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Parkinson Disease: HELP
Articles from Amsterdam
Based on 341 articles published since 2009
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These are the 341 published articles about Parkinson Disease that originated from Amsterdam during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14
1 Guideline European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain 2018

Nobili, F / Arbizu, J / Bouwman, F / Drzezga, A / Agosta, F / Nestor, P / Walker, Z / Boccardi, M / Anonymous911112. ·Department of Neuroscience (DINOGMI), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy. · Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain. · Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. · Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Cologne, Germany. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. · German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. · Division of Psychiatry, Essex Partnership University NHS Foundation Trust, University College London, London, UK. · Department of Psychiatry, Laboratoire du Neuroimagerie du Vieillissement (LANVIE), University of Geneva, Geneva, Switzerland. ·Eur J Neurol · Pubmed #29932266.

ABSTRACT: BACKGROUND AND PURPOSE: Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured. METHODS: Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion. RESULTS: Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline. CONCLUSIONS: Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.

2 Editorial The Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) ERS Clinical Research Collaboration: a new dawn in asthma research. 2018

Djukanovic, Ratko / Adcock, Ian M / Anderson, Gary / Bel, Elisabeth H / Canonica, Giorgio W / Cao, Hui / Chung, Kian Fan / Davies, Donna E / Genton, Céline / Gibson-Latimer, Toni / Hamerlijnck, Dominique / Heuvelin, Elise / Louis, Renaud / Korn, Stephanie / Kots, Maxim / Kwon, Namhee / Naddaf, Riad / Wagers, Scott S / Anonymous5211461 / Anonymous5221461. ·NIHR Southampton Respiratory Biomedical Research Unit, Faculty of Medicine, University Southampton, Southampton, UK. · National Heart and Lung Institute, Imperial College, London, London, UK. · Health Research Centre, University of Melbourne, Melbourne, Australia. · Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Personalized Medicine Clinic, Asthma and Allergy, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy and SANI-Severe Asthma Network Italy. · Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. · Airway Disease, National Heart and Lung Institute, Imperial College London, London, UK. · Institute for Health Research Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences, University of Southampton, Southampton, UK. · European Respiratory Society, Lausanne, Switzerland. · European Lung Foundation, Sheffield, UK. · Asthma UK, London, UK. · Dutch Lung Foundation, Amersfoort, The Netherlands. · EUPATI, Brussels, Belgium. · Atini, Amsterdam, The Netherlands. · Dept of Pulmonary Medicine, Centre Hospitalier Universitaire (CHU), Liege University, Liege, Belgium. · Universitätsmedizin Mainz, Mainz, Germany. · Chiesi Farmaceutici, Global Clinical Development, Parma, Italy. · Respiratory Medical Franchise, GSK, Brentford, UK. · TEVA Pharmaceuticals, Amsterdam, The Netherlands. · BioSci Consulting, Maasmechelen, Belgium. ·Eur Respir J · Pubmed #30498052.

ABSTRACT: -- No abstract --

3 Review The effects of cognitive behavioral and mindfulness-based therapies on psychological distress in patients with multiple sclerosis, Parkinson's disease and Huntington's disease: Two meta-analyses. 2019

Ghielen, Ires / Rutten, Sonja / Boeschoten, Rosa E / Houniet-de Gier, Marieke / van Wegen, Erwin E H / van den Heuvel, Odile A / Cuijpers, Pim. ·Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, de Boelelaan 1117, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, de Boelelaan 1117, Amsterdam, The Netherlands. Electronic address: i.ghielen@vumc.nl. · Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, de Boelelaan 1117, Amsterdam, The Netherlands. · Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Public Health, de Boelelaan 1117, Amsterdam, The Netherlands. · Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Psychology, Amsterdam, The Netherlands. · Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Rehabilitation Medicine, MOVE Research Institute Amsterdam, de Boelelaan, 1118, Amsterdam, The Netherlands. · Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, de Boelelaan 1117, Amsterdam, The Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, de Boelelaan 1117, Amsterdam, The Netherlands. · Amsterdam Public Health Research Institute, Department of Clinical Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, The Netherlands; Department of Clinical, Neuro & Developmental Psychology, VU University, Amsterdam, The Netherlands. ·J Psychosom Res · Pubmed #31126411.

