motor and nonmotor wearing-off symptoms, was administered to subjects attending two PD clinics. The Patient Questionnaire results were compared to the information gathered by the clinician from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36 and from a specific Clinical Assessment Question regarding loss of medication efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications, morning akinesia, other dopaminergic side effects, or none of the above. Examiners were blinded to study hypothesis and survey contents. Three hundred consecutive subjects with PD of <5 years duration were evaluated; the mean subject age was 72 ± 9.6 years and 60.2% were men. Subjects reporting wearing-off were significantly younger (69.9 vs. 74.7 years) and differed regarding duration of PD symptoms (3.7 vs. 3.1 years). Wearing-off was found in 181 subjects (62.6%) by one or more of the three measures. The most sensitive tool was the Patient Questionnaire, with 165 subjects (57.1%) indicating symptoms of wearing-off. Question 36 of the UPDRS was positive in 127 subjects (43.9%), and the Clinical Assessment Question identified 85 subjects (29.4%) as experiencing wearing-off. All of these results were found to differ significantly. The mean number of wearing-off symptoms reported by the 165 subjects indicating wearing-off on the clinical survey was 6.25, with tremor being the most common motor feature and tiredness the most common nonmotor feature. © 2005 Movement Disorder Society

The Hospital Anxiety And Depression Scale

Article

Jun 1983
ACTA PSYCHIAT SCAND

ABSTRACT– A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.

A systematic review of prevalence studies of depression in Parkinson's disease

Article

Jan 2008
MOVEMENT DISORD

Prevalence rates of depressive disorders in Parkinson's disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinson's disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta-analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed. © 2007 Movement Disorder Society

A short Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease: First psychometric approach

Article

Apr 2012
J NEUROL

The neuropsychiatric symptoms and behavioral disorders affecting Parkinson's disease (PD) patients are common and disabling. A PD-specific interview-based 12-item scale, the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease (SEND-PD), has been developed to assess the severity of neuropsychiatric manifestations. The present study is aimed at testing some basic psychometric attributes of this scale. A total of 633 consecutive patients and their caregivers were included in this cross-sectional, multicenter, observational study. In addition to the tested scale, the following assessments were applied: Hoehn and Yahr staging, Scales for Outcomes in Parkinson's Disease Motor and Psychiatric complications, MiniMental State Examination, Clinical Impression of Severity Index, and the Zarit Caregiver Burden Inventory. Patients in all stages of disease were included and 18.38 % were demented. The SEND-PD was responded by patients (86.16 %), caregivers (13.15 %), or both (0.69 %). Three factors (accounting for 66.63 % of the variance) were identified and considered as subscales: Psychotic symptoms, Mood/Apathy, and Impulse control disorders. The subscales showed satisfactory scaling assumptions (multitrait-item success rate 100 %) and internal consistency (alpha indices >0.70). The convergent validity with other measures of psychiatric symptoms and the discriminant validity to distinguish between categories of patients' age, duration and severity of disease, and dopaminergic treatment were satisfactory. The precision of the scale dimensions was acceptable. The SEND-PD performed as an acceptable, consistent, valid, and precise scale for evaluation of neuropsychiatric symptoms in Parkinson's disease.

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiat 134: 382-389; 592

Article

Apr 1979

The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.

Psychosis, apathy, depression and anxiety in Parkinson's disease

Article

Jan 2012
NEUROBIOL DIS

Psychiatric symptoms are important non-motor features in PD, which occur at high frequency and have significant impact on health related quality of life. This review concentrates on the prevalence, pathophysiology, diagnosis and treatment of depression, anxiety, apathy and psychosis. The pathophysiology of these disorders is complex, reflecting the widespread brainstem and cortical pathology in PD, with involvement of several neurotransmitters, including dopaminergic, serotonergic, noradrenergic and cholinergic systems. The diagnosis of psychiatric conditions, in particular affective disorders, is challenging because of the overlap of somatic features of psychiatric disorders and underlying movement disorder. The pathogenesis is likely to differ considerably from non-PD patients, and treatments used in general psychiatry services may not be as effective in PD and will require clearer clarification in well-designed clinical studies. Management strategies include adjustment of dopaminergic medication, use of psychotropic treatments and behavioural and psychological approaches. However, the future challenge will be to develop treatments developed specifically for the pathogenesis of these disorders in PD.

Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale

Article

Feb 2012
MOVEMENT DISORD

Impulse control disorders and related disorders (hobbyism-punding and dopamine dysregulation syndrome) occur in 15% to 20% of Parkinson's disease (PD) patients. We assessed the validity and reliability of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS), a rating scale designed to measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. A convenience sample of PD patients at a movement disorders clinic self-completed the QUIP-RS and were administered a semistructured diagnostic interview by a blinded trained rater to assess discriminant validity for impulse control disorders (n = 104) and related disorders (n = 77). Subsets of patients were assessed to determine interrater reliability (n = 104), retest reliability (n = 63), and responsiveness to change (n = 29). Adequate cutoff points (both sensitivity and specificity values >80% plus acceptable likelihood ratios) were established for each impulse control disorder and hobbyism-punding. Interrater and retest reliability (intraclass correlation coefficient r) were >0.60 for all disorders. Participants in an impulse control disorder treatment study who experienced full (t = 3.65, P = .004) or partial (t = 2.98, P = .01) response demonstrated significant improvement on the rating scale over time, while nonresponders did not (t = 0.12, P = .91). The QUIP-RS appears to be valid and reliable as a rating scale for impulse control disorders and related disorders in PD. Preliminary results suggest that it can be used to support a diagnosis of these disorders, as well as to monitor changes in symptom severity over time.

The Prevalence and Clinical Characteristics of Punding in Parkinson's Disease

Article

Mar 2011
MOVEMENT DISORD

Punding (the display of stereotyped, repetitive behaviors) is a relatively recently discovered feature of Parkinson's disease (PD). Little is known about the prevalence and clinical characteristics of punding in PD. In this review, four large scientific databases were comprehensively searched for literature in relation to punding prevalence and clinical correlates in the context of PD. Prevalence was found to vary greatly (between 0.34 to 14%), although there were large disparities in study populations, assessment methods, and criteria. We observed an association between punding, dopaminergic medications, and impulse control disorder. Other characteristics, which may be more common among punders, include a higher severity of dyskinesia, younger age of disease onset, longer disease duration, and male gender. More research in large clinical datasets is required in many areas before conclusions are drawn. The pathophysiology behind the punding phenomenon is also poorly understood at present, rendering it difficult to develop targeted therapy. The current mainstay of treatment is the reduction in the dose of dopaminergic medications, the evidence for other suggested therapies being purely empirical.

[Behavioral disorders in Parkinson's disease: from pathophysiology to the mastery of dopaminergic treatment].

Article

Oct 2010
REV NEUROL-FRANCE

Behavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment. Subthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations--essential fluctuations in the patient's psychological state--are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients' quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment. Better management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms. The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively.

Anxiety Disorders in Parkinson's Disease: Prevalence and Risk Factors

Article

May 2010
MOVEMENT DISORD

Anxiety disorders are common in Parkinson's disease (PD) patients, yet are poorly studied. We examined the prevalence of anxiety disorders in PD, investigated the association between anxiety, and presentation and progression of PD, and studied for the first time the contribution of putative risk factors for anxiety in PD. A case-series of 79 PD patients recruited from neurology out-patient clinics was examined for anxiety disorders using the DSM-IV criteria. The Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Staging of PD were employed to understand the relationship between anxiety disorders, and the clinical presentation and severity of PD. A validated survey assessed putative risk factors for anxiety in PD. Twenty-five percent of PD patients were diagnosed with anxiety. Panic disorder, generalised anxiety disorder and social phobia were prevalent anxiety disorders. Comorbid depression with anxiety was observed (14%). The severity but not the duration of PD was positively related to anxiety. PD patients with postural instability and gait dysfunction symptom clustering were more likely to experience anxiety than tremor-dominant patients. While levodopa dosage had no relationship to anxiety, experience of dyskinesias or on/off fluctuations increased the risk. Lateralisation of PD had no association with anxiety. Anxiety disorders decreased with age and young onset PD patients were more likely to experience anxiety than the late onset subjects. Anxiety adds to the complexity of PD, lowering patients' quality of life. Future research can be directed to identify reactive and organic nature of anxiety in PD.

