Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson’s Disease Thu, 27 Nov 2014 00:10:08 +0000 The role of Centella asiatica L. leaf extract was studied on the transgenic Drosophila model flies expressing normal human alpha synuclein (h-αS) in the neurons. The leaf extract was prepared in acetone and was subjected to GC-MS analysis. C. asiatica extract at final concentration of 0.25, 0.50, and 1.0 μL/mL was mixed with the diet and the flies were allowed feeding on it for 24 days. The effect of extract was studied on the climbing ability, activity pattern, lipid peroxidation, protein carbonyl content, glutathione content, and glutathione-S-transferase activity in the brains of transgenic Drosophila. The exposure of extract to PD model flies results in a significant delay in the loss of climbing ability and activity pattern and reduced the oxidative stress () in the brains of PD flies as compared to untreated PD flies. The results suggest that C. asiatica leaf extract is potent in reducing the PD symptoms in transgenic Drosophila model of Parkinson’s disease. Yasir Hasan Siddique, Falaq Naz, Smita Jyoti, Ambreen Fatima, Saba Khanam, Rahul, Fahad Ali, Syed Faiz Mujtaba, and Mohammad Faisal Copyright © 2014 Yasir Hasan Siddique et al. All rights reserved. Recurrent Falls in People with Parkinson’s Disease without Cognitive Impairment: Focusing on Modifiable Risk Factors Sun, 23 Nov 2014 08:03:21 +0000 Falls can be considered a disabling feature in Parkinson’s disease. We aimed to identify risk factors for falling, testing simultaneously the ability of disease-specific and balance-related measures. We evaluated 171 patients, collecting demographic and clinical data, including standardized assessments with the Unified Parkinson’s Disease Rating Scale (UPDRS), activities of daily living (ADL) and motor sections, modified Hoehn and Yahr Scale, Schwab and England, eight-item Parkinson’s Disease Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale-International (FES-I), Berg Balance Scale, Dynamic Gait Index, Functional Reach, and Timed Up and Go. ROC curves were constructed to determine the cutoff scores for all measures. Variables with entered a logistic regression model. The prevalence of recurrent falls was 30% (95% CI 24%–38%). In multivariate analysis, independent risk factors for recurrent falls were () levodopa equivalent dose (OR = 1.283 per 100 mg increase; 95% CI = 1.092–1.507), UPDRS-ADL > 16 points (OR = 10.0; 95% CI = 3.6–28.3), FES-I > 30 points (OR = 6.0; 95% CI = 1.6–22.6), and Berg ≤ 48 points (OR = 3.9; 95% CI = 1.2–12.7).We encourage the utilization of these modifiable risk factors in the screening of fall risk. Lorena R. S. Almeida, Guilherme T. Valença, Nádja N. Negreiros, Elen B. Pinto, and Jamary Oliveira-Filho Copyright © 2014 Lorena R. S. Almeida et al. All rights reserved. Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response Thu, 20 Nov 2014 07:01:36 +0000 Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects. Craig J. Hudson, Philip Seeman, and Mary V. Seeman Copyright © 2014 Craig J. Hudson et al. All rights reserved. Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson’s Disease? Mon, 17 Nov 2014 07:47:27 +0000 Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman’s rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin’s Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation. Krisztina Horváth, Zsuzsanna Aschermann, Péter Ács, Edit Bosnyák, Gabriella Deli, Endre Pál, József Janszky, Béla Faludi, Ildikó Késmárki, Sámuel Komoly, Magdolna Bokor, Eszter Rigó, Júlia Lajtos, Péter Klivényi, György Dibó, László Vécsei, Annamária Takáts, Adrián Tóth, Piroska Imre, Ferenc Nagy, Mihály Herceg, Anita Kamondi, Eszter Hidasi, and Norbert Kovács Copyright © 2014 Krisztina Horváth et al. All rights reserved. Oleanolic Acid Enhances the Beneficial Effects of Preconditioning on PC12 Cells Thu, 13 Nov 2014 07:10:28 +0000 Preconditioning triggers endogenous protection against subsequent exposure to higher concentrations of a neurotoxin. In this study, we investigated whether exposure to oleanolic acid (OA) enhances the protective effects of preconditioning on PC12 cells exposed to 6-hydroxydopamine (6-OHDA). A concentration response curve was constructed using 6-OHDA (50, 150, 300, and 600 μM). The experiment consisted of 6 groups: untreated, OA only, Group 1: cells treated with 6-OHDA (50 μM) for 1 hour, Group 2: cells treated with 6-OHDA (150 μM) for 1 hour, Group 