ABSTRACT: OBJECTIVE: Psychological distress has a high impact on quality of life in patients with multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Studies have shown that cognitive behavioral therapy (CBT) and mindfulness-based therapies (MBTs) are successful in reducing psychological distress in patients with anxiety, depressive, and chronic somatic disorders. We aimed to investigate the effectiveness of these therapies in MS, PD, and HD patients. METHODS: We performed a comprehensive literature search in PubMed, PsycINFO, Embase and the Cochrane Central Register of Controlled Trials up to March 2018. Randomized controlled trials (RCTs) investigating a CBT or MBT and reporting psychological outcome measures were included. Two separate meta-analyses were performed; one on studies comparing psychological therapy with a treatment as usual or waitlist condition and one on studies with active treatment control conditions. RESULTS: The first meta-analysis (N = 12 studies, 8 in MS and 4 in PD populations) showed a significant effect size of g = 0.51 in reducing psychological distress. The second meta-analysis (N = 7 studies, in MS populations) showed a mean effect size of g = 0.36. No RCTs were found in HD populations. The overall quality of the included studies was low and considerable heterogeneity was found. No evidence was found for publication bias. CONCLUSION: CBT and MBTs have a small to moderate effect on reducing psychological distress in patients with PD and MS. However, more research with better methodological quality and larger study samples is warranted, especially in HD patient populations.

4 Review Entanglement of Genetics and Epigenetics in Parkinson's Disease. 2019

van Heesbeen, H J / Smidt, Marten P. ·Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands. ·Front Neurosci · Pubmed #30983962.

ABSTRACT: Parkinson disease (PD) is a common neurodegenerative disorder that progresses with age, with an increasing number of symptoms. Some of the efforts to understand PD progression have been focusing on the regulation of epigenetic mechanisms, that generally include small molecular modifications to the DNA and histones that are essential for regulating gene activity. Here, we have pointed out difficulties to untangle genetic and epigenetic mechanisms, and reviewed several studies that have aimed for untangling. Some of those have enabled more solid claims on independent roles for epigenetic mechanisms. Hereby, evidence that specific DNA hydroxymethylation, global hyperacetylation, and histone deacetylase (HDAC) dependent regulation of

5 Review A systematic review of MEG-based studies in Parkinson's disease: The motor system and beyond. 2019

Boon, Lennard I / Geraedts, Victor J / Hillebrand, Arjan / Tannemaat, Martijn R / Contarino, Maria Fiorella / Stam, Cornelis J / Berendse, Henk W. ·Amsterdam UMC, location VUmc, Department of Neurology, Amsterdam Neuroscience, Amsterdam, the Netherlands. · Amsterdam UMC, location VUmc, Department of Clinical Neurophysiology and Magnetoencephalography Center, Amsterdam Neuroscience, Amsterdam, the Netherlands. · Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Neurology, Haga Teaching Hospital, The Hague, The Netherlands. ·Hum Brain Mapp · Pubmed #30843285.

ABSTRACT: Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD-affected brain. The available articles could be separated into motor network-focused and whole-brain focused studies. Motor network studies revealed PD-related changes in beta band (13-30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole-brain studies PD-related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD-specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care.

6 Review 22q11.2 Deletion Syndrome-Associated Parkinson's Disease. 2019

Boot, Erik / Bassett, Anne S / Marras, Connie. ·The Dalglish Family 22q Clinic for Adults, and Department of Psychiatry University Health Network Toronto Ontario Canada. · 's Heeren Loo Zorggroep Amersfoort The Netherlands. · Department of Nuclear Medicine, Academic Medical Center Amsterdam The Netherlands. · Toronto General Hospital Research Institute and Division of Cardiology, Department of Medicine University Health Network Toronto Ontario Canada. · Clinical Genetics Research Program and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health Toronto Ontario Canada. · Department of Psychiatry University of Toronto Toronto Ontario Canada. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease Research Toronto Western Hospital and University of Toronto Toronto Ontario Canada. · Division of Neurology, Department of Medicine University of Toronto Toronto Ontario Canada. ·Mov Disord Clin Pract · Pubmed #30746410.

ABSTRACT: Background: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early-onset Parkinson's disease (PD). Methods: We review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications. Results: 22q11.2DS-associated PD is responsible for approximately 0.5% of early-onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS-associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS-associated PD show a good response to levodopa. Conclusions: Further recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease-modifying treatments.

7 Review Movement Disorders in Treatable Inborn Errors of Metabolism. 2019

Ebrahimi-Fakhari, Darius / Van Karnebeek, Clara / Münchau, Alexander. ·Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Departments of Pediatrics and Clinical Genetics, Amsterdam University Medical Centres, Amsterdam, The Netherlands. · Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. ·Mov Disord · Pubmed #30557456.

