Comparison of the effectiveness, safety, and costs of anti-Parkinson drugs: A multiple-center retrospective study.

AIMS: This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs). METHODS: This is a multi-center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs-related adverse events. RESULTS: A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56-355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088-0.135/day for levodopa/benserazide; $0.070-0.126/day for carbidopa/levodopa; $0.112-0.138/day for piribedil; $0.290-0.332/day for pramipexole; $0.229-0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031). CONCLUSIONS: Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

Ambiental Factors in Parkinson's Disease Progression: A Systematic Review.

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 µm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.

Electroacupuncture for motor dysfunction and constipation in patients with Parkinson's disease: a randomised controlled multi-centre trial.

Background: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. Methods: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. Findings: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of -9.1 points (95% CI, -11.8 to -6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR -26.0 to 0.0) in the EA group and 2.5 points (IQR: -11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. Interpretation: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Funding: Shanghai "Science and Technology Innovation Action Plan" Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).

Salivary ATP13A2 is a potential marker of therapy-induced motor complications and is expressed by inclusions in submandibulary glands in Parkinson ´s disease.

Background: ATP13A2 holds promise as biomarker for Parkinsons disease (PD). No study has examined how salivary ATP13A2 is related to motor features in idiopathic PD. Methods: Salivary ATP13A2 concentration was evaluated with ELISA, and statistical correlations of ATP13A2 level with PD parameters were examined. The dose intensity of the dopaminergic medication regimen was expressed as levodopa equivalent daily dose (LEDD). ATP13A2 expression on histological sections of submandibular glands was evaluated using immunohistochemistry. Results: Salivary ATP13A2 was undetectable in many subjects (28 % of patients, 43.7 % of controls). However, all the patients with motor complications (n = 28) showed quantifiable levels of ATP13A2, that positively correlated with MDS-UPDRS (total, parts III and IV), and LEDD (p < 0.05). Dyskinetic patients showed the highest LEDD values (p < 0.05). The histological study revealed: a) ATP13A2 staining was very intense in duct cells and vascular endothelium, and b) two patterns of ATP13A2-positive deposits are observed: rounded inclusions of 10-20 µm in diameter located in the interlobular tissue of the patients, and amorphous aggregates inside duct lumen in controls and patients. Conclusions: The sensitivity of the ELISA assay was a major limitation for quantifying ATP13A2. However, salivary ATP13A2 was detected in all patients with motor complications, where a direct relationship among ATP13A2 concentration, levodopa equivalent daily dose, and MDS-UPDRS was found. Therefore, salivary ATP13A2 might be a reliable index of therapy-induced motor complications. ATP13A2 was expressed by rounded inclusions in the submandibulary gland of patients. This is the first description of ATP13A2-positive inclusions outside the nervous system.

Real-world safety and effectiveness of rotigotine in patients with Parkinson's disease: analysis of a post-marketing surveillance study in Japan.

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of rotigotine under daily clinical practice in Parkinson's disease patients. METHODS: The study was a prospective, non-interventional, observational study targeting patients who were treated with rotigotine for the first time, with a 1-year follow-up period from September 2013 to August 2016. RESULTS: There were 603 patients in the safety population and 599 patients in the effectiveness population. The mean age was 71.6 years, and the age group of ≥65 and ≥80 years accounted for 80% and 18.6% of all patients, respectively. The frequency of adverse drug reaction (ADR) was 34.3%, and common ADRs were application site reaction (20.2%), typical for transdermal patches. However, the majority of patients recovered or was recovering from these ADRs and were non-serious. Although ADRs related to non-motor symptoms of Parkinson's disease were observed, most of them were non-serious. Total scores of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) (ON-time) significantly decreased from baseline in the effectiveness population. In the analysis of overall improvement in 12 months of post-treatment, ≥70% of patients achieved mild or greater improvement. The safety profiles and improvements in the UPDRS-III score were similar in both the ≥80 years of age group and younger age group. CONCLUSION: There were no new or notable safety concerns observed, and the effectiveness of rotigotine was suggested in daily clinical practice.