3: cells treated with 6-OHDA (50 μM) for 30 minutes followed 6 hours later by treatment with 6-OHDA (150 μM) for 30 minutes, and Group 4: cells treated as in group 3 but also received OA immediately after the second 6-OHDA treatment. Cell viability and apoptotic ratio were assessed using the MTT and Annexin V staining tests, respectively. In preconditioned cells, we found that cell viability remained high following exposure to 6-OHDA (150 μM). OA treatment enhanced the protective effects of preconditioning. Similarly, with the annexin V apoptosis test, preconditioning protected the cell and this was enhanced by OA. Therefore, preexposure of PC12 cells to low 6-OHDA concentration can protect against subsequent toxic insults of 6-OHDA and OA enhances this protection. Babongile C. Ndlovu, Willie M. U. Daniels, and Musa V. Mabandla Copyright © 2014 Babongile C. Ndlovu et al. All rights reserved. Validation of the Persian Translation of the Swallowing Disturbance Questionnaire in Parkinson’s Disease Patients Mon, 27 Oct 2014 08:45:05 +0000 Dysphagia, as a common finding in Parkinson’s disease (PD) patients, was estimated to be present in 80–95% of this population during different stages of the disease. The Swallowing Disturbance Questionnaire (SDQ) was created as a self-rated dysphagia screening tool in PD. According to the guidelines for cross-cultural adaptation, Persian version of this questionnaire (SDQ-P) was developed. 59 Persian patients (39 men and 20 women) participated in the study. They responded to the SDQ-P and underwent videofluoroscopic swallowing study (VFSS). Aspiration during VFSS was compared with questionnaire results for each individual. Cronbach’s alpha coefficient for the questionnaire was 0.86 and based on SDQ-P 15 patients (25.4%) were dysphagic, while 10 patients (16.9%) showed aspiration during VFSS. SDQ-P sensitivity and specificity in predicting aspiration were 96.7 and 91.2%; therefore, the SDQ-P could be a prognostic tool for aspiration. The positive predictive value (PPV), the negative predictive value (NPV), and the pre- and posttest probabilities of aspiration were 0.67, 1, 16.9%, and 66.7%, respectively. In summary, this study demonstrated the reliability and also the feasibility of SDQ-P for screening of aspiration in Iranian patients with PD. Further evaluation of SDQ-P in larger subject population would be suggested. Ali Rajaei, S. Abolfazl Azargoon, Mohammad Hussein Nilforoush, Ebrahim Barzegar Bafrooei, Fereshteh Ashtari, and Ahmad Chitsaz Copyright © 2014 Ali Rajaei et al. All rights reserved. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA Thu, 23 Oct 2014 06:32:03 +0000 Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD) has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was (range from 0 to 16). The neuropsychiatric MDS-UPDRS part IA score was (range from 0 to 14). The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was (all, ). Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found. Mayela Rodríguez-Violante, Amin Cervantes-Arriaga, Salvador Velázquez-Osuna, Rodrigo Llorens-Arenas, Humberto Calderón-Fajardo, Dan Piña-Fuentes, and Pablo Martinez-Martin Copyright © 2014 Mayela Rodríguez-Violante et al. All rights reserved. Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson’s Disease Tue, 21 Oct 2014 11:17:58 +0000 Purpose. To investigate changes in vowel articulation with the electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) in dysarthric speakers with Parkinson’s disease (PD). Methods. Eight Quebec-French speakers diagnosed with idiopathic PD who had undergone STN DBS were evaluated ON-stimulation and OFF-stimulation (1 hour after DBS was turned off). Vowel articulation was compared ON-simulation versus OFF-stimulation using acoustic vowel space and formant centralization ratio, calculated with the first () and second formant () of the vowels /i/, /u/, and /a/. The impact of the preceding consonant context on articulation, which represents a measure of coarticulation, was also analyzed as a function of the stimulation state. Results. Maximum vowel articulation increased during ON-stimulation. Analyses also indicate that vowel articulation was modulated by the consonant context but this relationship did not change with STN DBS. Conclusions. Results suggest that STN DBS may improve articulation in dysarthric speakers with PD, in terms of range of movement. Optimization of the electrical parameters for each patient is important and may lead to improvement in speech fine motor control. However, the impact on overall speech intelligibility may still be small. Clinical considerations are discussed and new research avenues are suggested. Vincent Martel Sauvageau, Joël Macoir, Mélanie Langlois, Michel Prud’Homme, Léo Cantin, and Johanna-Pascale Roy Copyright © 2014 Vincent Martel Sauvageau et al. All rights reserved. Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease Wed, 15 Oct 2014 10:11:16 +0000 Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD. Natália Pessoa Rocha, Paula Luciana Scalzo, Izabela Guimarães Barbosa, Mariana Soares Souza, Isabela Boechat Morato, Érica Leandro Marciano Vieira, Paulo Pereira Christo, Antônio Lúcio Teixeira, and Helton José Reis Copyright © 2014 Natália Pessoa Rocha et al. All rights reserved. Random Whole Body Vibration over 5 Weeks Leads to Effects Similar to Placebo: A Controlled Study in Parkinson’s Disease Mon, 13 Oct 2014 09:12:05 +0000 Background. Random whole body vibration (WBV) training leads to beneficial short-term effects in patients with Parkinson’s disease (PD). However, the effect of WBV lasting several weeks is not clear. Objectives. The aim of this study was to assess a random WBV training over 5 weeks in PD. Methods. Twenty-one participants with PD were allocated to either an experimental or a placebo group matched by age, gender, and Hoehn&Yahr stage. The WBV training consisted of 5 series, 60 s each. In the placebo group, vibration was simulated. The primary outcome was the change of performance in Functional reach test (FRT), step-walk-turn task, biomechanical Gait Analysis, Timed up and go test (TUG), and one leg stance. Findings. In most of the parameters, there was no significant interaction of “timegroup.” Both groups improved significantly in Gait parameters, TUG, and one leg stance. Only in the FRT [; ] and in the TUG [; ] the experimental group performed significantly better than the placebo group. Conclusions. Random WBV training over 5 weeks seems to be less effective than reported in previous studies performing short-term training. The slight improvements in the FRT and TUG are not clinically relevant. Heiko Gaßner, Annette Janzen, Ansgar Schwirtz, and Petra Jansen Copyright © 2014 Heiko Gaßner et al. All rights reserved. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study Tue, 26 Aug 2014 12:49:27 +0000 The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD). Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2), and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, ). Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., ). However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, ) and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, ) than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD. Edit Bosnyák, Mihály Herceg, Endre Pál, Zsuzsanna Aschermann, József Janszky, Ildikó Késmárki, Sámuel Komoly, Kázmér Karádi, Tamás Dóczi, Ferenc Nagy, and Norbert Kovács Copyright © 2014 Edit Bosnyák et al. All rights reserved. Active Aging for Individuals with Parkinson’s Disease: Definitions, Literature Review, and Models Mon, 25 Aug 2014 05:24:42 +0000 Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson’s disease (PD). The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson’s Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging. Seyed-Mohammad Fereshtehnejad and Johan Lökk Copyright © 2014 Seyed-Mohammad Fereshtehnejad and Johan Lökk. All rights reserved. Executive Function and Postural Instability in People with Parkinson’s Disease Thu, 17 Jul 2014 09:54:42 +0000 The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson’s disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and Addenbrooke’s Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance, and gait. PD participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B, was associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD. Dong Xu, Michael H. Cole, Kerrie Mengersen, Peter A. Silburn, Feng Qiu, Cara Graepel, and Graham K. Kerr Copyright © 2014 Dong Xu et al. All rights reserved. Temporal Characteristics of High-Frequency Lower-Limb Oscillation during Freezing of Gait in Parkinson’s Disease Wed, 02 Jul 2014 09:32:00 +0000 A cardinal feature of freezing of gait (FOG) is high frequency (3–8 Hz) oscillation of the legs, and this study aimed to quantify the temporal pattern of lower-body motion prior to and during FOG. Acceleration data was