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Lewy body disease

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https://www.readbyqxmd.com/read/28103749/clinical-practice-with-anti-dementia-drugs-a-revised-third-consensus-statement-from-the-british-association-for-psychopharmacology
#1
John T O'Brien, Clive Holmes, Matthew Jones, Roy Jones, Gill Livingston, Ian McKeith, Peter Mittler, Peter Passmore, Craig Ritchie, Louise Robinson, Elizabeth L Sampson, John-Paul Taylor, Alan Thomas, Alistair Burns
The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B)...
December 1, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#2
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093795/the-natural-history-of-pure-autonomic-failure-a-u-s-prospective-cohort
#3
Horacio Kaufmann, Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Italo Biaggioni, Phillip A Low, Wolfgang Singer, David S Goldstein, Amanda C Peltier, Cyndia A Shibao, Christopher H Gibbons, Roy Freeman, David Robertson
OBJECTIVE: To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. METHODS: One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the U.S. Seventy-four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests...
January 17, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28088928/multi-modal-mri-investigation-of-volumetric-and-microstructural-changes-in-the-hippocampus-and-its-subfields-in-mild-cognitive-impairment-alzheimer-s-disease-and-dementia-with-lewy-bodies
#4
Elijah Mak, Silvy Gabel, Li Su, Guy B Williams, Robert Arnold, Luca Passamonti, Patricia Vazquez Rodríguez, Ajenthan Surendranathan, W Richard Bevan-Jones, James B Rowe, John T O'Brien
BACKGROUND: Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB). METHODS: A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation...
January 16, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28088604/alba-screening-instrument-asi-a-brief-screening-tool-for-lewy-body-dementia
#5
M M Garcia Basalo, M C Fernandez, M Ojea Quintana, J I Rojas, M J Garcia Basalo, E Bogliotti, N Campora, M Fernandez, W Berrios, E Cristiano, A Golimstok
BACKGROUND: Early detection of neurodegenerative diseases is essential for treatment and proper care of these patients. Screening tools available today are effective for several types of dementia. However, there is no one specific for Lewy Body Dementia (LBD). OBJECTIVES: The aim of this paper is to present a tool for early detection of LBD, accessible even for non-medical staff. METHODS: We stratified subjects (MMSE>20) into four groups: health controls (HC), Mild Cognitive Impairment (MCI), LBD and other dementias (Alzheimer and vascular)...
January 5, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/28088312/dementia-in-parkinson-s-disease
#6
REVIEW
Hasmet A Hanagasi, Zeynep Tufekcioglu, Murat Emre
Dementia can occur in a substantial number of patients with Parkinson's disease with a point prevalence close to 30%. The cognitive profile is characterized by predominant deficits in executive, visuospatial functions, attention and memory. Behavioral symptoms are frequent such as apathy, visual hallucinations and delusions. The most prominent associated pathology is Lewy body-type and biochemical deficit is cholinergic. Placebo-controlled randomized trials with cholinesterase inhibitors demonstrated modest but significant benefits in cognition, behavioral symptoms and global functions...
January 5, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28087304/sleep-and-neurodegeneration-a-critical-appraisal
#7
REVIEW
Jagan A Pillai, James B Leverenz
Sleep abnormalities are clearly recognized as distinct clinical symptom of concern in neurodegenerative disorders. Appropriate management of sleep related symptoms has a positive impact on the quality of life of patients with neurodegenerative disorders. This review provides an overview of mechanisms that are currently being considered that tie sleep with neurodegeneration. It appraises the literature regarding specific sleep changes among common neurodegenerative diseases with a focus on Alzheimer's disease and synucleinopathies (i...
