23 results match your criteria: "Kassel - both in Germany (B.M.); and Coeruleus Clinical Sciences[Affiliation]"
Article Synopsis
- * Recent efforts to stop smoking haven't been put into action yet, and it’s important to see what could happen if smoking rates stay the same or improve.
- * Researchers used models to predict health outcomes by 2050 based on different scenarios of smoking rates, showing that cutting smoking could greatly improve health and life expectancy.
Article Synopsis
- Researchers studied strokes from 1990 to 2021 to understand how many people get them and how they are affected around the world.
- In 2021, strokes caused about 7.3 million deaths and were a major cause of health problems, especially in specific regions like Southeast Asia and Oceania.
- There are differences in stroke risks based on where people live and their age, and some areas actually saw more strokes happening since 2015.
Lysosomal and synaptic dysfunction markers in longitudinal cerebrospinal fluid of de novo Parkinson's disease.
NPJ Parkinsons Dis
May 2024
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration and potentially relevant as biomarkers, but data on early Parkinson's disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy and synaptic function in cerebrospinal fluid (CSF) of drug-naïve de novo PD, and sex-/age-matched healthy controls (HC) cross-sectionally (88 PD, 46 HC) and longitudinally (104 PD, 58 HC) over 10 years. Multiple markers of autophagy, synaptic plasticity, and secretory pathways were reduced in PD.
View Article and Find Full Text PDFBackground: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals.
View Article and Find Full Text PDFBackground: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic.
View Article and Find Full Text PDFCinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.
Neurology
March 2024
From Biogen Inc. (R.M.H., K.F., M.Y., E.H., K.C.E., D.G., L.M., J.B.), Cambridge, MA; Biogen Inc. (T.F.), Maidenhead, United Kingdom; Formerly Biogen Inc. at time of study (E.N., J.M.C., T.D.); Clario (D.S.), Princeton, NJ; Biospective Inc. (B.J.B.), Montreal, Quebec, Canada; Nucleus Global (K.M.K.), Atlanta, GA; Coeruleus Clinical Sciences LLC (J.M.C.), Woodbridge, CT; Department of Neurology (B.M.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, and Scientific Employee with an Honorary Contract at German Center for Neurodegenerative Diseases (DZNE), Germany; Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.); and Edmond J. Safra Program in Parkinson's Disease (A.E.L.), Toronto, Ontario, Canada.
Background And Objectives: Sensitive, reliable, and scalable biomarkers are needed to accelerate the development of therapies for Parkinson disease (PD). In this study, we evaluate the biomarkers of early PD diagnosis, disease progression, and treatment effect collected in the SPARK.
Methods: Cinpanemab is a human-derived monoclonal antibody binding preferentially to aggregated forms of extracellular α-synuclein.
Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: Issues and interpretation of the results.
J Anal Toxicol
December 2023
Tactus Addiction Treatment Center, P.O. Box 154, Deventer 7400 AD, The Netherlands.
Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration however require other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath.
View Article and Find Full Text PDFMutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage.
Circulation
December 2022
Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (M.E., M.B.M., T.P., A.S., C.S., A.A., D.Y.S.-F., P.H.D., B.I.M.F., R.W.-G., M.G., C.M., K.Z., T.L., S.S., M.T., H.N., A.H., D.C.M., S.D., F.Q., E.P., R.L., S.K.F., D.N.M., T.B., S.B., N.H., M.B., E.K.).
Article Synopsis
- Phosphodiesterase 3A gain-of-function mutations lead to hypertension and stroke, but surprisingly do not cause cardiac hypertrophy or heart failure in affected patients, suggesting a potential protective mechanism in the heart.* -
- Researchers used CRISPR-Cas9 models and human stem cells to analyze the effects of these mutations, observing that new mutations could enhance enzyme activity and self-assembly while preserving normal heart structure despite high blood pressure.* -
- In their experiments, cardiac responses in mutant models showed adaptive changes in calcium cycling and similarities in heart function to normal (wild-type) rats, indicating the mutations might lead to beneficial heart adaptations under certain conditions.*
Trial of Prasinezumab in Early-Stage Parkinson's Disease.
