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NPJ Parkinson's Disease

C Marras, J C Beck, J H Bower, E Roberts, B Ritz, G W Ross, R D Abbott, R Savica, S K Van Den Eeden, A W Willis, C M Tanner
Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1)...
2018: NPJ Parkinson's Disease
Pablo Martinez-Martin, Jaime Kulisevsky, Pablo Mir, Eduardo Tolosa, Pilar García-Delgado, María-Rosario Luquin
Early clinical diagnosis of advanced Parkinson's disease (APD) may be difficult. This study aimed to validate a simple screening tool, the CDEPA questionnaire ("Cuestionario De Enfermedad de Parkinson Avanzada" [Questionnaire for Advanced Parkinson's Disease]), for the identification of APD in daily practice. The study included 173 consecutively selected patients with PD (40% were women, mean age was 68.4 ± 10.5 years), stratified according to the Hoehn and Yahr (HY) scale. The CDEPA questionnaire defined APD as the presence of severe disability requiring help for activities of daily living (ADL), motor fluctuations with limitation or inability to perform ADL, severe dysphagia, recurrent falls, or dementia...
2018: NPJ Parkinson's Disease
Jennifer G Goldman, Beth A Vernaleo, Richard Camicioli, Nabila Dahodwala, Roseanne D Dobkin, Terry Ellis, James E Galvin, Connie Marras, Jerri Edwards, Julie Fields, Robyn Golden, Jason Karlawish, Bonnie Levin, Lisa Shulman, Glenn Smith, Christine Tangney, Cathi A Thomas, Alexander I Tröster, Ergun Y Uc, Noreen Coyan, Crystal Ellman, Mike Ellman, Charlie Hoffman, Susan Hoffman, Don Simmonds
People with Parkinson's disease (PD) and their care partners frequently report cognitive decline as one of their greatest concerns. Mild cognitive impairment affects approximately 20-50% of people with PD, and longitudinal studies reveal dementia in up to 80% of PD. Through the Parkinson's Disease Foundation Community Choice Research Award Program, the PD community identified maintaining cognitive function as one of their major unmet needs. In response, a working group of experts across multiple disciplines was organized to evaluate the unmet needs, current challenges, and future opportunities related to cognitive impairment in PD...
2018: NPJ Parkinson's Disease
Faria Zafar, Ruksana Azhu Valappil, Sam Kim, Krisztina K Johansen, Anne Lynn S Chang, James W Tetrud, Peggy S Eis, Eli Hatchwell, J William Langston, Dennis W Dickson, Birgitt Schüle
The "Iowa kindred," a large Iowan family with autosomal-dominant Parkinson's disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7 Mb triplication of the alpha-synuclein genomic locus. Affected individuals present with an early-onset, severe parkinsonism-dementia syndrome. Here, we present a descendant of the Iowa kindred with novel, disease-associated non-motor findings of reduced heart rate variability, complete anosmia, and a rare skin condition called colloid milium...
2018: NPJ Parkinson's Disease
Fabio A Zucca, Renzo Vanna, Francesca A Cupaioli, Chiara Bellei, Antonella De Palma, Dario Di Silvestre, Pierluigi Mauri, Sara Grassi, Alessandro Prinetti, Luigi Casella, David Sulzer, Luigi Zecca
During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson's disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion...
2018: NPJ Parkinson's Disease
Amy K Reeve, John P Grady, Eve M Cosgrave, Emma Bennison, Chun Chen, Philippa D Hepplewhite, Christopher M Morris
Mitochondrial dysfunction within the cell bodies of substantia nigra neurons is prominent in both ageing and Parkinson's disease. The loss of dopaminergic substantia nigra neurons in Parkinson's disease is associated with loss of synapses within the striatum, and this may precede neuronal loss. We investigated whether mitochondrial changes previously reported within substantia nigra neurons were also seen within the synapses and axons of these neurons. Using high resolution quantitative fluorescence immunohistochemistry we determined mitochondrial density within remaining dopaminergic axons and synapses, and quantified deficiencies of mitochondrial Complex I and Complex IV in these compartments...
2018: NPJ Parkinson's Disease
Siddharth Kharkar, Jonathan Richard Ellenbogen, Michael Samuel, Alexandra Rizos, Monty Silverdale, K Ray Chaudhuri, Keyoumars Ashkan
INTRODUCTION: Deep brain stimulation (DBS) markedly improves motor function in advanced Parkinson's disease (PD), but its effect on sleep is less clear. PATIENTS AND METHODS: Forty PD patients who had subthalamic DBS (STN-DBS) were identified from an on-going non-motor naturalistic longitudinal study (NILS). All patients were followed up for at least 6 months, 26 patients had a 1 year follow-up. A total PDSS score of 100 or less, a score in any PDSS-item of 6 or less, and a Epworth score of 10 or more were classified as being significant...
2018: NPJ Parkinson's Disease
Courtney C Walton, Loren Mowszowski, Moran Gilat, Julie M Hall, Claire O'Callaghan, Alana J Muller, Matthew Georgiades, Jennifer Y Y Szeto, Kaylena A Ehgoetz Martens, James M Shine, Sharon L Naismith, Simon J G Lewis
The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks...
2018: NPJ Parkinson's Disease
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
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
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
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
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
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
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
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
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
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
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
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
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