Neuropsychiatric Symptoms in Parkinson's Disease

Article

Nov 2009
MOVEMENT DISORD

Neuropsychiatric symptoms are common in Parkinson's disease, even at the earliest stages, and have important consequences for quality of life and daily functioning, are associated with increased carer burden and increased risk for nursing home admission. In addition to cognitive impairment, a wide range of neuropsychiatric symptoms have been reported. In this article, the epidemiology, clinical course, diagnosis, and management of some of the most common neuropsychiatric symptoms in PD are discussed: depression, anxiety, apathy, fatigue, and psychotic symptoms. Although much is known regarding the prevalence and course of these symptoms, the empirical evidence for how to manage these symptoms is limited at best. There is thus an urgent need for systematic studies for the pharmacological and non-pharmacological management of these symptoms.

Assessment of hyper- and hypodopaminergic behaviors in Parkinson's disease

Article

Sep 2009
REV NEUROL-FRANCE

Le stéréotype du patient parkinsonien dépressif, anxieux et apathique est actuellement bouleversé par la description récente de troubles comportementaux sévères et destructeurs comme le jeu pathologique ou l’hypersexualité, liés à une addiction dopaminergique. Cependant, des modifications comportementales peuvent survenir sans addiction dopaminergique. Elles sont nombreuses et variées, bénéfiques ou néfastes, bénignes ou sévères, et largement sous-évaluées car elles ne sont pas rapportées spontanément par les patients. Nous proposons une échelle d’évaluation comportementale, spécifiquement adaptée à la maladie de Parkinson. Elle est basée sur les concepts « d’hypodopaminergie » qui reflèterait l’hypofonctionnement dopaminergique et « d’hyperdopaminergie » lié à une sur-stimulation dopaminergique. Ainsi, des troubles psychiques et comportementaux aigus liés aux fluctuations hyper- ou hypodopaminergiques accompagnent fréquemment les fluctuations motrices. Cette échelle est construite en 18 items, regroupés en quatre parties : évaluation psychique générale, apathie, fluctuations non motrices et comportements hyperdopaminergiques. Une cotation en cinq points (0–4, d’absent à sévère) pour chaque item se fait au cours d’un entretien semi-structuré. Des questions ouvertes permettent au patient de s’exprimer le plus librement possible et des questions fermées précisent l’évaluation en termes de sévérité. Cet outil, utile dans la gestion du suivi thérapeutique des patients, peut s’intégrer à l’examen neuropsychologique au même titre que l’évaluation cognitive.

Serotonin and Parkinson's Disease: On Movement, Mood, and Madness

Article

Jul 2009
MOVEMENT DISORD

An appreciation of the multiple roles that serotonin (5-HT) may play in Parkinson's disease (PD) has increased in recent years. Early pathological studies in PD demonstrated nonselective reductions of 5-HT in brain tissue but little correlation to comorbidities such as dyskinesia and mood disturbance. This, combined with treatment failures using serotonergic drugs in comparison to levodopa, meant the field was largely neglected until recently. The multitude of subtypes of 5-HT receptors in the brain and an increased understanding of the potential function 5-HT may play in modulating other neurotransmitter systems, including dopamine, GABA, and glutamate, have meant an expansion in efforts to develop potential serotonergic drugs for both motor and nonmotor symptoms in PD. However, several unanswered questions remain, and future studies need to focus on correlating changes in 5-HT neurotransmission in both pathological and in vivo imaging studies with a full clinical phenotype.