N Engl J Med
August 2022
From the Neuroscience and Rare Diseases, Discovery and Translational Area (G.P., K.I.T., A. Boulay, A.V., F.G.B., J.D., G.D., H.S., M.B., S.D., Š.H., T.K., G.A.K., D.U., A. Bonni), and Pharmaceutical Sciences (B.R.), Roche Pharma Research and Early Development (pRED), and Roche pRED Informatics (F.L., E.V.-V., M.L.), Roche Innovation Center Basel, and Product Development Neuroscience (S.Z., A.M., N. Pross, P.F., R.D., T.N.) and Product Development Safety (M.M., D.R.), F. Hoffmann-La Roche - all in Basel, Switzerland; University of Exeter Medical School, London (G.P.), Roche Products, Welwyn Garden City (J.A.-C., R.F.), and the Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne (N. Pavese) - all in the United Kingdom; the Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago (T.S.); Institute for Neurodegenerative Disorders, New Haven, CT (K.M., D.S.R.); the Department of Neurology, McGill University, and Montreal Neurological Institute, Montreal (R.B.P.); University San Raffaele Roma and the Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome (F.S.); Centre Hospitalier de la Timone, Marseille, France (J.-P.A.); Paracelsus-Elena-Klinik, Kassel (B.M.), the Department of Neurology, University Medical Center Göttingen, Göttingen (B.M.), Hertie Institute for Clinical Brain Research, University of Tübingen, and the German Center for Neurodegenerative Diseases, Tübingen (T.G.), the Institute of Neurosciences and Medicine, Brain and Behavior, Research Center Jülich, Jülich (J.D.), the Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (J.D.), and Excelya Germany, Freiburg (A.H.) - all in Germany; the Department of Neurology, University Hospital de La Princesa, Madrid (L.L.-M.), and University Clinic of Navarra, Pamplona (M.R.L.) - both in Spain; University of South Florida, Tampa (R.A.H.); University of Vermont Larner College of Medicine, Burlington (J.T.B.); University of Alabama Medical Center, Birmingham (A.P.N.); and the Department of Neurology, Innsbruck Medical University, Innsbruck, Austria (W.P.).
Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease.
Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks.
Trial of Cinpanemab in Early Parkinson's Disease.
N Engl J Med
August 2022
From the Edmond J. Safra Program in Parkinson's Disease, University Health Network, and the University of Toronto, Toronto (A.E.L.), and the Montreal Neurological Institute, Montreal (R.B.P.); the University of Pennsylvania, Philadelphia (A.D.S.); the Biostatistics Center, Massachusetts General Hospital (E.A.M.), Beth Israel Deaconess Medical Center (D.K.S.), and Harvard Medical School (E.A.M., D.K.S.), Boston, and Biogen, Cambridge (K.F., J.X., K.C.E., D.L.G., I.S., J.I., R.M.H., M.Y., S.B.H., T.D.) - all in Massachusetts; Medizinische Universität Innsbruck, Innsbruck, Austria (W.P.); Newcastle University, Newcastle upon Tyne (D.J.B.), and Biogen, Maidenhead (T.F.) - both in the United Kingdom; Aarhus University, Aarhus, Denmark (D.J.B.); the Center for Neurological Restoration, Cleveland Clinic, and Cleveland Clinic Lerner College of Medicine - both in Cleveland (H.H.F.); Clinical Investigation Center 1436, the Departments of Clinical Pharmacology and Neurosciences, NS-PARK-French Clinical Research Infrastructure Network, NeuroToul COEN Center, INSERM, University Hospital of Toulouse, and the University of Toulouse III - both in Toulouse, France (O.R.); Tel Aviv Sourasky Medical Center, and the Sackler School of Medicine and the Sagol School of Neuroscience, Tel Aviv University - both in Tel Aviv, Israel (N.G.); University San Raffaele and IRCCS San Raffaele - both in Rome (F.S.); the University of California, San Diego, La Jolla (C.M.T.), and the San Francisco Veterans Affairs Medical Center, San Francisco (C.M.T.); the University of Barcelona, Barcelona (E.T.); the Department of Neurology, University Medical Center Göttingen, Göttingen, and Paracelsus-Elena-Klinik, Kassel - both in Germany (B.M.); and Coeruleus Clinical Sciences, Woodbridge, CT (J.M.C.).
