Parkinson's Disease Behavior Research Articles

Granulocyte-colony stimulating factor improves Parkinson′s disease associated with co-morbid depression: An experimental exploratory study

Introduction:The present study was designed to evaluate the effect of granulocyte-colony stimulating factor (G-CSF) in the treatment of Parkinson's disease (PD), the second most common neurodegenerative disease characterized by muscle and movement disorder, often associated with depression. PD is very difficult to treat. Hence, the present study was aimed to evaluate the effect of G-CSF in PD associated with depression.Materials and Methods:Adult Wistar male rats weighing about 180-250 g were selected and divided into five groups in parallel designed method namely; control group (n = 5); sham operated group (n = 5); Vehicle group (n = 5); G-CSF group (70 μg/kg, s.c.) (n = 5) and L-DOPA group (n = 5). The rats were treated with 6-hydroxydopamine (6-OHDA) on day 0 and then treatment was continued for 14 day of L-DOPA/carbidopa, whereas G-CSF (70 μg/kg, s.c.) was given from day 1 to 6. Thereafter, adhesive removal and forced swim tests were conducted to evaluate the behavioral outcome of G-CSF treatment. The finding was correlated and analyzed with Nissl staining findings for the final conclusion.Results:The behavioral parameters were assessed and found to be ameliorate the symptoms of Parkinson's and reduced the depression like behavior in PD. The histological findings were supported the behavioral findings and showed pathological improvement.Conclusion:As a preliminary work, the present study first time suggested that G-CSF have a potential role in PD and associated depression.

Study on Xenotransplantation of Capsulated Porcine Choroid Plexus Cells in Rhesus PD Model

Introduction: Parkinson's disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The aim of study was to assay the potential therapeutic value of xenotransplantation of capsulated porcine choroid plexus (CP) cells to Parkinson's disease. Methods: CP cells were isolated from neonatal porcine choroid plexus, and the CP cells were encapsulated into APA CP cell capsule. Each capsule contained 2.7 CP cell clusters averagely. Nineteen adult male rhesus monkeys were made into hemi-parkinsonism by infusing MPTP into right internal carotid artery (ICA). Fifteen PD monkeys were shown typical PD features, behavior score for the rhesus was 10.93 ±3.7. The PD monkeys were randomized into three groups. Forty CP cell capsules were implanted into right caput nuclei caudate of the first group of 6 monkeys under CT guiding. Six monkeys were implanted with 40 empty capsules with same way in the second group. And the rhesus monkeys in the third group were just treated with sham surgery. Asymmetric rotation and neurological scores were assessed at 2 and 4 weeks post lesion and 2, 4, 8, 12, 16 and 24 weeks post implant. Histological analysis, anti-TH, ant-NGF and anti-NT-3 immunohistochemistry assays, were performed at termination of the study in 3 groups of rhesus. All recipients were not received any immunosuppressive protocol. Results: Twenty- four weeks after treatments, PD behavior score for the rhesus decreased by 9.3 ±1.8 points (p< 0·001) in CP cell implanted group, by 3.8 ±1.5 points in the sham group (p< 0·003) and by 4.2±1.1 in the empty capsules group. The CP cell capsules group showed a significantly improvement from baseline in behavior scores compared with the sham group and the empty capsules group. CP cell capsules were shown strong NGF and NT-3 positive staining. The Immunohistochemistry results also showed much more TH positive neurons in CP cells group compared to the sham group and the empty capsule group. Conclusion: Xenotransplantation of capsulated neonatal porcine CP cells shows positive value as potential therapy for Parkinson's disease in non-human primate model without immunosuppressive treatment.

