Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Median and Ulnar Neuropathy Assessment in Parkinson’s Disease regarding Symptom Severity and Asymmetry Mon, 24 Oct 2016 11:00:23 +0000 Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson’s disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient’s asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age ) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age , ). The Hoehn and Yahr disability scale and Unified Parkinson’s Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (), age at PD onset (), and H&Y scores () were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. Nilgul Yardimci, Ozlem Cemeroglu, Eda Ozturk, Gülsüm Gürlü, Esra Şahin, Saliha Bozkurt, Tugba Cengiz, Gulderen Karali, Hasim Cakirbay, and Atilla İlhan Copyright © 2016 Nilgul Yardimci et al. All rights reserved. Classification and Characteristics of Pain Associated with Parkinson’s Disease Wed, 05 Oct 2016 09:15:22 +0000 Neuropsychiatric symptoms and pain are among the most common nonmotor symptoms of Parkinson’s disease (PD). The correlation between pain and PD has been recognized since its classic descriptions. Pain occurs in about 60% of PD patients, two to three times more frequent in this population than in age matched healthy individuals. It is an early and potentially disabling symptom that can precede motor symptoms by several years. The lower back and lower extremities are the most commonly affected areas. The most used classification for pain in PD defines musculoskeletal, dystonic, central, or neuropathic/radicular forms. Its different clinical characteristics, variable relationship with motor symptoms, and inconsistent response to dopaminergic drugs suggest that the mechanism underlying pain in PD is complex and multifaceted, involving the peripheral nervous system, generation and amplification of pain by motor symptoms, and neurodegeneration of areas related to pain modulation. Although pain in DP is common and a significant source of disability, its clinical characteristics, pathophysiology, classification, and management remain to be defined. Marcelo Rezende Young Blood, Marcelo Machado Ferro, Renato Puppi Munhoz, Hélio Afonso Ghizoni Teive, and Carlos Henrique Ferreira Camargo Copyright © 2016 Marcelo Rezende Young Blood et al. All rights reserved. Patients’ Views on a Combined Action Observation and Motor Imagery Intervention for Parkinson’s Disease Thu, 29 Sep 2016 13:44:28 +0000 Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson’s disease (PD), methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD. Judith Bek, Jordan Webb, Emma Gowen, Stefan Vogt, Trevor J. Crawford, Matthew S. Sullivan, and Ellen Poliakoff Copyright © 2016 Judith Bek et al. All rights reserved. N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells Wed, 28 Sep 2016 11:58:52 +0000 Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson’s disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration. Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, and Virginia L. Scofield Copyright © 2016 Benxu Cheng et al. All rights reserved. Brain MR Contribution to the Differential Diagnosis of Parkinsonian Syndromes: An Update Wed, 28 Sep 2016 11:19:15 +0000 Brain magnetic resonance (MR) represents a useful and feasible tool for the differential diagnosis of Parkinson’s disease. Conventional MR may reveal secondary forms of parkinsonism and may show peculiar brain alterations of atypical parkinsonian syndromes. Furthermore, advanced MR techniques, such as morphometric-volumetric analyses, diffusion-weighted imaging, diffusion tensor imaging, tractography, proton MR spectroscopy, and iron-content sensitive imaging, have been used to obtain quantitative parameters useful to increase the diagnostic accuracy. Currently, many MR studies have provided both qualitative and quantitative findings, reflecting the underlying neuropathological pattern of the different degenerative parkinsonian syndromes. Although the variability in the methods and results across the studies limits the conclusion about which technique is the best, specific radiologic phenotypes may be identified. Qualitative/quantitative MR changes in the substantia nigra do not discriminate