13,661 results match your criteria Huntington Disease Dementia

Alterations in metal homeostasis occur prior to canonical markers in Huntington disease.

Sci Rep 2022 Jun 20;12(1):10373. Epub 2022 Jun 20.

Department of Neurology, Vanderbilt University Medical Center, 1611 21st Avenue South, Suite 1532, Nashville, TN, 37232, USA.

The importance of metal biology in neurodegenerative diseases such as Huntingtin Disease is well documented with evidence of direct interactions between metals such as copper, zinc, iron and manganese and mutant Huntingtin pathobiology. To date, it is unclear whether these interactions are observed in humans, how this impacts other metals, and how mutant Huntington alters homeostatic mechanisms governing levels of copper, zinc, iron and manganese in cerebrospinal fluid and blood in HD patients. Plasma and cerebrospinal fluid from control, pre-manifest, manifest and late manifest HD participants were collected as part of HD-Clarity. Read More

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Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities.

Lancet Neurol 2022 Jul;21(7):645-658

Centre for Huntington's disease, University of British Columbia, Vancouver, BC, Canada.

Huntington's disease is the most frequent autosomal dominant neurodegenerative disorder; however, no disease-modifying interventions are available for patients with this disease. The molecular pathogenesis of Huntington's disease is complex, with toxicity that arises from full-length expanded huntingtin and N-terminal fragments of huntingtin, which are both prone to misfolding due to proteolysis; aberrant intron-1 splicing of the HTT gene; and somatic expansion of the CAG repeat in the HTT gene. Potential interventions for Huntington's disease include therapies targeting huntingtin DNA and RNA, clearance of huntingtin protein, DNA repair pathways, and other treatment strategies targeting inflammation and cell replacement. Read More

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A biological classification of Huntington's disease: the Integrated Staging System.

Lancet Neurol 2022 Jul;21(7):632-644

CHDI Management/CHDI Foundation, Princeton, NJ, USA; Clinical Pharmacology Laboratory, Faculdade de Medicina de Lisboa, University of Lisbon, Lisbon, Portugal. Electronic address:

The current research paradigm for Huntington's disease is based on participants with overt clinical phenotypes and does not address its pathophysiology nor the biomarker changes that can precede by decades the functional decline. We have generated a new research framework to standardise clinical research and enable interventional studies earlier in the disease course. The Huntington's Disease Integrated Staging System (HD-ISS) comprises a biological research definition and evidence-based staging centred on biological, clinical, and functional assessments. Read More

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Huntington's disease: disappointments and new beginnings.

Carsten Saft

Lancet Neurol 2022 Jul;21(7):582-584

Department of Neurology, Huntington Centre North Rhine-Westphalia, Ruhr University Bochum, St. Josef Hospital, 44791 Bochum, Germany. Electronic address:

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Calcium-dependent cytosolic phospholipase A activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Mol Neurodegener 2022 Jun 15;17(1):42. Epub 2022 Jun 15.

Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known. Read More

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NMR spectroscopy, excited states and relevance to problems in cell biology - transient pre-nucleation tetramerization of huntingtin and insights into Huntington's disease.

G Marius Clore

J Cell Sci 2022 Jun 15;135(12). Epub 2022 Jun 15.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.

Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for analyzing three-dimensional structure and dynamics of macromolecules at atomic resolution. Recent advances have exploited the unique properties of NMR in exchanging systems to detect, characterize and visualize excited sparsely populated states of biological macromolecules and their complexes, which are only transient. These states are invisible to conventional biophysical techniques, and play a key role in many processes, including molecular recognition, protein folding, enzyme catalysis, assembly and fibril formation. Read More

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Does physical activity improve motor function and gait in huntington disease? A systematic review and meta-analysis.

Rev Neurol 2022 06;74(12):392-402

Universitat Internacional de Catalunya, Sant Cugat del Vallès, España.

Introduction: Huntington's disease (HD) is a degeneration of the brain.

Objective: To assess the evidence of the physical activity (PA) to improve motor function, gait speed, and walking endurance in individuals with HD.

Materials And Methods: Two reviewers independently screened references and selected relevant studies to identify randomized controlled trials (RCT), from MEDLINE/PubMed, CENTRAL, PEDro, Scopus, CINAHL, Web of Science databases from inception to September 2021. Read More

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A New Perspective on Huntington's Disease: How a Neurological Disorder Influences the Peripheral Tissues.

