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Lewy body dementia

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https://www.readbyqxmd.com/read/29349556/neuropathology-correlates-of-cognitive-assessments
#1
Francesca M Brett, Hugh Kearney
BACKGROUND: Alzheimer's disease and other dementias are the fourth largest contributors to neurological disability and the second largest contributor to deaths from neurological disease. Described in the 1980s as 'the silent epidemic' these disorders principally, though not exclusively, affect persons 80 years or older, and in developed countries, this 'old old' population continues to grow. Definitive diagnosis of the underlying cause of the neurodegenerative disease relies on neuropathological evaluation...
January 18, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29344344/acetylcholinesterase-inhibitors-in-treatment-resistant-psychotic-depression
#2
Chris Smart, Hamish McAllister-Williams, David Andrew Cousins
Dopamine receptor antagonists can be effective in psychotic depression but response is not assured. Visual hallucinations may arise from a dysregulation of brain cholinergic systems and acetylcholinesterase inhibitors (AChEIs) can treat such hallucinations in dementia with Lewy bodies (DLB). AChEIs have been used in schizophrenia with some success but their efficacy and tolerability in psychotic depression is unclear. This striking case illustrates AChEIs specifically targeting multimodal hallucinations in treatment-resistant depression...
January 2018: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/29337452/-neurology
#3
Isabelle Chopard, David Benninger, Jean-François Demonet, Renaud Du Pasquier, Lorenz Hirt, Thierry Kuntzer, Patrik Michel, Bernard Nater, Jan Novy, Andrea Rossetti, Olivier Rouaud, Philippe Ryvlin, Myriam Schluep, Marie Theaudin
Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29332010/oligogenic-genetic-variation-of-neurodegenerative-disease-genes-in-980-postmortem-human-brains
#4
Michael J Keogh, Wei Wei, Juvid Aryaman, Ian Wilson, Kevin Talbot, Martin R Turner, Chris-Anne McKenzie, Claire Troakes, Johannes Attems, Colin Smith, Safa Al Sarraj, Chris M Morris, Olaf Ansorge, Stuart Pickering-Brown, Nick Jones, James W Ironside, Patrick F Chinnery
BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls...
January 13, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29330884/synapsin-iii-is-a-key-component-of-%C3%AE-synuclein-fibrils-in-lewy-bodies-of-pd-brains
#5
Francesca Longhena, Gaia Faustini, Tatiana Varanita, Michela Zaltieri, Vanessa Porrini, Isabella Tessari, Pietro Luigi Poliani, Cristina Missale, Barbara Borroni, Alessandro Padovani, Luigi Bubacco, Marina Pizzi, PierFranco Spano, Arianna Bellucci
Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III...
January 13, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29324989/synaptic-markers-of-cognitive-decline-in-neurodegenerative-diseases-a-proteomic-approach
#6
Erika Bereczki, Rui M Branca, Paul T Francis, Joana B Pereira, Jean-Ha Baek, Tibor Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland
Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups...
January 9, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29321140/cerebrospinal-fluid-alzheimer-biomarkers-can-be-useful-for-discriminating-dementia-with-lewy-bodies-from-alzheimer-s-disease-at-the-prodromal-stage
#7
Olivier Bousiges, Stephanie Bombois, Susanna Schraen, David Wallon, Muriel Muraine Quillard, Audrey Gabelle, Sylvain Lehmann, Claire Paquet, Elodie Amar-Bouaziz, Eloi Magnin, Carole Miguet-Alfonsi, Xavier Delbeuck, Thomas Lavaux, Pierre Anthony, Nathalie Philippi, Frederic Blanc
BACKGROUND: Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is not straightforward, especially in the early stages of disease. We compared AD biomarkers (phospho-Tau181, total-Tau, Aβ42 and Aβ40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing especially on the prodromal stage. METHODS: A total of 1221 CSF were collected in different memory centres (ePLM network) in France and analysed retrospectively...
January 10, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29311330/gba1-deficiency-negatively-affects-physiological-%C3%AE-synuclein-tetramers-and-related-multimers
#8
Sangjune Kim, Seung Pil Yun, Saebom Lee, George Essien Umanah, Veera Venkata Ratnam Bandaru, Xiling Yin, Peter Rhee, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Hojae Lee, Xiaobo Mao, Donghoon Kim, Akhilesh Pandey, Gabsang Lee, Valina L Dawson, Ted M Dawson, Han Seok Ko
Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#9
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29305919/pathological-role-of-lipid-interaction-with-%C3%AE-synuclein-in-parkinson-s-disease
#10
REVIEW
Mari Suzuki, Kazunori Sango, Keiji Wada, Yoshitaka Nagai
Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In sporadic PD and DLB, normally harmless αSyn proteins without any mutations might gain toxic functions by unknown mechanisms. Thus, it is important to elucidate the factors promoting the toxic conversion of αSyn, towards understanding the pathogenesis of and developing disease-modifying therapies for PD and DLB. Accumulating biophysical and biochemical studies have demonstrated that αSyn interacts with lipid membrane, and the interaction influences αSyn oligomerization and aggregation...
January 3, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29305061/a-refined-concept-%C3%AE-synuclein-dysregulation-disease
#11
REVIEW
Hideki Mochizuki, Chi-Jing Choong, Eliezer Masliah
α-synuclein (αSyn) still remains a mysterious protein even two decades after SNCA encoding it was identified as the first causative gene of familial Parkinson's disease (PD). Accumulation of αSyn causes α-synucleinopathies including PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent advances in therapeutic approaches offer new antibody-, vaccine-, antisense-oligonucleotide- and small molecule-based options to reduce αSyn protein levels and aggregates in patient's brain. Gathering research information of other neurological disease particularly Alzheimer's disease, recent disappointment of an experimental amyloid plaques busting antibody in clinical trials underscores the difficulty of treating people who show even mild dementia as damage in their brain may already be too extensive...
