Parkinsonian Disorders —Advances in Research and Treatment 2013 Edition Q. Ashton Acton, PhD General Editor SCHOLARLYEDITIONS™Copyright ©2013 by ScholarlyEditions!" Published by ScholarlyEditions," Atlanta, Georgia. Limit of Liability/Disclaimer of Warranty: While the publisher and authors have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or com- pleteness of the contents of this book and specifically disclaim any im- plied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a profes- sional where appropriate. 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Parkinson’s Disease ..............- Index . .Introduction Parkinsonian Disorders—Advances in Research and Treatment / 2013 Edition is a Scholarly Editions™ book that delivers timely, authoritative, and comprehensive information about Parkinson's Disease. The editors have built Parkinsonian Disorders—Advances in Re- search and Treatment / 2013 Edition on the vast information databases of ScholarlyNews.“ You can expect the information about Parkinson’s Disease in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and rel- evant. The content of Parkinsonian Disorders—Advances in Research and Treatment / 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources (except content about patents), and all of it is written, assembled, and edited by the editors at ScholarlyEditions" and available exclusively from us. You now have ‘a source you can cite with authority, confidence, and credibility. More information is available at http: //www.scholarlyEditions.com/.Chapter 1 Lewy Body Disease Newcastle University, Newcastle-upon-Tyne: Glucocerebrosidase mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease By a News Reporter-Staff News Editor at Health & Medicine Week — Current study results on Neurochemistry have been published. Accord- ing to news originating from Newcastle-upon-Tyne, United Kingdom, by NewsRx correspondents, research stated, “Lewy body disease (LBD) de- velopment is enhanced by mutations in the GBA gene coding for gluco- cerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to eval- uate if lysosomal changes contribute to the pathogenesis of idiopathic LBD.” Our news journalists obtained a quote from the research from New- castle University, “Analysis of post-mortem frontal cortex tissue from 7 GBA mutation carriers with LBD, 5 GBA mutation carriers with no signs of neurological disease and human neural stem cells exposed to a GCase inhibitor was used to determine how GBA mutation contributes to LBD. GBA mutation carriers demonstrated a significantly reduced level of GCase protein and enzyme activity and retention of glucocere- brosidase isoforms within the endoplasmic reticulum (ER). This was associated with enhanced expression of the lysosomal markers LAMP1 and LAMP2, though the expression of ATP13A2 and Cathepsin D was reduced, along with the decreased activity of Cathepsin D. The ER un- folded protein response (UPR) regulator BiP/GRP78 was reduced by GBA mutation and this was a general phenomenon in LBD. Despite elevation of GRP94 in LBD, individuals with GBA mutations showed reduced GRP94 expression, suggesting an inadequate UPR. Finally, hu- man neural stem cell cultures showed that inhibition of GCase causesCHAPTER 1 LEWY BODY DISEASE acute reduction of BiP, indicating that the UPR is affected by reduced glucocerebrosidase activity.” According to the news editors, the research concluded: “The results indicate that mutation in GBA leads to additional lysosomal abnormal- ities, enhanced by an impaired UPR, potentially causing a-synuclein accumulation.” For more information on this research see: Glucocerebrosidase mu- tations alter the endoplasmic reticulum and lysosomes in Lewy body disease. Journal of Neurochemistry, 2012;123(2):298-309. (Wiley- Blackwell - http://www.wiley.com/; Journal of Neurochemistry - http://onlinelibrary.wiley.com/journal/10.1111/ (ISSN) 1471-4159) The news correspondents report that additional information may be obtained from M. Kurzawa-Akanbi, Medical Toxicology Centre, Wolfson Building, Newcastle University, Newcastle upon Tyne, UK. (2013 Jan 04) Massachusetts General Hospital, Boston: Brain amyloid and cognition in Lewy body diseases By a News Reporter-Staff News Editor at Mental Health Weekly Di- gest — Fresh data on Dementia and Mental Illness are presented in a new report. According to news reporting from Boston, Massachusetts, by NewsRx journalists, research stated, “Many patients with PD de- velop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia.” The news correspondents obtained a quote from the research from Massachusetts General Hospital, “We sought to confirm this hypoth- esis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkin- sonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCD, 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neuro- logic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were ob- tained in many patients. PiB retention was expressed as the distribu- tion volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amy- loid burden increased with age and with the presence of the ApoE e4 allele in all patient groups. Only in the DLB group was amyloid de- position associated with impaired cognition. DLB subjects have higher 2CHAPTER 1 LEWY BODY DISEASE amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB.” According to the news reporters, the researchers concluded: “Early amyloid deposits in DLB relative to PDD may account for their differ- ence in the timing of dementia and parkinsonism.” For more information on this research see: Brain amyloid and cog- nition in Lewy body diseases. Movement Disorders, 2012;27(8):965-73. (Wiley-Blackwell - http: //www.wiley.com/; Movement Disorders - http://onlinelibrary.wiley.com/journal/10.1002/ (ISSN) 1531-8257) Our news journalists report that additional information may be ob- tained by contacting S.N. Gomperts, Massachusetts General Hospital, Boston, Massachusetts, United States. (2012 Aug 13)Chapter 2 Parkinson’s Disease Banner Sun Health Research Institute, Sun Ci Quantitative appraisal of ventricular cerebrospinal fluid biomarkers in neuropathologically diagnosed Parkinson's disease cases lacking Alzheimer's disease pathology By a News Reporter-Staff News Editor at Cardiovascular Week — In- vestigators publish new report on Pain and Central Nervous System. According to news originating from Sun City, Arizona, by NewsRx cor- respondents, research stated, “Identifying biomarkers that distinguish Parkinson’s disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early- stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropatho- logically diagnosed PD subjects lacking Alzheimer’s disease (AD) neu- ropathology.” Our news journalists obtained a quote from the research from Banner Sun Health Research Institute, “In the present study, we assessed these biomarkers as well as p-tau(181), Aß42, and S100B by ELISA in PD (n=43) and NC (n=49) cases. The p- tau(181)/Aß42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau(181)/Aß42 had a significant odds ratio: OR=1.42 (95% confidence interval [CI], 1.12-1.84), p=0.006. Among the molecules in- vestigated, intriguing correlations were observed that require further investigation.” According to the news editors, the research concluded: “Our results suggest coexistent AD CSF biomarkers within the PD group notwith- standing that it was selected to minimize AD neuropathological le- sions.”CHAPTER 2 PARKINSON’S DISEASE For more information on this research see: Quantitative appraisal of ventricular cerebrospinal fluid biomarkers in neuropathologically diag- nosed Parkinson's disease cases lacking Alzheimer’s disease pathology. Biomarker Insights, 2013;8():19-28. The news correspondents report that additional information may be obtained from C.L. Maarouf, The Longtine Center for Neurodegener- ative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, United States. (2013 Apr 22) Sun Yat-Sen University, Guangdong: Neurotransmitter receptors and cognitive dysfunction in Alzheimer’s disease and Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Current study results on Neurobiology have been pub- lished. According to news reporting from Guangdong, People’s Republic of China, by NewsRx journalists, research stated, “Cognitive dysfunc- tion is one of the most typical characteristics in various neurodegen- erative diseases such as Alzheimer’s disease and Parkinson’s disease (advanced stage). Although several mechanisms like neuronal apopto- sis and inflammatory responses have been recognized to be involved in the pathogenesis of cognitive dysfunction in these diseases, recent stud- ies on neurodegeneration and cognitive dysfunction have demonstrated a significant impact of receptor modulation on cognitive changes.” The news correspondents obtained a quote from the research from Sun Yat-Sen University, “The pathological alterations in various recep- tors appear to contribute to cognitive impairment and/or deterioration with correlation to diversified mechanisms. This article recapitulates the present understandings and concepts underlying the modulation of different receptors in human beings and various experimental mod- els of Alzheimer’s disease and Parkinson’s disease as well as a con- ceptual update on the underlying mechanisms. Specific roles of sero- tonin, adrenaline, acetylcholine, dopamine receptors, and N-methyl-D- aspartate receptors in Alzheimer’s disease and Parkinson’s disease will be interactively discussed. Complex mechanisms involved in their sig- naling pathways in the cognitive dysfunction associated with the neu- rodegenerative diseases will also be addressed. Substantial evidence has suggested that those receptors are crucial neuroregulators con- tributing to cognitive pathology and complicated correlations exist be- tween those receptors and the expression of cognitive capacities. The pathological alterations in the receptors would, therefore, contribute to cognitive