Sleepwalking in Parkinson’s disease: a questionnaire-based survey

Sleepwalking (SW) corresponds to a complex sleep-associated behavior that includes locomotion, mental confusion, and amnesia. SW is present in about 10% of children and 2-3% of adults. In a retrospective series of 165 patients with Parkinson's disease (PD), we found adult-onset ("de novo") SW "de novo" in six (4%) of them. The aim of this study was to assess prospectively and systematically the frequency and characteristics of SW in PD patients. A questionnaire including items on sleep quality, sleep disorders, and specifically also SW and REM sleep behavior disorder (RBD), PD characteristics and severity, was sent to the members of the national PD patients organization in Switzerland. In the study, 36/417 patients (9%) reported SW, of which 22 (5%) had adult-onset SW. Patients with SW had significantly longer disease duration (p = 0.035), they reported more often hallucinations (p = 0.004) and nightmares (p = 0.003), and they had higher scores, suggestive for RBD in a validated questionnaire (p = 0.001). Patients with SW were also sleepier (trend to a higher Epworth Sleepiness Scale score, p = 0.055). Our data suggest that SW in PD patients is (1) more common than in the general population, and (2) is associated with RBD, nightmares, and hallucinations. Further studies including polysomnographic recordings are needed to confirm the results of this questionnaire-based analysis, to understand the relationship between SW and other nighttime wandering behaviors in PD, and to clarify the underlying mechanisms.

Impulsive Behavior and Associated Clinical Variables in Parkinson's Disease

Parkinson's disease (PD) is a degenerative brain disorder accompanied by the loss of dopaminergic neurons and the presence of motor and non-motor symptoms. We performed a cross-sectional, questionnaire-based analysis of impulsive behavior in our PD clinic population to assess prevalence and associated characteristics. We found a higher prevalence of impulsive behavior (29.7%) than previously reported, and found multiple, concurrent impulsive behaviors in 26% of subjects reporting impulsive behavior. Our findings contribute to the growing awareness of impulsive behavior in PD, and support the need for longitudinal studies to assess changes in impulsive behaviors in Parkinson's patients.

Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease?

Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

Risk and learning in impulsive and nonimpulsive patients with Parkinson's disease

Relatively little is known about the interaction between behavioral changes, medication, and cognitive function in Parkinson's disease (PD). We examined working memory, learning and risk aversion in PD patients with and without impulsive or compulsive behavior (ICB) and compared the results with those in a group of age-matched control subjects. Parkinson patients with PD+ICB had poorer working memory performance than either controls or PD patients without ICB. PD+ICB patients also showed decreased learning from negative feedback and increased learning from positive feedback in off compared with on dopaminergic medication. This interaction between medication status and learning was the opposite of that found in the PD patients without a diagnosis of ICB. Finally, the PD group showed increased risk preference on medication relative to controls, and the subgroup of PD+ICB patients with pathological gambling were overall more risk prone than the PD group. Thus, medication status and an impulsive behavioral diagnosis differentially affect several behaviors in PD.

The pattern of habitual sedentary behavior is different in advanced Parkinson's disease

Physical behavior changes in Parkinson's disease (PD), however, objective evidence of this is lacking. This study explored methods to objectively quantify sedentary behavior (SB) in advanced PD with the aim of identifying changes that could impact on the burden of disease. We compared the SB of 17 PD (UPDRS III 29.1 ± 5.5; disease duration 12.5 ± 6.4; H&Y (3 & 4) and 17 aged and gender matched healthy subjects. SB was measured objectively over a 7 day period using the activPAL accelerometer. SB was defined as sitting or lying and described in terms of the volume and pattern of SB. Comparison between PD and controls showed that whilst there was no difference in the volume of sedentary time (P = 0.15), there was a significant difference in distribution (P < 0.01) and pattern of accumulation of sedentary time (P < 0.01). Bouts of SB in people with PD tend to last longer than that of controls, whilst the total time spent inactive is the same for the two groups. These results suggest that PD leads to a change in the pattern of SB but not the volume. This may be interpreted as a strategy to conserve energy to maximize function. Studying the pattern of SB appears promising and has the potential to help us to understand the impact of PD and the consequences of changes in SB on the burden of disease.