ABSTRACT: There are several hundred single-gene disorders that we classify as inborn errors of metabolism. Inborn errors of metabolism are often rare and highly heterogeneous multisystem diseases with non-neurological and neurological manifestations, commonly with onset during childhood. Movement disorders are among the most common neurological problems in inborn errors of metabolism, but, in many cases, remain poorly defined. Although movement disorders are usually not the only and often not the presenting symptom, their recognition can facilitate a diagnosis. Movement disorders contribute substantially to the morbidity in inborn errors of metabolism and can have a significant impact on quality of life. Common metabolic movement disorders include the monoamine neurotransmitter disorders, disorders of amino and organic acid metabolism, metal storage disorders, lysosomal storage disorders, congenital disorders of autophagy, disorders of creatine metabolism, vitamin-responsive disorders, and disorders of energy metabolism. Importantly, disease-modifying therapies exist for a number of inborn errors of metabolism, and early recognition and treatment can prevent irreversible CNS damage and reduce morbidity and mortality. A phenomenology-based approach, based on the predominant movement disorder, can facilitate a differential diagnosis and can guide biochemical, molecular, and imaging testing. The complexity of metabolic movement disorders demands an interdisciplinary approach and close collaboration of pediatric neurologists, neurologists, geneticists, and experts in metabolism. In this review, we develop a general framework for a phenomenology-based approach to movement disorders in inborn errors of metabolism and discuss an approach to identifying the "top ten" of treatable inborn errors of metabolism that present with movement disorders-diagnoses that should never be missed. © 2018 International Parkinson and Movement Disorder Society.

8 Review Proteomics of neurodegenerative diseases: analysis of human post-mortem brain. 2019

Li, K W / Ganz, Andrea B / Smit, August B. ·Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands. ·J Neurochem · Pubmed #30289976.

ABSTRACT: Dementias are prevalent brain disorders in the aged population. Dementias pose major socio-medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These studies confirmed known cellular changes, and in addition identified novel proteins that may underlie distinct aspects of the diseases. This article is part of the special issue "Proteomics".

9 Review Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests. 2018

Hoogland, Jeroen / van Wanrooij, Lennard L / Boel, Judith A / Goldman, Jennifer G / Stebbins, Glenn T / Dalrymple-Alford, John C / Marras, Connie / Adler, Charles H / Junque, Carme / Pedersen, Kenn F / Mollenhauer, Brit / Zabetian, Cyrus P / Eslinger, Paul J / Lewis, Simon J G / Wu, Ruey-Meei / Klein, Martin / Rodriguez-Oroz, Maria C / Cammisuli, Davide M / Barone, Paolo / Biundo, Roberta / de Bie, Rob M A / Schmand, Ben A / Tröster, Alexander I / Burn, David J / Litvan, Irene / Filoteo, J Vincent / Geurtsen, Gert J / Weintraub, Daniel / Anonymous2521562. ·Department of Neurology, Academic Medical Center Amsterdam, The Netherlands. · Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Rush University Medical Center, Chicago, Illinois, USA. · New Zealand Brain Research Institute, Brain Research New Zealand - Rangahau Roro Aotearoa, Christchurch, New Zealand. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. · Arizona Parkinson's Disease Consortium, Mayo Clinic Arizona, Scottsdale, Arizona, USA and Banner Sun Health Research Institute, Sun City, Arizona, USA. · Department of Medicine, Faculty of Medicine, IDIBAPS, University of Barcelona, Barcelona, Spain. · The Norwegian Centre for Movement Disorders, Department of Neurology, and Memory Clinic, Stavanger University Hospital, Stavanger, Norway. · Paracelsus-Elena-Klinik, Kassel, Germany, and University Medical Center Goettingen, Department of Neurology, Goettingen, Germany. · VA Puget Sound Health Care System and Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. · Department of Neurology, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA. · Brain & Mind Centre, The University of Sydney, Sydney, Australia. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Medical Psychology, section Medical Neuropsychology, VU University Medical Center, Amsterdam, The Netherlands. · Department of Neurology, Hospital Donostia, Donostia, San Sebastian and Ikerbasque, Basque Foundation for Science, Bilbao, Spain. · Fifth Local Sanitary Unit, Hospital Psychology, Pisa, Italy and Department of Surgical, Medical, Molecular, and Critical Area Pathology, Pisa University School of Medicine, Pisa, Italy. · Center for Neurodegenerative Diseases (CEMAND) Neuroscience Section, Department of Medicine University of Salerno, Salerno, Italy. · San Camillo Hospital IRCCS, Venice, Italy. · Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Psychology, University of Amsterdam, The Netherlands. · Department of Clinical Neuropsychology and Center for Neuromodulation, Barrow Neurological Institute, Phoenix, Arizona, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Neurosciences University of California San Diego, Parkinson and Other Movement Disorders Center, San Diego, California, USA. · Department of Psychiatry, University of California San Diego, and VA San Diego Healthcare System, San Diego, California, USA. · Departments of Psychiatry and Neurology, University of Pennsylvania School of Medicine, and Parkinson's Disease and Mental Illness Research, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. ·Mov Disord · Pubmed #30216541.

ABSTRACT: BACKGROUND: Numerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies. METHODS: Data from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2-step meta-analytic approach using standardized scores compared performance in PD with normative data. RESULTS: Pooled estimates of the differences between PD and site-specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between-study variability that could not be accounted for and led to inconclusive results. CONCLUSIONS: Normed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site-specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society.

