The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ian G Mckeith - One of the best experts on this subject based on the ideXlab platform.
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research criteria for the diagnosis of prodromal dementia with Lewy Bodies
Neurology, 2020Co-Authors: Ian G Mckeith, Alan J Thomas, Bradley F. Boeve, Tanis J. Ferman, John T Obrien, Hiroshige Fujishiro, Kejal Kantarci, Frederic Blanc, Cristina Muscio, Ronald B PostumaAbstract:The prodromal phase of dementia with Lewy Bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy Bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
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neuropsychiatric symptoms and cognitive profile in mild cognitive impairment with Lewy Bodies
Psychological Medicine, 2018Co-Authors: Paul C Donaghy, Johnpaul Taylor, Nicola Barnett, Kirsty Olsen, Sean J Colloby, J J Lloyd, George Petrides, Ian G Mckeith, John T Obrien, Alan J ThomasAbstract:BACKGROUND: The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy Bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD). METHODS: Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy Bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy. RESULTS: MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD. CONCLUSIONS: MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
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diagnosis and management of dementia with Lewy Bodies fourth consensus report of the dlb consortium
Neurology, 2017Co-Authors: Ian G Mckeith, Johnpaul Taylor, Bradley F. Boeve, Dennis W Dickson, Dag Aarsland, James E Galvin, Glenda M Halliday, Daniel Weintraub, Johannes AttemsAbstract:The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy Bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
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dementia with Lewy Bodies
2011Co-Authors: Ian G MckeithAbstract:Dementia with Lewy Bodies is relatively common cause of degenerative dementia in older people. This debilitating disorder is comprised of core features including dementia, fluctuating cognition, motor parkinsonism, and visual hallucinations, as well as other symptoms such as rapid eye movement sleep behavior disorder, olfactory dysfunction, autonomic dysfunction, sensitivity to neuroleptics, anxiety, depression, and delusions. Pharmacotherapy, so far exclusively symptomatic, should be implemented with caution and only when symptoms are disturbing and after non-pharmacological interventions fail. Treatment with acetylcholinesterase inhibitors (AChEi), such as donepezil and rivastimine, is considered a first line therapy. There is substantial evidence that AChEi address cognitive as well as behavioral symptoms without substantially increasing parkinsonism. Dopaminergic treatment for motor symptoms requires balancing risk of worsened psychosis and is consider only moderately beneficial.
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dementia with Lewy Bodies
Handbook of Clinical Neurology, 2007Co-Authors: Ian G MckeithAbstract:Publisher Summary Dementia with Lewy Bodies (DLB) is a clinicopathological syndrome, which account for up to 20% of all elderly cases of dementia reaching autopsy, with a clinical presentation primarily characterized by cognitive decline leading to dementia, accompanied in majority of cases by extrapyramidal motor features and additional neuropsychiatric features. It is considered a part of a larger spectrum of LB disease that exhibit diverse clinical presentations, including Parkinson's disease (PD0, primary autonomic failure, and REM sleep behavior disorder (RBD). The central characteristic of DLB is a progressive dementia with marked impairments in visuoperceptual, attentional, and executive functions reflecting a combination of cortical and subcortical damage. Fluctuating cognition, recurrent visual hallucinations (VHs) and extrapyramidal motor symptoms are the core features by which DLB can be clinically recognized. At autopsy DLB is neuropathologically indistinguishable from dementia occurring late in the course of Parkinson's disease (PDD). ChEIs offer the greatest benefits for symptomatic improvement in both psychotic and cognitive features of DLB without significant compromise of motor function.
John T Obrien - One of the best experts on this subject based on the ideXlab platform.