Int J Mol Sci 2022 May 29;23(11). Epub 2022 May 29.

Undad de Investigación, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), 11002 Cádiz, Spain.

Huntington's disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. Read More

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Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein.

Int J Mol Sci 2022 May 29;23(11). Epub 2022 May 29.

Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, USA.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicated in the spreading of pathological α-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological α-Syn in the extracellular space and prevent/inhibit disease/s in the relevant animal models. Read More

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Structural Basis of Huntingtin Fibril Polymorphism Revealed by Cryogenic Electron Microscopy of Exon 1 HTT Fibrils.

J Am Chem Soc 2022 Jun 9;144(24):10723-10735. Epub 2022 Jun 9.

Laboratory of Molecular and Chemical Biology of Neurodegeneration, School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

The lack of detailed insight into the structure of aggregates formed by the huntingtin protein (HTT) has hampered the efforts to develop therapeutics and diagnostics targeting pathology formation in the brain of patients with Huntington's disease. To address this knowledge gap, we investigated the structural properties of in vitro-generated fibrils from exon1 of the huntingtin protein by cryogenic electron microscopy and single-particle analyses. We show that wildtype and mutant exon1 of the huntingtin protein form nonhelical fibrils with a polyglutamine amyloid core composed of β-hairpins with unique characteristics that have not been previously observed with other amyloid filaments. Read More

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Cognitive Syndromes Associated With Movement Disorders.

Continuum (Minneap Minn) 2022 06;28(3):726-749

Purpose Of Review: This article reviews the recognition and management of cognitive syndromes in movement disorders, including those with parkinsonism, chorea, ataxia, dystonia, and tremor.

Recent Findings: Cognitive and motor syndromes are often intertwined in neurologic disorders, including neurodegenerative diseases such as Parkinson disease, atypical parkinsonian syndromes, Huntington disease, and other movement disorders. Cognitive symptoms often affect attention, working memory, and executive and visuospatial functions preferentially, rather than language and memory, but heterogeneity can be seen in the various movement disorders. Read More

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Thalamocortical Projections Are Significantly Impaired in the R6/2 Mouse Model of Huntington's Disease.

eNeuro 2022 May-Jun;9(3). Epub 2022 Jun 22.

Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Read More

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CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease.

Acta Neuropathol Commun 2022 Jun 3;10(1):83. Epub 2022 Jun 3.

Department of Neuroscience, School of Medicine, University of Minnesota, 321 Church St. SE, Jackson Hall Room 6-145, Minneapolis, MN, USA.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. HTT mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of the basal ganglia. Transcriptional perturbations in synaptic genes and neuroinflammation are key processes that precede MSN dysfunction and motor symptom onset. Read More

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From older to younger generations: Intergenerational transmission of health-related roles in families with Huntington's disease.

J Aging Stud 2022 Jun 27;61:101027. Epub 2022 Apr 27.

CINTESIS, University of Aveiro, Aveiro, Portugal. Electronic address:

Background And Objectives: Older generations play relevant roles in the well-being of younger generations, namely by influencing their health management. Literature regarding the influence in families affected by highly incapacitating hereditary diseases, such as Huntington's disease (HD), however, is scarce. This study addresses the intergenerational flow of health-related roles, from older to younger generations in families with HD, that is, who plays what roles towards whom while considering age, gender, kinship and genetic status in both generations. Read More

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Interrogating amyloid aggregation with aggregation-induced emission fluorescence probes.

Biomaterials 2022 Jul 26;286:121605. Epub 2022 May 26.

Medical Device Research Institute, Institute for NanoScale Science and Technology, College of Science and Engineering, Flinders University, South Australia, 5042, Australia. Electronic address:

To date, approximately 50 proteins have been identified that can misfold and aggregate to form amyloid fibrils and cause neurodegenerative diseases such as Alzheimer disease, Parkinson disease and Huntington disease. The formation of the amyloid fibrils from the precursor proteins and how pre-fibrils and fibrils formation relate to disease have remained elusive. To assist our understanding of the amyloid fibrils, many molecular fluorescence probes, such as thioflavin-T, have been developed to help investigating area including pre-fibrils and fibrils detection, structures of amyloid aggregates, the staining of amyloid in vitro, ex vivo and in vivo. Read More

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Imaging of Synaptic Density in Neurodegenerative Disorders.

J Nucl Med 2022 Jun;63(Suppl 1):60S-67S

Neuroscience Discovery Research, Translational Imaging, AbbVie, North Chicago, Illinois.