10 Review Neurofilaments as biomarkers in neurological disorders. 2018

Khalil, Michael / Teunissen, Charlotte E / Otto, Markus / Piehl, Fredrik / Sormani, Maria Pia / Gattringer, Thomas / Barro, Christian / Kappos, Ludwig / Comabella, Manuel / Fazekas, Franz / Petzold, Axel / Blennow, Kaj / Zetterberg, Henrik / Kuhle, Jens. ·Department of Neurology, Medical University of Graz, Graz, Austria. michael.khalil@medunigraz.at. · Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, Netherlands. · Department of Neurology, Ulm University Hospital, Ulm, Germany. · Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Department of Health Sciences, University of Genoa, Genoa, Italy. · Ospedale Policlinico San Martino IRCCS, Genoa, Italy. · Department of Neurology, Medical University of Graz, Graz, Austria. · Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. · Unit of Clinical Neuroimmunology, Department of Neurology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain. · UCL Institute of Neurology, Department of Molecular Neurosciences, Moorfields Eye Hospital and The National Hospital for Neurology and Neurosurgery, London, UK. · Departments of Neurology, Ophthalmology and Expertise Center for Neuro-ophthalmology, Amsterdam UMC, Amsterdam, Netherlands. · Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. · Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. · Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK. · UK Dementia Research Institute at UCL, London, UK. · Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. jens.kuhle@usb.ch. ·Nat Rev Neurol · Pubmed #30171200.

ABSTRACT: Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.

11 Review Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia. 2018

Walker, Zuzana / Gandolfo, Federica / Orini, Stefania / Garibotto, Valentina / Agosta, Federica / Arbizu, Javier / Bouwman, Femke / Drzezga, Alexander / Nestor, Peter / Boccardi, Marina / Altomare, Daniele / Festari, Cristina / Nobili, Flavio / Anonymous2310976. ·Division of Psychiatry, University College London, London, UK. z.walker@ucl.ac.uk. · St Margaret's Hospital, Essex Partnership University NHS Foundation Trust, Epping, CM16 6TN, UK. z.walker@ucl.ac.uk. · Alzheimer Operative Unit, IRCCS S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, University Hospitals of Geneva, Geneva University, Geneva, Switzerland. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. · Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain. · Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. · Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Cologne, Germany. · German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. · Queensland Brain Institute, University of Queensland and the Mater Hospital, Brisbane, Australia. · LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, University of Geneva, Geneva, Switzerland. · LANE - Laboratory of Alzheimer's Neuroimaging & Epidemiology, IRCCS S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. · Department of Neuroscience (DINOGMI), University of Genoa & Clinical Neurology Polyclinic IRCCS San Martino-IST, Genoa, Italy. flaviomariano.nobili@hsanmartino.it. ·Eur J Nucl Med Mol Imaging · Pubmed #29779045.

ABSTRACT: PURPOSE: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson's disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. METHODS: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. RESULTS: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. CONCLUSION: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia.

12 Review International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. 2018

Fox, Susan H / Katzenschlager, Regina / Lim, Shen-Yang / Barton, Brandon / de Bie, Rob M A / Seppi, Klaus / Coelho, Miguel / Sampaio, Cristina / Anonymous1591441. ·Edmund J. Safra Program, Movement Disorder Clinic, Toronto Western Hospital, Toronto, Ontario, Canada. · University of Toronto Department of Medicine, Toronto, Ontario, Canada. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital, Vienna, Austria. · Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, University of Malaya, Kuala Lumpur, Malaysia. · Rush University Medical Center, Chicago, Illinois, USA. · Jesse Brown VA Medical Center, Chicago, Illinois, USA. · Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Santa Maria Hospital, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal. · Cure Huntington's Disease Initiative (CHDI) Management/CHDI Foundation, Princeton, NJ, USA. · Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal. ·Mov Disord · Pubmed #29570866.

ABSTRACT: OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

13 Review The neurobiology of impulse control disorders in Parkinson's disease: from neurotransmitters to neural networks. 2018

Vriend, Chris. ·Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. c.vriend@vumc.nl. · Department of Anatomy & Neurosciences, VU University Medical Center, p/a sec. ANW O|2, PO Box 7007, 1007MB BT, Amsterdam, the Netherlands. c.vriend@vumc.nl. · Amsterdam Neuroscience, Amsterdam, The Netherlands. c.vriend@vumc.nl. ·Cell Tissue Res · Pubmed #29383446.

ABSTRACT: Impulse control disorders (ICD) are common neuropsychiatric disorders that can arise in Parkinson's disease (PD) patients after commencing dopamine replacement therapy. Approximately 15% of all patients develop these disorders and many more exhibit subclinical symptoms of impulsivity. ICD is thought to develop due to an interaction between the use of dopaminergic medication and an as yet unknown neurobiological vulnerability that either pre-existed before PD onset (possibly genetic) or is associated with neural alterations due to the PD pathology. This review discusses genes, neurotransmitters and neural networks that have been implicated in the pathophysiology of ICD in PD. Although dopamine and the related reward system have been the main focus of research, recently, studies have started to look beyond those systems to find new clues to the neurobiological underpinnings of ICD and come up with possible new targets for treatment. Studies on the whole-brain connectome to investigate the global alterations due to ICD development are currently lacking. In addition, there is a dire need for longitudinal studies that are able to disentangle the contributions of individual (genetic) traits and secondary effects of the PD pathology and chronic dopamine replacement therapy to the development of ICD in PD.