impairments and/or deterioration in Alzheimer’s disease and Parkinson’s disease.” According to the news reporters, the research concluded: “Future research may shed light on new clues for the treatment of cognitive 5CHAPTER 2 PARKINSON’S DISEASE dysfunction in neurodegenerative diseases by targeting specific alter- ations in these receptors and their signal transduction pathways in the frontal-striatal, fronto-striato-thalamic, and mesolimbic circuitries.” For more information on this research see: Neurotransmitter re- ceptors and cognitive dysfunction in Alzheimer’s disease and Parkin- son’s disease. Progress In Neurobiology, 2012;97(1):1-13. (Else- vier - www.elsevier.com; Progress In Neurobiology - http://www. elsevier.com/wps/product /cws_home/412) Our news journalists report that additional information may be ob- tained by contacting Y. Xu, Dept. of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, People’s Taiwan. (2013 Apr 22) University of Pennsylvania, Philadelphia: Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease By a News Reporter-Staff News Editor at Ivy League Week — Cur- rent study results on Parkinson’s disease have been published, Accord- ing to news reporting out of Philadelphia, Pennsylvania, by NewsRx editors, research stated, “I-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4- phenylpyridinium ion (MPP(+)), which then targets the dopaminergic neurons causing neuronal death.” Our news journalists obtained a quote from the research from the University of Pennsylvania, “Here, we demonstrate that mitochondrion- targeted human cytochrome P450 2D6 (CYP2D6), supported by mito- chondrial adrenodoxin and adrenodoxin reductase, can efficiently cat- alyze the metabolism of MPTP to MPP(+), as shown with purified en- zymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dys- function and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxy- gen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differ- entiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6CHAPTER 2 PARKINSON’S DISEASE inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline.” According to the news editors, the research concluded: “These stud- ies show for the first time that dopaminergic neurons expressing mi- tochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine.” For more information on this research sce: Metabolism of 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease. Journal of Biological Chemistry, 2013;288(6):4436-51. (American Society for Bio- chemistry and Molecular Biology - www.asbmb.org; Journal of Biologi- cal Chemistry - http://www. jbc.org/) Our news journalists report that additional information may be ob- tained by contacting P. Bajpai, Dept. of Animal Biology and Marie Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6046, United States. (2013 Apr 16) University of Lille: The spectrum of cognitive disorders in Parkinson's disease: A data-driven approach By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Research findings on Movement Disorders are discussed in a new report. According to news reporting originating from Lille, France, by NewsRx correspondents, research stated, “The objective of this study was to identify different cognitive phenotypes in Parkinson’s disease (PD) using a data-driven approach. A model-based cluster anal- ysis was conducted on the neuropsychological test results of 558 PD patients from 2 European movement disorder centers (Lille, n = 403; Maastricht, n = 155).” Our news editors obtained a quote from the research from the Uni- versity of Lille, “The number of clusters was determined according to their clinical relevance as well as on the basis of 3 statistical crite- ria: the cubic cluster criterion, the pseudo F statistic, and the total squared correlation ratio (R2). A factorial discriminant analysis was performed to assess the quality of the cluster’s separation. Descriptive variables were used to further characterize the clusters. A 5-cluster model was considered the clinically most relevant. The 5 clusters com- prised: (1) cognitively intact patients (19.39%); (2) patients without cog- nitive deficits but with slight mental slowing (41.29%); (3) patients with slightly impaired overall cognitive efficiency and deficits in all cognitive domains except recognition memory (12.93%); (4) patients with severe mental slowing, impaired overall cognitive efficiency, and severe cog- nitive impairment in all domains, including memory (23.88%); and (5)CHAPTER 2 PARKINSON’S DISEASE patients with very severe impairment in all cognitive domains (2.51%). Cognitively intact patients were significantly younger and had received more years of formal education. Patients in the last 3 clusters had more severe motor symptoms, longer disease duration, and more axial signs. In the last cluster, most patients were demented.” According to the news editors, the research concluded: “Our results confirm the heterogeneity of cognitive presentations in PD, ranging from cognitively intact patients with rather high levels of performance in each cognitive domain to very severely impaired patients.” For more information on this research see: The spectrum of cogni- tive disorders in Parkinson’s disease: A data-driven approach. Move- ment Disorders, 2013;28(2):183-189. Movement Disorders can be con- tacted at: Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - http: //www.wiley.com/; Movement Dis- orders - http://onlinelibrary.wiley.com/journal/10.1002/ (ISSN) 1531-8257) The news editors report that additional information may be obtained by contacting K. Dujardin, University of Lille, Medical Center, Dept. of Biostat, Lille, France. (2013 Apr 15) Retinal Nerve Fiber Layer Thinning in Dementia Associated with Parkinson’s Disease, Dementia with Lewy Bodies, and Alzheimer’s Disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Fresh data on Dementia and Mental Illness are presented in a new report. According to news reporting originating in Madrid, Spain, by NewsRx journalists, research stated, “Optical coherence to- mography is a simple, high-resolution technique to quantify the thick- ness of retinal nerve fiber layer (RNFL). Previous studies have shown that degenerative changes occur in optic nerve fibers and are mani- fested as thinning of RNLF in patients with Alzheimer’s disease (AD).” The news reporters obtained a quote from the research, “However, there are no studies on the thickness of the RNLF in other types of dementia, such as dementia with Lewy bodies and dementia associated with Parkinson’s disease. In this study, patients fulfilling diagnostic for AD (n = 10), dementia with Lewy bodies (n = 10), dementia associated with Parkinson’s disease (n = 10), and cognitively normal age-matched controls (n = 10) underwent optical coherence tomography examina- tions to measure RNLF thickness. There was a significant decrease in RNLF thickness in each type of dementia compared to the control group (Mann-Whitney test, all p&It; 0.001). Although patients with dementia with Lewy bodies may have a greater thinning than both patients with AD and dementia associated with Parkinson's disease, the differences were statistically nonsignificant (Kruskal-Wallis test, p = 0.525). The 8CHAPTER 2 PARKINSON’S DISEASE thickness of the RNLF correlated significantly (p &t; 0.001) with both the Mini-Mental State Examination and the Mattis Dementia Rating Scale scores in all types of dementia; that is to say, the greater the cogni- tive deterioration, the greater the reduction of thickness of the RNLF.” According to the news reporters, the research concluded: “The find- ings from this study show that retinal involvement measured by optical coherence tomography may also be present in non-AD dementias.” For more information on this research see: Retinal Nerve Fiber Layer Thinning in Dementia Associated with Parkinson's Disease, Dementia with Lewy Bodies, and Alzheimer’s Disease. Journal of Alzheimers Disease, 2013;34(3):659-664. Journal of Alzheimers Disease can be contacted at: Ios Press, Nieuwe Hemweg 6B, 1013 Bg Amster- dam, Netherlands. Our news correspondents report that additional information may be obtained by contacting T. Moreno-Ramos, Center Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. (2013 Apr 08) University of Florence: Daytime course of sleepiness in de novo Parkinson’s disease patients By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Researchers detail new data in Sleep Research. According to news reporting from Florence, Italy, by NewsRx journalists, research stated, “Normal subjects show an increase of sleepiness in the morning, early afternoon and before sleep. In the advanced stages of Parkinson’s disease (PD) the mean level of sleepiness is quite high, while with re- spect to healthy subjects it seems to be unchanged in the early stages.” The news correspondents obtained a quote from the research from the University of Florence, “The aim of this study was to evaluate the time-course of the sleepiness level during the wakefulness period in un- treated patients with early-stage Parkinson’s disease. Eighteen Parkin- son’s disease patients who had never been treated before with dopamin- ergic drugs (male = 9, female = 9, age: 68.39 ± 1.89, mean ± standard error) and 18 healthy subjects (male = 9, female = 9, age: 67.22 ± 1.98) were recruited for this study. All subjects underwent con- tinuous actigraphic recording for three consecutive days, during which they also completed the Karolinska Sleepiness Scale (KSS) once an hour throughout wakefulness. Our results showed a higher level of sleepi- ness in the patients than the controls in the hours following awakening and in the early afternoon, specifically at 08:00 and 14:00 hours (08:00 hours, PD patients, KSS: 3 ± 0.3 versus healthy subjects, KSS: 2 ± 0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 ± 0.5 versus healthy subjects, KSS: 3 ± 0.3, P < 0.05).”CHAPTER 2 PARKINSON’S DISEASE According to the news reporters, the