between different parkinsonisms. In the absence of extranigral abnormalities, the diagnosis of PD is more probable, whereas basal ganglia changes (mainly in the putamen) suggest the diagnosis of an atypical parkinsonian syndrome. In this context, changes in pons, middle cerebellar peduncles, and cerebellum suggest the diagnosis of MSA, in midbrain and superior cerebellar peduncles the diagnosis of PSP, and in whole cerebral hemispheres (mainly in frontoparietal cortex with asymmetric distribution) the diagnosis of Corticobasal Syndrome. Giovanni Rizzo, Stefano Zanigni, Roberto De Blasi, Daniela Grasso, Davide Martino, Rodolfo Savica, and Giancarlo Logroscino Copyright © 2016 Giovanni Rizzo et al. All rights reserved. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders” Thu, 22 Sep 2016 14:49:44 +0000 Given the relationship between anticholinergic activity (AA) and Alzheimer’s disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh. Koji Hori, Kimiko Konishi, Misa Hosoi, Hiroi Tomioka, Masayuki Tani, Yuka Kitajima, and Mitsugu Hachisu Copyright © 2016 Koji Hori et al. All rights reserved. Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway Wed, 21 Sep 2016 10:58:06 +0000 The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD. Wei Zhang, Hong He, Hujie Song, Junjie Zhao, Tao Li, Leitao Wu, Xiaojun Zhang, and Jianzong Chen Copyright © 2016 Wei Zhang et al. All rights reserved. Analysis of LRRK2, SNCA, and ITGA8 Gene Variants with Sporadic Parkinson’s Disease Susceptibility in Chinese Han Population Wed, 07 Sep 2016 11:47:34 +0000 Background. Parkinson’s disease (PD) is an age-related neurodegenerative disease affected by multiple genetic and environmental factors. We performed a case-control study on candidate gene to scrutinize whether genetic variants in LRRK2, SNCA, and ITGA8 genes could be associated with sporadic PD in Chinese Han population. Methods. Five single-nucleotide polymorphisms (SNPs) of LRRK2 (rs1491942), SNCA (rs2301134, rs2301135, and rs356221), and ITGA8 (rs7077361) were selected and genotyped among 583 unrelated PD patients and 558 healthy controls. Results. Rs1491942 of LRRK2 gene had a significantly higher genotype frequency () and allelic G/C frequencies () in PD patients than controls. Rs2301135 of SNCA gene also showed an obvious difference in genotype frequency () and allelic G/C frequencies () between PD patients and controls. SNPs rs2301134 and rs356221 of SNCA gene and rs7077361 of ITGA8 gene lacked the significant association with the susceptibility of PD in Chinese Han population. Conclusions. Our study firstly expresses that rs1491942 of LRRK2 and rs2301135 of SNCA gene are substantially associated with sporadic Parkinson’s disease in Chinese Han population. Jie Fang, Kehui Yi, Mingwei Guo, Xingkai An, Hongli Qu, Qing Lin, Min Bi, and Qilin Ma Copyright © 2016 Jie Fang et al. All rights reserved. Cognitive Training in Parkinson’s Disease: A Review of Studies from 2000 to 2014 Mon, 05 Sep 2016 16:24:27 +0000 Cognitive deficits are prevalent among patients with Parkinson’s disease (PD), in both early and late stages of the disease. These deficits are associated with lower quality of life, loss of independence, and institutionalization. To date, there is no effective pharmacological treatment for the range of cognitive impairments presented in PD. Cognitive training (CT) has been explored as an alternative approach to remediating cognition in PD. In this review we present a detailed summary of 13 studies of CT that have been conducted between 2000 and 2014 and a critical examination of the evidence for the effectiveness and applicability of CT in PD. Although the evidence shows that CT leads to short-term, moderate improvements in some cognitive functions, methodological inconsistencies weaken these results. We discuss several key limitations of the literature to date, propose methods of addressing these questions, and outline the future directions that studies of CT in PD should pursue. Studies need to provide more detail about the cognitive profile of participants, include larger sample sizes, be hypothesis driven, and be clearer about the training interventions and the outcome measures. Daniel Glizer and Penny A. MacDonald