14 Review Global scales for cognitive screening in Parkinson's disease: Critique and recommendations. 2018

Skorvanek, Matej / Goldman, Jennifer G / Jahanshahi, Marjan / Marras, Connie / Rektorova, Irena / Schmand, Ben / van Duijn, Erik / Goetz, Christopher G / Weintraub, Daniel / Stebbins, Glenn T / Martinez-Martin, Pablo / Anonymous2421195. ·Department of Neurology, Safarik University, Kosice, Slovakia. · Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovakia. · Rush University Medical Center, Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Chicago, Illinois, USA. · Sobell Department of Motor Neuroscience & Movement Disorders and the National Hospital for Neurology & Neurosurgery, London, UK. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada. · Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC, Masaryk University, Brno, Czech Republic. · Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, Leiden University Medical Centre, Leiden, and Centre of Mental Health Care Delfland, Delft, Netherlands. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Parkinson's Disease and Mental Health Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. · National Centre of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #29168899.

ABSTRACT: BACKGROUND: Cognitive impairment is a common nonmotor manifestation of Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1 or more of the cognitive domains to severe dementia. The International Parkinson and Movement Disorder Society commissioned the assessment of the clinimetric properties of cognitive rating scales measuring global cognitive performance in PD to make recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the scales used to assess global cognitive performance in PD, and the identified scales were reviewed and rated as "recommended," "recommended with caveats," "suggested," or "listed" by the panel using previously established criteria. RESULTS: A total of 12 cognitive scales were included in this review. Three scales, the Montreal Cognitive Assessment, the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease-Cognitive Rating Scale, were classified as "recommended." Two scales were classified as "recommended with caveats": the Mini-Mental Parkinson, because of limited coverage of executive abilities, and the Scales for Outcomes in Parkinson's Disease-Cognition, which has limited data on sensitivity to change. Six other scales were classified as "suggested" and 1 scale as "listed." CONCLUSIONS: Because of the existence of "recommended" scales for assessment of global cognitive performance in PD, this task force suggests that the development of a new scale for this purpose is not needed at this time. However, global cognitive scales are not a substitute for comprehensive neuropsychological testing. © 2017 International Parkinson and Movement Disorder Society.

15 Review Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson's disease: A systematic review and meta-analysis. 2017

Eusebi, Paolo / Giannandrea, David / Biscetti, Leonardo / Abraha, Iosief / Chiasserini, Davide / Orso, Massimiliano / Calabresi, Paolo / Parnetti, Lucilla. ·Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy. · Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, Perugia, Italy. · Neurology Unit, Department of Specialist Medicine, USL Umbria 1 North area, Gubbio and Gualdo Tadino Hospital, Gubbio, Italy. · Oncoproteomics Laboratory, VU University Medical Center, Amsterdam, The Netherlands. · IRCCS Fondazione Santa Lucia, Rome, Italy. ·Mov Disord · Pubmed #28880418.

ABSTRACT: BACKGROUND: The accumulation of misfolded α-synuclein aggregates is associated with PD. However, the diagnostic value of the α-synuclein levels in CSF is still under investigation. METHODS: A comprehensive search of the literature was performed, yielding 34 studies eligible for meta-analysis. We included studies that reported data on CSF total, oligomeric and phosphorylated α-synuclein in patients with PD and healthy participants, neurological controls, or other parkinsonisms. Standardized mean differences were pooled using random-effects models, and heterogeneity was reported as I RESULTS: Concentrations of α-synuclein species in PD did not show significant differences with respect to the levels found in other parkinsonisms. Total α-synuclein was significantly reduced in PD when compared with controls (standardized mean differences -0.48; P < .001, I CONCLUSION: Most of the studies were at high risk of bias and have concerns regarding applicability. Diagnostic performance of CSF α-synuclein species is still below what would be considered acceptable for their introduction in clinical practice. Future research should focus on combining α-synuclein species with other biochemical markers as well on improving the standardization of current assays. © 2017 International Parkinson and Movement Disorder Society.

16 Review Therapeutic potential of autophagy-enhancing agents in Parkinson's disease. 2017

Moors, Tim E / Hoozemans, Jeroen J M / Ingrassia, Angela / Beccari, Tommaso / Parnetti, Lucilla / Chartier-Harlin, Marie-Christine / van de Berg, Wilma D J. ·Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. t.moors@vumc.nl. · Department of Pathology, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy. · Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy. · UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, University of Lille, Lille, F-59000, France. · Inserm, UMR-S 1172, Team "Early stages of Parkinson's disease", F-59000, Lille, France. ·Mol Neurodegener · Pubmed #28122627.