obtained from sensors attached to the back, thighs, shanks, and feet in 14 Parkinson’s disease patients performing timed-up-and-go tasks, and clinical assessment of FOG was performed by two experienced raters from video. A total of 23 isolated FOG events, defined as occurring at least 5 s after gait initiation and with no preceding FOG, were identified from the clinical ratings. The corresponding accelerometer records were analyzed within a 4 s window centered at the clinical onset of freezing. FOG-related high-frequency oscillation (an increase in power in the 3–8 Hz band >3 SD from baseline) followed a distal to proximal onset pattern, appearing at the feet, shanks, thighs, and then back over a period of 250 ms. Peak power tended to decrease as the focus of oscillation moved from feet to back. There was a consistent delay (mean 872 ms) between the onset of high frequency oscillation at the feet and clinical onset of FOG. We infer that FOG is characterized by high frequency oscillation at the feet, which progresses proximally and is mechanically damped at the torso. Don A. Yungher, Tiffany R. Morris, Valentina Dilda, James M. Shine, Sharon L. Naismith, Simon J. G. Lewis, and Steven T. Moore Copyright © 2014 Don A. Yungher et al. All rights reserved. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão), as Evaluated by a Parkinson’s Disease Model in Rats Wed, 25 Jun 2014 10:28:14 +0000 Myracrodruon urundeuva Fr. All. (Anacardiaceae) is a Brazilian medicinal species, which is common to the Northeastern Brazilian semiarid region, whose stem-bark is widely used in folk medicine. It is an endangered species, presenting as main bioactive components tannins and chalcones. In this work, we studied the neuroprotective effects of a standardized extract from cultivated M. urundeuva (SEMU), in a model of Parkinson’s disease. Thus, a unilateral injection of 6-OHDA was done into the rat right stratum. The animals were submitted to stereotaxic surgery, then treated with SEMU (5, 10, 20, or 40 mg/kg, p.o.) for 2 weeks, subjected to behavioral tests, and euthanized for striata dissections and neurochemical, histological, and immunohistochemical analyses. We showed, for the first time, that SEMU reverted behavioral alterations seen in the 6-OHDA-lesioned group and partially blocked the decrease in DA and DOPAC contents. The numbers of viable neurons and TH immunopositive cells were increased by SEMU. In addition, the SEMU-treated 6-OHDA groups showed lower numbers of GFAP and OX-42 immunopositive cells. The neuroprotective action of SEMU is possibly related to the antioxidant and anti-inflammatory properties of M. urundeuva, pointing out to its potential use in the prevention or treatment of neurodegenerative conditions, such as Parkinson’s disease. Iana Calou, Mary Anne Bandeira, Wellida Aguiar-Galvão, Gilberto Cerqueira, Rafaelly Siqueira, Kelly Rose Neves, Gerly Anne Brito, and Glauce Viana Copyright © 2014 Iana Calou et al. All rights reserved. Serum Leptin Concentrations in Turkish Parkinson’s Disease Population Mon, 28 Apr 2014 08:05:10 +0000 Objectives. To investigate leptin levels and their relationship to body composition and demographic and clinical characteristics of Turkish patients with Parkinson’s disease (PD). Patients and Methods. Forty eligible PD patients and 25 healthy controls were included in the study. Body composition measurements (height, weight, waist circumference (WC), and body mass index (BMI)) of the whole sample and clinical findings of PD patients were evaluated in the on-state. A single 5 mL fasting blood sample was obtained from each participant in the morning. Severity of PD was evaluated using the Hoehn and Yahr scale and the Unified Parkinson’s Disease Rating Scale. Results. The mean age of the patients and controls was and years, while the mean BMI was and and the mean leptin levels were and  ng/mL, respectively. Only age and gender were correlated with leptin levels. There was a significant difference () in leptin levels between male ( ng/mL) and female ( ng/mL) PD patients. Among the male PD patients, older age and higher BMI and WC values were associated with higher mean leptin levels. There was not any significant relationship between leptin levels and clinical findings in PD patients. Conclusion. These results may suggest that leptin levels have no determinative role in the follow-up of PD patients with regard to the severity and clinical prognosis of PD. Betul Ozdilek