PET technology has produced many radiopharmaceuticals that target specific brain proteins and other measures of brain function. Recently, a new approach has emerged to image synaptic density by targeting the synaptic vesicle protein 2A (SV2A), an integral glycoprotein in the membrane of synaptic vesicles and widely distributed throughout the brain. Multiple SV2A ligands have been developed and translated to human use. Read More

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Canadian healthcare capacity gaps for disease-modifying treatment in Huntington's disease: a survey of current practice and modelling of future needs.

BMJ Open 2022 Jun 1;12(6):e062740. Epub 2022 Jun 1.

Division of Neurology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada.

Objectives: Disease-modifying therapies in development for Huntington's disease (HD) may require specialised administration and additional resource capacity. We sought to understand current and future capacity for HD management in Canada considering the possible introduction of an intrathecal (IT) disease-modifying treatment (DMT).

Design, Setting And Participants: Using a case study, mixed methods framework, online surveys followed by semistructured interviews were conducted in late 2020 and early 2021. Read More

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mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.

Sci Rep 2022 May 28;12(1):8982. Epub 2022 May 28.

Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP: 31270-901, Brazil.

Glutamate receptors, including mGluR5, are involved in learning and memory impairments triggered by aging and neurological diseases. However, each condition involves distinct molecular mechanisms. It is still unclear whether the mGluR5 cell signaling pathways involved in normal brain aging differ from those altered due to neurodegenerative disorders. Read More

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Phospholipid Profiles Are Selectively Altered in the Putamen and White Frontal Cortex of Huntington's Disease.

Nutrients 2022 May 16;14(10). Epub 2022 May 16.

Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong 2522, Australia.

Huntington's disease (HD) is a genetic, neurodegenerative illness that onsets in late adulthood as a series of progressive and terminal cognitive, motor, and psychiatric deficits. The disease is caused by a polyQ mutation in the Huntingtin gene (), producing a polyglutamine expansion in the Huntingtin protein (HTT). HTT interacts with phospholipids in vitro; however, its interactions are changed when the protein is mutated in HD. Read More

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The Reversible Carnitine Palmitoyltransferase 1 Inhibitor (Teglicar) Ameliorates the Neurodegenerative Phenotype in a Drosophila Huntington's Disease Model by Acting on the Expression of Carnitine-Related Genes.

Molecules 2022 May 13;27(10). Epub 2022 May 13.

Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-CNR, Via Pietro Castellino 111, 80131 Naples, Italy.

Huntington's disease (HD) is a dramatic neurodegenerative disorder caused by the abnormal expansion of a CAG triplet in the huntingtin gene, producing an abnormal protein. As it leads to the death of neurons in the cerebral cortex, the patients primarily present with neurological symptoms, but recently metabolic changes resulting from mitochondrial dysfunction have been identified as novel pathological features. The carnitine shuttle is a complex consisting of three enzymes whose function is to transport the long-chain fatty acids into the mitochondria. Read More

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Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.

Int J Mol Sci 2022 May 23;23(10). Epub 2022 May 23.

Institute of Organismic and Molecular Evolution, Faculty of Biology, Johannes Gutenberg University, Hans-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany.

Huntington's disease (HD) is caused by the production of a mutant huntingtin (HTT) with an abnormally long poly-glutamine (polyQ) tract, forming aggregates and inclusions in neurons. Previous work by us and others has shown that an increase or decrease in polyQ-triggered aggregates can be passive simply due to the interaction of proteins with the aggregates. To search for proteins with active (functional) effects, which might be more effective in finding therapies and mechanisms of HD, we selected among the proteins that interact with HTT a total of 49 pairs of proteins that, while being paralogous to each other (and thus expected to have similar passive interaction with HTT), are located in different regions of the protein interaction network (suggesting participation in different pathways or complexes). Read More

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Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma.

Int J Mol Sci 2022 May 17;23(10). Epub 2022 May 17.

Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 27721 Libechov, Czech Republic.

(1) Background: Huntington's disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Read More

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Structural Abnormalities of the Optic Nerve and Retina in Huntington's Disease Pre-Clinical and Clinical Settings.

Int J Mol Sci 2022 May 13;23(10). Epub 2022 May 13.

Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Read More

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A Glimpse of Molecular Biomarkers in Huntington's Disease.

Int J Mol Sci 2022 May 12;23(10). Epub 2022 May 12.