Background: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease.
Methods: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks.
Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients.
NPJ Parkinsons Dis
September 2021
Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy.
A prodromal phase of Parkinson's disease (PD) may precede motor manifestations by decades. PD patients' siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort.
View Article and Find Full Text PDFAlpha-synuclein research: defining strategic moves in the battle against Parkinson's disease.
NPJ Parkinsons Dis
July 2021
German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
With the advent of the genetic era in Parkinson's disease (PD) research in 1997, α-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an economic impact of $51.9 billion in the US alone.
View Article and Find Full Text PDFNovel Associations of and With REM Sleep Behavior Disorder.
Neurology
March 2021
From the Department of Human Genetics (K.M., E.Y., U.R., L.K., G.A.R., Z.G.-O.), Montreal Neurological Institute (K.M., E.Y., U.R., L.K., J.A.R., F.A., S.B.L., D.S., G.A.R., R.B.P., Z.G.-O.), Department of Neurology and Neurosurgery (J.A.R., F.A., S.B.L., D.S., G.A.R., R.B.P., Z.G.-O.), Centre de Recherche en Biologie Structurale (J.-F.T.), and Department of Pharmacology and Therapeutics (J.-F.T.), McGill University, Montréal, Quebec, Canada; Sleep Disorders Unit (I.A.), Pitié Salpêtrière Hospital, Paris Brain Institute and Sorbonne University, France; Oxford Parkinson's Disease Centre (OPDC) (M.T.M.H.) and Nuffield Department of Clinical Neurosciences (M.T.M.H.), University of Oxford, UK; Center for Advanced Research in Sleep Medicine (J.Y.M., J.-F.G., A.D., R.B.P.), Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal-Hôpital du Sacré-Coeur de Montréal; Departments of Psychiatry (J.Y.M.) and Neurosciences (A.D.), Université de Montréal; Department of Psychology (J.-F.G.), Université du Québec à Montréal, Canada; National Reference Center for Narcolepsy (Y.D.), Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Inserm U1061, France; Clinical Neurology Unit (G.L.G., M.V., F.J., A.B.), Department of Neurosciences, University Hospital of Udine; DMIF (G.L.G.) and Department of Medicine (DAME) (M.V.), University of Udine, Italy; Sleep Disorders Clinic (B.H., A.S., E.H.), Department of Neurology, Medical University of Innsbruck, Austria; Department of Neurology (K.S., D.K.) and Centre of Clinical Neuroscience (K.S., D.K.), Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic; Department of Neurology (W.O., A.J., F.S.-D.), Philipps University, Marburg, Germany; Department of Biomedical, Metabolic and Neural Sciences (G.P.), University of Modena and Reggio-Emilia; IRCCS (G.P.), Institute of Neurological Sciences of Bologna; Neurology Unit (E.A.), Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona; Department of Medical Sciences and Public Health (M.F., M.P.), Sleep Disorder Research Center, University of Cagliari, Italy; Paracelsus-Elena-Klinik (B.M., C.T., F.S.-D.), Kassel; Department of Neurosurgery (B.M., C.T.), University Medical Centre Göttingen, Germany; Sleep and Neurology Unit (V.C.D.C.), Beau Soleil Clinic; EuroMov Digital Health in Motion (V.C.D.C.), University of Montpellier IMT Mines Ales; University Lille North of France (C.C.M.), Department of Clinical Neurophysiology and Sleep Center, CHU Lille; Department of Sleep Medicine and Neuromuscular Disorders (A.H.), University of Müenster, Germany; Department of Neurological Sciences (L.F.-S.), Università Vita-Salute San Raffaele, Milan, Italy; Laboratory for Sleep Disorders (F.D., M.V.) and Department of Neurology (F.D., M.V.), St. Dimpna Regional Hospital, Geel; Department of Neurology (F.D.), University Hospital Antwerp, Edegem, Belgium; Sleep Disorder Unit (B.A.), Carémeau Hospital, University Hospital of Nîmes, France; and Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN.