and Gulay Kenangil Copyright © 2014 Betul Ozdilek and Gulay Kenangil. All rights reserved. Dopamine Cytotoxicity Involves Both Oxidative and Nonoxidative Pathways in SH-SY5Y Cells: Potential Role of Alpha-Synuclein Overexpression and Proteasomal Inhibition in the Etiopathogenesis of Parkinson's Disease Wed, 02 Apr 2014 13:27:56 +0000 Background. The cytotoxic effects of dopamine (DA) on several catecholaminergic cell lines involve DA oxidation products like reactive oxygen species (ROS) and toxic quinones and have implications in the pathogenesis of sporadic Parkinson's disease (PD). However, many molecular details are yet to be elucidated, and the possible nonoxidative mechanism of dopamine cytotoxicity has not been studied in great detail. Results. Cultured SH-SY5Y cells treated with DA (up to 400 M) or lactacystin (5 M) or DA (400 M) plus N-acetylcysteine (NAC, 2.5 mM) for 24 h are processed accordingly to observe the cell viability, mitochondrial dysfunctions, oxidative stress parameters, proteasomal activity, expression of alpha-synuclein gene, and intracellular accumulation of the protein. DA causes mitochondrial dysfunction and extensive loss of cell viability partially inhibited by NAC, potent inhibition of proteasomal activity marginally prevented by NAC, and overexpression with accumulation of intracellular alpha-synuclein partially preventable by NAC. Under similar conditions of incubation, NAC completely prevents enhanced production of ROS and increased formation of quinoprotein adducts in DA-treated SH-SY5Y cells. Separately, proteasomal inhibitor lactacystin causes accumulation of alpha-synuclein as well as mitochondrial dysfunction and cell death. Conclusions. DA cytotoxicity includes both oxidative and nonoxidative modes and may involve overexpression and accumulation of alpha-synuclein as well as proteasomal inhibition. Kalpita Banerjee, Soumyabrata Munshi, Oishimaya Sen, Vishmadeb Pramanik, Tapasi Roy Mukherjee, and Sasanka Chakrabarti Copyright © 2014 Kalpita Banerjee et al. All rights reserved. Minimal Clinically Important Difference in Parkinson’s Disease as Assessed in Pivotal Trials of Pramipexole Extended Release Tue, 01 Apr 2014 12:28:38 +0000 Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS) scores in early Parkinson’s disease (EPD) and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR) was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials. Robert A. Hauser, Mark Forrest Gordon, Yoshikuni Mizuno, Werner Poewe, Paolo Barone, Anthony H. Schapira, Olivier Rascol, Catherine Debieuvre, and Mandy Fräßdorf Copyright © 2014 Robert A. Hauser et al. All rights reserved. Nonmotor Symptoms in a Malaysian Parkinson’s Disease Population Tue, 01 Apr 2014 07:52:09 +0000 Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson’s disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson’s disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (: 0.727, ). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson’s disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study. Shahrul Azmin, Abdul Manaf Khairul Anuar, Hui Jan Tan, Wan Yahya Nafisah, Azman Ali Raymond, Othman Hanita, Shamsul Azhar Shah, and Mohamed Ibrahim Norlinah Copyright © 2014 Shahrul Azmin et al. All rights reserved. Neuropsychiatric Symptoms in an Inpatient Parkinson’s Disease Sample Wed, 12 Mar 2014 11:37:19 +0000 Background. Neuropsychiatric symptoms are common in idiopathic Parkinson’s disease (PD), and hospitalization for delirium, depression, psychosis, and anxiety is sometimes required. A minimal amount of data exists on these patients. Methods. Charts of all patients admitted to a psychiatric hospital between 2006 and 2009 with a diagnosis of PD were reviewed. Forty-three met entry criteria and were reviewed. Initial and discharge diagnoses, comorbid psychiatric diagnoses, length of stay, and living arrangements before and after hospitalization are described. Results. Consistent with previous research, this study showed evidence of comorbid psychiatric disorders within PD. Conclusions. The long-term goal of this area of study would be to reduce neuropsychiatric symptoms and improve quality of life in order to reduce inpatient hospital stays. Nicole C. R. McLaughlin, Irene Piryatinsky, Gary Epstein-Lubow, Louis Marino, and Joseph H. Friedman Copyright © 2014 Nicole C. R. McLaughlin et al. All rights reserved. Trends in Antiparkinsonian Medication Use in New Zealand: 1995–2011 Tue, 04 Mar 2014 