research concluded: “We sug- gest that some daytime hours are sensitive windows showing the first increase of sleepiness which will spread later to the whole daytime.” For more information on this research see: Daytime course of sleepi- ness in de novo Parkinson’s disease patients. Journal of Sleep Re- search, 2013;22(2):197-200. (Wiley-Blackwell - http: //www.wiley. com/; Journal of Sleep Research - http: //onlinelibrary.wiley. com/journal/10.1111/ (ISSN) 1365-2869) Our news journalists report that additional information may be ob- tained by contacting F. Giganti, Sleep Laboratory, Dept. of Psychology, University of Florence, Florence, Italy. (2013 Apr 08) Indiana University-Purdue University, Indianapolis: Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson’s disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — A new study on Life Science Research is now available. According to news reporting originating in Indianapolis, Indiana, by NewsRx journalists, research stated, “Suppression of excessively syn- chronous beta-band oscillatory activity in the brain is believed to sup- press hypokinetic motor symptoms of Parkinson’s disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS).” The news reporters obtained a quote from the research from In- diana University-Purdue University, “This type of synchrony control was shown to destabilize the synchronized state in networks of sim- ple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson’s disease ex- hibits complex intermittent synchronous patterns, far from the ideal- ized synchronous dynamics used to study the delayed feedback stimu- lation. This study explores the action of delayed fecdback stimulation on partially synchronized oscillatory dynamics, similar to what one ob- serves experimentally in parkinsonian patients. We employ a compu- tational model of the basal ganglia networks which reproduces experi- mentally observed fine temporal structure of the synchronous dynam- ics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that 10CHAPTER 2 PARKINSON’S DISEASE delayed feedback DBS in Parkinson’s disease may boost rather than suppress synchronization and is unlikely to be clinically successful.” According to the news reporters, the research concluded: “The study also indicates that delayed feedback stimulation may not necessarily ex- hibit a desynchronization effect when acting on a physiologically real- istic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.” For more information on this research see: Failure of delayed feed- back deep brain stimulation for intermittent pathological synchroniza- tion in Parkinson’s disease. Plos One, 2013;8(3):e58264. (Public Library of Science - www.plos.org; Plos One - www.plosone.org) Our news correspondents report that additional information may be obtained by contacting A. Dovzhenok, Dept. of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States. (2013 Apr 01) Columbia University, New York City: Motor control abnormalities in Parkinson's disease By a News Reporter-Staff News Editor at Ivy League Week — Investi- gators discuss new findings in Health and Medicine. According to news originating from New York City, New York, by NewsRx correspondents, research stated, “The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms.” Our news journalists obtained a quote from the research from Columbia University, “Motor symptoms can also be described in terms of motor control, a level of description that explains how movement vari- ables, such as a limb’s position and speed, are controlled and coordi- nated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neu- ral prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of under- standing, however, remains limited, partly because of limitations in our knowledge of normal motor control.” According to the news editors, the research concluded: “In this ar- ticle, we review the concept of motor control and describe a few motor 11CHAPTER 2 PARKINSON’S DISEASE symptoms that illustrate the challenges in understanding such symp- toms as motor control abnormalities.” For more information on this research see: Motor control abnor- malities in Parkinson's disease. Cold Spring Harbor Perspectives In Medicine, 2012;2(6):a009282. The news correspondents report that additional information may be obtained from P. Mazzoni, Motor Performance Laboratory, The Neu- rological Institute, Columbia University, New York, New York, United States. (2013 Mar 26) National Hospital Organization, Yamaguchi: lodine-123 metaiodobenzylguanidine imaging can predict future cardiac events in Japanese patients with Parkinson’s disease By a News Reporter-Staff News Editor at Asia Business Newsweekly — Researchers detail new data in Parkinson’s disease. According to news reporting originating from Yamaguchi, Japan, by VerticalNews correspondents, research stated, “Iodine-123 metaiodobenzylguanidine (1-123-MIBG) myocardial scintigraphy provides useful diagnostic infor- mation in differentiating Parkinson's disease (PD) from other neurolog- ical diseases. Moreover, a number of studies have reported that 1-123- MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients.” Our news editors obtained a quote from the research from National Hospital Organization, “The aim of the present study was to investigate the cardiovascular predictive value of cardiac I-123-MIBG imaging in patients with PD. Seventy-eight patients with PD were retrospectively studied, All patients underwent I-123-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated, During a mean follow-up of 27 +/- A 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection frac- tion (LVEF) was normal in the HF patients. I-123-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 +/- A 0.21 vs. 1.34 +/- A 0.08, p = 0.019; 31.9 +/- A5.5 vs. 38.2 +/- A 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with de- layed H/M (R = -0.357, p< 0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed 12CHAPTER 2 PARKINSON’S DISEASE H/M were independently associated with HF (p = 0.014, p = 0.029, re- spectively). Kaplan-Meier analysis revealed that patients with abnor- mal WR(> 37 %) and delayed H/M (< 1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, re- spectively). WR showed stronger predictive power than delayed H/M in Kaplan-Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD.” According to the news editors, the research concluded: “Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.” For more information on this research see: Iodine-123 metaiodoben- zylguanidine imaging can predict future cardiac events in Japanese patients with Parkinson's disease. Annals of Nuclear Medicine, 2013;27(2):123-131. Annals of Nuclear Medicine can be contacted at: Springer, 233 Spring St, New York, NY 10013, USA. (Springer - www.springer.com; Annals of Nuclear Medicine - http://www. springerlink.com/content/0914-7187/) The news editors report that additional information may be ob- tained by contacting T. Kinbara, National Hospital Organization, Kan- mon Med Center, Dept. of Neurol, Shimonoseki, Yamaguchi 7528510, Japan. (2013 Mar 26) Johns Hopkins University, Baltimore: New Synaptic and Molecular Targets for Neuroprotection in Parkinson's Disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - Investigators discuss new findings in Parkinson’s disease. According to news originating from Baltimore, Maryland, by NewsRx correspondents, research stated, “The defining anatomical feature of Parkinson’s disease (PD) is the degeneration of substantia nigra pars compacta (SNc) neurons, resulting in striatal dopamine (DA) deficiency and in the subsequent alteration of basal ganglia physiology. Treat- ments targeting the dopaminergic system alleviate PD symptoms but. are not able to slow the neurodegenerative process that underlies PD progression.” Our news journalists obtained a quote from the research from Johns Hopkins University, “The nucleus striatum comprises a complex net- work of projecting neurons and interneurons that integrates different neural signals to modulate the activity of the basal ganglia circuitry. In this review we describe new potential molecular and synaptic striatal targets for the development of both symptomatic and neuroprotective strategies for PD. In particular, we focus on the interaction between adenosine A2A receptors and dopamine D2 receptors, on the role of a 13CHAPTER 2 PARKINSON’S DISEASE correct assembly of NMDA receptors, and on the sGC/cGMP/PKG path- way.” According to the news editors, the research concluded: “More- over, we also discuss the possibility to target the cell death program parthanatos and the kinase LRRK2 in order to develop new putative neuroprotective agents for PD acting on dopaminergic nigral neurons as well as on other basal ganglia structures.” For more information on this research see: New Synaptic and Molec- ular Targets for Neuroprotection in Parkinson's Disease. Movement Disorders, 2013:28(1):51-60. Movement Disorders can be contacted at: Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - http: //www.wiley.com/; Movement Disorders - http://onlinelibrary.wiley.com/journal/10.1002/ (ISSN) 1531-8257) The news correspondents report that additional information may be obtained from P. Calabresi, Johns Hopkins University, Sch Med, Balti- more, MD, United States. (2013 Mar 25) University of Pisa: Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopaminergic dysfunction By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - Investigators discuss new findings in Neurology. Accord- ing to news reporting originating from Pisa, Italy, by NewsRx corre- spondents, research stated, “The investigation of the relationship be- tween affective symptoms and dopamine transporter (DAT) density pro- vided conflicting data in both Parkinson’s disease (PD) and non-PD pa- tients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account.” Our news editors obtained a quote from the research from the Uni- versity of Pisa, “To investigate the relationship between affective symp- toms and presynaptic dopaminergic function in de novo PD patients. Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anx- iety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression In- ventory (BDI). Six patients had a formal diagnosis of depression. All patients performed 1I-123-FP-CIT SPECT, and semi-quantitative stri- atal indices were calculated. Disease severity, as measured by Uni- fied Parkinson’s Disease Rating Scale (UPDRSIII), was inversely cor- related with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (1.329; r.423, respec- tively, right and left), BDI (7.377; 1.360, respectively, right and left) and HAM-A (1.338; r.340, respectively, right and left). After controlling 14CHAPTER 2 PARKINSON’S DISEASE for age, disease duration and severity, and Mini Mental State Exam- ination (MMSE), no significant reduction in r-values was observed (P < 0.05). Our data support the existence of a relationship between de- pressive and anxious symptoms and the striatal I-123-FP-CIT uptake.” According to the news editors, the research concluded: “The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.” For more information on this research see: Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopamin- ergic dysfunction. European Journal of Neurology, 2013;20(3):480- 485. European Journal of Neurology can be contacted at: Wiley- Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley- Blackwell -http: //www.wiley .com/; European Journal of Neurology - http://onlinelibrary.wiley.com/journal/10.1111/ (ISSN) 1468-1331) The news editors report that additional information may be obtained by contacting R. Ceravolo, University of Pisa, Reg Center Nucl Med, Pisa, Italy. (2013 Mar 25) University of Regensburg: What is measured with verbal fluency tests in Parkinson's disease patients at different stages of the disease? By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - Fresh data on Neural Transmission are presented in a new report. According to news reporting originating in Regensburg, Ger- many, by NewsRx journalists, research stated, “Verbal fluency tests (VFT) are often used to assess executive functioning in Parkinson’s disease (PD). Various cognitive functions may, however, impair perfor- mance on VFT.” The news reporters obtained a quote from the research from the Uni- versity of Regensburg, “Furthermore, since PD is a progressive neu- rodegenerative disease, it is also not clear whether deficits on VET re- flect impairments in the same cognitive functions throughout the differ- ent disease stages, This study will investigate what is measured with VET in PD, in particular at different disease stages. Eighty-eight PD patients and 65 healthy participants, matched for age, gender, and ed- ucation, were included. All were assessed with semantic and phonemic VET and tests assessing executive functions, memory, and psychomo- tor speed. Mild and moderate PD patients did not differ in the number of words generated on both VFT. However, mild and moderate PD pa- tients differed significantly with regard to the size of the largest clusteraa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE dementia (p &It;0.001), than in cognitively normal subjects with Parkin- son’s disease. When compared with cognitively normal subjects with Parkinson’s disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cogni- tive impairment. When compared with control subjects and cognitively normal subjects with Parkinson’s disease, saccade amplitudes were sig- nificantly reduced in the groups with mild cognitive impairment or de- mentia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson’s disease groups. The strongest predictor of aver- age fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impair- ment and disease severity contributed to a predictive model for fixation duration [F(2,76)=12.52, p=0.001], but medication dose did not (r=0.18, n=78, p=0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson’s disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself.” According to the news reporters, the research concluded: “The pro- longation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson’s disease, suggests a disease-specific impact on the networks directing visual exploration, al- though the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.” For more information on this research see: Visual exploration in Parkinson’s disease and Parkinson’s disease dementia. Brain, 2013:136(Pt 3):739-50. (Oxford University Press - http://www -oup com/; Brain - brain.oxfordjournals.org) Our news journalists report that additional information may be obtained by contacting N.K. Archibald, Consultant Neurologist, The James Cook University Hospital, Middlesbrough, TS4 3BW, UK. (2013 Mar 18) University of Naples: Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson's disease by levodopa By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — New research on Parkinson’s disease is the subject of a report. According to news reporting from Naples, Italy, by NewsRx journalists, research stated, “Brain activity during rest is characterized by slow (0.01-0.1 Hz) fluctuations of blood oxygenation level-dependent 17aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE Medical University, Graz: Levodopa changes brain motor network function during ankle movements in Parkinson’s disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Investigators publish new report on Parkinson’s disease. According to news reporting originating from Graz, Austria, by NewsRx correspondents, research stated, “Bradykinesia-the cardinal symptom in Parkinson’s disease (PD)-affects both upper and lower limbs. While several functional imaging studies investigated the impact of levodopa on movement-related neural activity in Parkinson’s disease during up- per limb movements, analogue studies on lower limb movements are rare.” Our news editors obtained a quote from the research from Medical University, “We studied 20 patients with PD (mean age 66.8 ± 7.2 years) after at least 12 h drug withdrawal (OFF-state) and a second time approximately 40 min after oral administration of 200 mg levodopa (ON-state) behaviourally and by functional magnetic resonance imag- ing ((MRI) at 3 T during externally cued active ankle movements of the more affected foot at fixed rate. Results were compared with that ob- tained in ten healthy controls (HC) to separate pure pharmacological from disease-related levodopa-induced effects and to allow for interac- tion analyses. Behaviourally, all patients improved by at least 20 % re- garding the motor score of the Unified Parkinson’s disease rating scale after levodopa-challenge (mean scores OFF state: 38.4 ± 10.1; ON-state: 25.5 ± 8.1). On {MRI, levodopa application elicited in- creased activity in subcortical structures (contralateral putamen and thalamus) in the patients. In contrast, no significant levodopa-induced activation changes were found in HC. The interaction between ‘PD/HC group factor’ and ‘levodopa OFF/ON’ did not show significant results.” According to the news editors, the research concluded: “Given the levodopa-induced activation increases in the putamen and thalamus with unilateral ankle movements in patients with PD but not in HC, we speculate that these regions show the most prominent response to levodopa within the cortico-subcortical motor-circuit in the context of nigrostriatal dysfunction.” For more information on this research see: Levodopa changes brain motor network function during ankle movements in Parkinson’s dis- ease. Journal of Neural Transmission, 2013;120(3):423-33. (Springer - www.springer.com; Journal of Neural Transmission - http://www. springerlink.com/content /0300-9564/) The news editors report that additional information may be obtained by contacting P. Schwingenschuh, Dept. of Neurology, Medical Univer- sity of Graz, Auenbruggerplatz 22, 8036, Graz, Austria. (2013 Mar 11) 21aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE in early Parkinson’s disease (PD). MRI and neuropsychological assess- ment were obtained at baseline and follow-up (mean ± standard deviation=35.50 ± 1.88 months) in a group of 16 early-PD patients (H & Y stage=II and disease duration=5 years) and 15 healthy controls matched for age, gender, and years of education.” The news reporters obtained a quote from the research from Hos- pital Clinic, “FreeSurfer software was used for the analysis of cortical thickness as well as for cortical and subcortical volumetric analyses. Voxel-based morphometry analysis was performed using SPM8. Com- pared to controls, PD patients showed greater regional cortical thinning in bilateral frontotemporal regions as well as greater over-time total GM loss and amygdalar volume reduction. PD patients and controls presented similar over-time changes in cognitive functioning.” According to the news reporters, the research concluded: “In early- PD patients, global GM loss, amygdalar atrophy, and cortical thin- ning in frontotemporal regions are specifically associated with the PD- degenerative process.” For more information on this research see: Progression of cortical thinning in early Parkinson’s disease. Movement Disor- ders, 2012;27(14):1746-53. (Wiley-Blackwell - http: //www.wiley. com/; Movement Disorders - http://onlinelibrary.wiley.com/ journal/10.1002/ (ISSN) 1531-8257) Our news correspondents report that additional information may be obtained by contacting N. Ibarretxe-Bilbao, Centro de Investiga- cion en Red de Enfermedades Neurodegenerativas, Hospital Clinic de Barcelona, Catalonia, Spain. (2013 Mar 04) Korea University School of Medicine, Seoul: Clinical characteristics of impulse control and repetitive behavior disorders in Parkinson's disease By a News Reporter-Staff News Editor at Mental Health Weekly Di- gest — Investigators discuss new findings in Behavior Disorders. Ac- cording to news reporting out of Seoul, South Korea, by NewsRx ed- itors, research