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dementia with lewy bodies and Parkinson's

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https://www.readbyqxmd.com/read/28637099/aggregation-and-phosphorylation-of-%C3%AE-synuclein-with-proteinase-k-resistance-in-focal-%C3%AE-synucleinopathy-predominantly-localized-to-the-cardiac-sympathetic-nervous-system
#1
Nei Fukasawa, Takahiro Fukuda, Masato Nagaoka, Tohru Harada, Hiroyuki Takahashi, Masahiro Ikegami
Aggregates of α-synuclein, a major component of Lewy bodies (LBs) and Lewy neurites (LNs), are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system (ENS), cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin, in incidental Lewy body disease (ILBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF) [1-3]. Here we report focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system (SNS)...
June 21, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#2
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633628/olfactory-testing-in-consecutive-patients-referred-with-suspected-dementia
#3
Ib Thrane Christensen, Elna-Marie Larsson, Ida E Holm, Ole B F Nielsen, Stig Andersen
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia. METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study)...
June 20, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28630086/psychosocial-therapy-for-parkinson-s-related-dementia-study-protocol-for-the-invest-randomised-controlled-trial
#4
Sheree A McCormick, Kathryn R McDonald, Sabina Vatter, Vasiliki Orgeta, Ellen Poliakoff, Sarah Smith, Monty A Silverdale, Bo Fu, Iracema Leroi
INTRODUCTION: Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation...
June 19, 2017: BMJ Open
https://www.readbyqxmd.com/read/28626918/marinesco-bodies-and-substantia-nigra-neuron-density-in-parkinson-s-disease
#5
Robert D Abbott, James S Nelson, G Webster Ross, Jane H Uyehara-Lock, Caroline M Tanner, Kamal H Masaki, Lenore J Launer, Lon R White, Helen Petrovitch
AIM: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal aging and is high in Alzheimer's disease, dementia with Lewy bodies, and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons. Whether MB have a role in this process is unknown. Our aim is to examine the association of MB with SN neuron density in Parkinson's disease (PD) in the Honolulu-Asia Aging Study...
June 19, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28622212/a-retrospective-study-of-pimavanserin-use-in-a-movement-disorders-clinic
#6
Joseph H Friedman
Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis. No "naturalistic" treatment results have yet been published. Charts from the movement disorders clinic were reviewed for all patients who received this drug as treatment for psychosis associated with primary parkinsonism due to α-synucleinopathies. Data of 10 patients with idiopathic Parkinson disease, including 1 with a long history of schizophrenia, 4 with dementia with Lewy bodies, and 1 with multiple-system atrophy, were reviewed...
June 16, 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28602509/neurochip-an-updated-version-of-the-neurox-genotyping-platform-to-rapidly-screen-for-variants-associated-with-neurological-diseases
#7
Cornelis Blauwendraat, Faraz Faghri, Lasse Pihlstrom, Joshua T Geiger, Alexis Elbaz, Suzanne Lesage, Jean-Christophe Corvol, Patrick May, Aude Nicolas, Yevgeniya Abramzon, Natalie A Murphy, J Raphael Gibbs, Mina Ryten, Raffaele Ferrari, Jose Bras, Rita Guerreiro, Julie Williams, Rebecca Sims, Steven Lubbe, Dena G Hernandez, Kin Y Mok, Laurie Robak, Roy H Campbell, Ekaterina Rogaeva, Bryan J Traynor, Ruth Chia, Sun Ju Chung, John A Hardy, Alexis Brice, Nicholas W Wood, Henry Houlden, Joshua M Shulman, Huw R Morris, Thomas Gasser, Rejko Krüger, Peter Heutink, Manu Sharma, Javier Simón-Sánchez, Mike A Nalls, Andrew B Singleton, Sonja W Scholz
Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy...