12:58:17 +0000 Prescribing trends for medications are influenced by development of new drugs, changes in knowledge about efficacy and side effects, and priorities set by funding agencies. Changes in the utilization of antiparkinsonian agents in the outpatient community in New Zealand were investigated by using the national prescription database for the period 1995–2011. The dispensed volumes of antiparkinsonian agents were converted into number of defined daily doses per 1000 inhabitants per day for analysis. Increases in the dispensed volumes of levodopa (77%), amantadine (350%), and catechol-o-methyl transferase inhibitors (326%) occurred during the study period. Conversely, decreases in the dispensed volumes of anticholinergics (48%), selegiline (82%), and dopamine agonists (6.2%) were observed. New Zealand has seen a substantial increase of the amount of levodopa dispensed in the past 17 years. This increase appears to be related to an increase in the number of people taking the medication. We are unable to extrapolate this change to an increase in the prevalence of PD, given levodopa is used in the treatment of a number of medical conditions. The changes in other antiparkinsonian medications largely reflect changes in availability (increases in entacapone and ropinirole) and best practice treatment (declines in anticholinergics, selegiline, and tolcapone). T. L. Pitcher, M. R. MacAskill, and T. J. Anderson Copyright © 2014 T. L. Pitcher et al. All rights reserved. Long-Term Mortality Analysis in Parkinson’s Disease Treated with Deep Brain Stimulation Mon, 03 Mar 2014 08:58:41 +0000 Background. Few data have been published regarding long-term mortality in patients with Parkinson’s disease treated with DBS. Methods. This study analyzed long-term mortality rates, causes, and correlates in PD patients treated with DBS. Results. 184 consecutive patients were included; mean follow-up was 50 months. Fifteen deaths occurred (total 8.15%, annual mortality rate 1.94%). Mean age at disease onset and at surgery was and years, respectively. Mean disease duration until death was years. Most deaths related to stroke, myocardial infarction, other vascular/heart disorders, or severe infection; one suicide was recorded. Deceased PD patients were mostly male and had lower motor benefit after DBS, but univariate analysis failed to show significant differences regarding gender and motor benefit. Survival was 99% and 94% at 3 and 5 years. Conclusions. Long-term survival is to be expected in PD patients treated with DBS, possibly higher than previously expected. Death usually supervenes due to vascular events or infection. Sofia Rocha, Ana Monteiro, Paulo Linhares, Clara Chamadoira, Margarida Ayres Basto, Carina Reis, Cláudia Sousa, Joana Lima, Maria José Rosas, João Massano, and Rui Vaz Copyright © 2014 Sofia Rocha et al. All rights reserved. Quantitative Electromyographic Analysis of Reaction Time to External Auditory Stimuli in Drug-Naïve Parkinson’s Disease Sun, 02 Mar 2014 10:36:50 +0000 Evaluation of motor symptoms in Parkinson’s disease (PD) is still based on clinical rating scales by clinicians. Reaction time (RT) is the time interval between a specific stimulus and the start of muscle response. The aim of this study was to identify the characteristics of RT responses in PD patients using electromyography (EMG) and to elucidate the relationship between RT and clinical features of PD. The EMG activity of 31 PD patients was recorded during isometric muscle contraction. RT was defined as the time latency between an auditory beep and responsive EMG activity. PD patients demonstrated significant delays in both initiation and termination of muscle contraction compared with controls. Cardinal motor symptoms of PD were closely correlated with RT. RT was longer in more-affected side and in more-advanced PD stages. Frontal cognitive function, which is indicative of motor programming and movement regulation and perseveration, was also closely related with RT. In conclusion, greater RT is the characteristic motor features of PD and it could be used as a sensitive tool for motor function assessment in PD patients. Further investigations are required to clarify the clinical impact of the RT on the activity of daily living of patients with PD. Do-Young Kwon, Byung Kyu Park, Ji Won Kim, Gwang-Moon Eom, Junghwa Hong, Seong-Beom Koh, and Kun-Woo Park Copyright © 2014 Do-Young Kwon et al. All rights reserved. Utilizing