stated, “Impulse control and repetitive behavior disor- ders (ICRBs) are a group of diseases including impulse control disorder (ICD), repetitive behavior disorder (RB), and dopamine dysregulation syndrome (DDS). This study determined the prevalence and associated characteristics of ICRBs in Parkinson’s disease (PD) patients.” Our news journalists obtained a quote from the research from the Korea University School of Medicine, “Included were 297 patients, in- terviewed with the questionnaire for impulsive-compulsive disorders in PD for screening of various ICRBs. Questionnaire results and clini- cal characteristics were analyzed. The ICRB prevalence among PD pa- tients was 15.5 % (46 of 297), with 35 patients with ICD, 20 with RB, and 25aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE Our news editors obtained a quote from the research, “Sporadically, a stop signal is also delivered after a short interval following the go sig- nal, prompting participants to inhibit their already started response to the go signal. Functional MRI studies using this paradigm have im- plicated the activation of the subthalamic nucleus in motor inhibition. We directly recorded subthalamic nucleus activity from bilaterally im- planted deep brain stimulation electrodes in a group of 10 patients with Parkinson’s disease, during performance of the stop signal task. Re- sponse inhibition was associated with specific changes in subthalamic activity in three different frequency bands. Response preparation was associated with a decrease in power and cortico-subthalamic coherence in the beta band (12-30 Hz), which was smaller and shorter when the response was successfully inhibited. In the theta band, we observed an increase in frontal cortico-subthalamic coherence related to the pres- ence of the stop signal, which was highest when response inhibition was unsuccessful. Finally, a specific differential pattern of gamma activity was observed in the ‘on’ motor state. Performance of the response was associated with a significant increase in power and cortico-subthalamic coherence, while successful inhibition of the response was associated with a bilateral decrease in subthalamic power and cortico-subthalamic coherence. Importantly, this inhibition-related decrease in gamma ac- tivity was absent in the four patients with dopamine-agonist related impulse-control disorders.” According to the news editors, the research concluded: “Our results provide direct support for the involvement of the subthalamic nucleus in response inhibition and suggest that this function may be mediated by a specific reduction in gamma oscillations in the cortico-subthalamic connection.” For more information on this research see: The subthalamic nu- cleus is involved in successful inhibition in the stop-signal task: A local field potential study in Parkinson’s disease. Experimental Neu- rology, 2013;239():1-12. Experimental Neurology can be contacted at: Academic Press Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA. (Elsevier - wwwelsevier.com; Experimental Neurology - http: //www.elsevier.com/wps/product /cws_home/ 622828) The news editors report that additional information may be obtained by contacting M. Alegre, Center Invest Biomed Red Enfermedades Neu- rodegenerat, Madrid, Spain. (2013 Feb 25) 29aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE University of Oxford: The role of the basal ganglia in action imitation: neuropsychological evidence from Parkinson’s disease patients By a News Reporter-Staff News Editor at Ivy League Week - A new study on Brain Research is now available. According to news originat- ing from Oxford, United Kingdom, by NewsRx correspondents, research stated, “Though previous studies have suggested that the basal ganglia are necessarily involved in action imitation, their precise role is unclear. An important source of evidence concerns patients with Parkinson's dis- ease (PD) who suffer basal ganglia impairments.” Our news journalists obtained a quote from the research from the University of Oxford, “Some studies report poor execution of observed meaningful (MF) transitive (tool-related) actions but normal perfor- mance with intransitive (non-tool-related) MF and meaningless (ML) actions (Leiguarda et al. in Brain 120:75-90, 1997; Leiguarda 2001 in Neuroimage 14:137-141). In other cases, though, patients with le- sions involving the basal ganglia appear impaired in imitating ML as compared to meaningful MF transitive pantomimes. Here, we tested a group of PD patients ina full 2.x 2 design with MF transitive and intran- sitive pantomimes and matched ML movements. PD patients generated higher scores when imitating MF transitive actions than ML-matched actions. On the other hand, ML than MF intransitive actions did not differ significantly.” According to the news editors, the research concluded: “The perfor- mance of the patients on imitating ML transitive actions also correlated with their performance on the Corsi block test of visuospatial memory and their scores at the test of verbal fluency for phonemic categories (FAS) while MF intransitive actions correlated with FAS and the neu- rological evaluation (UPDRS) The results are discussed in terms of the factors that load on visual memory for action reproduction, as well as the possible role of the basal ganglia in communicative actions (for MF intransitive actions).” For more information on this research see: The role of the basal ganglia in action imitation: neuropsychological evidence from Parkin- son’s disease patients. Experimental Brain Research, 2013;224(2):211- 220. Experimental Brain Research can be contacted at: Springer, 233 Spring St, New York, NY 10013, USA. (Springer - www.springer.com; Experimental Brain Research - http: //www.springerlink.com/ content /0014-4819/) The news correspondents report that additional information may be obtained from C. Bonivento, University of Oxford, Dept. of Expt Psy- chol, Oxford OX2 38UD, United Kingdom. (2013 Feb 12) 32CHAPTER 2 PARKINSON’S DISEASE DZNE, Tubingen: TUG Test Instrumentation for Parkinson’s disease patients using Inertial Sensors and Dynamic Time Warping By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Investigators publish new report on Neurodegenerative Diseases. According to news reporting originating in Tubingen, Ger- many, by NewsRx journalists, research stated, “The Timed Up and Go (TUG) test is a clinical tool widely used to evaluate balance and mobil- ity, e. g. in Parkinson's disease (PD). This test includes a sequence of functional activities, namely: sit-to-stand, 3-meters walk, 180 degrees turning, walk back, and turn-to-sit.” The news reporters obtained a quote from the research from DZNE, “The work introduces a new method to instrument the TUG test us- ing a wearable inertial sensor unit (DynaPort Hybrid, McRoberts B. V., NL) attached on the lower back of the person. It builds on Dynamic ‘Time Warping (DTW) for detection and duration assessment of associ- ated state transitions. An automatic assessment to substitute a manual evaluation with visual observation and a stopwatch is aimed at to gain objective information about the patients. The algorithm was tested on data of 10 healthy individuals and 20 patients with Parkinson’s disease (10 patients for early and late disease phases respectively).” According to the news reporters, the research concluded: “The al- gorithm successfully extracted the time information of the sit-to-stand, turn and turn-to-sit transitions.” For more information on this research see: TUG Test Instrumen- tation for Parkinson’s disease patients using Inertial Sensors and Dy- namic Time Warping. Biomedical Engineering-Biomedizinische Tech- nik, 2012;57():354-357. Biomedical Engineering-Biomedizinische Tech- nik can be contacted at: Walter De Gruyter & Co, Genthiner Strasse 13, D-10785 Berlin, Germany. Our news correspondents report that additional information may be obtained by contacting M.R. Adame, German Center Neurodegenerat Dis, DZNE, Tubingen, Germany. (2013 Feb 11) Shandong University of Technology, Zibo: Osteoporosis risk and bone mineral density levels in patients with Parkinson's disease: A meta-analysis By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Data detailed on Bone and Mineral Research have been presented. According to news reporting from Zibo, People’s Republic of China, by NewsRx journalists, research stated, “Parkinson's disease (PD) and osteoporosis are common diseases which affect a substantial 33CHAPTER 2 PARKINSON’S DISEASE portion of the elderly population. Accumulating evidence supports that PD patients have a high risk for osteoporosis in recent years.” The news correspondents obtained a quote from the research from the Shandong University of Technology, “The purpose of the present study is to perf(o)rm a meta-analysis on the risk of osteoporosis and bone mineral density (BMD) levels in PD patients. We searched all ar- ticles indexed in Medline, SciVerse Scopus and Cochrane Library pub- lished up to January 2012 concerning the association between PD and risk of osteoporosis or BMD levels. In total, 15 studies were included in the meta-analysis. The results indicated that PD patients are at higher risk for osteoporosis (summary OR = 1.18, 95% CI = [1.09, 1.271) than healthy controls. The gender subgroup analysis suggested that PD male patients have a higher risk for osteoporosis than female pa- tients (female patients: summary OR = 1.16, 95% CI = [1.07, 1.26]; male patients: summary OR = 2.44, 95% CI = [1.37, |). Further meta-analysis showed that PD patients have a lower hip, lumbar spine and femoral neck BMD than healthy controls. The gender subgroup analysis found a lower BMD in PD female patients than controls, while no obvious difference was observed in PD male patients and controls.” According to the news reporters, the research concluded: “This meta-analysis suggested that PD patients are at higher risk for osteo- porosis and have lower BMD