ATP13A2 levels in serum and cerebrospinal fluid in patients with idiopathic Parkinson's disease.

BACKGROUND: The enzyme ATP13A2 holds promise as biomarker in Parkinson's disease (PD). No study has examined the content of ATP13A2 in serum and cerebrospinal fluid (CSF) in idiopathic PD cohorts, or how ATP13A2 relates to the clinical features of the disease. METHODS: ATP13A2 concentration was evaluated with ELISA and immunoblotting. Correlations of serum and CSF ATP13A2 with clinical parameters were examined. The antiparkinsonian medication regimen was expressed as levodopa equivalent dose (LED, mg/day). RESULTS: Serum ATP13A2 concentration was similar in patients and controls, and it correlated with LED and MDS-UPDRS part-IV score (p < .0001), a scale which allows evaluating motor complications. LED also correlated with MDS-UPDRS part-IV score (p < .0001). Serum ATP13A2 concentration and LED were higher in patients with motor complications than in patients without motor complications (p < .0001). The ratio of serum ATP13A2 concentration versus LED was calculated, and mean value was similar in patients with or without motor complications. ATP13A2 concentration in the CSF was undetectable in many subjects because the ELISA assay was hampered by its detection limit. Immunoblotting indicated that CSF ATP13A2 content was higher in patients relative to controls (p = .0002), and no clinical correlations were found. CONCLUSIONS: Increasing LED enhanced serum ATP13A2 concentration and facilitated the development of motor complications. There is a direct relationship between serum ATP13A2 level and the dose intensity of the antiparkinsonian dopaminergic medication. The associations between serum ATP13A2 and LED suggest that serum ATP13A2 content might be a marker of dopamine replacement therapy.

Cerebrospinal fluid lactoperoxidase level is enhanced in idiopathic Parkinson's disease, and correlates with levodopa equivalent daily dose.

Lactoperoxidase (LPO) is proposed to play a role in the pathogenesis of Parkinson's disease (PD). This enzyme has been reported to be enhanced in the cerebrospinal fluid (CSF) in parkinsonian patients. The objective was to look at the relationship of LPO in the CSF and serum with clinical features of idiopathic PD. LPO concentration was analyzed through ELISA techniques. Correlation of CSF or serum LPO and MDS-UPDRS, dopaminergic medication, and other clinical parameters was examined. The findings revealed that LPO concentration in the CSF, not serum, was found to be elevated in patients with PD relative to controls (p < 0.001). CSF LPO concentration negatively correlated with MDS-UPDRS part-IV score (p < .0001), a rating scale that allows evaluating motor complications. CSF LPO level inversely correlated with the dose intensity of the dopaminergic medication regimen, as evaluated with levodopa equivalent dose or LED (mg/day; p < .0001). LED value positively correlated with MDS-UPDRS part-IV score (p < .0001). To sum up, the findings indicate that CSF LPO is found to be elevated in the CSF of PD patients, and this enzyme holds promise as potential biomarker for diagnosis of PD. Increasing the dose intensity of the dopaminergic medication regimen attenuates the elevation in LPO levels in the CSF, and it facilitates the development of motor complications in patients. The pathophysiological mechanisms that seem to be responsible for LPO increase would include dopamine deficiency, oxidative stress, and less likely, microbial infection.

EQUIDopa: A responsive web application for the levodopa equivalent dose calculator.