Drug therapies for Parkinson's disease: A database analysis of patient compliance and persistence

Background: Evaluating medication adherence in Parkinson's disease (PD) is important to avoid erroneously attributing suboptimal patient outcomes from poor compliance to disease progression or adverse responses to medications. Objective: This study of patients with PD who were new to PD drug therapy examined patient compliance and persistence, by drug, to provide a comprehensive investigation of medication-taking behavior in PD. Methods: A retrospective analysis of patients receiving a new PD drug between March 1 and May 31, 2007, was conducted, using the IMS Health longitudinal prescription database, which contains ∼50% of all retail prescriptions and <150 million patients in the United States. Patients were considered to have received a new PD drug if they initiated PD therapy for the first time, added adjunctive PD therapy, or switched one PD drug for another. Patients were categorized as naive to PD therapy (NT) or having prior PD therapy (PT), which included adjunctive use and switches. The PD medications evaluated were rasagiline, levodopa/carbidopa, levodopa/carbidopa/entacapone, the catechol-O-methyltransferase (COMT) inhibitors (entacapone and tolcapone), pramipexole, ropinirole, and selegiline. The study consisted of a 12-month look-back period (during which patients were required to be active in the database), a 3-month selection period (during which patients received their first prescription), and a 12-month observation period. Compliance was measured using the medication possession ratio (MPR; defined as the number of days' supply of medication divided by the number of available days of therapy, from first dispense date in the selection period to last dispense date in the observation period); noncompliance was defined as an MPR ≤80%. Persistence was measured as the duration (days) of uninterrupted therapy. Results: A total of 29,682 patients with PD (19,673 NT, 10,009 PT) received a new PD drug and were analyzed. Of the 19,510 patients included in the compliance analysis, 10,438 (53.5%) had compliance rates >80% and 9072 (46.5%) were noncompliant. For all patients (NT and PT), compliance rates were significantly higher for patients taking rasagiline than for those taking other PD medications (all P < 0.001). For all patients, the highest mean number of persistent days of treatment (147.5) was reported for rasagiline, followed by levodopa/carbidopa/ entacapone (146.9); persistence for both of these drugs was significantly higher than that for the comparator medications (rasagiline vs levodopa/carbidopa, P = 0.002; rasagiline vs pramipexole, P = 0.003; rasagiline vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001; levodopa/carbidopa/entacapone vs levodopa/carbidopa, P = 0.005; levodopa/carbidopa/entacapone vs pramipexole, P = 0.006; levodopa/carbidopa/entacapone vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001). Almost half of the patients (13,103; 44.1%) remained on their PD medication ≥90 days. Conclusions: This study found a differential compliance and persistence across PD drug therapies. The compliance rate for rasagiline was significantly higher than that for all of the other PD medications. In addition, rasagiline and levodopa/carbidopa/entacapone were associated with significantly higher persistence rates than were the other PD medications.

Excessive hoarding in Parkinson's disease

Hoarding is seen in several psychiatric conditions, but has not been specifically assessed in Parkinson's disease (PD). This study investigates hoarding tendency amongst patients with PD, and its association with impulsive-compulsive spectrum behaviors (ICBs). We compare clinical features, measures of hoarding, impulse buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in 39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD - ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders. Compulsive shoppers scored higher than other varieties of ICB on excessive acquisition measures. Hoarding correlated positively with impulsive buying, obsessive-compulsive symptoms, PD duration, and negatively with self-control measures. Using multivariate regression analyzes, the presence of ICBs and measures of impulsive buying were the only variables independently associated with hoarding in PD. The association of hoarding with other ICBs and low trait impulse control suggests that excessive hoarding is related to the spectrum of impulsive behaviors in PD.

Impulse control disorders in Parkinson's disease in a Chinese population

Background: Dopamine agonists have been used as first-line treatments for patients with Parkinson's disease (PD) during its early stage, and several impulse control disorder (ICD) behaviors have been reported to be associated with their use. Objective: To investigate the association between ICD behaviors and the use of agonists in Chinese patients with PD and associated risk factors. Methods: Self-report screening questionnaires were mailed to 400 PD patients treated with anti-parkinsonian drugs in our clinical database and their spouses (served as control group). Those who screened positive for ICD behaviors by questionnaire were further interviewed over the telephone by a movement disorder specialist to confirm the diagnosis. Results: A total of 11 (3.53%) patients were diagnosed with ICD behaviors as follows: lifetime pathological gambling (1, 0.32%); subclinical or clinical hypersexuality (6, 1.92%); binge eating (1, 0.32%); dopamine dysregulation syndrome (2, 0.64%); and compulsive internet browsing (1, 0.32%). ICD behaviors were associated with an increased mean levodopa equivalent daily dosage and alcohol use ( p = 0.005 and p = 0.002, respectively). Patients using dopamine agonists were significantly ( p = 0.003) more likely to be diagnosed with an ICD (6.3%) as compared to those who were not (0.6%). Conclusion: PD patients who took dopamine agonists were more likely to report ICD behaviors in Chinese PD.