levels than healthy controls overall.” For more information on this research see: Osteoporosis risk and bone mineral density levels in patients with Parkinson’s disease: A meta-analysis. Bone, 2013;52(1):498-505. Bone can be contacted at: Elsevier Science Inc, 360 Park Ave South, New York, NY 10010-1710, USA. (Elsevier - www.elsevier.com; Bone - http://www.elsevier. com/wps/product/cws_home/ 525233) Our news journalists report that additional information may be ob- tained by contacting Y. Zhao, Shandong Univ Technol, Shandong Prov Res Center Bioinformat Engn & Technical, Zibo 255049, People’s Re- public of China. (2013 Feb 11) University of Chicago: Aberrant plasti motor in| ‘ion in Parkinson’s disease ity and “learned” By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Current study results on Physiology have been published. According to news reporting from Chicago, Iinois, by NewsRx editors, the research stated, “Parkinson's disease (PD) is a progressive neurode- generative movement disorder characterized by severe loss of substan- tia nigra dopamine (DA) neurons. The target region of substantia nigra DA neurons is the dorsal striatum.” The news correspondents obtained a quote from the research from the University of Chicago, “According to the classic model, activation 34CHAPTER 2 PARKINSON’S DISEASE of DA receptors on striatal medium spiny neurons (MSNs) modulates their intrinsic excitability. Activation of D1 receptors makes MSNs in the direct ‘Go’ pathway more excitable, whereas activation of D2 recep- tors makes MSNs in the indirect ‘NoGo’ pathway less excitable. There- fore increased DA increases the responsiveness of the Go pathway while decreases the responsiveness of the NoGo pathway. Both mechanisms increase motor output. Conversely, diminished DA will favor the in- hibitory NoGo pathway. Therefore, DA has direct, ‘on-line’ effect on motor performance, However, in addition to modulating the intrinsic excitability of MSNs ‘on-line’, DA also modulates corticostriatal plas- ticity, therefore could potentially produce cumulative and long-lasting changes in corticostriatal throughput. Studies in my lab suggest that DA blockade leads to both direct motor performance impairment and D2 receptor dependent NoGo learning (‘learned’ motor inhibition) that gradually deteriorates motor performance. NoGo learning is experience dependent and task specific. It is different from blocked learning since NoGo learning impairs future performance even after DA is restored. More recent data from my lab suggest that NoGo learningin the absence of DA arises from increased LTP at the indirect pathway corticostriatal synapses and contributes significantly to PD-like motor symptoms.” According to the news reporters, the research concluded: “Our data and hypotheses suggest a novel therapeutic strategy for PD that targets directly signaling molecules for corticostriatal plasticity (e.g. the cAMP pathway and downstream signaling molecules) and prevents aberrant plasticity under conditions of DA denervation.” For more information on this research see: Aberrant plasticity and “Jearned” motor inhibition in Parkinson’s disease. Sheng Li Xue Bao lacta Physiologica Sinica], 2012;64(5):543-9. Our news journalists report that additional information may be ob- tained by contacting X.X. Zhuang, Neurobiology Department, Univer- sity of Chicago, Chicago, IL, United States. (2013 Feb 11) Veterans Affairs Medical Center, Houston: Anxiety disorders, physical illnesses, and health care utilization in older male veterans with Parkinson disease and comorbid depression By a News Reporter-Staff News Editor at Psychology & Psychiatry Jour- nal — Current study results on Geriatrics and Gerontology have been published. According to news reporting from Houston, Texas, by Verti- calNews journalists, research stated, “This study examined the rates of anxiety and depressive disorders, physical illnesses, and health service use in male patients 55 years or older with a diagnosis of Parkinson discase who were seen at least twice at the 10 medical centers in theCHAPTER 2 PARKINSON’S DISEASE Veterans Affairs Healthcare Network of the South Central region of the United States. Of the 273 male patients diagnosed between October 1, 1997, and September 30, 2009, 62 (22.7%) had a depressive disorder.” The news correspondents obtained a quote from the research from Veterans Affairs Medical Center, “The overall prevalence of anxiety disorders was 12.8%; patients with comorbid depression had a 5-fold greater prevalence of anxiety disorders than those without depression (35.5% vs 6.2%, p<.0001). Patients with comorbid depression also had increased prevalence of all physical illnesses examined and more out- patient clinic and mental health visits.” According to the news reporters, the research concluded: “Patients with Parkinson disease and comorbid depression are more likely to have anxiety disorders and several physical illnesses, to be using antipsy- chotic and dementia medicines, and to have increased health service utilization than those without depression.” For more information on this research see: Anxicty disorders, phys- ical illnesses, and health care utilization in older male veterans with Parkinson disease and comorbid depression. Journal of Geriatric Psy- chiatry and Neurology, 2012;25(4):233-9. Journal of Geriatrie Psychi- atry and Neurology can be contacted at: SAGE Publications, USA , 2455 Teller Road, Thousand Oaks, CA 91320, USA. (Sage Publications - http://www.sagepub.com/; Journal of Geriatric Psychiatry and Neurology - jgp.sagepub.com) Our news journalists report that additional information may be ob- tained by contacting S.U. Qureshi, 1VA Houston HSR&D Center of Ex- cellence, Health Services Research and Development Service, Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, United States. Publisher contact information for the Journal of Geriatric Psychi- atry and Neurology is: SAGE Publications, USA , 2455 Teller Road, Thousand Oaks, CA 91320, USA. (2013 Feb 09) Cleveland Clinic: Falls Related to Accidental Deactivation of Deep Brain Stimulators in Patients h Parkinson’s Disease Living in Long Term Care Facilities By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Investigators publish new report on Parkinson's disease. According to news reporting out of Cleveland, Ohio, by NewsRx editors, research stated, “This case series highlights three patients with Parkin- son’s disease residing at nursing home facilities whose deep brain stim- ulators were accidentally deactivated for varying lengths of time, which was associated with an increase in falls.” 36CHAPTER 2 PARKINSON’S DISEASE Our news journalists obtained a quote from the research from Cleve- land Clinic, “In all three cases, neither the patients nor the caregivers were aware of the random deactivations/reactivations.” According to the news editors, the research concluded: “We propose a specific care plan for these patients that includes further education of caregivers regarding deep brain stimulators and regular checks of the review device, especially when there is concern about a patient’s mobility or balance that is out of character.” For more information on this research see: Falls Related to Acci- dental Deactivation of Deep Brain Stimulators in Patients With Parkin- son’s Disease Living in Long Term Care Facilities. Journal of the Amer- ican Medical Directors Association, 2013;14(1):58-59. Journal of the American Medical Directors Association can be contacted at: Elsevier Science Inc, 360 Park Ave South, New York, NY 10010-1710, USA. (Elsevier - www.elsevier.com; Journal of the American Medical Direc- tors Association - http: //www.elsevier.com/wps/product /cws_ home/ 704824) Our news journalists report that additional information may be ob- tained by contacting B. Tousi, Cleveland Clinic, Center Neurol Restorat, Cleveland, OH 44106, United States. (2013 Feb 04) Spectroscopic changes associated with mild cognitive impairment and dementia in Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - Fresh data on Health and Medicine are presented in a new report. According to news reporting originating in Barcelona, Spain, by NewsRx journalists, research stated, “Frontal subcortical cognitive de- fects are predominant in Parkinson’s disease (PD). Temporal lobe dys- function seems more relevant for progression to dementia.” The news reporters obtained a quote from the research, “We aimed to study the relative importance of temporal lobe defects versus execu- tive impairment in the progression to dementia in PD by using proton magnetic resonance spectroscopy ((1)H-MRS). The (1)H-MRS features of PD patients with intact cognition (PD-CgInt; n=16), mild cognitive impairment (MCI; n=15) and dementia (PDD; n=15) were compared, to delineate the metabolic alterations correlating with cognitive status. Metabolite concentrations were acquired from voxels localized to the hippocampus and dorsolateral prefrontal cortex (DL-PFC). Cognitive status was established following the Movement Disorder Society PDD criteria, administering the Clinical Dementia Rating Scale and Mat- tis Dementia Rating Scale. The Parkinson’s Disease Cognitive Rating Scale (PD-CRS) was used to correlate (1)H-MRS with neuropsychology. N-acetylaspartate (NAA) concentrations in the right DL-PFC were de- creased in PD-MCI compared with PD-CgInt patients (p=0.002), and 37CHAPTER 2 PARKINSON’S DISEASE correlated with frontal subcortical tasks. Decreased NAA concentra- tions in the left hippocampus in PDD compared to PD-MCI (p=0.03) cor- related with confrontation naming. The present findings support that executive impairment is related to dorsolateral prefrontal dysfunction from the early stages, while progression to dementia is linked to the additional impairment of temporal lobe structure: According to the news reporters, the research concluded: “The PD- CRS was able to capture the differential impairment of prefrontal ver- sus temporal cortical