Fast Spin Echo MRI to Reduce Image Artifacts and Improve Implant/Tissue Interface Detection in Refractory Parkinson’s Patients with Deep Brain Stimulators Tue, 25 Feb 2014 12:37:01 +0000 Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detect DBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity. Methods. Using an IRB approved protocol 8 advanced PD patients were imaged within MR conditional safety guidelines at low RF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences. The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads. Results and Discussion. Spin echo and fast spin echo based low SAR sequences provided acceptable image quality with comparable image blooming (enlargement) of stimulator leads. The mean lead diameters were  mm for 2D,  mm for 3D, and  mm for 3D MPRAGE sequence. Conclusion. Low RF power spin echo and fast spin echo based 2D and 3D FSE sequences provide acceptable image quality adjacent to DBS leads. The smallest artifactual blooming of stimulator leads is present on 3D FSE while the largest signal void appears in the 3D MPRAGE sequence. Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, and Rafael R. Rojas Copyright © 2014 Subhendra N. Sarkar et al. All rights reserved. Orthostatic Hypotension in Patients with Parkinson’s Disease and Atypical Parkinsonism Sun, 02 Feb 2014 09:08:28 +0000 Orthostatic hypotension (OH) is one of the commonly occurring nonmotor symptoms in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP). We aimed to review current evidences on epidemiology, diagnosis, treatment, and prognosis of OH in patients with IPD and AP. Major electronic medical databases were assessed including PubMed/MEDLINE and Embase up to February 2013. English-written original or review articles with keywords such as “Parkinson’s disease,” “atypical parkinsonism,” and “orthostatic hypotension” were searched for relevant evidences. We addressed different issues such as OH definition, epidemiologic characteristics, pathophysiology, testing and diagnosis, risk factors for symptomatic OH, OH as an early sign of IPD, prognosis, and treatment options of OH in parkinsonian syndromes. Symptomatic OH is present in up to 30% of IPD, 80% of multiple system atrophy (MSA), and 27% of other AP patients. OH may herald the onset of PD before cardinal motor symptoms and our review emphasises the importance of its timely diagnosis (even as one preclinical marker) and multifactorial treatment, starting with patient education and lifestyle approach. Advancing age, male sex, disease severity, and duration and subtype of motor symptoms are predisposing factors. OH increases the risk of falls, which affects the quality of life in PD patients. Seyed-Mohammad Fereshtehnejad and Johan Lökk Copyright © 2014 Seyed-Mohammad Fereshtehnejad and Johan Lökk. All rights reserved. Mortality in Levodopa-Treated Parkinson's Disease Tue, 28 Jan 2014 07:34:30 +0000 Parkinson’s disease (PD) is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960’s, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers. We undertook this retrospective study of 211 deceased PD patients to determine the factors associated with mortality in levodopa-treated PD. Our findings confirm that PD is associated with increased mortality in both men and women. Unlike the majority of other mortality studies, we found that women have a greater reduction in lifespan compared to men. We also found that patients with early onset PD (onset at the age of 50 or before) have reduced survival relative to PD patients with later ages of onset. A final important finding is that survival is equal in PD patients treated with levodopa early (within 2 years or less of PD onset) versus later. John C. Morgan, Lillian J. Currie, Madaline B. Harrison, James P. Bennett Jr., Joel M. Trugman, and G. Frederick Wooten Copyright © 2014 John C. Morgan et al. All rights reserved. Influence of Hypertension on Neurocognitive Domains in Nondemented Parkinson’s Disease Patients Thu, 23 Jan 2014 07:05:18 +0000 Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson’s disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson’s Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated. Jacob D. Jones, Charles Jacobson, Martina Murphy, Catherine Price, Michael S. Okun, and Dawn Bowers Copyright © 2014 Jacob D. Jones et al. All rights reserved. Restless Legs Syndrome and Its Associated Risk Factors in Parkinson’s Disease Thu, 19 Dec 2013 15:01:25 +0000 Introduction. Restless legs syndrome has been shown to negatively impact the quality of life of patients. Studies have shown an association between restless legs syndrome and Parkinson’s disease. We attempted to investigate the prevalence of restless legs syndrome in Parkinson’s disease patients and to identify associated risk factors. Method. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criterion was a Mini Mental State Examination score of less than 21/30. The International Restless Legs Syndrome Study Group criterion was used to identify patients with restless legs syndrome. Results. A total of 113 patients were recruited. The prevalence rate of restless legs syndrome in our cohort was 9.7% and was significantly associated with a younger onset of Parkinson’s disease (), male gender (), higher Mini Mental State Examination score (), and less advanced Hoehn & Yahr stage (). Conclusion. The prevalence rate of restless legs syndrome in our Parkinson’s disease population is in keeping with other studies published worldwide. The significance of the association between a younger onset of Parkinson’s disease and restless legs syndrome needs to be further investigated. Shahrul Azmin, Abdul Manaf Khairul Anuar, Wan Yahya Nafisah, Hui Jan Tan, Azman Ali Raymond, Othman Hanita, Shamsul Azhar Shah, and Mohamed Ibrahim Norlinah Copyright © 2013 Shahrul Azmin et al. All rights reserved. Progression of Voice and Speech Impairment in the Course of Parkinson's Disease: A Longitudinal Study Tue, 10 Dec 2013 13:31:47 +0000 Impairment of voice and speech occurs in the majority of patients in the course of Parkinson's disease (PD). The aim of the current study was to survey the changes of voice and speech performance in the individual patients over time. 80 patients with PD and 60 healthy speakers were tested and retested after at least 12 months (average time interval: 32.5 months). Participants had to read a given text which was digitally recorded as a source for the perceptual and acoustic analysis. Stage of the disease and global motor impairment were rated according to the accepted scales. As a result, abnormalities of voice and speech were already present in mildly affected patients and there were significant deteriorations of quality of voice and articulatory velocity and precision between baseline and followup examination which showed no correlation with the time interval between the visits. Summarized, voice, and speech performance were found to further deteriorate in the individual patient in the course of time although global motor impairment was widely stable which might be a hint for nondopaminergic mechanisms of progression of dysarthrophonia. Further investigations are warranted to get a better insight into the dynamics of the progression of voice and speech impairment in PD as a precondition for the development of therapeutic approaches. S. Skodda, W. Grönheit, N. Mancinelli, and U. Schlegel Copyright © 2013 S. Skodda et al. All rights reserved. Predictors of Cognitive Decline in the Early Stages of Parkinson's Disease: A Brief Cognitive Assessment Longitudinal Study Tue, 05 Nov 2013 18:14:38 +0000 Our objectives were to perform a longitudinal assessment of mental status in early stage Parkinson’s disease (PD) patients, with brief neuropsychological tests, in order to find predictive factors for cognitive decline. Sixty-one, early stage, and nondemented patients were assessed twice, over a 2-year interval, with a global cognitive test (mini-mental state examination (MMSE)) and a frontal function test (frontal assessment battery (FAB)) and motor function scales. Dementia and hallucinations were diagnosed according to the DSM-IV criteria. Cognitive function scores did not decrease significantly, except for FAB lexical fluency score. Four patients presented with dementia at followup. The MMSE score below cut-off, worse gait dysfunction, the nontremor motor subtype, and hallucinations were significantly related to dementia. Rigidity and speech dysfunction were related to dementia and a decrease in FAB scores. We can conclude that decline in the MMSE and FAB scores is small and heterogeneous in the early stages of PD. Scores below cut-off in the MMSE could be helpful to predict dementia. Nontremor motor deficits could be predictive factors for frontal cognitive decline and dementia. Paulo Bugalho and Miguel Viana-Baptista Copyright © 2013 Paulo Bugalho and Miguel Viana-Baptista. All rights reserved.