Copyright © 2016 Daniel Glizer and Penny A. MacDonald. All rights reserved. Parkinson’s Disease and Homocysteine: A Community-Based Study in a Folate and Vitamin B12 Deficient Population Wed, 31 Aug 2016 16:28:33 +0000 Background. Homocysteine (Hcy) levels were higher in patients with Parkinson’s disease (PD). This could be partially explained by levodopa treatment. Whether untreated PD patients have higher Hcy levels is contradictory. Methods. A community-based study was conducted using a two-stage approach for subjects ≥ 55 years to find PD patients in 3 towns of Lüliang City. Blood samples were collected. Serum Hcy, folate, and vitamin B12 concentrations were measured. For each untreated PD patient, 5 controls were selected matched with age and sex to evaluate the relationship between Hcy levels and PD. Results. Of 6338 eligible residents, 72.7% participated in the study. 31 PD cases were identified. The crude prevalence of PD for people ≥ 55 years was 0.67%. Blood samples were collected from 1845 subjects, including 17 untreated PD patients. There was no difference for concentrations of serum Hcy, folate, and vitamin B12 between cases and controls (). In univariate and multivariate analysis, there was significant inverse relation between PD and current smoking (). No other factor was significant statistically. Conclusions. The prevalence of PD was comparable to earlier studies in China. Hyperhomocysteinemia was not a risk factor of PD, as well as folate and vitamin B12 deficiency. Zhang Wei, Wang Tiandong, Li Yang, Meng Huaxing, Min Guowen, Fang Yalan, and Niu Xiaoyuan Copyright © 2016 Zhang Wei et al. All rights reserved. Outlining a Population “at Risk” of Parkinson’s Disease: Evidence from a Case-Control Study Mon, 29 Aug 2016 11:47:55 +0000 The multifactorial pathogenesis of Parkinson’s Disease (PD) requires a careful identification of populations “at risk” of developing the disease. In this case-control study we analyzed a large Italian population, in an attempt to outline general criteria to define a population “at risk” of PD. We enrolled 300 PD patients and 300 controls, gender and age matched, from the same urban geographical area. All subjects were interviewed on demographics, family history of PD, occupational and environmental toxicants exposure, smoking status, and alcohol consumption. A sample of 65 patients and 65 controls also underwent serum dosing of iron, copper, mercury, and manganese by means of Inductively Coupled-Plasma-Mass-Spectrometry (ICP-MS). Positive family history, toxicants exposure, non-current-smoker, and alcohol nonconsumer status occurred as significant risk factors in our population. The number of concurring risk factors overlapping in the same subject impressively increased the overall risk. No significant differences were measured in the metal serum levels. Our findings indicate that combination of three to four concurrent PD-risk factors defines a condition “at risk” of PD. A simple stratification, based on these questionnaires, might be of help in identifying subjects suitable for neuroprotective strategies. Tommaso Schirinzi, Giuseppina Martella, Alessio D’Elia, Giulia Di Lazzaro, Paola Imbriani, Graziella Madeo, Leonardo Monaco, Marta Maltese, and Antonio Pisani Copyright © 2016 Tommaso Schirinzi et al. All rights reserved. Drosophila Mutant Model of Parkinson’s Disease Revealed an Unexpected Olfactory Performance: Morphofunctional Evidences Sun, 28 Aug 2016 07:40:46 +0000 Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatments. Francescaelena De Rose, Valentina Corda, Paolo Solari, Patrizia Sacchetti, Antonio Belcari, Simone Poddighe, Sanjay Kasture, Paolo Solla, Francesco Marrosu, and Anna Liscia Copyright © 2016 Francescaelena De Rose et al. All rights reserved. The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease Thu, 25 Aug 2016 16:12:36 +0000 Factors related with hyperhomocysteinemia (HHcy) and the impact of HHcy in Parkinson’s disease (PD) are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy) and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson’s disease. Among 60 patients (29 males, 48.3%) with PD, the stage of the disease, the severity of clinical symptoms, and the patients’ cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY), Unified Parkinson’s Disease Rating Scale (UPDRS) II and III, and Mini-Mental State Examination (MMSE), respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy ​​levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy ​​levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy ​​and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases. Bilge Kocer, Hayat Guven, Isik Conkbayir, Selim Selcuk Comoglu, and Sennur Delibas Copyright © 2016 Bilge Kocer et al. All rights reserved. Alpha-Synuclein in Parkinson’s Disease: From Pathogenetic Dysfunction to Potential Clinical Application Wed, 17 Aug 2016 14:18:00 +0000 Parkinson’s disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson’s disease. The SNCA gene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism of α-synuclein in Parkinson’s disease remains obscure. Recent research showed that various α-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson’s disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction of α-synuclein associated with Parkinson’s disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target. Lingjia Xu and Jiali Pu Copyright © 2016 Lingjia Xu and Jiali Pu. All rights reserved. The Cognition of Maximal Reach Distance in Parkinson’s Disease Mon, 15 Aug 2016 09:18:47 +0000 This study aimed to investigate whether the cognition of spatial distance in reaching movements was decreased in patients with Parkinson’s disease (PD) and whether this cognition was associated with various symptoms of PD. Estimated and actual maximal reaching distances were measured in three directions in PD patients and healthy elderly volunteers. Differences between estimated and actual measurements were compared within each group. In the PD patients, the associations between “error in cognition” of reaching distance and “clinical findings” were also examined. The results showed that no differences were observed in any values regardless of dominance of hand and severity of symptoms. The differences between the estimated and actual measurements were negatively deviated in the PD patients, indicating that they tended to underestimate reaching distance. “Error in cognition” of reaching distance correlated with the items of posture in the motor section of the Unified Parkinson’s Disease Rating Scale. This suggests that, in PD patients, postural deviation and postural instability might affect the cognition of the distance from a target object. Satoru Otsuki and Masanori Nagaoka Copyright © 2016 Satoru Otsuki and Masanori Nagaoka. All rights reserved. Mitochondria: Key Organelle in Parkinson’s Disease Sun, 07 Aug 2016 05:58:46 +0000 Rubén Gómez-Sánchez, José M. Bravo-San Pedro, Matthew E. Gegg, Rosa A. González-Polo, and José M. Fuentes Copyright © 2016 Rubén Gómez-Sánchez et al. All rights reserved. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson’s Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study Thu, 04 Aug 2016 07:09:52 +0000 The receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer’s disease and related to the disease pathology. Even though Parkinson’s disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate receptor binding levels in Parkinson’s brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with alterations. Binding density for the -specific radioligand [3H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased receptor binding in PD brains. In a separate study, we looked for changes in receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression. Nadja Bredo Rasmussen, Mikkel Vestergaard Olesen, Tomasz Brudek, Per Plenge, Anders Bue Klein, Jenny E. Westin, Karina Fog, Gitta Wörtwein, and Susana Aznar Copyright © 2016 Nadja Bredo Rasmussen et al. All rights reserved. Comparison of Test Your Memory and Montreal Cognitive Assessment Measures in Parkinson’s Disease Tue, 05 Jul 2016 11:52:31 +0000 Background. MoCA is widely used in Parkinson’s disease (PD) to assess cognition. The Test Your Memory (TYM) test is a cognitive screening tool that is self-administered. Objectives. We sought to determine (a) the optimal value of TYM to discriminate between PD patients with and without cognitive deficits on MoCA testing, (b) equivalent MoCA and