BACKGROUND AND OBJECTIVE: Levodopa/carbidopa intestinal gel infusion is a treatment option for patients of advanced stage of Parkinson's disease. This treatment requires the time-consuming and error-prone conversion of orally taken antiparkinson drugs into an equivalent replacing dose of levodopa/carbidopa, which is delivered via pump. In order to facilitate and speed up this conversion process, we developed a specific user-friendly application that would be available online or as a standalone mobile application. Such an application has now been written and designed in collaboration with a computer scientist and physician, who is also intended to be the final user. METHODS: The levodopa equivalent dose calculations are based on previous studies and data reported in the literature. Two related on-line conversion applications were analyzed and evaluated. The primary objectives of the application were determined, and basic functionalities were outlined. The application was implemented using modern development tools and frameworks. RESULTS: The application has proven to be effective and easy to use in our clinical setting. It can serve as a control for manual calculations made by medical staff. It can also be applied as a useful tool in levodopa/carbidopa intestinal gel infusion courses for the advanced treatment of Parkinson's disease. CONCLUSION: The presented application could replace the tedious and error-prone levodopa equivalent dose conversion of antiparkinson drugs efficiently. In comparison to related on-line conversion applications, this specific application provides more functionality, reduces the risk of user errors, and can be run on a variety of devices. The conversion value provided by the application is only an estimate. The effect of the drugs is specific for each individual patient, which could not be considered in the calculations. Therefore, the responsibility of using the results of the application rests with the clinical judgment of the user. Nevertheless, the application can give us a good starting point for the initial pump setting, which would be adjusted further during the titration period, according to the patient's response.

Anxiety and Levodopa Equivalent Daily Dose Are Potential Predictors of Sleep Quality in Patients With Parkinson Disease in Taiwan.

Background and Purpose: Non-motor symptoms of Parkinson disease (PD) have a strong negative impact on the health-related quality of life (QoL) of patients with PD. Sleep disturbance is an important non-motor symptom because of its high prevalence. However, previous studies investigating the determinants of sleep quality in patients with PD have revealed inconsistent results. Our study evaluated the correlations between sleep quality in patients with PD and disease-related variables, medications used depression, anxiety, and QoL and identified the determinants of sleep disturbance in people with PD in Taiwan. Methods: A total of 134 patients with PD were recruited from the outpatient clinic. We examined the correlations between the Parkinson disease sleep scale-2 (PDSS-2) scores and different variables, namely the Unified Parkinson Disease Rating Scale, Parkinson disease questionnaire, Beck Depression Inventory, and Beck Anxiety Inventory (BAI). Logistic regression analysis was used to assess the potential predictive variables for sleep quality in patients with PD. Results: Among our participants, 47.8% were classified as poor sleepers (PDSS-2 = 15-60). Correlation analysis demonstrated that poor sleepers exhibited longer disease durations, higher levodopa equivalent daily doses (LEDDs), higher PD severity, more depression and anxiety symptoms, poorer QoL, more frequent unemployed status, higher hypnotics use, higher dependency for activities of daily living, more motor impairments, and more therapy-related complications. Logistic regression revealed that the LEDD was a significant predictive factor of sleep quality. Conclusion: Poor sleepers constituted approximately half of our patients with PD. The participants experienced more favorable sleep if they were currently working. Increased PD duration, severity, depression or anxiety symptoms, and doses of dopaminergic therapy were significantly associated with poor sleep quality. Continued working, attempts to treat comorbid anxiety or depression, and avoidance of overdosage of dopaminergic treatments may improve sleep quality in patients with PD.

Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center.

OBJECTIVE: Deep brain stimulation (DBS) is an established treatment modality for Parkinson disease (PD). The first DBS for PD in the Philippines was performed at the Philippine Movement Disorder Surgery Center in 2006. There are no Philippine data on DBS for PD. We aim to determine the motor improvement and reduction in medication dosage of all patients with PD who underwent DBS at the Philippine Movement Disorder Surgery Center. METHODS: This is a retrospective study of all patients with PD (n = 17) who underwent DBS from 2006 to 2016. The change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor and levodopa equivalent dose were determined. RESULTS: There was a statistically significant reduction in the UPDRS motor in all patients off medication at 3 months (48.2%; P = 0.004), 1 year (47.3%; P = 0.026), 2 years (48.4%; P = 0.021), and 3 years (66.0%; P = 0.032) after DBS and on medication at 3 months (43.3%; P = 0.023), 6 months (24.7%; P = 0.053), and 1 year (38.1%; P = 0.033). A significant reduction in the dosage of PD medications was also seen until the second year of follow-up (52.3%; P < 0.001). Adverse events included an attempted suicide and a device-related infection. CONCLUSIONS: DBS for PD improves the UPDRS motor score in the off-medication and on-medication state, with the maximal benefit seen at 3 years after surgery and reduces PD medication dosage by half. Although the benefit from DBS is undeniable, the high cost of the procedure precludes more patients from benefitting from it. There is a need for government support to expand access to DBS.

Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome.

OBJECTIVECurrently, there is no treatment that slows or halts the progression of Parkinson's disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson's disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinson's disease at the time of deep brain stimulation (DBS) surgery.METHODSStandard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery.RESULTSAll 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinson's Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft.CONCLUSIONSPeripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.Clinical trial registration no.: NCT01833364 (clinicaltrials.gov).

Deep brain stimulation for Parkinson's disease: meta-analysis of results of randomized trials at varying lengths of follow-up.

OBJECTIVE Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson's disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up. METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups. RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99-4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar. CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.

Effects of dopaminergic drug adjustment on executive function in different clinical stages of Parkinson's disease.

BACKGROUND: Effects of dopaminergic medication on executive function in patients with Parkinson's disease (PD) are inconsistent. OBJECTIVE: We examined the effect of dopaminergic medication on executive function in 24 drug-naïve PD patients (de novo group) and in 21 PD patients on chronic dopaminergic medication (chronic medication group). METHODS: PD patients without dementia were included in this study. For the de novo group patients, dopaminergic medication was initiated, and the dose was increased to improve motor symptoms. For the chronic medication group patients, dopaminergic medication was adjusted to relieve clinical problems. All participants were tested prior to and at 4-7 months after the drug initiation/adjustment. Executive function was assessed by using the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Motor function was assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS; part III). Improvement in executive function was compared with a simultaneous change in levodopa equivalent doses (LED) of dopaminergic medication and with improvement in motor functions. RESULTS: The mean standardized BADS scores showed no significant improvement in both the groups. In the de novo group, percent improvement in the standardized BADS scores showed a significant positive correlation with the LED, but not with percent improvement in UPDRS part III. In the chronic medication group, percent improvement in the standardized BADS scores was negatively correlated with change in the LED, but not with percent improvement in UPDRS part III. Multiple regression analysis using improvement in the standardized BADS score as a dependent variable and patient's background factors (ie, age, education, disease duration, and motor and executive assessments at baseline) as independent variable showed that improvement in the executive assessment is significantly correlated with the LED only in the de novo group. CONCLUSION: Effects of dopaminergic drug adjustment on executive function differ according to the patient's clinical stage and depend on LED in de novo stage.

Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients.

We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

Postural deformities in Parkinson's disease -Mutual relationships among neck flexion, fore-bent, knee-bent and lateral-bent angles and correlations with clinical predictors.

BACKGROUND: Various postural deformities appear during progression of Parkinson's disease (PD), but the underlying pathophysiology of these deformities is not well understood. The angle abnormalities seen in individual patients may not be due to distinct causes, but rather they may have occurred in an interrelated manner to maintain a balanced posture. METHODS: We measured the neck flexion (NF), fore-bent (FB), knee-bent (KB) and lateral-bent (LB) angles in 120 PD patients, and examined their mutual relationships, and correlations with clinical predictors such as sex, age, disease duration, Hoehn and Yahr (H&Y) stage, medication dose (levodopa equivalent dose, LED; total dose of dopamine agonists, DDA). The relationship between the side of the initial symptoms and the direction of LB angle was also investigated. RESULTS: Our main findings were: (1) Significant relationships between NF and KB, NF and LB, FB and KB, KB and LB were observed. (2) NF angle was larger in males than in females, but FB, KB and LB angles showed no significant difference between the sexes. (3) FB and KB angles became larger with advancing age. (4) NF and FB angles were associated with disease duration. (5) NF, FB, KB and LB angles all increased significantly with increase of H&Y stage. (6) FB angle was significantly associated with LED, but DDA did not show a significant relationship with any of the measured angles. (7) Direction of LB angle was not associated with the side of initial symptoms. CONCLUSIONS: Postural abnormalities are interrelated, possibly to maintain a balanced posture.