Prevalence and clinical correlates of apathy in Parkinson's disease: A community-based study

Article

Oct 2008

The objective of this study was to examine the prevalence and clinical correlates of apathy in a population-based sample of patients with Parkinson's disease (PD) and to assess whether apathy may present as a primary behavioural disturbance independent from depression and cognitive impairment. A total of 232 patients derived from an epidemiological study of PD in Rogaland county, Western Norway, completed a comprehensive evaluation of motor, cognitive, and depressive symptoms. Apathy was assessed with the motivation/initiative item of the Unified Parkinson's Disease Rating Scale. The majority of the population had mild to moderate PD with mean disease duration of 9.1+/-5.7 years. Apathy was diagnosed in 38% of the 232 patients. In 11% of the total sample apathy coexisted with depression and dementia, whereas 10% had apathy and depression without dementia, 6.5% apathy and dementia without depression, and 9% were apathetic without dementia or depression (data missing in 1.5% patients). Apathy was significantly associated with higher depression scores, lower cognitive functioning, and more severe motor symptoms. When excluding patients with depression, dementia, cognitive impairment with no dementia (population-based age- and education-corrected norms for the Mini-Mental State Examination), and those using psychotropic medication, 5% of the 232 patients had apathy. In conclusion, our study shows that apathy is common in the general PD population, may present as an independent behavioural disorder, and suggests that apathy in PD may be related to dysfunction of the nigro-striatal pathway or that brain pathology underlying apathy and progression of motor symptoms develops in parallel.

The Bech-Refaelsen Mania Rating Scale and the Hamilton Depression Scale

Article

May 1979

In a study of 18 patients with manic symptomatology and 31 patients with melancholic symptomatology the Bech-Rafaelsen Mania Scale (BRMS) and the Hamilton Depression Scale (HDS) have been compared. The results showed that the inter-observer reliability of the BRMS was adequate compared with the HDS. Both scales are constructed for assessing the severity of manic or melancholic states, and no difference was found in the total BRMS or HDS score between the various diagnostic groups, when the patients were classified by an index of the course and symptomatology otive disorder, using the Multi-axial Classificetion System for Affective Disorders (MULTI-CLAD). The homogeneity of the BRMS seemed more adequate than that of the HDS, when each item was correlated to the corresponding total score. Although the homogeneity of the BRMS needs to be evaluated by other statistical models than correlation analysis, our results seem to indicate that the improvement in assessing manic-melancholic states quantitatively is a matter of redefining items or incorporating new items in the melancholic rather than the manic part of these rating scales.

The Measurement Of Observer Agreement For Categorical Data

Article

Apr 1977

This paper presents a general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies. The procedure essentially involves the construction of functions of the observed proportions which are directed at the extent to which the observers agree among themselves and the construction of test statistics for hypotheses involving these functions. Tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interobserver agreement are developed as generalized kappa-type statistics. These procedures are illustrated with a clinical diagnosis example from the epidemiological literature.

What factors improve the accuracy of clinical diagnosis in Parkinson's disease? A clinicopathologic study

Article

Jul 1992

Many authorities have drawn attention to the difficulties in clinically distinguishing Parkinson's disease (PD) from other parkinsonian syndromes. We assessed the clinical features of 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic PD according to their pathologic findings. Seventy-six percent of these cases were confirmed to have PD. By using selected criteria (asymmetrical onset, no atypical features, and no possible etiology for another parkinsonian syndrome) the proportion of true PD cases identified was increased to 93%, but 32% of pathologically confirmed cases were rejected on this basis. These observations suggest that studies based on consultant diagnosis of PD, using standard diagnostic criteria, will include cases other than PD, thus distorting results from clinical trials and epidemiologic studies. The strict use of additional criteria can reduce misdiagnosis but at the cost of excluding genuine PD cases.

Sexual addiction screening test

Article

Jul 1991
Tenn Nurse

P Carnes

The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease

Article

Jul 1988

The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.

The Positive and Negative Syndrome Scale (PANSS) for schizophrenia

Article

Feb 1987
SCHIZOPHRENIA BULL

The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.