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research criteria for the diagnosis of prodromal dementia with Lewy Bodies
Neurology, 2020Co-Authors: Ian G Mckeith, Alan J Thomas, Bradley F. Boeve, Tanis J. Ferman, John T Obrien, Hiroshige Fujishiro, Kejal Kantarci, Frederic Blanc, Cristina Muscio, Ronald B PostumaAbstract:The prodromal phase of dementia with Lewy Bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy Bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
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neuropsychiatric symptoms and cognitive profile in mild cognitive impairment with Lewy Bodies
Psychological Medicine, 2018Co-Authors: Paul C Donaghy, Johnpaul Taylor, Nicola Barnett, Kirsty Olsen, Sean J Colloby, J J Lloyd, George Petrides, Ian G Mckeith, John T Obrien, Alan J ThomasAbstract:BACKGROUND: The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy Bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD). METHODS: Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy Bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy. RESULTS: MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD. CONCLUSIONS: MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
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longitudinal assessment of global and regional atrophy rates in alzheimer s disease and dementia with Lewy Bodies
NeuroImage: Clinical, 2015Co-Authors: Li Su, Michael J. Firbank, Guy B Williams, Rosie Watson, Andrew M Blamire, John T ObrienAbstract:Background & objective Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy Bodies (DLB), and investigated associations with clinical measures.
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visual perception in parkinson disease dementia and dementia with Lewy Bodies
Neurology, 2004Co-Authors: Urs Peter Mosimann, John T Obrien, George Mather, Keith Wesnes, David J Burn, Ian G MckeithAbstract:Objective: To quantify visual discrimination, space-motion, and object-form perception in patients with Parkinson disease dementia (PDD), dementia with Lewy Bodies (DLB), and Alzheimer disease (AD). Methods: The authors used a cross-sectional study to compare three demented groups matched for overall dementia severity (PDD: n = 24; DLB: n = 20; AD: n = 23) and two age-, sex-, and education-matched control groups (PD: n = 24, normal controls [NC]: n = 25). Results: Visual perception was globally more impaired in PDD than in nondemented controls (NC, PD), but was not different from DLB. Compared to AD, PDD patients tended to perform worse in all perceptual scores. Visual perception of patients with PDD/DLB and visual hallucinations was significantly worse than in patients without hallucinations. Conclusions: Parkinson disease dementia (PDD) is associated with profound visuoperceptual impairments similar to dementia with Lewy Bodies (DLB) but different from Alzheimer disease. These findings are consistent with previous neuroimaging studies reporting hypoactivity in cortical areas involved in visual processing in PDD and DLB.
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dementia with Lewy Bodies and ad are not associated with occipital lobe atrophy on mri
Neurology, 2001Co-Authors: Huub A. M. Middelkoop, Wiesje M Van Der Flier, Emma J Burton, Adrian J Lloyd, S M Paling, Robert Barber, Clive Ballard, Ian G Mckeith, John T ObrienAbstract:Dementia with Lewy Bodies (DLB) is associated with occipital changes in blood flow and metabolism, but structural changes in this region have not previously been assessed. The authors performed volumetric MRI measurement of the occipital lobe blind to the diagnosis in 23 subjects with DLB, 25 with AD, and 24 age-matched control subjects. There were no significant differences between groups in occipital lobe volume. The authors conclude gross structural changes in the occipital lobe do not occur in patients with mild to moderate DLB or AD.
Bradley F. Boeve - One of the best experts on this subject based on the ideXlab platform.