ABSTRACT: Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson's Disease (PD). Genetic studies have identified mutations in genes encoding for components of the autophagy-lysosomal pathway (ALP), including glucosidase beta acid 1 (GBA1), that are associated with increased risk for developing PD. Observations in PD brain tissue suggest an aberrant regulation of autophagy associated with the aggregation of α-synuclein (α-syn). As autophagy is one of the main systems involved in the proteolytic degradation of α-syn, pharmacological enhancement of autophagy may be an attractive strategy to combat α-syn aggregation in PD. Here, we review the potential of autophagy enhancement as disease-modifying therapy in PD based on preclinical evidence. In particular, we provide an overview of the molecular regulation of autophagy and targets for pharmacological modulation within the ALP. In experimental models, beneficial effects on multiple pathological processes involved in PD, including α-syn aggregation, cell death, oxidative stress and mitochondrial dysfunction, have been demonstrated using the autophagy enhancers rapamycin and lithium. However, selectivity of these agents is limited, while upstream ALP signaling proteins are involved in many other pathways than autophagy. Broad stimulation of autophagy may therefore cause a wide spectrum of dose-dependent side-effects, suggesting that its clinical applicability is limited. However, recently developed agents selectively targeting core ALP components, including Transcription Factor EB (TFEB), lysosomes, GCase as well as chaperone-mediated autophagy regulators, exert more specific effects on molecular pathogenetic processes causing PD. To conclude, the targeted manipulation of downstream ALP components, rather than broad autophagy stimulation, may be an attractive strategy for the development of novel pharmacological therapies in PD. Further characterization of dysfunctional autophagy in different stages and molecular subtypes of PD in combination with the clinical translation of downstream autophagy regulation offers exciting new avenues for future drug development.

17 Review Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope? 2017

Carvalho, Andreia Neves / Firuzi, Omidreza / Gama, Maria Joao / Horssen, Jack van / Saso, Luciano. ·Instituto de Investigação do Medicamento (iMED.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof Gama Pinto, 1649-003, Lisboa, Portugal. · Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. · Instituto de Investigação do Medicamento (iMED.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. · Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands. · Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy. ·Curr Drug Targets · Pubmed #27033198.

ABSTRACT: Oxidative stress is a pathological feature common to a multitude of neurological diseases. The production of reactive oxygen species (ROS) is the main mechanism underlying this cellular redox imbalance. Antioxidants protect biological targets against ROS, therefore, they have been considered as attractive potential therapeutic agents to counteract ROS-mediated neuronal damage. However, despite encouraging in vitro and preclinical in vivo data, the clinical efficacy of antioxidant treatment strategies is marginal and most clinical trials using antioxidants as therapeutic agents in neurodegenerative diseases have yielded disappointing outcomes. This might in part be due to the need of adjustment in concentrations and time parameters between preclinical studies and clinical settings. Moreover new efficient delivery methods need to be investigated, particularly taking into account that a successful therapeutic agent for neurological diseases should readily cross the blood-brain barrier (BBB). In that sense, the use of compounds that cross the BBB and boost the endogenous antioxidant defense machinery, by activating for instance the Nrf2 pathway, or compounds that are able to modulate ROS production, such as NOX enzyme inhibitors, seems to represent a more promising approach to combat oxidative stress in the central nervous system (CNS). Here we present a brief overview of the main players in oxidative stress and outline evidences of their involvement in Parkinson's disease, Alzheimer's disease, Huntington's disease and multiple sclerosis. Finally, we review and critically discuss the potential of antioxidants as therapeutics for central nervous system disorders with a special focus on emerging novel therapeutic strategies.

18 Review Intestinal dysfunction in Parkinson's disease: Lessons learned from translational studies and experimental models. 2016

Pellegrini, C / Colucci, R / Antonioli, L / Barocelli, E / Ballabeni, V / Bernardini, N / Blandizzi, C / de Jonge, W J / Fornai, M. ·Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy. · Department of Pharmacy, University of Parma, Parma, Italy. · Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. ·Neurogastroenterol Motil · Pubmed #27611012.

ABSTRACT: BACKGROUND: Symptoms of digestive dysfunction in patients with Parkinson's disease (PD) occur at all stages of the disease, often preceding the onset of central motor symptoms. On the basis of these PD-preceding symptoms it has been proposed that PD could initiate in the gut, and that the presence of alpha-synuclein aggregates, or Lewy bodies in the enteric nervous system might represent one of the earliest signs of the disease. Following this hypothesis, much research has been focused on the digestive tract to unravel the mechanisms underlying the onset and progression of PD, with particular attention to the role of alterations in enteric neurotransmission in the pathophysiology of intestinal motility disturbances. There is also evidence suggesting that the development of central nigrostriatal neurodegeneration is associated with the occurrence of gut inflammation, characterized by increments of tissue pro-inflammatory markers and oxidative stress, which might support conditions of bowel neuromotor abnormalities. PURPOSE: The present review intends to provide an integrated and critical appraisal of the available knowledge on the alterations of enteric neuromuscular pathways regulating gut motor activity both in humans and preclinical models of PD. Moreover, we will discuss the possible involvement of neuro-immune mechanisms in the pathophysiology of aberrant gastrointestinal gut transit and neuromuscular activity in the small and large bowel.