Manic Response to Levodopa Therapy

Article

Oct 1971

Levodopa (L-dopa) is at present the most effective drug for the treatment of Parkinson's disease1 but psychiatric side effects have been reported in 10 per cent of treated cases. These are confusional hallucinating symptoms, depression, anxiety and euphoric reactions.2 , 3 The pure manic response reported below occurred in a patient whose clinical symptoms of Parkinson's disease were reversed by treatment with L-dopa. Case Report A 69-year-old retired drawbridge tender with an 8-year history of right-sided Parkinson tremor and rigidity was given small doses of L-dopa, which were gradually increased. There was no improvement until suddenly, when a dosage level of 3 . . .

Compulsive Buying: A Report of 20 Cases

Article

Jul 1994

Compulsive buying is a probably common but little studied disorder. To further characterize this syndrome, the authors assessed 20 compulsive buyers. Twenty consecutive psychiatric patients with problematic buying behavior characterized as (1) uncontrollable; (2) markedly distressing, time-consuming, and/or resulting in family, social, vocational, and/or financial difficulties; and (3) not occurring only in the context of hypomanic or manic symptoms were evaluated with structured diagnostic interviews. Family histories of psychiatric disorders and patients' responses to psychological and biological treatments were also assessed. Nineteen (95%) of the compulsive buyers studied had lifetime diagnoses of major mood disorders. Sixteen (80%) had lifetime diagnoses of anxiety disorders, 8 (40%) had impulse control disorders, and 7 (35%) had eating disorders. First-degree relatives displayed a high prevalence of mood disorders. Nine (69%) of 13 patients receiving thymoleptics at the time of compulsive buying episodes reported reduction or remission of their buying symptoms. Compulsive buying may cause significant psychological, interpersonal, and financial difficulties; may co-occur with other psychiatric disorders; may be treatable; and, thus, should be further studied as a mental disorder in its own right. To this end, preliminary operational criteria for its diagnosis are proposed.

Evaluating patient-based outcome measures for use in clinical trials

Article

Feb 1998

Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies

Article

May 2000

Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating effects of DRT and a negative affective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed.

Nonmotor fluctuations in Parkinson's disease: Frequent and disabling

Article

Sep 2002

To assess the frequency and disability caused by nonmotor fluctuations (NMF) in PD. A structured questionnaire was administered to 50 patients with PD with motor fluctuations (MF), focused on 54 nonmotor symptoms classified in three subgroups: 26 dysautonomic, 21 cognitive and psychiatric, and seven pain/sensory NMF. The link between each NMF and the motor state was determined. Patients were asked to grade their disability from 0 (no disability) to 4 (maximum discomfort) and to specify which kind of fluctuation subgroup (motor or nonmotor) was the most incapacitating. A statistical analysis was performed to determine the frequency of each NMF and to determine whether the level of disability resulting from NMF could be correlated to the main characteristics of the population. All patients had had at least one type of NMF, most of which were associated with the "off" state. Anxiety (66%), drenching sweats (64%), slowness of thinking (58%), fatigue (56%), and akathisia (54%) were the most frequent NMF. Some symptoms such as anxiety or dyspnea correlated with a greater level of disability. The total number of NMF was found to be correlated with the motor disability. Incapacity resulting from the dysautonomic fluctuations was also significantly correlated with levodopa treatment. Surprisingly, 28% of the patients stated that NMF involved a greater degree of disability than MF. Nonmotor fluctuations are frequent and debilitating in PD.

Dopamine dysregulation syndrome in Parkinson’s disease

Article

Sep 2004

Dopamine replacement therapy in Parkinson's disease ameliorates motor symptoms. However, it has recently been recognized that a small sub-group of patients suffer motor and behavioural disturbances attributable to taking quantities of medication well beyond the dose required to treat their motor disabilities. This review examines the phenomenology of dopamine dysregulation syndrome in relation to the current understanding of basal ganglia function and its impact on long-term management. Cortico-striato-thalamic circuits are implicated in the behavioural and motor disturbances associated with compulsive medication use in Parkinson's disease. Advances in understanding of the role of dopamine in psychostimulant addiction are important in helping to understand dopamine dysregulation. Recognition of dopamine dysregulation syndrome and characterization of its phenomenology supports the notion that the medication used to treat Parkinson's disease can disrupt basal ganglia mediated motor and behavioural functioning. Refinement of clinical strategies to predict, identify and manage this syndrome will aid the future treatment of motor and non-motor complications of Parkinson's disease.