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research criteria for the diagnosis of prodromal dementia with Lewy Bodies
Neurology, 2020Co-Authors: Ian G Mckeith, Alan J Thomas, Bradley F. Boeve, Tanis J. Ferman, John T Obrien, Hiroshige Fujishiro, Kejal Kantarci, Frederic Blanc, Cristina Muscio, Ronald B PostumaAbstract:The prodromal phase of dementia with Lewy Bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy Bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
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18f av 1451 uptake differs between dementia with Lewy Bodies and posterior cortical atrophy
Movement Disorders, 2019Co-Authors: Zuzana Nedelska, Bradley F. Boeve, Scott A Przybelski, David S Knopman, Jonathan Graffradford, Timothy G Lesnick, Keith A. Josephs, Daniel A. Drubach, Ronald C. Petersen, Clifford R. JackAbstract:BACKGROUND Posterior cortical atrophy and dementia with Lewy Bodies are 2 distinct clinical syndromes, yet they can overlap in symptoms and occipital hypometabolism. Patients with dementia with Lewy Bodies often have overlapping Alzheimer's disease pathology. Similarly, Lewy Bodies can be found in patients with posterior cortical atrophy. We investigated differences in the distribution and magnitude of F18-AV-1451 uptake in patients with these 2 syndromes. METHODS Consecutive patients with probable dementia with Lewy Bodies (n = 33), posterior cortical atrophy (n = 18), and cognitively unimpaired controls (n = 100) underwent 18 F-AV-1451 positron emission tomography. Regional differences in AV-1451 uptake were assessed using voxel-wise and an atlas-based approach. The greatest differences in AV-1451 uptake between patient groups were identified using area under receiver operating curve statistics, and a composite region was derived. RESULTS AV-1451 uptake in both patient groups was predominantly localized to the lateral occipital regions, but the magnitude of uptake was markedly greater in posterior cortical atrophy compared with dementia with Lewy Bodies. The posterior cortical atrophy group showed the greatest AV-1451 uptake throughout all the gray matter compared with that in other groups. The occipital composite region, consisting of superior, middle, and inferior occipital cortices, distinguished posterior cortical atrophy from dementia with Lewy Bodies (area under the curve >0.97; P < 0.001, Bonferroni-corrected) with excellent sensitivity (88%) and specificity (100%). CONCLUSIONS Posterior cortical atrophy and dementia with Lewy Bodies can share clinical features, and although the pattern of AV-1451 uptake in occipital cortices overlaps between these 2 syndromes, its magnitude is significantly higher in posterior cortical atrophy. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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18 f av 1451 uptake differs between dementia with Lewy Bodies and posterior cortical atrophy
Movement Disorders, 2019Co-Authors: Zuzana Nedelska, Bradley F. Boeve, Scott A Przybelski, David S Knopman, Jonathan Graffradford, Timothy G Lesnick, Keith A. Josephs, Daniel A. Drubach, Ronald C. Petersen, Clifford R. JackAbstract:BACKGROUND Posterior cortical atrophy and dementia with Lewy Bodies are 2 distinct clinical syndromes, yet they can overlap in symptoms and occipital hypometabolism. Patients with dementia with Lewy Bodies often have overlapping Alzheimer's disease pathology. Similarly, Lewy Bodies can be found in patients with posterior cortical atrophy. We investigated differences in the distribution and magnitude of F18-AV-1451 uptake in patients with these 2 syndromes. METHODS Consecutive patients with probable dementia with Lewy Bodies (n = 33), posterior cortical atrophy (n = 18), and cognitively unimpaired controls (n = 100) underwent 18 F-AV-1451 positron emission tomography. Regional differences in AV-1451 uptake were assessed using voxel-wise and an atlas-based approach. The greatest differences in AV-1451 uptake between patient groups were identified using area under receiver operating curve statistics, and a composite region was derived. RESULTS AV-1451 uptake in both patient groups was predominantly localized to the lateral occipital regions, but the magnitude of uptake was markedly greater in posterior cortical atrophy compared with dementia with Lewy Bodies. The posterior cortical atrophy group showed the greatest AV-1451 uptake throughout all the gray matter compared with that in other groups. The occipital composite region, consisting of superior, middle, and inferior occipital cortices, distinguished posterior cortical atrophy from dementia with Lewy Bodies (area under the curve >0.97; P < 0.001, Bonferroni-corrected) with excellent sensitivity (88%) and specificity (100%). CONCLUSIONS Posterior cortical atrophy and dementia with Lewy Bodies can share clinical features, and although the pattern of AV-1451 uptake in occipital cortices overlaps between these 2 syndromes, its magnitude is significantly higher in posterior cortical atrophy. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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diagnosis and management of dementia with Lewy Bodies fourth consensus report of the dlb consortium