19 Review Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease. 2016

Ferrer, Isidro / Garcia-Esparcia, Paula / Carmona, Margarita / Carro, Eva / Aronica, Eleonora / Kovacs, Gabor G / Grison, Alice / Gustincich, Stefano. ·Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, University of BarcelonaBarcelona, Spain; Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de LlobregatBarcelona, Spain. · Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Neuroscience Group, Research Institute HospitalMadrid, Spain. · Department of Neuropathology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands. · Institute of Neurology, Medical University of Vienna Vienna, Austria. · Scuola Internazionale Superiore di Studi Avanzati (SISSA), Area of Neuroscience Trieste, Italy. ·Front Aging Neurosci · Pubmed #27458372.

ABSTRACT: Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

20 Review Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease. 2016

Mahlknecht, Philipp / Pechlaner, Raimund / Boesveldt, Sanne / Volc, Dieter / Pinter, Bernardette / Reiter, Eva / Müller, Christoph / Krismer, Florian / Berendse, Henk W / van Hilten, Jacobus J / Wuschitz, Albert / Schimetta, Wolfgang / Högl, Birgit / Djamshidian, Atbin / Nocker, Michael / Göbel, Georg / Gasperi, Arno / Kiechl, Stefan / Willeit, Johann / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands. · Divisions of Human Nutrition, Wageningen University, Wageningen, The Netherlands. · Study Center Confraternitaet-PKJ Vienna, Vienna, Austria. · Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Applied Systems Research and Statistics, Johannes Kepler University Linz, Linz, Austria. · Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. klaus.seppi@uki.at. ·Mov Disord · Pubmed #27159493.

ABSTRACT: INTRODUCTION: The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD. METHODS: Odor identification with the 16-item Sniffin' Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts. RESULTS: Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve ≥0.90; sensitivities ≥83.3%; specificities ≥82.0%) and from non-PD patients (areas under the curve ≥0.91; sensitivities ≥84.1%; specificities ≥84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%). CONCLUSIONS: Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

21 Review Lysosomal Dysfunction and α-Synuclein Aggregation in Parkinson's Disease: Diagnostic Links. 2016

Moors, Tim / Paciotti, Silvia / Chiasserini, Davide / Calabresi, Paolo / Parnetti, Lucilla / Beccari, Tommaso / van de Berg, Wilma D J. ·Department of Anatomy and Neurosciences, Section Quantitative Morphology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. · Department of Pharmaceutical Sciences, Section of Nutrition and Food Science, University of Perugia, Perugia, Italy. · Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy. · Fondazione Santa Lucia-Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy. ·Mov Disord · Pubmed #26923732.

ABSTRACT: Lysosomal impairment is increasingly recognized as a central event in the pathophysiology of PD. Genetic associations between lysosomal storage disorders, including Gaucher disease and PD, highlight common risk factors and pathological mechanisms. Because the autophagy-lysosomal system is involved in the intralysosomal hydrolysis of dysfunctional proteins, lysosomal impairment may contribute to α-synuclein aggregation in PD. The degradation of α-synuclein is a complex process involving different proteolytic mechanisms depending on protein burden, folding, posttranslational modifications, and yet unknown factors. In this review, evidence for lysosomal dysfunction in PD and its intimate relationship with α-synuclein aggregation are discussed, after which the question of whether lysosomal proteins may serve as diagnostic biomarkers for PD is addressed. Changes in lysosomal enzymes, such as reduced glucocerebrosidase and cathepsin levels, have been observed in affected brain regions in PD patients. The detection of lysosomal proteins in CSF may provide a read-out of lysosomal dysfunction in PD and holds promise for the development of diagnostic PD biomarkers. Initial PD biomarker studies demonstrated altered lysosomal enzyme activities in CSF of PD patients when compared with controls. However, CSF lysosomal enzyme activities alone could not discriminate between PD patients and controls. The combination of CSF lysosomal markers with α-synuclein species and indicators of mitochondrial dysfunction, inflammation, and other pathological proteins in PD may be able to facilitate a more accurate diagnosis of PD. Further CSF biomarker studies are needed to investigate the utility of CSF lysosomal proteins as measures of disease state and disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.

22 Review Systematic Review of the Relationship between Vitamin D and Parkinson's Disease. 2016

Rimmelzwaan, Lisanne M / van Schoor, Natasja M / Lips, Paul / Berendse, Henk W / Eekhoff, Elisabeth M W. ·Department of Internal Medicine section Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. · Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. · Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands. ·J Parkinsons Dis · Pubmed #26756741.

