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NPJ Parkinson's Disease

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https://www.readbyqxmd.com/read/29761156/viewpoint-and-practical-recommendations-from-a-movement-disorder-specialist-panel-on-objective-measurement-in-the-clinical-management-of-parkinson-s-disease
#1
REVIEW
Per Odin, K Ray Chaudhuri, Jens Volkmann, Angelo Antonini, Alexander Storch, Espen Dietrichs, Zvezdan Pirtošek, Tove Henriksen, Malcolm Horne, David Devos, Filip Bergquist
Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life)...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29707617/detection-of-endogenous-s1292-lrrk2-autophosphorylation-in-mouse-tissue-as-a-readout-for-kinase-activity
#2
Jillian H Kluss, Melissa M Conti, Alice Kaganovich, Aleksandra Beilina, Heather L Melrose, Mark R Cookson, Adamantios Mamais
Parkinson's disease-linked mutations in LRRK2 enhance the kinase activity of the protein, therefore targeting LRRK2 kinase activity is a promising therapeutic approach. Phosphorylation at S935 of LRRK2 and of its Rab GTPase substrates have proven very useful biomarkers to monitor its kinase activity. Complementary to these approaches autophosphorylation of LRRK2 can be used as a direct kinase activity readout but to date detection of autophosphorylation at endogenous levels in vivo has been limited. We developed a fractionation-based enrichment method to successfully detect endogenous S1292 LRRK2 autophosphorylation in mouse tissues and highlight S1292 as a physiological readout candidate for LRRK2 kinase activity in vivo...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29675463/caregiver-burden-and-caregiver-appraisal-of-psychiatric-symptoms-are-not-modulated-by-subthalamic-deep-brain-stimulation-for-parkinson-s-disease
#3
Philip E Mosley, Michael Breakspear, Terry Coyne, Peter Silburn, David Smith
Subthalamic deep brain stimulation is an advanced therapy that typically improves quality of life for persons with Parkinson's disease (PD). However, the effect on caregiver burden is unclear. We recruited 64 persons with PD and their caregivers from a movement disorders clinic during the assessment of eligibility for subthalamic DBS. We used clinician-, patient- and caregiver-rated instruments to follow the patient-caregiver dyad from pre- to postoperative status, sampling repeatedly in the postoperative period to ascertain fluctuations in phenotypic variables...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29644335/neuromelanin-detection-by-magnetic-resonance-imaging-mri-and-its-promise-as-a-biomarker-for-parkinson-s-disease
#4
REVIEW
David Sulzer, Clifford Cassidy, Guillermo Horga, Un Jung Kang, Stanley Fahn, Luigi Casella, Gianni Pezzoli, Jason Langley, Xiaoping P Hu, Fabio A Zucca, Ioannis U Isaias, Luigi Zecca
The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29644334/objective-measurement-in-routine-care-of-people-with-parkinson-s-disease-improves-outcomes
#5
Parisa Farzanehfar, Holly Woodrow, Michelle Braybrook, Sarah McGregor, Andrew Evans, Frank Nicklason, Malcolm Horne
It is common in medicine to titrate therapy according to target ranges of objectively measured parameters. Objective measurement of motor function is available for Parkinson's Disease (PD), making it possible to optimise therapy and clinical outcomes. In this study, an accelerometry based measurement and predefined target ranges were used to assess motor function in a Northern Tasmania PD cohort managed by a Movement Disorder clinic. Approximately 40% ( n  = 103) of the total PD population participated in this study and motor scores were within target in 22%...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29582000/rhythmic-abilities-and-musical-training-in-parkinson-s-disease-do-they-help
#6
V Cochen De Cock, D G Dotov, P Ihalainen, V Bégel, F Galtier, C Lebrun, M C Picot, V Driss, N Landragin, C Geny, B Bardy, S Dalla Bella
Rhythmic auditory cues can immediately improve gait in Parkinson's disease. However, this effect varies considerably across patients. The factors associated with this individual variability are not known to date. Patients' rhythmic abilities and musicality (e.g., perceptual and singing abilities, emotional response to music, and musical training) may foster a positive response to rhythmic cues. To examine this hypothesis, we measured gait at baseline and with rhythmic cues in 39 non-demented patients with Parkinson's disease and 39 matched healthy controls...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29581999/astrocyte-dysfunction-following-molybdenum-associated-purine-loading-could-initiate-parkinson-s-disease-with-dementia
#7
REVIEW
Christopher A Bourke
Sporadic or idiopathic Parkinson's disease is a movement disorder with a worldwide distribution, a long pre-clinical latent period and a frequent association with dementia. The combination of molybdenum deficiency and purine ingestion could explain the movement disorder, the distribution, the latent period and the dementia association. Recent studies in sheep have shown that molybdenum deficiency enables some dietary purines to accumulate in the central nervous system. This causes astrocyte dysfunction, altered neuromodulation and eventually irreversible central nervous system disease...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29560414/management-of-constipation-in-patients-with-parkinson-s-disease