May 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28595550/new-tracers-and-new-perspectives-for-molecular-imaging-in-lewy-body-diseases
#8
Matteo Bauckneht, Dario Arnaldi, Flavio Nobili, Dag Aarsland, Silvia Morbelli
The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28591814/abnormal-gray-matter-shape-thickness-and-volume-in-the-motor-cortico-subcortical-loop-in-idiopathic-rapid-eye-movement-sleep-behavior-disorder-association-with-clinical-and-motor-features
#9
Shady Rahayel, Ronald B Postuma, Jacques Montplaisir, Christophe Bedetti, Simona Brambati, Julie Carrier, Oury Monchi, Pierre-Alexandre Bourgouin, Malo Gaubert, Jean-François Gagnon
Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a major risk factor for Parkinson's disease and dementia with Lewy bodies. Anatomical gray matter abnormalities in the motor cortico-subcortical loop areas remain under studied in iRBD patients. We acquired T1-weighted images and administrated quantitative motor tasks in 41 patients with polysomnography-confirmed iRBD and 41 healthy subjects. Cortical thickness and voxel-based morphometry (VBM) analyses were performed to investigate local cortical thickness and gray matter volume changes, vertex-based shape analysis to investigate shape of subcortical structures, and structure-based volumetric analyses to investigate volumes of subcortical and brainstem structures...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28585223/a-molecular-tweezer-ameliorates-motor-deficits-in-mice-overexpressing-%C3%AE-synuclein
#10
Franziska Richter, Sudhakar R Subramaniam, Iddo Magen, Patrick Lee, Jane Hayes, Aida Attar, Chunni Zhu, Nicholas R Franich, Nicholas Bove, Krystal De La Rosa, Jacky Kwong, Frank-Gerrit Klärner, Thomas Schrader, Marie-Françoise Chesselet, Gal Bitan
Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies. Accordingly, therapeutic approaches targeting the toxic α-synuclein assemblies are attractive for these incurable disorders...
June 5, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28578695/sirt1-ameliorates-oxidative-stress-induced-neural-cell-death-and-is-down-regulated-in-parkinson-s-disease
#11
Preeti Singh, Peter S Hanson, Christopher M Morris
BACKGROUND: Sirtuins (SIRTs) are NAD(+) dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson's disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress...
June 2, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28572021/death-certificates-data-and-causes-of-death-in-patients-with-parkinsonism
#12
Mariana Moscovich, Gabriela Boschetti, Adriana Moro, Helio A G Teive, Anhar Hassan, Renato P Munhoz
INTRODUCTION: Assessment of variables related to mortality in Parkinson disease (PD) and other parkinsonian syndromes relies, among other sources, on accurate death certificate (DC) documentation. We assessed the documentation of the degenerative disorder on DCs and evaluated comorbidities and causes of death among parkinsonian patients. METHODS: Demographic and clinical data were systematically and prospectively collected on deceased patients followed at a tertiary movement disorder clinic...
May 26, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28566609/progressive-b%C3%A3-lint-s-syndrome-in-a-patient-demonstrating-dementia-with-lewy-bodies
#13
Yasuhisa Sakurai, Yoshifumi Nakashima
We herein report a 65-year-old man demonstrating dementia with Lewy bodies who first presented with Bálint's syndrome. Two years later, a mild cognitive impairment was noted. From three years after onset, he developed progressive parkinsonism, visual hallucination, and autonomic dysfunction, in line with the deterioration of the cognitive function. Single photon emission computed tomography with a (99m)Tc-ethylcysteinate dimer performed two years after onset revealed hypoperfusion in the restricted area of the bilateral superior parietal lobule, which extended to the lateral occipital cortices within two years...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28564592/alteration-of-mitochondrial-protein-pdha1-in-lewy-body-disease-and-park14
#14
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies. Mitochondria play a vital role in energy production, and the pathogenesis of PD is associated with altered cellular metabolism due to mitochondrial dysfunction. The pyruvate dehydrogenase (PDH) complex provides a primary step in aerobic glucose metabolism by catalyzing the oxidative decarboxylation of pyruvate to acetyl CoA. Pyruvate dehydrogenase alpha 1 (PDHA1) forms the core structure of the PDH complex...