January 2, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29297596/neuropathology-of-autonomic-dysfunction-in-synucleinopathies
#12
REVIEW
Elizabeth A Coon, Jeremy K Cutsforth-Gregory, Eduardo E Benarroch
The synucleinopathies-Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure-result from distinct patterns of abnormal α-synuclein aggregation throughout the nervous system. Autonomic dysfunction in these disorders results from variable involvement of the central and peripheral autonomic networks. The major pathologic hallmark of Parkinson's disease and dementia with Lewy bodies is Lewy bodies and Lewy neurites; of multiple system atrophy, oligodendroglial cytoplasmic inclusions; and of pure autonomic failure, peripheral neuronal cytoplasmic inclusions...
January 3, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29296658/longitudinal-patterns-of-potentially-inappropriate-medication-use-following-incident-dementia-diagnosis
#13
Christine M Ramsey, Danijela Gnjidic, George O Agogo, Heather Allore, Daniela Moga
Introduction: Potentially inappropriate medication (PIM) use in older adults with dementia is an understudied area. We assessed longitudinal changes in PIM exposure by dementia type following dementia diagnosis. Methods: We followed 2448 participants aged ≥65 years (52% women, 85.5% Caucasian, mean age 80.9 ± 7.5 years) diagnosed with dementia after enrollment in the National Alzheimer's Coordinating Center (2005-2014). We estimated the association between dementia type and PIM annually for 2 years after diagnosis, using Generalized Estimating Equations...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29282408/behavioural-and-psychological-symptoms-of-dementia-correlates-and-impact-on-caregiver-distress
#14
Adreesh Mukherjee, Atanu Biswas, Arijit Roy, Samar Biswas, Goutam Gangopadhyay, Shyamal Kumar Das
Aims: To evaluate the behavioural and psychological symptoms of dementia (BPSD), to determine their correlation with types and stages of dementia and patient demographics, and to assess the impact on caregiver distress. Methods: This cross-sectional study recruited consecutive dementia patients and caregivers who attended our cognitive clinic. Standard criteria were used to classify types of dementia. BPSD were assessed with the Neuropsychiatric Inventory, and its distress scale was used for caregiver distress...
September 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/29278715/accumulation-of-beta-synuclein-in-cortical-neurons-is-associated-with-autophagy-attenuation-in-the-brains-of-dementia-with-lewy-body-patients
#15
Tracey Evans, Wai Ling Kok, Katrina Cowan, Megan Hefford, Oleg Anichtchik
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls...
December 23, 2017: Brain Research
https://www.readbyqxmd.com/read/29261640/the-added-value-of-dynamic-18f-florbetapir-pet-in-the-assessment-of-dementia-with-lewy-bodies
#16
Diego Alfonso López Mora, Valle Camacho, Alberto Lleó, Alejandro Fernández, Ignasi Carrió
Dementia with Lewy bodies (DLB) is the most common cause of dementia after Alzheimer disease. It is often underdiagnosed because of the overlapping with Alzheimer disease symptoms. We report the F-FDG and F-florbetapir dynamic PET images (early and delay phases) of an 83-year-old woman with cognitive impairment associated with visual hallucinations and parkinsonism due to probable DLB. This image highlights that the early phases of F-florbetapir may reflect regional cerebral perfusion with a pattern very similar to that of regional glucose metabolism in DLB...
December 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29260408/practical-treatment-of-lewy-body-disease-in-the-clinic-patient-and-physician-perspectives
#17
Elisabet Londos
This article describes the practical considerations in the clinical medical treatment in dementia with Lewy body (DLB) patients. It is illustrated with the voice of a DLB sufferer and his wife. According to our experience, emanating from a 15 year collaboration between a doctor and a nurse at a memory clinic, there are several possible therapeutical entrances. However, the order in which the medication is introduced is of great importance to avoid aggravation of other DLB symptoms. We start the treatment with cholinesterase inhibitor and memantine, and; thereafter, we treat the most disturbing symptom...
December 19, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/29258624/a-selenium-species-in-cerebrospinal-fluid-predicts-conversion-to-alzheimer-s-dementia-in-persons-with-mild-cognitive-impairment
#18
Marco Vinceti, Annalisa Chiari, Marcel Eichmüller, Kenneth J Rothman, Tommaso Filippini, Carlotta Malagoli, Jennifer Weuve, Manuela Tondelli, Giovanna Zamboni, Paolo F Nichelli, Bernhard Michalke
BACKGROUND: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. METHODS: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin...
December 19, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29249935/loss-of-neuroprotective-factors-in-neurodegenerative-dementias-the-end-or-the-starting-point
#19
REVIEW
Luisa Benussi, Giuliano Binetti, Roberta Ghidoni
Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29248892/peripheral-inflammation-in-prodromal-alzheimer-s-and-lewy-body-dementias
#20
Eleanor King, John Tiernan O'Brien, Paul Donaghy, Christopher Morris, Nicola Barnett, Kirsty Olsen, Carmen Martin-Ruiz, John-Paul Taylor, Alan J Thomas
OBJECTIVES: There is growing evidence for the role of systemic inflammation in Alzheimer's disease (AD) and other neurodegenerative diseases; however the systemic inflammatory profile in dementia with Lewy bodies (DLB) has never before been investigated. This study aimed to characterise systemic inflammatory mediators in established DLB and AD, as well as in their prodromal, mild cognitive impairment (MCI) phases. METHODS: We obtained plasma samples from patients with DLB (n=37), AD (n=20), MCI with DLB profile (n=38), MCI with AD profile (n=20) and healthy control subjects (n=20)...
December 16, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
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