TYM scores, and (c) interrater reliability in TYM testing. Methods. We assessed the discriminant ability of TYM and the equivalence between TYM and MoCA scores and measured the interrater reliability between three raters. Results. Of the 135 subjects that completed both tests, 55% had cognitive impairment according to MoCA. A MoCA score of 25 was equivalent to a TYM score of 43-44. The area under the receiver operator characteristic (ROC) curve for TYM to differentiate between PD-normal and PD-cognitive impairment was 0.82 (95% CI 0.75 to 0.89). The optimal cutoff to distinguish PD-cognitive impairment from PD-normal was ≤45 (sensitivity 90.5%, specificity 59%) thereby correctly classifying 76.3% of patients with PD-cognitive impairment. Interrater agreement was high (0.97) and TYM was completed in under 7 minutes (interquartile range 5.33 to 8.52 minutes). Conclusions. The TYM test is a useful and less resource intensive screening test for cognitive deficits in PD. Emily J. Henderson, Howard Chu, Daisy M. Gaunt, Alan L. Whone, Yoav Ben-Shlomo, and Veronica Lyell Copyright © 2016 Emily J. Henderson et al. All rights reserved. Parkinson’s Disease: New Insights into Pathophysiology and Rehabilitative Approaches Thu, 30 Jun 2016 14:46:59 +0000 Vincenza Frisardi, Andrea Santamato, and Binith Cheeran Copyright © 2016 Vincenza Frisardi et al. All rights reserved. Goal Setting for Cognitive Rehabilitation in Mild to Moderate Parkinson’s Disease Dementia and Dementia with Lewy Bodies Wed, 29 Jun 2016 15:11:30 +0000 Alongside the physical symptoms associated with Parkinson’s disease dementia and dementia with Lewy bodies, health services must also address the cognitive impairments that accompany these conditions. There is growing interest in the use of nonpharmacological approaches to managing the consequences of cognitive disorder. Cognitive rehabilitation is a goal-orientated behavioural intervention which aims to enhance functional independence through the use of strategies specific to the individual’s needs and abilities. Fundamental to this therapy is a person’s capacity to set goals for rehabilitation. To date, no studies have assessed goal setting in early-stage Parkinson’s disease dementia or dementia with Lewy bodies. Semistructured interviews were carried out with 29 participants from an ongoing trial of cognitive rehabilitation for people with these conditions. Here, we examined the goal statements provided by these participants using qualitative content analysis, exploring the types and nature of the goals set. Participants’ goals reflected their motivations to learn new skills or improve performance in areas such as technology-use, self-management and orientation, medication management, and social and leisure activities. These results suggest that goal setting is achievable for these participants, provide insight into the everyday cognitive difficulties that they experience, and highlight possible domains as targets for intervention. The trial is registered with ISRCTN16584442 (DOI 10.1186/ISRCTN16584442 13/04/2015). Tamlyn J. Watermeyer, John V. Hindle, Julie Roberts, Catherine L. Lawrence, Anthony Martyr, Huw Lloyd-Williams, Andrew Brand, Petra Gutting, Zoe Hoare, Rhiannon Tudor Edwards, and Linda Clare Copyright © 2016 Tamlyn J. Watermeyer et al. All rights reserved. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson’s Disease Sun, 19 Jun 2016 06:54:43 +0000 Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF) at rest in patients with Parkinson’s disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample -test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease. Jie Xiang, Xiuqin Jia, Huizhuo Li, Jiawei Qin, Peipeng Liang, and Kuncheng Li Copyright © 2016 Jie Xiang et al. All rights reserved. Chaperone-Mediated Autophagy and Mitochondrial Homeostasis in Parkinson’s Disease Thu, 16 Jun 2016 11:57:20 +0000 Parkinson’s disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked. This review summarizes the studies revealing the link between autophagy and mitochondrial function. Discussions are focused on the connections between CMA and mitochondrial failure and on the role of MEF2D, a neuronal survival factor, in mediating the regulation of mitochondria