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lewy body dementia and Parkinson's

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https://www.readbyqxmd.com/read/28088312/dementia-in-parkinson-s-disease
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#7
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
#8
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/28050656/the-recommendations-of-a-consensus-panel-for-the-screening-diagnosis-and-treatment-of-neurogenic-orthostatic-hypotension-and-associated-supine-hypertension
#9
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/28044062/opening-up-the-dna-methylome-of-dementia
#10
R Delgado-Morales, M Esteller
Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28028735/mapping-of-surface-exposed-epitopes-of-in-vitro-and-in-vivo-aggregated-species-of-alpha-synuclein
#11
Leire Almandoz-Gil, Veronica Lindström, Jessica Sigvardson, Philipp J Kahle, Lars Lannfelt, Martin Ingelsson, Joakim Bergström
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal deposits observed in Parkinson's disease and dementia with Lewy bodies. The objective of the study was to identify surface-exposed epitopes of alpha-synuclein in vitro and in vivo formed aggregates. Polyclonal immunoglobulin Y antibodies were raised against short linear peptides of the alpha-synuclein molecule. An epitope in the N-terminal region (1-10) and all C-terminal epitopes (90-140) were found to be exposed in an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant monomeric, oligomeric, and fibrillar alpha-synuclein...
December 27, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28003435/genetic-compendium-of-1511-human-brains-available-through-the-uk-medical-research-council-brain-banks-network-resource
#12
Michael J Keogh, Wei Wei, Ian Wilson, Jon Coxhead, Sarah Ryan, Sara Rollinson, Helen Griffin, Marzena Kurzawa-Akanbi, Mauro Santibanez-Koref, 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, James W Ironside, Patrick F Chinnery
Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368)...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27976608/network-functional-connectivity-and-whole-brain-functional-connectomics-to-investigate-cognitive-decline-in-neurodegenerative-conditions
#13
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...
December 15, 2016: Functional Neurology
https://www.readbyqxmd.com/read/27956085/effects-of-%C3%AE-synuclein-on-axonal-transport
#14
Laura A Volpicelli-Daley
Lewy bodies and Lewy neurites composed primarily of α-synuclein characterize synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Despite decades of research on the impact of α-synuclein, little is known how abnormal inclusion made of this protein compromise neuronal function. Emerging evidence suggests that defects in axonal transport caused by aggregated α-synuclein contribute to neuronal dysfunction. These defects appear to occur well before the onset of neuronal death...
December 9, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27941373/added-value-of-combined-semi-quantitative-and-visual-123i-fp-cit-spect-analyses-for-the-diagnosis-of-dementia-with-lewy-bodies
#15
Nicolas Nicastro, Valentina Garibotto, Gilles Allali, Frederic Assal, Pierre R Burkhard
PURPOSE OF THE REPORT: To assess the validity of a semi-quantitative I-FP-CIT SPECT method, compared to the commonly used visual analysis, in patients with probable dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also studied DLB specific uptake impairment pattern and correlation of uptake in the presence or absence of parkinsonism. MATERIALS AND METHODS: Among 1202 scans performed at our center from 2003 to 2015, we identified 93 subjects with probable DLB (mean age 76...
December 9, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27938414/the-effects-of-the-novel-a53e-alpha-synuclein-mutation-on-its-oligomerization-and-aggregation
#16
Diana F Lázaro, Mariana Castro Dias, Anita Carija, Susanna Navarro, Carolina Silva Madaleno, Sandra Tenreiro, Salvador Ventura, Tiago F Outeiro
α-synuclein (aSyn) is associated with both sporadic and familial forms of Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease. In particular, multiplications and point mutations in the gene encoding for aSyn cause familial forms of PD. Moreover, the accumulation of aSyn in Lewy Bodies and Lewy neurites in disorders such as PD, dementia with Lewy bodies, or multiple system atrophy, suggests aSyn misfolding and aggregation plays an important role in these disorders, collectively known as synucleinopathies...
December 9, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27928840/development-of-assessment-toolkits-for-improving-the-diagnosis-of-the-lewy-body-dementias-feasibility-study-within-the-diamond-lewy-study
#17
Alan J Thomas, John Paul Taylor, Ian McKeith, Claire Bamford, David Burn, Louise Allan, John O'Brien
OBJECTIVE: The Lewy body dementias (LBD, dementia with Lewy bodies and Parkinson's disease dementia) are the second most common cause of neurodegenerative dementia but remain under-recognised, with long delays from initial assessment to diagnosis. Whilst validated instruments have been developed for key symptoms, there is no brief instrument for overall diagnostic assessment suitable for routine practice. We here report the development of such assessment toolkits. METHODS: We developed the LBD assessment toolkits in three stages...
December 8, 2016: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/27927762/urinary-incontinence-incident-parkinsonism-and-parkinson-s-disease-pathology-in-older-adults
#18
Noa M Buchman, Sue E Leurgans, Raj J Shah, Veronique VanderHorst, Robert S Wilson, Yaacov G Bachner, David Tanne, Julie A Schneider, David A Bennett, Aron S Buchman
OBJECTIVE: To test the hypothesis that urinary incontinence (UI) is associated with incident parkinsonism in older adults. METHODS: We used data from 2,617 older persons without dementia. Assessment included baseline self-report UI and annual structured exam which assessed parkinsonian signs, motor performances, cognitive function, and self-report disabilities. We used a series of Cox proportional hazards models to examine the association of UI with parkinsonism and adverse health outcomes and a mixed-effect model to examine the association of UI with the annual rate of cognitive decline...
December 7, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#19
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27899296/targeting-the-norepinephrinergic-system-in-parkinson-s-disease-and-related-disorders-the-locus-coeruleus-story
#20
REVIEW
Yannick Vermeiren, Peter P De Deyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are related, progressive and debilitating neurodegenerative disorders with hallmark features that include a variety of motor and non-motor symptoms (behavioral, autonomic and cognitive dysfunction). For almost half a century, the motor aspects have been attributed to Lewy pathology (LP) predominantly in the substantia nigra (SN), causing a major loss of dopaminergic neurons. However, the relative success of dopaminergic replacement therapies for alleviation of solely the parkinsonian features has prompted researchers to further explore other monoaminergic strategies which may tackle all PD-related aspects...
November 27, 2016: Neurochemistry International
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