January 10, 2017: Chest
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#8
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28077166/threonine-175-a-novel-pathological-phosphorylation-site-on-tau-protein-linked-to-multiple-tauopathies
#9
Alexander J Moszczynski, Wencheng Yang, Robert Hammond, Lee Cyn Ang, Michael J Strong
Microtubule associated protein tau (tau) deposition is associated with a spectrum of neurodegenerative diseases collectively termed tauopathies. We have previously shown that amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci) is associated with tau phosphorylation at Thr(175) and that this leads to activation of GSK3β which then induces phosphorylation at tau Thr(231). This latter step leads to dissociation of tau from microtubules and pathological tau fibril formation. To determine the extent to which this pathway is unique to ALS, we have investigated the expression of pThr(175) tau and pThr(231) tau across a range of frontotemporal degenerations...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28072380/network-functional-connectivity-and-whole-brain-functional-connectomics-to-investigate-cognitive-decline-in-neurodegenerative-conditions
#10
REVIEW
O Dipasquale, Mara Cercignani
Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC...
October 2016: Functional Neurology
https://www.readbyqxmd.com/read/28069058/endosulfine-alpha-inhibits-membrane-induced-%C3%AE-synuclein-aggregation-and-protects-against-%C3%AE-synuclein-neurotoxicity
#11
Daniel Ysselstein, Benjamin Dehay, Isabel M Costantino, George P McCabe, Matthew P Frosch, Julia M George, Erwan Bezard, Jean-Christophe Rochet
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in the pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Evidence suggests that the self-assembly of aSyn conformers bound to phospholipid membranes in an aggregation-prone state plays a key role in aSyn neurotoxicity. Accordingly, we hypothesized that protein binding partners of lipid-associated aSyn could inhibit the formation of toxic aSyn oligomers at membrane surfaces...
January 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28064175/neuroimaging-of-inflammation-in-memory-and-related-other-disorders-nimrod-study-protocol-a-deep-phenotyping-cohort-study-of-the-role-of-brain-inflammation-in-dementia-depression-and-other-neurological-illnesses
#12
W Richard Bevan-Jones, Ajenthan Surendranathan, Luca Passamonti, Patricia Vázquez Rodríguez, Robert Arnold, Elijah Mak, Li Su, Jonathan P Coles, Tim D Fryer, Young T Hong, Guy Williams, Franklin Aigbirhio, James B Rowe, John T O'Brien
INTRODUCTION: Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis...
January 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28062571/performance-of-a-condensed-protocol-that-reduces-effort-and-cost-of-nia-aa-guidelines-for-neuropathologic-assessment-of-alzheimer-disease
#13
Margaret E Flanagan, Desiree A Marshall, Jane B Shofer, Kathleen S Montine, Peter T Nelson, Thomas J Montine, C Dirk Keene
Concerns regarding resource expenditures have been expressed about the 2012 NIA-AA Sponsored Guidelines for neuropathologic assessment of Alzheimer disease (AD) and related dementias. Here, we investigated a cost-reducing Condensed Protocol and its effectiveness in maintaining the diagnostic performance of Guidelines in assessing AD, Lewy body disease (LBD), microvascular brain injury, hippocampal sclerosis (HS), and congophilic amyloid angiopathy (CAA). The Condensed Protocol consolidates the same 20 regions into 5 tissue cassettes at ∼75% lower cost...
January 6, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#14
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28059471/specific-patterns-of-neuronal-loss-in-the-pulvinar-nucleus-in-dementia-with-lewy-bodies
#15
Daniel Erskine, Alan J Thomas, Johannes Attems, John-Paul Taylor, Ian G McKeith, Christopher M Morris, Ahmad A Khundakar
BACKGROUND: Complex visual hallucinations occur in 70%-80% of dementia with Lewy bodies patients and significantly affect well-being. Despite the prevalence of visual hallucinations in dementia with Lewy bodies, the neuropathological basis of this phenomenon is poorly understood. The pulvinar nucleus of the thalamus has not previously been neuropathologically examined, but has been linked to visual hallucinations in dementia with Lewy bodies. The objective of this study was to investigate whether neuropathological or morphometric changes occur in the pulvinar nucleus in dementia with Lewy bodies cases that may contribute to visual hallucinations...