in the context of CMA. These new findings highlight the need to further explore the possibility of targeting the MEF2D-mitochondria-CMA network in both understanding the PD pathogenesis and developing novel therapeutic strategies. Ruixin Yang, Guodong Gao, Zixu Mao, and Qian Yang Copyright © 2016 Ruixin Yang et al. All rights reserved. Evaluation of Nonmotor Symptoms in Diagnosis of Parkinsonism and Tremor Tue, 14 Jun 2016 11:40:44 +0000 Background. Nonmotor symptoms particularly olfactory dysfunction, RBD, depression, hallucinations, and constipation are currently not included in the typical clinical criteria for diagnosing Lewy body Parkinsonian disorders (LBPD). The aim of this study is to determine the diagnostic value of nonmotor symptoms in patients presenting with Parkinsonism and tremor. Methods. All new patients seen between January 2007 and May 2013 in the Movement Disorders Specialist Clinics of the Royal Melbourne Hospital (RMH), who were referred with a possible neurodegenerative syndrome or concerns of Parkinsonism and/or tremor, were included. Patients underwent routine evaluation with the four-minute “Sniffin Sticks” test, RBD, depression, and constipation. Results. 291 patients were included in the analysis. Conclusion. We found that lower olfaction scores based on “Sniffin Sticks” testing combined with reports of depression and constipation are independent predictors for the diagnosis of the spectrum of Lewy body Parkinsonian disorders (LBPD). Parkinson’s disease (PD) cannot be reliably clinically differentiated from other causes of Parkinsonism that share symptomatology and structural abnormalities. Andrew H. Evans and Chiun-Hian Chai Copyright © 2016 Andrew H. Evans and Chiun-Hian Chai. All rights reserved. The Association between C9orf72 Repeats and Risk of Alzheimer’s Disease and Amyotrophic Lateral Sclerosis: A Meta-Analysis Wed, 08 Jun 2016 09:57:17 +0000 C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasian populations. However, the relationship between C9orf72 repeats and Alzheimer’s disease (AD) was not clear. Additionally, there were few articles assessing C9orf72 in other ethnicities with ALS. In this meta-analysis, we aimed to investigate the relationship between C9orf72 repeat expansions (≥30 repeats) and intermediate repeat copies (20–29 repeats) and AD or ALS. The results suggested positive correlations between C9orf72 repeat expansions and the risk of Alzheimer’s disease (OR = 6.36, 95% CI = 3.13–12.92, and ), while intermediate repeat copies of C9orf72 gene were not associated with the risk of the disease. C9orf72 repeat expansions were positively correlated with the risk of familial and sporadic ALS (OR = 293.25, 95% CI = 148.17–580.38, and ; OR = 35.57, 95% CI = 19.61–64.51, and ). There was a positive correlation between the gene variations and ALS risk among Caucasians and Asians (OR = 57.56, 95% CI = 36.73–90.22, and ; OR = 6.35, 95% CI = 1.39–29.02, and ). Li Shu, Qiying Sun, Yuan Zhang, Qian Xu, Jifeng Guo, Xinxiang Yan, and Beisha Tang Copyright © 2016 Li Shu et al. All rights reserved. Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation Mon, 06 Jun 2016 06:16:48 +0000 Cardinal motor features of Parkinson’s disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD. Francesca Magrinelli, Alessandro Picelli, Pierluigi Tocco, Angela Federico, Laura Roncari, Nicola Smania, Giampietro Zanette, and Stefano Tamburin Copyright © 2016 Francesca Magrinelli et al. All rights reserved. Characteristics of Nonmotor Symptoms in Progressive Supranuclear Palsy Sun, 05 Jun 2016 06:43:28 +0000 Objectives. To explore the clinical correlates of nonmotor symptoms (NMS) in progressive supranuclear palsy (PSP) and their differences from healthy controls and patients with Parkinson’s disease (PD). Methods. Twenty-seven PSP patients, 27 age- and gender-matched healthy controls (HC), and 27 age- and gender-matched PD patients were included for this case-control study. NMS were assessed using the Nonmotor Symptoms Scale (NMSS, including 9 domains). Results. All PSP patients reported NMS. The frequency and severity of “sleep/fatigue,” “mood/apathy,” “attention/memory,” “gastrointestinal,” “sexual dysfunction,” and “miscellaneous” domains in PSP