Objective: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD).
Methods: We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests.
β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies.
Neurology
December 2020
From the Division of Clinical Geriatrics (D.F., S.G.-P., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., Z.N., C.G.S., M.L.S., V.J.L., C.R.J., K.K.), Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Department of Neurology and Alzheimer Center (A.W.L.), VU University Medical Center, Amsterdam, the Netherlands; Clinical Memory Research Unit (E.L.), Department of Clinical Sciences, Lund University, Malmö, Sweden; Day Hospital of Geriatrics (F.B.), Memory Resource and Research Centre (CM2R) of Strasbourg; Department of Geriatrics (F.B.), Hopitaux Universitaires de Strasbourg; University of Strasbourg and French National Centre for Scientific Research (CNRS) (F.B.), ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg (FMTS), Team Imagerie Multimodale Integrative en Sante (IMIS)/ICONE, Strasbourg, France; Department of Neurology (Z.N., J.H.), Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Paracelsus-Elena-Klinik (B.M.), Kassel; and University Medical Center (B.M.), Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany; Fundació ACE (C.A.), Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain; International Clinical Research Center (J.H.), St. Anne's University Hospital Brno, Czech Republic; Department of Neuroscience Imaging and Clinical Sciences and CESI (L.B.), University G d'Annunzio of Chieti-Pescara, Chieti, Italy; Centre for Age-Related Medicine (K.O., D.A.), Stavanger University Hospital; Stavanger Medical Imaging Laboratory (SMIL) (K.O.), Department of Radiology, Stavanger University Hospital; Department of Electrical Engineering and Computer Science (K.O.), University of Stavanger, Norway; Department of Neurology (M.G.K.), University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Slovenia; Institute of Psychiatry, Psychology and Neuroscience (D.A.) and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Objective: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype.
Methods: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort.
In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease.
Neurology
September 2020
From the Department of Neurology (L.M.C., S.M.), University of Pittsburgh, PA; Banner Sun Health Research Institute (T.G.B., G.E.S.), Sun City, AZ; University of Iowa (M.C.B., C.S.C., C.C.-G.), Iowa City; Department of Neurology (C.H.A.), Mayo Clinic College of Medicine, Scottsdale, AZ; St. Michael's Hospital (D.G.M.), Toronto, Canada; University of Texas Southwestern Medical School (C.L.W.), Dallas; Icahn School of Medicine at Mount Sinai (J.F.C.), New York, NY; Institute for Neurodegenerative Disorders (D.J.), New Haven, CT; BioLegend Inc. (P.T.), Dedham, MA; Indiana University (T.F.), Indianapolis; The Michael J. Fox Foundation for Parkinson's Research (V.A., C.M.K., L.R., K.D.D.), New York, NY; and Department of Neurology (B.M.), Center of Parkinsonism and Movement Disorders Paracelsus-Elena Klinik Kassel and University Medical Center Göttingen, Germany.
Objective: The Systemic Synuclein Sampling Study (S4) measured α-synuclein in multiple tissues and biofluids within the same patients with Parkinson disease (PD) vs healthy controls (HCs).
Methods: S4 was a 6-site cross-sectional observational study of participants with early, moderate, or advanced PD and HCs. Motor and nonmotor measures and dopamine transporter SPECT were obtained.
variants in REM sleep behavior disorder: A multicenter study.