Neurology, 2017Co-Authors: Ian G Mckeith, Johnpaul Taylor, Bradley F. Boeve, Dennis W Dickson, Dag Aarsland, James E Galvin, Glenda M Halliday, Daniel Weintraub, Johannes AttemsAbstract:The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy Bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
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av 1451 tau and β amyloid positron emission tomography imaging in dementia with Lewy Bodies
Annals of Neurology, 2017Co-Authors: Kejal Kantarci, Bradley F. Boeve, Val J Lowe, Matthew L Senjem, Timothy G Lesnick, Nikki Tosakulwong, Anthony J Spychalla, Jeffrey L Gunter, Julie A Fields, Jonathan GraffradfordAbstract:Objective: Patients with probable dementia with Lewy Bodies often have Alzheimer's disease-related pathology. Our objective was to determine the pattern of positron emission tomography tau tracer AV-1451 uptake in patients with probable dementia with Lewy Bodies, compared to Alzheimer's disease, and its relationship to β-amyloid deposition on positron emission tomography. Methods: Consecutive patients with clinically probable dementia with Lewy Bodies (n=19) from the Mayo Clinic Alzheimer's Disease Research Center underwent MRI, AV-1451 and Pittsburgh compound-B positron emission tomography examinations. Age and sex matched groups of Alzheimer's disease dementia (n=19) patients and clinically normal controls (n=95) from an epidemiological cohort served as a comparison groups. Atlas-based and voxel-based analyses were performed. Results: The Alzheimer's disease dementia group had significantly higher AV-1451 uptake than the probable dementia with Lewy Bodies group, and medial temporal uptake completely distinguished Alzheimer's disease dementia from probable dementia with Lewy Bodies. Patients with probable dementia with Lewy Bodies had greater AV-1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable dementia with Lewy Bodies, the uptake in these regions correlated with global Pittsburgh compound-B uptake (Spearman rho= 0.63; p=0.006). Interpretation: Medial temporal lobe AV-1451 uptake distinguishes Alzheimer's disease dementia from probable dementia with Lewy Bodies, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV-1451 uptake in probable dementia with Lewy Bodies and its association with global Pittsburgh compound-B uptake suggest an atypical pattern of tau deposition in dementia with Lewy Bodies. This article is protected by copyright. All rights reserved.
Michel Goedert - One of the best experts on this subject based on the ideXlab platform.
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the α synucleinopathies parkinson s disease dementia with Lewy Bodies and multiple system atrophy
Annals of the New York Academy of Sciences, 2006Co-Authors: Maria Grazia Spillantini, Michel GoedertAbstract:Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Neuropathologically, it is characterized by the degeneration of populations of nerve cells that develop filamentous inclusions in the form of Lewy Bodies and Lewy neurites. Recent work has shown that the filamentous inclusions of Parkinson's disease are made of the protein alpha-synuclein and that rare, familial forms of Parkinson's disease are caused by missense mutations in the alpha-synuclein gene. Besides Parkinson's disease, the filamentous inclusions of two additional neurodegenerative diseases, namely, dementia with Lewy Bodies and multiple system atrophy, have also been found to be made of alpha-synuclein. Recombinant alpha-synuclein has been shown to assemble into filaments with similar morphologies to those found in the human diseases and with a cross-beta fiber diffraction pattern. The new work has established the alpha-synucleinopathies as a major class of neurodegenerative disease.
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filamentous α synuclein inclusions link multiple system atrophy with parkinson s disease and dementia with Lewy Bodies
Neuroscience Letters, 1998Co-Authors: Maria Grazia Spillantini, Ross Jakes, R A Crowther, Nigel J Cairns, Peter L Lantos, Michel GoedertAbstract:α-Synuclein forms the major component of Lewy Bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy Bodies. Here we show that α-synuclein is also the major component of the filamentous inclusions of multiple system atrophy which comprises several neurodegenerative diseases with a shared filamentous pathology in nerve cells and glial cells. These findings provide an unexpected link between multiple system atrophy and Lewy body disorders and establish that α-synucleinopathies constitute a major class of human neurodegenerative disorder.