Compulsive eating and weight gain related to dopamine agonist use

Article

Apr 2006

Dopamine agonists have been implicated in causing compulsive behaviors in patients with Parkinson's disease (PD). These have included gambling, hypersexuality, hobbyism, and other repetitive, purposeless behaviors ("punding"). In this report, we describe 7 patients in whom compulsive eating developed in the context of pramipexole use. All of the affected patients had significant, undesired weight gain; 4 had other comorbid compulsive behaviors. In the 5 patients who lowered the dose of pramipexole or discontinued dopamine agonist treatment, the behavior remitted and no further weight gain occurred. Physicians should be aware that compulsive eating resulting in significant weight gain may occur in PD as a side-effect of dopamine agonist medications such as pramipexole. Given the known risks of the associated weight gain and obesity, further investigation is warranted.

Anxiety disorders in Parkinson’s disease

Article

Feb 2005
Adv Neurol

Irene H Richard

Anxiety disorders frequently occur in association with PD and may be important causes of morbidity. Actual prevalence rates are uncertain, but estimates suggest that up to 40% of patients with PD experience substantial anxiety. This percentage is greater than expected, particularly for an elderly population. In addition, the age at onset of anxiety in PD (and particularly panic disorder) is later than would be expected from current information regarding the natural course of anxiety disorders. Virtually all of the types of anxiety disorders have been described in PD, but panic disorder, GAD, and social phobia appear to be the ones most commonly encountered. Although most patients with motor fluctuations experience greater anxiety during the "off" phase, this is not a universal phenomenon. Anxiety frequently develops before the motor features do, suggesting that anxiety may not represent psychological and social difficulties in adapting to the illness but rather may be linked to specific neurobiologic processes that occur in PD. Most evidence points to disturbances in central noradrenergic systems, but other neurotransmitters (e.g., serotonin, dopamine) may be involved as well. Studies suggest that right hemispheric disturbances may be particularly important for the genesis of anxiety, especially panic and OCD. Whether antiparkinsonian medications themselves contribute to anxiety needs clarification. Anxiety and depression frequently coexist in PD. It remains to be determined whether anxiety in patients with PD reflects one of the following pathologies: (a) an underlying depressive mood disorder, (b) a particular subtype of depression (atypical depression, anxious or agitated depression), or (c) an independent psychiatric disturbance. The relationship between anxiety and dementia in PD is not clear, but current evidence suggests that cognitive dysfunction is not related to the presence of anxiety symptoms in this disorder. The optimal pharmacologic treatment for anxiety in patients with PD has not been established, nor has the effect of PD surgery on anxiety symptoms.

Dissociating apathy and depression in Parkinson disease

Article

Aug 2006
NEUROLOGY

To examine the hypothesis that apathy is a core feature of Parkinson disease (PD) and that apathy can be dissociated from depression. Eighty patients with PD and 20 patients with dystonia completed depression and apathy measures including the Marin Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), and Centers for Epidemiologic Studies-Depression Scale (CES-D). There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, 41/80) than in dystonia (frequency = 20%, 4/20). Apathy in the absence of depression was frequent in PD and did not occur in dystonia (PD = 28.8%, dystonia = 0%). Patients with Parkinson disease (PD) experienced significantly higher frequency and severity of apathy when compared with patients with dystonia. Apathy may be a "core" feature of PD and occurs in the absence of depression.

Characteristics of apathy in Parkinson's disease

Article

Apr 2007

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.