ABSTRACT: BACKGROUND: Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD. OBJECTIVE: Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies. METHODS: A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies. RESULTS: A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory. CONCLUSION: The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD.

23 Review [Hypersexuality and other impulse control disorders in Parkinson's disease]. 2016

Nelis, Elise A / Berendse, Henk W / van den Heuvel, Odile A. ·VU medisch centrum, Amsterdam. ·Ned Tijdschr Geneeskd · Pubmed #26732226.

ABSTRACT: Impulse control disorders (ICD) in Parkinson's disease (PD) pose a therapeutic challenge. This article provides a description of the symptoms and management strategies of ICD in PD. We present two men aged 52 and 69 with ICD, especially hypersexuality, in response to dopaminergic medication. In the first case the symptoms of hypersexuality and gambling decreased after reducing the dose of the dopamine-agonist. In the second case the hypersexuality symptoms decreased after addition of naltrexon. It is important to recognize the symptoms of ICD in PD because of the large impact on social and relational functioning. It is of great importance to repeatedly ask the patient and their partner about these symptoms, since feelings of shame and guild hamper spontaneous report. The first step of treatment consists of reducing the dose of dopaminergic medication and/or to switch from dopamine-agonist to levodopa. Although the research on effective treatment options has been limited so far, treatment alternatives from the addiction field seem promising.

24 Review Apathy in Parkinson's disease: A systematic review and meta-analysis. 2015

den Brok, Melina G H E / van Dalen, Jan Willem / van Gool, Willem A / Moll van Charante, Eric P / de Bie, Rob M A / Richard, Edo. ·Department of Neurology, Academic Medical Center Amsterdam, The Netherlands. · Department of General Practise, Academic Medical Center Amsterdam, The Netherlands. · Department of Neurology, Radboud University Medical Center Nijmegen, The Netherlands. ·Mov Disord · Pubmed #25787145.

ABSTRACT: Apathy is a frequently reported neuropsychiatric symptom in Parkinson's disease (PD), but its prevalence and clinical correlates are debated. We aimed to address these issues by conducting a systematic review and meta-analysis. Embase, Medline/PubMed, and PsychINFO databases were searched for relevant studies. Data were extracted by two independent observers, using predefined extraction forms tailored specifically to the research question. From 1,702 titles and abstracts, 23 studies were selected. Meta-analysis showed a prevalence of apathy in PD of 39.8% (n = 5,388, 905% CI 34.6-45.0%). Apathy was associated with higher age (3.3 years, 95% CI = 1.7-4.9), lower mean Mini-Mental State Evaluation (MMSE) score (-1.4 points, 95% CI = -2.1 to -0.8), an increased risk of co-morbid depression (relative risk [RR] = 2.3, 95% CI = 1.9-2.8), higher Unified Parkinson's Disease Rating Scale (UPDRS) motor score (6.5 points, 95% CI = 2.6-10.3), and more severe disability (Hedges-G = 0.5, 95% CI = 0.3-0.6). Half of the patients with apathy had concomitant depression (57.2%, 95% CI = 49.4-64.9%), and this estimate was similar after exclusion of patients with cognitive impairment (52.5%, 95% CI = 42.2%-62.8%). In conclusion, we found that apathy affects almost 40% of patients with PD. Several factors influence reported prevalence rates, contributing to the considerable heterogeneity in study results. Half of patients with apathy do not suffer from concomitant depression or cognitive impairment, confirming its status as a separate clinical syndrome in PD. The pervasiveness of apathy in PD warrants research into its treatment, although different underlying pathophysiological mechanisms may require different treatment strategies. Treatment of apathy could improve patient quality of life, reduce caregiver burden, alleviate disability by increasing motivation for self-care, and reduce cognitive impairment by improving executive functioning.

25 Review The human histaminergic system in neuropsychiatric disorders. 2015

Shan, Ling / Bao, Ai-Min / Swaab, Dick F. ·Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China; Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, The Netherlands; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA; Neurobiology Research, Veterans Administration Greater Los Angeles Health Care System, 16111 Plummer Street, North Hills, CA 91343, USA. · Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: baoaimin@zju.edu.cn. · Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, The Netherlands. ·Trends Neurosci · Pubmed #25575625.

ABSTRACT: Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary nucleus, from where they project to many brain areas. The histaminergic system is involved in basic physiological functions, such as the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, cognition, and attention, which are all severely affected in neuropsychiatric disorders. Here, we present recent postmortem findings on the alterations in this system in neuropsychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight the need to validate animal models for these diseases and also for Tourette's syndrome (TS) in relation to alterations in the histaminergic system. Moreover, we discuss the potential for, and concerns over, the use of novel histamine 3 receptor (H3R) antagonists/inverse agonists as treatment for such disorders.

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