areas.” For more information on this research see: Spectroscopic changes as- sociated with mild cognitive impairment and dementia in Parkinson’s disease. Dementia and Geriatric Cognitive Disorders, 2012;34(5-6):312- 8. (Karger - http://www.karger.com/; Dementia and Geriatric Cognitive Disorders - http: //content.karger.com/ProdukteDB/ produkte. asp?Akt ion=JournalHome&ProduktNr=224226) Our news correspondents report that additional information may be obtained by contacting J. Pagonabarraga, Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Spain. (2013 Feb 04) University of Messina: Periodontal health and caries prevalence evaluation in patients affected by Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous System Week — Investigators discuss new findings in Neurodegener- ative Diseases. According to news originating from Messina, Italy, by NewsRx correspondents, research stated, “Parkinson's disease (PD) is a progressive neurodegenerative disorder related to the loss or absence of dopaminergic neurons in the brain, These deficits result in slowness of movement, tremor, rigidity, and dysfunction of behaviour” Our news journalists obtained a quote from the research from the University of Messina, “These symptoms negatively influence the pa- tient’s capability to carry out the daily oral hygiene manoeuvres. The aim of this work is to record the oral health condition of PD patients evaluated at the IRCSS Bonino-Puleio in Messina. The oral health of 45 consecutive PD patients (study group) with neurologic diagnosis based on United Kingdom Brain Bank Criteria has been compared with that of another 45 no PD patients of the same age (control group). The evalu- ation of the general oral condition was recorded underlining tooth loss, active periodontal disease, and presence of untreated caries. The fre- quency of untreated caries, periodontal diseases, and missing teeth of the study group was significantly higher than in control group.” According to the news editors, the research concluded: “Based on the data results, clinicians should direct high attention to the oral hygiene 38CHAPTER 2 PARKINSON’S DISEASE of patients with PD, above all at the early stages of the caries or peri- odontal disease, in order to prevent serious evolution of those pathologic dental conditions that may finally result in the tooth extraction event.” For more information on this research see: Periodontal health and caries prevalence evaluation in patients affected by Parkinson's dis- ease. Parkinson's Disease, 2012;2012():541908. (Hindawi Publish- ing - www.hindawi.com; Parkinson’s Disease - http: //www.hindawi. com/journals/pd/) The news correspondents report that additional information may be obtained from M. Cicciu, Dept. of Human Pathology, University of Messina School of Dentistry, 98100 Messina, Italy. (2013 Feb 04) University of Washington, Seattle: The effects of instructions on dual-task walking and cognitive task performance in people with Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Investigators discuss new findings in Pain and Central Nervous System. According to news originating from Seattle, Wash- ington, by NewsRx correspondents, research stated, “Gait impairments are prevalent among people with Parkinson’s disease (PD). Instructions to focus on walking can improve walking in PD, but the use of such a cognitive strategy may be limited under dual-task walking conditions, when walking is performed simultaneously with concurrent cognitive or motor tasks.” Our news journalists obtained a quote from the research from the University of Washington, “This study examined how dual-task per- formance of walking and a concurrent cognitive task was affected by instructions in people with PD compared to healthy young and older in- dividuals. Dual-task walking and cognitive task performance was char- acterized under two sets of instructions as follows: (1) focus on walking and (2) focus on the cognitive task. People with PD and healthy adults walked faster when instructed to focus on walking. However, when fo- cused on walking, people with PD and young adults demonstrated de- clines in the cognitive task. This suggests that dual-task performance is flexible and can be modified by instructions in people with PD, but walk- ing improvements may come at a cost to cognitive task performance. The ability to modify dual-task performance in response to instructions or other task and environmental factors is critical to mobility in daily life.” According to the news editors, the research concluded: “Future re- search should continue to examine factors that influence dual-task per- formance among people with PD.” For more information on this research see: The effects of instruc- tions on dual-task walking and cognitive task performance in people 39CHAPTER 2 PARKINSON’S DISEASE with Parkinson’s disease. Parkinson’s Disease, 2012;2012():671261. (Hindawi Publishing - www.hindawi.com; Parkinson’s Disease - http: //www.hindawi.com/journals/pd/) The news correspondents report that additional information may be obtained from V.E. Kelly, Dept. of Rehabilitation Medicine, University of Washington, 1959 NE Pacific Street, PO Box 356490, Seattle, WA 98125, United States. (2013 Feb 04) Tokyo Medical University: How far do the complaints of patients with Parkinson’s disease reflect motor fluctuation? Quantitative analysis using a portable gait rhythmogram By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - Current study results on Pain and Central Nervous Sys- tem have been published. According to news reporting out of Tokyo, Japan, by NewsRx editors, research stated, “In advanced-stage Parkin- son’s disease (PD), motor fluctuation is a frequent and disabling prob- lem. Assessment of motor fluctuation depends on patient’s subjective self-statement.” Our news journalists obtained a quote from the research from Tokyo Medical University, “We examined whether the subjective fluctuation matched the objective motor fluctuation defined by gait disorders. Us- ing a new device, the portable gait rhythmogram, we recorded gait ca- dence and acceleration continuously over the 24-hour period in 54 pa- tients with PD and 17 normal controls, for the quantitative evaluation of motor fluctuation. The patients were asked to estimate motor fluctu- ation every hour. In 44 of 54 patients, changes in the cadence were as- sociated with simultaneous changes in acceleration. We examined the subjective fluctuation in these 44 patients who were confirmed to have motor fluctuation. Nineteen (82.7%) of 23 patients who felt no fluctua- tion showed distinct gait disorders. During off time, they walked with marked short or bradykinetic stepping. No matching changes were ob- served in either the cadence or acceleration in 11 (52.4%) of 21 patients who perceived motor fluctuation. No synchronization was noted in 30 (68.2%) of the 44 patients, between the times of subjectively assessed motor fluctuation and those of quantitative analysis of gait disorder.” According to the news editors, the research concluded: “This discrep- ancy suggests that the objective continuous recording of the cadence and acceleration is necessary to understand motor fluctuation.” For more information on this research see: How far do the com- plaints of patients with Parkinson’s disease reflect motor fluctuation? Quantitative analysis using a portable gait rhythmogram. Isrn Neurol- ogy, 2012;2012():372030. 40CHAPTER 2 PARKINSON’S DISEASE Our news journalists report that additional information may be ob- tained by contacting H. Utsumi, Dept. of Neurology, Tokyo Medical University, Tokyo 160-0023, Japan. (2013 Jan 28) Aligarh Muslim University: Effect of L-ascorbic Acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week ~ Investigators publish new report on Neuroscience. Accord- ing to news reporting originating in Aligarh, India, by NewsRx jour- nalists, research stated, “In the present study, the effect of L-ascorbie acid (AA) was studied on the climbing ability of the Parkinson’s disease (PD) model Drosophila expressing normal human alpha synuclein (h- as) in the neurons. These flies show locomotor dysfunction as the age progresses.” The news reporters obtained a quote from the research from Aligarh Muslim University, “AA at final concentration of 11.35 x 10(-5) M, 22.71 x 10(-5) M, 45.42 x 10(-5) M, and 68.13 x 10(-5) M was added to the diet, and the flies were allowed to feed for 21 days. AA at 11.35 x 10(-5) M did not show any significant delay in the loss of climbing ability of PD model flies. However, AA at 22.71 x 10(-5) M, 45.42 x 10(-5) M, and 68.13 x 10(- 5) M showed a dose dependent significant (p &1t;.05) delay in the loss of climbing ability of PD model flies as compared to the untreated PD flies. The total protein concentration in brain homogenate was measured in treated as well as control groups after 21 days, no significant difference was obtained between treated as well as control (PD flies and I-dopa) groups.” According to the news reporters, the research concluded: “The re- sults suggest that AA is potent in delaying the climbing disability of the PD model flies expressing h-as in the neurons.” For more information on this research see: Effect of L-ascorbic Acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease. The International Journal of Neuro- science, 2012;122(12):704-9. Our news correspondents report that additional information may be obtained by contacting S. Khan, Drosophila Transgenic Laboratory, Section of Genetics, Dept. of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, India. (2013 Jan 21) 41CHAPTER 2 PARKINSON’S DISEASE Barrow Neurological Institute, Phoenix: A about falls to distinguish balance and gait Parkinson's disease By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week — Fresh data on Neuroscience are presented in a new report. According to news originating from Phoenix, Arizona, by NewsRx cor- respondents, research stated, “Although gait and balance difficulties