May 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28556415/symptoms-associated-with-lewy-body-disease-in-mild-cognitive-impairment
#15
Paul C Donaghy, Nicola Barnett, Kirsty Olsen, John-Paul Taylor, Ian G McKeith, John T O'Brien, Alan J Thomas
OBJECTIVE: Dementia with Lewy bodies (DLB) is associated with a range of cognitive and non-cognitive symptoms. We aimed to identify if some of these symptoms might aid early diagnosis of Lewy body disease in cases of mild cognitive impairment (MCI). METHODS: Lewy body MCI (MCI-LB; n = 36), Alzheimer's disease MCI (MCI-AD; n = 21), DLB (n = 36), AD (n = 21) and control (n = 20) participants were recruited. An interview-based questionnaire about the presence of symptoms thought to be associated with Lewy body disease was completed by participants with, where possible, their carer/relative...
May 29, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28554421/the-new-diagnostic-criteria-for-parkinson-s-disease
#16
Ronald B Postuma, Daniela Berg
This chapter summarizes the advances in diagnosis of Parkinson's disease (PD) that were encapsulated in new International Parkinson Disease and Movement Disorders Society diagnostic criteria for PD. Numerous changes in our understanding of PD have occurred, including our understanding of the nonmotor profile of disease, the recognition of PD as a synucleinopathy, identification of genetic causes, novel hypotheses about spread of disease, etc. These have been reflected in a new definition of PD, which includes a clinicogenetic subtype of PD, removes dementia with Lewy Bodies as an exclusion criterion against PD, and recognizes multiple stages of early disease...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28548708/glucocerebrosidase-mutations-and-neuropsychiatric-phenotypes-in-parkinson-s-disease-and-lewy-body-dementias-review-and-meta-analyses
#17
REVIEW
Byron Creese, Emily Bell, Iskandar Johar, Paul Francis, Clive Ballard, Dag Aarsland
Heterozygous mutations in glucocerebrosidase gene (GBA) are a major genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, there has been a considerable focus on the relationship between GBA mutations and emergence of cognitive impairment and neuropsychiatric symptoms in these diseases. Here, we review the literature in this area, with a particular focus, including meta-analysis, on the key neuropsychiatric symptoms of cognitive impairment, psychosis, and depression in Parkinson's disease...
May 26, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28538394/123i-ioflupane-brain-spect-and-123i-mibg-cardiac-planar-scintigraphy-combined-use-in-uncertain-parkinsonian-disorders
#18
Susanna Nuvoli, Angela Spanu, Maria Rita Piras, Antonio Nieddu, Aldo Mulas, Gaia Rocchitta, Grazia Galleri, Pier Andrea Serra, Giuseppe Madeddu
We evaluated the clinical usefulness of the combined use of I-ioflupane brain single photon emission computed tomography (SPECT) and I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinson's disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28527219/tmem230-accumulation-in-granulovacuolar-degeneration-bodies-and-dystrophic-neurites-of-alzheimer-s-disease
#19
Sandra L Siedlak, Yingfei Jiang, Mikayla L Huntley, Luwen Wang, Ju Gao, Fei Xie, Jingyi Liu, Bo Su, George Perry, Xinglong Wang
Transmembrane Protein 230 (TMEM230) is a newly identified protein associated with Parkinson's disease (PD) found in Lewy bodies and Lewy neurites of patients with PD or dementia with Lewy body disease. However, TMEM230 has not yet been investigated in the most common neurodegenerative disorder, Alzheimer's disease (AD). Here, we demonstrate that the expression of TMEM230 is specifically increased in neurons in AD patients. Importantly, both granulovacuolar degeneration (GVD) and dystrophic neurites (DNs), two prominent characteristic pathological structures associated with AD, contain TMEM230 aggregates...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#20
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
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