#8
REVIEW
Anna J Pedrosa Carrasco, Lars Timmermann, David J Pedrosa
A considerable body of research has recently emerged around nonmotor symptoms in Parkinson's disease (PD) and their substantial impact on patients' well-being. A prominent example is constipation which occurs in up to two thirds of all PD-patients thereby effecting psychological and social distress and consequently reducing quality of life. Despite the significant clinical relevance of constipation, unfortunately little knowledge exists on effective treatments. Therefore this systematic review aims at providing a synopsis on clinical effects and safety of available treatment options for constipation in PD...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29507872/optimizing-parkinson-s-disease-diagnosis-the-role-of-a-dual-nuclear-imaging-algorithm
#9
REVIEW
J William Langston, Jesse C Wiley, Michele Tagliati
The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29387783/systematic-evaluation-of-levodopa-carbidopa-intestinal-gel-patient-responder-characteristics
#10
David G Standaert, James T Boyd, Per Odin, Weining Z Robieson, Jorge Zamudio, Krai Chatamra
Levodopa-carbidopa intestinal gel (LCIG, carbidopa-levodopa enteral suspension in the United States) is a treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. The objective of this investigation was to identify the baseline characteristics predictive of treatment response, measured by improvement in motor symptom severity, in advanced PD patients treated with LCIG during a 54-week, open-label phase 3 study. Patients with ≥1 h improvement from baseline in "Off" time were categorized as "Responders"; whereas those with <1 h improvement, any worsening, or no post-baseline assessment were "Non-Responders"...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29367946/erratum-variable-frequency-of-lrrk2-variants-in-the-latin-american-research-consortium-on-the-genetics-of-parkinson-s-disease-large-pd-a-case-of-ancestry
#11
Mario Cornejo-Olivas, Luis Torres, Mario R Velit-Salazar, Miguel Inca-Martinez, Pilar Mazzetti, Carlos Cosentino, Federico Micheli, Claudia Perandones, Elena Dieguez, Victor Raggio, Vitor Tumas, Vanderci Borges, Henrique B Ferraz, Carlos R M Rieder, Artur Shumacher-Schuh, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, Francisco Lopera, Jorge Chang-Castello, Brennie Andreé-Munoz, Sarah Waldherr, Dora Yearout, Cyrus P Zabetian, Ignacio F Mata
[This corrects the article DOI: 10.1038/s41531-017-0020-6.].
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29354684/optimizing-olfactory-testing-for-the-diagnosis-of-parkinson-s-disease-item-analysis-of-the-university-of-pennsylvania-smell-identification-test
#12
James F Morley, Abigail Cohen, Laura Silveira-Moriyama, Andrew J Lees, David R Williams, Regina Katzenschlager, Christopher Hawkes, Julie P Shtraks, Daniel Weintraub, Richard L Doty, John E Duda
The 40-item University of Pennsylvania Smell Identification Test (UPSIT) is an effective instrument to detect olfactory dusfunction in Parkinson's disease (PD). It is not clear, however, whether tests of this length are necessary to detect such dysfunction. Several studies have suggested that detection of certain odors is selectively compromised in PD, and that a test comprised of these odors could be shorter and more specific for this purpose. Therefore, we attempted to identify a subset of UPSIT odors that distinguish PD from controls with similar or improved test characteristics compared to the full test...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29354683/the-use-of-accelerometry-as-a-tool-to-measure-disturbed-nocturnal-sleep-in-parkinson-s-disease
#13
Sarah McGregor, Philip Churchward, Katarzyna Soja, Denise O'Driscoll, Michelle Braybrook, Hamid Khodakarami, Andrew Evans, Parisa Farzanehfar, Garun Hamilton, Malcolm Horne
Sleep disturbances are common in Parkinson's disease (PD). We used the Parkinson's KinetiGraph (PKG), an objective movement recording system for PD to assess night time sleep in 155 people aged over 60 and without PD (controls), 72 people with PD (PwP) and 46 subjects undergoing a Polysomnogram (PSG: 36 with sleep disorder and 10 with normal sleep). The PKG system uses a wrist worn logger to capture acceleration and derive a bradykinesia score (BKS) every 2 min over 6 days. The BKS ranges from 0-160 with higher scores associated with lesser mobility...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29238748/non-motor-symptoms-in-progressive-supranuclear-palsy-prevalence-and-severity
#14
Fabiana Giada Radicati, Pablo Martinez Martin, Chiara Fossati, Kallol Ray Chaudhuri, Margherita Torti, Carmen Rodriguez Blazquez, Laura Vacca, Fabrizio Stocchi
NMSs have been extensively studied in PD patients but not in other forms of parkinsonism such as Progressive Supranuclear Palsy (PSP). The primary objective of this study was to analyze the frequency, severity and the type of non-motor symptoms (NMS) in PSP patients using the non-motor symptoms scale (NMSS). The secondary objective was to differentiate NMS between PSP and Parkinson's disease (PD). We enrolled in this cross-sectional study 50 consecutive PSP and 100 matched Parkinson's disease (PD) patients, in the proportion PSP/PD = 1/2, matched in age, sex, and disease duration...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29214211/targeted-kinase-inhibition-relieves-slowness-and-tremor-in-a-drosophila-model-of-lrrk2-parkinson-s-disease