often occur together in Parkinson’s disease (PD) patients, it is believed that they are actually two eparate symptoms. However, there are no simple tests to distinguish them.” Our news journalists obtained a quote from the research from Bar- row Neurological Institute, “We have developed the self-administered Barrow Neurological Institute (BNI) question to distinguish between gait and balance issues in PD and it was tested in 102 consecutive PD patients. The responses were compared with those of the walking and balance question (item # 2.12) of the Movement Disorder Society- sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and the MDS-UPDRS motor examination and its sub- sets such as gait and postural stability (PS). Fifty-five patients reported balance difficulty on the BNI question and 64 reported walking and bal- ance difficulty on the MDS-UPDRS question. Of the patients who re- ported balance difficulty on the BNI question, 74.5% had a PS score=2 and 25.4% fell at least three times per month. Of the patients who reported walking and balance difficulty on the MDS-UPDRS question, only 59.4% had a PS score=2 and only 10.9% fell three or more times per month.” According to the news editors, the research concluded: “These sta- tistically significant results suggest that the BNI question is better able to detect balance difficulty and its associated falls in PD and can be a supplement to the MDS-UPDRS or a stand-alone question to evaluate balance difficulty and its associated falls in PD.” For more information on this research see: A simple question about falls to distinguish balance and gait difficulties in Parkinson's disease. The International Journal of Neuroscience, 2012;122(12):710-5. The news correspondents report that additional information may be obtained from A, Lieberman, Muhammad Ali Parkinson Center (MAPC), Barrow Neurological Institute, St Joseph’s Hospital and Med- ical Center, Phoenix, Arizona 85013, United States. (2013 Jan 21) 42CHAPTER 2 PARKINSON’S DISEASE Carlos III Institute of Health, Madrid: Markov blanket-based approach for learning multi-dimensional i i i n to predict the European Quality of -5 Dimensions (EQ-5D) from the 39-item Parkinson's Disease Questionnaire (PDQ-39) By a News Reporter-Staff News Editor at Pain & Central Nervous Sys- tem Week - A new study on Biomedical Informatics is now available. According to news reporting originating in Madrid, Spain, by NewsRx journalists, research stated, “Multi-dimensional Bayesian network clas- sifiers (MBCs) are probabilistic graphical models recently proposed to deal with multi-dimensional classification problems, where each in- stance in the data set has to be assigned to more than one class variable. In this paper, we propose a Markov blanket-based approach for learning MBCs from data.” The news reporters obtained a quote from the research from the Carlos III Institute of Health, “Basically, it consists of determining the Markov blanket around each class variable using the HITON algorithm, then specifying the directionality over the MBC subgraphs. Our ap- proach is applied to the prediction problem of the European Quality of Life-5 Dimensions (EQ-5D) from the 39-item Parkinson’s Disease Ques- tionnaire (PDQ-39) in order to estimate the health-related quality of life of Parkinson’s patients. Fivefold cross-validation experiments were carried out on randomly generated synthetic data sets, Yeast data set, as well as on a real-world Parkinson's disease data set containing 488 patients.” According to the news reporters, the research concluded: “The exper- imental study, including comparison with additional Bayesian network- based approaches, back propagation for multi-label learning, multi- label k-nearest neighbor, multinomial logistic regression, ordinary least squares, and censored least absolute deviations, shows encouraging re- sults in terms of predictive accuracy as well as the identification of de- pendence relationships among class and feature variables.” For more information on this research see: Markov blanket-based approach for learning multi-dimensional Bayesian network classifiers: An application to predict the European Quality of Life-5 Dimensions (EQ-5D) from the 39-item Parkinson’s Disease Questionnaire (PDQ- 39). Journal of Biomedical Informatics, 2012;45(6):1175-1184. Jour- nal of Biomedical Informatics can be contacted at: Academic Pri Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA. (Elsevier - www.elsevier.com; Journal of Biomedical Informatics -http://www.elsevier.com/wps/product /ews_home/ 622857) Our news correspondents report that additional information may be obtained by contacting H. Borchani, Reina Sofia Fdn, Alzheimer Center, Carlos III Inst HIth, CIBERNED, Madrid 28031, Spain. (2013 Jan 21) 43aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.CHAPTER 2 PARKINSON’S DISEASE nocturnal sleep variables. Deficits in objectively assessed daytime alert- ness in Parkinson’s disease appear to be a function of both the disease and the medications and their doses used.” According to the news editors, the research concluded: “The appar- ent divergent dose-dependent effects of drug class in Parkinson’s dis- ease are anticipated by basic science studies of the sleep/wake cycle un- der different pharmacological agents.” For more information on this research see: Daytime alert- ness in Parkinson’s disease: potentially dose-dependent, divergent effects by drug class. Movement Disorders, 2012;27(9):1118-24. (Wiley-Blackwell - http: //www.wiley.com/; Movement Disorders - http://onlinelibrary.wiley.com/journal/10.1002/ (ISSN) 1531-8257) The news editors report that additional information may be ob- tained by contacting D.L. Bliwise, Dept. of Neurology, Emory Univer- sity School of Medicine, Atlanta, Georgia, United States. (2012 Oct 22) Juntendo University School of Medicine, Tokyo: VPS35 mutation in Japanese patients with typical Parkinson's disease By a News Roporter-Staff News Editor at China Weekly News — In- vestigators discuss new findings in Parkinson’s disease. According to news reporting originating in Tokyo, Japan, by VerticalNews journal- ists, research stated, “Vacuolar protein sorting 35 (VPS35) was recently reported to be a pathogenic gene for late-onset autosomal dominant Parkinson’s disease (PD), using exome sequencing. To date, VPS35 mu- tations have been detected only in whites with PD.” The news reporters obtained a quote from the research from the Juntendo University School of Medicine, “The aim of the present study was to determine the incidence and clinical features of Asian PD pa- tients with VPS35 mutations. We screened 7 reported nonsynonymous missense variants of VPS35, including p.D620N, known as potentially disease-associated variants of PD, in 300 Japanese index patients with autosomal dominant PD and 433 patients with sporadic PD (SPD) by direct sequencing or high-resolution melting (HRM) analysis. In addi- tion, we screened 579 controls for the p.D620N mutation by HRM anal- ysis. The p.D620N mutation was detected in 3 patients with autosomal dominant PD (1.0%), in 1 patient with SPD (0.23%), and in no controls. None of the other reported variants of VPS35 were detected. Haplo- type analysis suggested at least 3 independent founders for Japanese patients with p.D620N mutation. Patients with the VPS35 mutation showed typical tremor-predominant PD. We report Asian PD patients with the VPS35 mutation. Although VPS35 mutations are uncommon in PD, the frequency of such mutation is relatively higher in Japanese 86aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this 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book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.INDEX Nervous System Diseases and Conditions, 80, 129 Netherlands, 9, 73, 129, 130, 139, 143 Neural Networks, 102 Neural Transmission, 15, 16. 52, 108, 140 Neurobiology, 5, 6, 28, 35, 66, 68, 110, 135, 136, 147, 151 Neuroblastoma, 80, 137 Neurochemistry, 1, 2, 45, 46, 80 Neurodegenerative Diseases, 5, 6, 33, 38, 57, 76, 84, 100, 102, 130, 131, 134 Neuroimaging, 24, 30, 66, 132 Neurology, 6, 14, 15, 21, 26-28, 36, 38, 40, 41, 46-49, 57, 59- 62, 76, 78, 83, 84, 86, 87, 92, 100, 104, 107, 118, 128, 131- 193, 145, 146, 151 Neurons, 6, 7, 10, 13, 14, 22, 34, 35, 38, 41, 44, 45, 49, 50, 56, 65, 70, 71, 75, 76, 79-81, 84, 87, 95, 98, 100, 103, 104, 108, 109, 113, 119, 126, 128, 131, 184, 136, 141, 146-148 Neuropathology, 4, 75, 87 Neuroprotective Agents, 14 Neuropsychology, 37, 101, 125 Neuroscience, 18, 22, 30, 41, 42, 49, 54, 55, 71, 73, 77, 85, 94, 102, 109-111, 114, 119, 125, 133, 139, 148 Neurotoxins, 102 New Jersey, 63 New York, 37, 55, 71, 73, 83, 84, 91, 92, 94, 101, 103, 106, 107 New York City, 11, 83 Newcastle-upon-Tyne, 1 Nijmegen, 129, 130 Nitric Oxide, 70, 106, 113 Norepinephrine, 126 North Dakota, 79, 80 Norway, 62 Novato, 84, 85 Obesity, 127, 160, 163, 164 Ohio, 36 Olfactory Bulb, 84, 185 Oncology, 7, 137 Optical Coherence Tomography, 8 a Oregon, 146 Organelles, 22, 136 Osaka, 113, 114 Osteoporosis, 33, 34 Oxford, 17, 18, 20, 23, 32, 51, 56, 57, 69, 70, 74, 75, 89, 92, 93, 120, 122, 138, 141, 152, 153 Oxidants, 126 Padova, 128, 129 Pain and Central Nervous System, 4, 39, 40, 67, 98 Paris, 95, 148, 155 Parkinsonism, 2, 3, 20, 23, 69, 70, 89, 108, 120, 122, 134, 144, 145, 149 Parkinsonism and Related Disor- ders, 20, 22, 69, 89 Parkinson’s Disease, 4-57, 59, 60, 62-155, 157, 158, 160, 163, 164 Patent, 116, 155-159, 161, 162, 164 Pathology, 5, 22, 39, 52, 71, 75, 76, 83, 101, 127, 135, 140, 150, 160, 163, 164 Pennsylvania, 6, 7, 97, 131, 132, 135, 136 People’s Republic of China, 5, 33, 34, 45, 110, 136, 144 Perfusion, 83, 93 Perugia, 140, 141 Philadelphia, 6, 7, 83, 131, 132, 135, 136 Phoenix, 42, 64 Physiology, 13, 34, 52, 98, 136, 146, 148, 160 Pisa, 14,15 168aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.aa You have either reached a page that is unavailable for viewing or reached your viewing limit for this book.