group were significantly higher than those in HC group (). The frequency of “mood/apathy,” “attention/memory,” and “sexual dysfunction” domains and the severity of “attention/memory” and “gastrointestinal” domains in PSP group were significantly higher than those in PD group (). The “attention/memory” domain in PSP had a significant but weak-to-moderate correlation with age (, ) and onset age (, ). Conclusions. NMS are common in PSP patients. Patients with PSP seem to be subjected to more frequent and severe specific NMS compared to healthy aging subjects and PD patients. Older PSP patients and late-onset patients are likely to be subjected to cognitive decline. Ruwei Ou, Wei Song, Qianqian Wei, Ke Chen, Bei Cao, Yanbing Hou, Bi Zhao, and Huifang Shang Copyright © 2016 Ruwei Ou et al. All rights reserved. Essential Oils May Lead α-Synuclein towards Toxic Fibrils Formation Tue, 24 May 2016 09:10:48 +0000 α-Synuclein (α-Syn) fibrillation links with Parkinson’s disease (PD) and several related syndromes. It is believed that exposure to the factors which promote fibrillation may induce and progress such neurodegenerative diseases (NDs). Herein, the effects of some wildly used essential oils including Myrtus communis (M. communis) on α-Syn fibrillation were examined. M. communis particularly increased α-Syn fibrillation in a concentration dependent manner. Given that applications of M. communis are very extensive in Asian societies, especially Zoroastrians, this study was extended towards its role on α-Syn fibrillation/cytotoxicity. By using a unilamellar vesicle, it was shown that the aggregated species with tendency to perturb membrane were increased in the presence of M. communis. In this regard, the cytotoxicity of α-Syn on SH-SH5Y cells was also increased significantly. Inappropriately, the effects of fibrillation inhibitors, baicalein and cuminaldehyde, were modulated in the presence of M. communis. However, major components of M. communis did not induce fibrillation and also the effect of M. communis was limited on other fibrinogenic proteins. Assuming that essential oils have the ability to pass through the blood brain barrier (BBB) along with the popular attention on aromatherapy for the incurable ND, these findings suggest an implementation of fibrillation tests for essential oils. Dina Morshedi and Mahour Nasouti Copyright © 2016 Dina Morshedi and Mahour Nasouti. All rights reserved. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease Thu, 19 May 2016 14:15:22 +0000 Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, ) upregulated ferroportin 1 expression and significantly () decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% () and DNA fragmentation by 29% () and increased cell viability by 22% (). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% () and intracellular iron by 28% (), indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1. Qi Xu, Anumantha G. Kanthasamy, Huajun Jin, and Manju B. Reddy Copyright © 2016 Qi Xu et al. All rights reserved. Parkinson’s Disease: The Mitochondria-Iron Link Tue, 17 May 2016 14:31:32 +0000 Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson’s disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences—mitochondrial dysfunction, iron accumulation, and oxidative damage—generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson’s disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation—by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways—is a viable therapy for retarding this cycle. Yorka Muñoz, Carlos M. Carrasco, Joaquín D. Campos, Pabla Aguirre, and Marco T. Núñez Copyright © 2016 Yorka Muñoz et al. All rights reserved. Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease Tue, 17 May 2016 12:49:15 +0000 At present, patients with advanced Parkinson’s disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only for receptors containing the α-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation of receptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce through receptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD. Antonio Daniele, Francesco Panza, Antonio Greco, Giancarlo Logroscino, and Davide Seripa Copyright © 2016 Antonio Daniele et al. All rights reserved.