January 6, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28058207/memory-loss-five-new-things
#16
Ferenc Deak, Nidhi Kapoor, Calin Prodan, Linda A Hershey
PURPOSE OF REVIEW: Memory loss can be due to a wide variety of causes. We provide new information about the biology of common genetic and acquired causes of memory loss in older adults. RECENT FINDINGS: New data are available about the genetics of Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia. Amyloid PET, FDG-PET, and MRI have improved our understanding of how mild cognitive impairment evolves to AD. Several studies have shown links between concussion and chronic traumatic encephalopathy...
December 2016: Neurology. Clinical Practice
https://www.readbyqxmd.com/read/28057070/distinct-pattern-of-enteric-phospho-alpha-synuclein-aggregates-and-gene-expression-profiles-in-patients-with-parkinson-s-disease
#17
Martina Barrenschee, Dimitri Zorenkov, Martina Böttner, Christina Lange, François Cossais, Amelie Bernadette Scharf, Günther Deuschl, Susanne A Schneider, Mark Ellrichmann, Annette Fritscher-Ravens, Thilo Wedel
Phosphorylated alpha-synuclein (p-α-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) are neuropathological hallmarks of Parkinson's disease (PD) in the central nervous system (CNS). Since they have been also demonstrated in the enteric nervous system (ENS) of PD patients, the aim of the study was to analyze enteric p-α-syn positive aggregates and intestinal gene expression. Submucosal rectal biopsies were obtained from patients with PD and controls and processed for dual-label-immunohistochemistry for p-α-syn and PGP 9...
January 5, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28053029/mutant-%C3%AE-synuclein-overexpression-induces-stressless-pacemaking-in-vagal-motoneurons-at-risk-in-parkinson-s-disease
#18
Efrat Lasser-Katz, Alon Simchovitz, Wei-Hua Chiu, Wolfgang H Oertel, Ronit Sharon, Hermona Soreq, Jochen Roeper, Joshua A Goldberg
: α-Synuclein overexpression (ASOX) drives the formation of toxic aggregates in neurons vulnerable in Parkinson's disease (PD), including dopaminergic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsal motor nucleus of the vagus (DMV). Just as these populations differ in when they exhibit α-synucleinopathies during PD pathogenesis, they could also differ in their physiological responses to ASOX. An ASOX-mediated hyperactivity of SN dopamine neurons, which was caused by oxidative dysfunction of Kv4...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28050656/the-recommendations-of-a-consensus-panel-for-the-screening-diagnosis-and-treatment-of-neurogenic-orthostatic-hypotension-and-associated-supine-hypertension
#19
REVIEW
Christopher H Gibbons, Peter Schmidt, Italo Biaggioni, Camille Frazier-Mills, Roy Freeman, Stuart Isaacson, Beverly Karabin, Louis Kuritzky, Mark Lew, Phillip Low, Ali Mehdirad, Satish R Raj, Steven Vernino, Horacio Kaufmann
Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy. Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management. To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards 'best practices' when treating patients with nOH and associated supine hypertension...
January 3, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28045661/screening-and-brief-intervention-for-obesity-in-primary-care-a-parallel-two-arm-randomised-trial
#20
Paul Aveyard, Amanda Lewis, Sarah Tearne, Kathryn Hood, Anna Christian-Brown, Peymane Adab, Rachna Begh, Kate Jolly, Amanda Daley, Amanda Farley, Deborah Lycett, Alecia Nickless, Ly-Mee Yu, Lise Retat, Laura Webber, Laura Pimpin, Susan A Jebb
BACKGROUND: Obesity is a common cause of non-communicable disease. Guidelines recommend that physicians screen and offer brief advice to motivate weight loss through referral to behavioural weight loss programmes. However, physicians rarely intervene and no trials have been done on the subject. We did this trial to establish whether physician brief intervention is acceptable and effective for reducing bodyweight in patients with obesity. METHODS: In this parallel, two-arm, randomised trial, patients who consulted 137 primary care physicians in England were screened for obesity...
October 21, 2016: Lancet
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