Laboratorio de Apoyo a la Investigación, Hospital General Universitario Dr. Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain.

Huntington's disease (HD) is a devastating neurodegenerative disorder that is caused by an abnormal expansion of CAG repeats in the Huntingtin () gene. Although the main symptomatology is explained by alterations at the level of the central nervous system, predominantly affecting the basal ganglia, a peripheral component of the disease is being increasingly acknowledged. Therefore, the manifestation of the disease is complex and variable among CAG expansion carriers, introducing uncertainty in the appearance of specific signs, age of onset and severity of disease. Read More

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Identification of the Transcriptional Biomarkers Panel Linked to Pathological Remodelling of the Eye Tissues in Various HD Mouse Models.

Cells 2022 05 18;11(10). Epub 2022 May 18.

Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

Ocular abnormalities are becoming associated with a spectrum of pathological events in various neurodegenerative diseases. Huntington's disease (HD) is just such an example of a fatal neurological disorder, where mutated genes (CAG trinucleotide expansions in the gene) have widespread expression, leading to the production of mutant Huntingtin (mHTT) protein. It is well known that mutant HTT protein is prone to form toxic aggregates, which are a typical pathological feature, along with global transcriptome alterations. Read More

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Restoration of BDNF, DARPP32, and D2R Expression Following Intravenous Infusion of Human Immature Dental Pulp Stem Cells in Huntington's Disease 3-NP Rat Model.

Cells 2022 05 17;11(10). Epub 2022 May 17.

Genetics Laboratory, Instituto Butantan, São Paulo 05503-900, SP, Brazil.

Huntington's disease (HD) is a neurodegenerative inherited genetic disorder, which leads to the onset of motor, neuropsychiatric and cognitive disturbances. HD is characterized by the loss of gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). To date, there is no treatment for HD. Read More

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Natural Products from Plants and Algae for Treatment of Alzheimer's Disease: A Review.

Biomolecules 2022 May 12;12(5). Epub 2022 May 12.

Faculty of Applied Biosciences and Process Technology, Anhalt University of Applied Sciences, Bernburger Straße 55, 06366 Koethen, Germany.

Neurodegenerative disorders including Parkinson's disease (PD), Huntington's disease (HD) and the most frequent, Alzheimer's disease (AD), represent one of the most urgent medical needs worldwide. Despite a significantly developed understanding of disease development and pathology, treatments that stop AD progression are not yet available. The recent approval of sodium oligomannate (GV-971) for AD treatment in China emphasized the potential value of natural products for the treatment of neurodegenerative disorders. Read More

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Harmine prevents 3-nitropropionic acid-induced neurotoxicity in rats via enhancing NRF2-mediated signaling: Involvement of p21 and AMPK.

Eur J Pharmacol 2022 Jul 25;927:175046. Epub 2022 May 25.

Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Oxidative stress induced neurotoxicity is increasingly perceived as an important neuropathologic mechanism underlying the motor and behavioral phenotypes associated with Huntington's disease (HD). Repeated exposure to 3-nitropropionic acid (3-NP) induces neurotoxic changes which closely simulate the neuropathological and behavioral characteristics of HD. This study aimed at evaluating the prophylactic effects of the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) inhibitor "harmine" against 3-NP-indued neurotoxicity and HD-like symptoms. Read More

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In vitro fertilization with preimplantation genetic testing for monogenetic diseases versus unassisted conception with prenatal diagnosis for Huntington disease: a cost-effectiveness analysis.

Fertil Steril 2022 Jul 23;118(1):56-64. Epub 2022 May 23.

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon.

Objective: To investigate if in vitro fertilization (IVF) with preimplantation genetic testing for monogenic disease is cost effective for heterozygous individuals with Huntington disease vs. unassisted conception with prenatal diagnosis.

Design: Cost-effectiveness analysis in a theoretical cohort of 3,851 couples, where one individual is heterozygous for Huntington disease. Read More

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Healthcare resource utilization and costs in individuals with Huntington's disease by disease stage in a US population.

J Med Econ 2022 Jan-Dec;25(1):722-729

CHDI Management/CHDI Foundation, Princeton, NJ, USA.

Aims: To quantify healthcare resource utilization (HRU) and costs by disease stage in individuals with Huntington's disease (HD) in a US population.

Materials And Methods: This retrospective cohort study used administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases between 1 January 2009 and 31 December 2018. Individuals with an HD claim between 1 January 2010 and 31 December 2017 were selected. Read More

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