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α synuclein in filamentous inclusions of Lewy Bodies from parkinson s disease and dementia with Lewy Bodies
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Maria Grazia Spillantini, Ross Jakes, R A Crowther, Masato Hasegawa, Michel GoedertAbstract:Lewy Bodies and Lewy neurites are the defining neuropathological characteristics of Parkinson’s disease and dementia with Lewy Bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy Bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy Bodies are stained strongly by antiBodies directed against amino-terminal and carboxyl-terminal sequences of α-synuclein, showing the presence of full-length or close to full-length α-synuclein. The number of α-synuclein-stained structures exceeded that immunoreactive for ubiquitin, which is currently the most sensitive marker of Lewy Bodies and Lewy neurites. Staining for α-synuclein thus will replace staining for ubiquitin as the preferred method for detecting Lewy Bodies and Lewy neurites. We have isolated Lewy body filaments by a method used for the extraction of paired helical filaments from Alzheimer’s disease brain. By immunoelectron microscopy, extracted filaments were labeled strongly by anti-α-synuclein antiBodies. The morphologies of the 5- to 10-nm filaments and their staining characteristics suggest that extended α-synuclein molecules run parallel to the filament axis and that the filaments are polar structures. These findings indicate that α-synuclein forms the major filamentous component of Lewy Bodies and Lewy neurites.
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alpha synuclein in Lewy Bodies
Nature, 1997Co-Authors: Maria Grazia Spillantini, John Q. Trojanowski, M L Schmidt, Virginia M Y Lee, Ross Jakes, Michel GoedertAbstract:Lewy Bodies, a defining pathological characteristic of Parkinson's disease and dementia with Lewy Bodies (DLB)1,2,3,4, constitute the second most common nerve cell pathology, after the neurofibrillary lesions of Alzheimer's disease. Their formation may cause neurodegeneration, but their biochemical composition is unknown. Neurofilaments and ubiquitin are present5,6,7,8, but it is unclear whether they are major components of the filamentous material of the Lewy body9,10. Here we describe strong staining of Lewy Bodies from idiopathic Parkinson's disease with antiBodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease11. α-Synuclein may be the main component of the Lewy body in Parkinson's disease. We also show staining for α-synuclein of Lewy Bodies from DLB, indicating that the Lewy Bodies from these two diseases may have identical compositions.
Dennis W Dickson - One of the best experts on this subject based on the ideXlab platform.
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diagnosis and management of dementia with Lewy Bodies fourth consensus report of the dlb consortium
Neurology, 2017Co-Authors: Ian G Mckeith, Johnpaul Taylor, Bradley F. Boeve, Dennis W Dickson, Dag Aarsland, James E Galvin, Glenda M Halliday, Daniel Weintraub, Johannes AttemsAbstract:The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy Bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
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abnormal daytime sleepiness in dementia with Lewy Bodies compared to alzheimer s disease using the multiple sleep latency test
Alzheimer's Research & Therapy, 2014Co-Authors: Tanis J. Ferman, Dennis W Dickson, David S Knopman, Glenn E Smith, Ronald C. Petersen, Neill R Graffradford, Ryan J Uitti, Zbigniew K Wszolek, Jay A Van Gerpen, Joseph E. ParisiAbstract:Introduction Excessive daytime sleepiness is a commonly reported problem in dementia with Lewy Bodies (DLB). We examined the relationship between nighttime sleep continuity and the propensity to fall asleep during the day in clinically probable DLB compared to Alzheimer’s disease (AD) dementia.