Neurology
August 2020
From the Department of Human Genetics (L.K., U.R., G.A.R., Z.G.-O.), Montreal Neurological Institute (L.K., J.A.R., U.R., E.L., F.A., R.B.P., G.A.R., Z.G.-O.), and Department of Neurology and Neurosurgery (J.A.R., F.A., R.B.P., G.A.R., Z.G.-O.), McGill University, Montréal; Oxford Parkinson's Disease Centre (M.T.M.H.) and Nuffield Department of Clinical Neurosciences (M.T.M.H.), University of Oxford, UK; Sleep Disorders Unit (I.A.), Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, Paris; National Reference Center for Narcolepsy, Sleep Unit (Y.D.), Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Inserm U1061, France; Sleep Disorders Unit, Department of Neurology (B.H., A.S.), Medical University of Innsbruck, Austria; Department of Clinical Neurophysiology and Sleep Center (C.C.M.), University Lille North of France, CHU Lille; Sleep Disorder Unit (B.A.), Carémeau Hospital, University Hospital of Nîmes, France; Department of Biomedical and Neuromotor Sciences (DIBINEM) (G.P., E.A.), Alma Mater Studiorum, University of Bologna; IRCCS (G.P., E.A.), Istituto delle Scienze Neurologiche, Bologna; Department of Neurological Sciences (L.F.-S.), Università Vita-Salute San Raffaele, Milan, Italy; Department of Neurology with Institute of Translational Neurology (A.H.), University of Muenster, Germany; Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati, OH; Sleep and Neurology Unit (V.C.D.C.), Beau Soleil Clinic, Montpellier; EuroMov (V.C.D.C.), University of Montpellier, France; Paracelsus-Elena-Klinik (B.M., F.S.-D., C.T.), Kassel; Department of Neurology (B.M., C.T.), University Medical Centre Goettingen; Department of Neurology (F.S.-D., W.O.), Philipps University, Marburg, Germany; Department of Neurology and Centre of Clinical Neuroscience (K.S., D.K.), Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic; Department of Medical Sciences and Public Health, Sleep Disorder Research Center (M.F., M.P.), University of Cagliari, Italy; Laboratory for Sleep Disorders (F.D., M.V.) and Department of Neurology (F.D., M.V.), St. Dimpna Regional Hospital, Geel, Belgium; Department of Medicine (DAME) (M.T., M.V.), University of Udine, Italy; Department of Clinical and Movement Neurosciences (M.T.), UCL Queen Square Institute of Neurology, London, UK; Clinical Neurology Unit (G.L.G., M.V.), Department of Neurosciences, University Hospital of Udine; DMIF (G.L.G.), University of Udine, Italy; Centre d'Études Avancées en Médecine du Sommeil (J.-F.G., A.D., J.Y.M., R.B.P.), Hôpital du Sacré-Cœur de Montréal; and Departments of Psychology (J.-F.G.), Neurosciences (A.D.), and Psychiatry (J.Y.M.), Université du Québec à Montréal, Canada.
Objective: To study the role of variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration.
Methods: A total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. was fully sequenced using molecular inversion probes and Sanger sequencing.
Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study.
Brain
March 2019
Department of Neurology, McGill University, Montreal General Hospital, Montreal, Canada.
Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion.
View Article and Find Full Text PDFLongitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.
Neurology
November 2017
From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego.
Objective: To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them.
Methods: CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes.
Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease.
Neurology
April 2017
From the Institute of Neuroscience (L.R., B.G., S.L., A.J.Y., R.M., G.D., T.K.K., D.J.B.), Clinical Ageing Research Unit, Newcastle University; Department of Geriatric Medicine (G.D.), University of Edinburgh, UK; School of Medicine & Menzies Health Institute (T.K.K.), Griffith University, Australia; and Paracelsus-Elena Klinik, Kassel and University Medical Centre (Institute of Neuropathology and Department of Neurosurgery) (B.M.), Göttingen, Germany.
Objective: This prospective observational study investigates the role of CSF biomarkers in predicting progression of dopa-resistant gait impairments in Parkinson disease (PD) in the first 36 months from diagnosis.