A systematic review of the effectiveness of rivastigmine for the treatment of behavioral disturbances in dementia and other neurological disorders

Article

Feb 2008
CURR MED RES OPIN

Dementia is frequently associated with behavioral disturbances, some of which have a significant impact on patient quality of life and the likelihood of institutionalization. Cholinergic systems, among other neurotransmitters in the brain, appear to be involved with different behaviors, such as psychosis, depression, agitation, and personality changes. This paper reviews the clinical data on the effectiveness of rivastigmine, a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, in ameliorating behavioral disturbances in different patient populations. Relevant articles were identified through MEDLINE searches with no date restrictions. In particular, rivastigmine has shown efficacy in treating behavioral disturbances in patients with a wide range of dementias - Alzheimer's disease, vascular dementia, fronto-temporal dementia, mixed dementia, Lewy body dementia, Parkinson's disease with dementia, and schizophrenia with dementia. Most of the studies have been open-label clinical trials with behavior as a secondary endpoint. The behavior domains that most consistently showed improvement were apathy/indifference, anxiety, delusions (psychosis), and hallucinations. The major limitation of this review is that the effects on behavioral symptoms were usually secondary endpoints in clinical trials. The efficacious effects of treatment with rivastigmine on various behavioral disturbances provide supporting evidence that cholinergic mechanisms, among other neurotransmitters, are involved in the manifestation of some behavioral and psychological symptoms of dementia.

Apathy following subthalamic stimulation in Parkinson disease: A dopamine responsive symptom

Article

May 2008
MOVEMENT DISORD

To evaluate the effects of the dopamine D2-D3 agonist ropinirole in patients who developed apathy after complete withdrawal from dopaminergic medication following successful subthalamic nucleus (STN) stimulation for advanced Parkinson disease (PD). We assessed apathy (Apathy Scale, Apathy Inventory), mood (Montgomery-Asberg Depression Rating Scale), cognitive functions (Mattis Dementia rating scale, frontal score, executive tests) and motor state (UPDRS-III) in 8 PD patients treated with STN stimulation without dopaminergic treatment and who became apathetic. Assessments were made at baseline and after 6 weeks of ropinirole treatment (7.2 +/- 5.9 mg/d; range 1-18 mg/d). Apathy improved with ropinirole in all but 1 patient (54 +/- 24%; range 0-78%). Mood also improved (75 +/- 31%; range 0-100%), but not in correlation with the change in apathy. Cognitive performance was not modified. Stimulation contacts were located within the STN in all patients except the one who remained apathetic in spite of ropinirole treatment (zona incerta). We suggest that apathy, which was compensated for by an enhancement of D2-D3 receptor stimulation in PD patients with STN stimulation: (1) depends on a dopaminergic deficit in associativo-limbic areas of the brain and (2) can be avoided if a dopaminergic agonist is administered postoperatively.

Prevalence of anxi-ety disorders and anxiety subtypes in patients with Parkinson's dis-ease

Jan 2009
1333-1338

Pontone
Williams Jr Gm
Anderson
Ke

Pontone GM, Williams JR, Anderson KE, et al. Prevalence of anxi-ety disorders and anxiety subtypes in patients with Parkinson's dis-ease. Mov Disord 2009;24:1333-1338.

Impulse control disor-ders in Parkinson disease: a cross-sectional study of 3090 patients

Jan 2010
589-595

D Weintraub
J Koester
Potenza
Mn

Weintraub D, Koester J, Potenza MN, et al. Impulse control disor-ders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010;67:589-595.

Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmaco-logic treatment?

Jan 2000
869-872

Ja Molina
Mj
A Fraile

Molina JA, S ainz-Artiga MJ, Fraile A, et al. Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmaco-logic treatment? Mov Disord 2000;15:869-872.

The Mini-International Neuropsychiatric Interview (M.I.N.I.): the develop-ment and validation of a structured diagnostic psychiatric inter-view for DSM-IV and ICD-10

Jan 1998
22-33

Sheehan Dv
Y Lecrubier
Sheehan
Kh

Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the develop-ment and validation of a structured diagnostic psychiatric inter-view for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:22-33.

International validation of a behavioral scale in Parkinson's disease without dementia: NEUROPSYCHIATRIC ASSESSMENT IN PD

Abstract

No full-text available

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