Validation of the questionnaire for impulsive‐compulsive disorders in Parkinson's disease

As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.

Pathological gambling amongst Parkinson's disease and ALS patients in an online community (PatientsLikeMe.com)

Pathological gambling (PG) has been identified in Parkinson's disease (PD), but such gambling behaviors may also occur in amyotrophic lateral sclerosis (ALS). We sought to estimate the prevalence of PG amongst members of a web-based community, PatientsLikeMe.com. A survey was constructed, consisting of demographic information, the South Oaks Gambling Screen (SOGS), the K-6 measure of distress, and items related to motivation for gambling. Data were obtained from 236 ALS patients and 208 PD patients. Of the PD patients, 13% were classified as problem gamblers compared with 3% of ALS patients (chi(2) = 14.005, P <or= 0.001). PD patients reported thoughts about gambling to be more distressing, harder to resist and more outside their control than ALS patients. Thus, the higher prevalence of compulsive behavior in PD may relate to damaged reward pathways or medication rather than to the effects of living with a chronic progressive neurological disorder per se.

Detrended Fluctuation Analysis of Temporal Variation of the Center of Pressure (COP) during Quiet Standing in Parkinsonian Patients

[Purpose] Parkinson's disease (PD) leads to stance instability in the late stage of the disease. Conventional studies of the center of pressure (COP) have difficulties characterizing postural instability in the early stage of PD. The present study analyzed stabilograms of PD patients using a recently developed method, detrended fluctuation analysis (DFA). [Subjects] The subjects were 7 PD patients in stages I-III of Hoehn and Yahr, and 10 age-matched healthy elderly (HE) persons. [Method] COP signals were measured during quiet standing, and subjected to DFA and conventional analysis. DFA parameters (scaling exponents) relating COP fluctuation to time interval showed similar behaviors both in PD and HE subjects. Both in the anterior-posterior (AP) and medio-lateral (ML) directions, three exponents, α1, α2 and α were obtained for short- and long-term fluctuations, and the whole range, respectively. [Results] Magnitudes α, α1 and α2 were almost the same: α1 ≈1.5, α2 ≈1.0, and α ≈1.3. The crossover points dividing the short- and long-term fluctuations in the AP direction, however, differed between PD and HE subjects. The former was about 0.6 times shorter than the latter. [Conclusion] PD patients may control upright posture with the similar postural strategies to HE subjects, but the switching times between the short- and long-term strategies may be different.

Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease

This article briefly reviews findings from studies on neuromelanin (NM)-bound ferric iron, which provide unique insights into the physiological functions of NM and possible pathophysiological mechanisms underlying dopaminergic neuronal cell death in Parkinson's disease (PD). NM is considered an endogenous iron-binding molecule of pigmented neurons and is believed to play a physiological role in intraneuronal iron homeostasis. In PD, where nigral iron levels are increased, saturation of high-affinity iron-binding sites on NM may overwhelm the protective capacity of this molecule, leading instead to an increase in redox-active iron, and subsequent cellular damage both in vitro and in vivo. Available data also suggest that the iron released from NM affects the ubiquitin–proteasome system in mitochondria, leading to the failure to clear proteins such as α-synuclein and to the development of abnormal α-synuclein-immunopositive Lewy bodies that contribute to dopaminergic nerve cell death in PD. NM-bound ferric iron mimics certain characteristic features of the human disease in vitro and in vivo (face validity), in conformity with the theoretical rationale for PD (construct validity) and predicts aspects of PD behaviour and neurobiology (predictive validity) that makes it a valid experimental model with which to study the mechanisms of dopaminergic neurodegeneration in PD.

Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity

The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

Sleep disturbances in patients with parkinsonism

Altered sleep and vigilance are among the most frequent symptoms, besides parkinsonism, in movement disorders. As many as 60% of patients with Parkinson's disease (PD) experience insomnia, 15-59% show rapid eye movement (REM) sleep behavior disorders (RBDs), and 30% show excessive daytime sleepiness. Insomnia is a distressing difficulty to maintain sleep, which is exacerbated by motor disability, painful dystonia, restless legs, dysuria, anxiety and depressed mood. Improving night-time motor control by overnight treatment with levodopa, transdermal or long-acting dopamine agonists, or bilateral subthalamus stimulation, can improve sleep continuity. RBDs are violent, enacted dreams that expose the patient or their sleeping partner to night-time injuries. A striking improvement of parkinsonism is observed during these behaviors in PD. RBDs are thought to be caused by lesions in the REM sleep atonia system, and can, in association with other early markers of neurodegenerative diseases, such as olfactory, cognitive and autonomic disturbances, precede parkinsonism by several years. Daytime sleepiness, often with a narcolepsy-like phenotype, is a common occurrence in PD, owing to lesions in the arousal systems of the brain. The use of dopamine agonists increases the risk of sleep attacks, especially when driving, suggesting a drug-disease interaction.

How schizophrenia and depression disrupt reward circuitry

Altered reward behavior in Parkinson's disease (PD) is supported by observations of a placebo effect, prevalence of addiction to dopamine agonists, incidence of compulsive reward-seeking behaviors, and disturbed affective symptoms in PD patients. However, it is not clear how dopamine neuron loss causes or supports these aberrant reward behaviors and alterations in affect. For example, striatal dopamine transporter loss has a small, significant relationship with depression and anxiety in mild/moderate PD, but not in severe PD. Also, dopamine loss itself does not appear to predict depression or anhedonia, the diminished capacity to experience pleasure. Other neuropsychiatric disorders such as schizophrenia and depression may provide models of disturbed reward biology that may prove useful when thinking about altered reward circuitry and behavior in PD and other neurological disorders.

Assessment of psychiatric complications in Parkinson's disease: The SCOPA‐PC

The objective of this study was to develop a clinimetric sound scale that addresses both psychotic and compulsive complications in Parkinson's disease (PD). The SCales for Outcomes in PArkinson's disease-Psychiatric Complications (SCOPA-PC) was developed by modifying the items of the Parkinson Psychosis Rating Scale (PPRS) and including an item on compulsive behavior in PD. To evaluate the validity of the SCOPA-PC, 106 PD patients were assessed. A subsample of 43 patients was assessed for interrater and test-retest reliability. Construct validity was evaluated using the Neuropsychiatric Inventory (NPI) and the South Oaks Gambling Scale (SOGS). Interrater and test-retest reliability for the total score was 0.95 and 0.91 (intraclass correlation coefficient), respectively. For the items, the interrater reliability ranged from 0.62 to 0.96 (weighted kappa) and the test-retest reliability ranged from 0.54 to 0.88 (weighted kappa). Cronbach's alpha was 0.68. The correlation between the SCOPA-PC total score and the NPI was 0.41. The correlation between SCOPA-PC items and NPI items that addressed similar constructs ranged from 0.34 to 0.68, whereas the correlation between the item on compulsive behavior and the SOGS was 0.49. In conclusion, the SCOPA-PC is a reliable, valid, and easily-administered semistructured questionnaire for both psychotic and compulsive complications in PD.

Medication-Related Impulse Control and Repetitive Behaviors in Parkinson Disease

A range of behaviors presumed to be related to aberrant or excessive dopaminergic medications are being increasingly recognized in Parkinson disease. These behaviors are linked by their incentive- or reward-based and repetitive natures and include pathological gambling, hypersexuality, compulsive shopping, compulsive eating, hobbyism, and compulsive medication use. Such behaviors can have potentially devastating psychosocial consequences and are often hidden. Whether these behaviors are simply related to dopaminergic medications interacting with an underlying individual vulnerability or whether the primary pathological features of Parkinson disease play a role is not known. We reviewed the literature on these behaviors in Parkinson disease, including definitions, epidemiological and potential pathophysiological features, and management. The study of these behaviors allows not only improved clinical management but also greater insight into a biologically mediated complex behavioral model.

Prevalence of repetitive and rewardseeking behaviors in Parkinson disease

Prevalence of repetitive and rewardseeking behaviors in Parkinson disease