Methods: Quantitative gait analysis was carried out longitudinally using an instrumented walkway (GAITRite) in 108 people with PD and 130 age-matched controls. A subgroup of 44 people with PD underwent lumbar puncture from which a battery of CSF biomarkers was measured: β-amyloid 1-42 and 1-40 (Aβ42 and Aβ40), total and phosphorylated tau protein (t-tau/p-tau), and α-synuclein (αSyn).
Monitoring of 30 marker candidates in early Parkinson disease as progression markers.
Neurology
July 2016
From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106).
Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI).
Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study.
Neurology
January 2014
From the Institute for Ageing and Health (A.J.Y., G.W.D., M.J.F., D.J.B.), Industrial Statistics Research Unit (S.Y.C.), and Institute of Genetic Medicine (G.H., P.F.C.), Newcastle University; John van Geest Centre for Brain Repair (D.P.B., J.R.E., R.A.B.), Department of Clinical Neurosciences (C.N., S.W.-R., J.B.R.), Behavioural and Clinical Neuroscience Institute (C.N., S.W.-R., J.B.R., T.W.R.), MRC Cognition and Brain Sciences Unit (C.N., S.W.-R., J.B.R.), Departments of Psychiatry (J.T.O.) and Psychology (T.W.R.), University of Cambridge, UK; School of Medicine (T.K.K.), Griffith University, Australia; Paracelsus-Elena-Klinik (B.M.), Kassel, and Göttingen University; Institute for Neuropathology (N.K.), Prion and Dementia Research Unit, University Medical Centre Göttingen, Germany; Centre for Human Psychopharmacology (K.W.), Swinburne University, Melbourne, Australia; and Department of Medicine (D.J.W.), Imperial College London, UK.
Objective: To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.
Methods: Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE.
Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study.
Neurology
October 2013
From the Neurogenomics Laboratory (H.D., K.D., K.C.L., A.N.H., K.D., A.T.-L., C.R.S.), Harvard Medical School and Brigham & Women's Hospital, Cambridge; Biomarkers Program (K.D., K.C.L., A.N.H., K.D., A.T.-L., M.T.H., U.S.S., B.M., N.M., V.K., S.N.G., D.J.S., M.A.S., M.G.S., B.T.H., J.H.G., C.R.S.), Harvard NeuroDiscovery Center, Boston; Department of Neurology (J.J.L., U.S.S., A.-M.W., A.W.F., A.Y.H., N.M., V.K., S.N.G., M.A.S., B.T.H., J.H.G., C.R.S.), Massachusetts General Hospital, Boston; Department of Neurology (M.T.H., A.Y.H., D.J.S., L.R.S., C.R.S.), Brigham and Women's Hospital, Boston, MA; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; and Division of Neurology, the Ottawa Hospital, University of Ottawa (M.G.S.), Canada.
Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD).
Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.
Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort.
Neurology
October 2013
From the Center of Parkinsonism and Movement Disorders (B.M., E.T., F.S.-D., T.W., J.E., M.S., E.L., C.T.), Paracelsus-Elena-Klinik, Kassel; Department of Neurosurgery (B.M., N.K.F., C.T.), University Medical Centre, Goettingen; Department of Psychology (E.T.), University Kassel; Section of Clinical and Molecular Neurogenetics at the Department of Neurology (K.R.K., K.L., C.K.), University of Luebeck; Departments of Neuropathology (B.M.) and Medical Statistics (T.F.), University Medical Centre, Goettingen, Germany; Program in Neuroscience (M.G.S.), Ottawa Hospital Research Institute; Division of Neurology, The Ottawa Hospital, University of Ottawa, Canada; and ReSearch Pharmaceutical Services (R.K.), Nuremberg, Germany.
Objective: To determine nonmotor signs (NMS) and evaluate the utility of several diagnostic tools in patients with de novo Parkinson disease (PD).
Methods: This is a large single-center study of the DeNoPa cohort, including frequency-matched healthy controls. This study covers motor signs, NMS, and a combination of diagnostic tests including olfactory testing, transcranial sonography of substantia nigra (TCS), and polysomnography (PSG).