#15
Amy C Cording, Nicolas Shiaelis, Stavroula Petridi, C Adam Middleton, Laurence G Wilson, Christopher J H Elliott
In a number of Drosophila models of genetic Parkinson's disease (PD) flies climb more slowly than wild-type controls. However, this assay does not distinguish effects of PD-related genes on gravity sensation, "arousal", central pattern generation of leg movements, or muscle. To address this problem, we have developed an assay for the fly proboscis extension response (PER). This is attractive because the PER has a simple, well-identified reflex neural circuit, in which sucrose sensing neurons activate a pair of "command interneurons", and thence motoneurons whose activity contracts the proboscis muscle...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29184902/vertebrate-food-products-as-a-potential-source-of-prion-like-%C3%AE-synuclein
#16
REVIEW
Bryan Andrew Killinger, Viviane Labrie
The aberrant aggregation of the protein α-synuclein is thought to be involved in Parkinson's disease (PD). However, the factors that lead to initiation and propagation of α-synuclein aggregation are not clearly understood. Recently, the hypothesis that α-synuclein aggregation spreads via a prion-like mechanism originating in the gut has gained much scientific attention. If α-synuclein spreads via a prion-like mechanism, then an important question becomes, what are the origins of this prion-like species? Here we review the possibility that α-synuclein aggregation could be seeded via the ingestion of a prion-like α-synuclein species contained within food products originating from vertebrates...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29152558/erratum-author-correction-using-a-smartphone-based-self-management-platform-to-support-medication-adherence-and-clinical-consultation-in-parkinson-s-disease
#17
Rashmi Lakshminarayana, Duolao Wang, David Burn, K Ray Chaudhuri, Clare Galtrey, Natalie Valle Guzman, Bruce Hellman, Ben James, Suvankar Pal, Jon Stamford, Malcolm Steiger, R W Stott, James Teo, Roger A Barker, Emma Wang, Bastiaan R Bloem, Martijn van der Eijk, Lynn Rochester, Adrian Williams
[This corrects the article DOI: 10.1038/s41531-016-0003-z.].
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29071302/paraquat-and-mptp-induce-neurodegeneration-and-alteration-in-the-expression-profile-of-micrornas-the-role-of-transcription-factor-nrf2
#18
Qingqing Wang, Nan Ren, Zhipeng Cai, Qingxia Lin, Zhangjing Wang, Qunwei Zhang, Siying Wu, Huangyuan Li
Both transcription factors (TFs) and microRNAs (miRNAs) can exert a widespread impact on gene expression. In the present study, we investigated the role of Nrf2 in paraquat-induced intracorporeal neurodegeneration and miRNA expression by exposing Nrf2 wild-type and knockout mice to paraquat (PQ) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exposure to 10 mg/kg PQ or 30 mg/kg MPTP caused damage to nerve cells in the substantia nigra (SN) in both Nrf2 (+/+) and Nrf2 (-/-) ICR mice, which included cell morphological changes, detectable apoptosis and a significant reduction in the number of dopaminergic (DA) neurons...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29057315/mitochondrial-impairment-in-microglia-amplifies-nlrp3-inflammasome-proinflammatory-signaling-in-cell-culture-and-animal-models-of-parkinson-s-disease
#19
Souvarish Sarkar, Emir Malovic, Dilshan S Harishchandra, Shivani Ghaisas, Nikhil Panicker, Adhithiya Charli, Bharathi N Palanisamy, Dharmin Rokad, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
The NLRP3 inflammasome signaling pathway is a major contributor to the neuroinflammatory process in the central nervous system. Oxidative stress and mitochondrial dysfunction are key pathophysiological processes of many chronic neurodegenerative diseases, including Parkinson's disease (PD). However, the inter-relationship between mitochondrial defects and neuroinflammation is not well understood. In the present study, we show that impaired mitochondrial function can augment the NLRP3 inflammasome-driven proinflammatory cascade in microglia...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28920076/falling-upward-with-parkinson-s-disease
#20
REVIEW
Stephen A Buetow, Pablo Martínez-Martín, Brendan McCormack
Falls can injure, even kill. No one with Parkinson's disease (PD) wants to fall by accident. However, the potential nastiness of falls does not preclude a more nuanced understanding of the personal meaning that falls can have. Rather than view falls as a problem to fear and manage solely by preventing and repairing harm, people with PD and those who care for them may recast falls as a mixed blessing. Falls may be a resource, skill, and catalyst for personal growth. We discuss how falls may give rise to opportunities in interrelated domains: capabilities, credo, character, creativity, chronemics, and connectedness...
2017: NPJ Parkinson's Disease
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