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convergence of pathology in dementia with Lewy Bodies and alzheimer s disease a role for the novel interaction of alpha synuclein and presenilin 1 in disease
Brain, 2014Co-Authors: Ashley R Winslow, Dennis W Dickson, Simon Moussaud, Liya Zhu, Katherine L Post, Oksana Berezovska, Pamela J McleanAbstract:A growing number of PSEN1 mutations have been associated with dementia with Lewy Bodies and familial Alzheimer’s disease with concomitant α-synuclein pathology. The objective of this study was to determine if PSEN1 plays a direct role in the development of α-synuclein pathology in these diseases. Using mass spectrometry, immunoelectron microscopy and fluorescence lifetime image microscopy based on Forster resonance energy transfer (FLIM-FRET) we identified α-synuclein as a novel interactor of PSEN1 in wild-type mouse brain tissue. The interaction of α-synuclein with PSEN1 was detected in post-mortem brain tissue from cognitively normal cases and was significantly increased in tissue from cases with dementia with Lewy Bodies and familial Alzheimer’s disease associated with known PSEN1 mutations. We confirmed an increased interaction of PSEN1 and α-synuclein in cell lines expressing well characterized familial Alzheimer’s disease PSEN1 mutations, L166P and delta exon 9, and demonstrated that PSEN1 mutations associate with increased membrane association and accumulation of α-synuclein. Our data provides evidence of a molecular interaction of PSEN1 and α-synuclein that may explain the clinical and pathophysiological overlap seen in synucleinopathies, including Parkinson’s disease, dementia with Lewy Bodies, and some forms of Alzheimer’s disease.
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multimodality imaging characteristics of dementia with Lewy Bodies
Neurobiology of Aging, 2012Co-Authors: Kejal Kantarci, Joseph E. Parisi, Bradley F. Boeve, Dennis W Dickson, Val J Lowe, Stephen D Weigand, Matthew L Senjem, Scott A Przybelski, David S Knopman, Glenn E SmithAbstract:Abstract Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Our objective was to determine whether the 11C-Pittsburgh Compound-B (PiB) retention and regional hypometabolism on positron emission tomography (PET) and regional cortical atrophy on magnetic resonance imaging (MRI) are complementary in characterizing patients with DLB and differentiating them from AD. We studied age-, gender-, and education-matched patients with a clinical diagnosis of DLB (n = 21), AD (n = 21), and cognitively normal subjects (n = 42). Hippocampal atrophy, global cortical PiB retention and occipital lobe metabolism in combination distinguished DLB from AD better than any of the measurements alone (area under the receiver operating characteristic = 0.98). Five of the DLB and AD patients who underwent autopsy were distinguished through multimodality imaging. These data demonstrate that magnetic resonance imaging and PiB positron emission tomography contribute to characterizing the distinct pathological mechanisms in patients with AD compared with DLB. Occipital and posterior parietotemporal lobe hypometabolism is a distinguishing feature of DLB and this regional hypometabolic pattern is independent of the amyloid pathology.
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rapid eye movement sleep behavior disorder and subtypes in autopsy confirmed dementia with Lewy Bodies
Movement Disorders, 2012Co-Authors: Brittany N Dugger, Joseph E. Parisi, Bradley F. Boeve, Dennis W Dickson, Melissa E Murray, Hiroshige Fujishiro, Tanis J. FermanAbstract:OBJECTIVE—To determine whether dementia with Lewy Bodies with or without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. METHODS—Patients with dementia with Lewy Bodies who have probable rapid eye movement sleep behavior sleep disorder (n=71) were compared to those without it (n=19) on demographics, clinical variables (core features of dementia with Lewy Bodies, dementia duration, rate of cognitive/motor changes) and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). RESULTS—Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% versus 47%), and had a shorter duration of dementia (mean 8 years versus 10 years), earlier onset of parkinsonism (mean 2 years versus 5 years), and earlier onset of visual hallucinations (mean 3 years versus 6 years). These patients also had a lower Braak neurofibrillary tangle stage (Stage IV versus Stage VI) and lower neuritic plaque scores (18% frequent versus 85% frequent), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared to those who developed the sleep disorder after dementia onset. Women with autopsyconfirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage.
