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dementia with lewy bodies and Parkinson's

Jana Janssens, Yannick Vermeiren, Erik Fransen, Tony Aerts, Debby Van Dam, Sebastiaan Engelborghs, Peter P De Deyn
Introduction: Given the challenges concerning the differential diagnosis of dementia, we investigated the possible added value of monoaminergic compounds to the standard cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Particularly, regarding the AD versus dementia with Lewy bodies (DLB) comparison, monoamines or their metabolites might have added discriminative value as there is a more severe neuropathological burden in the locus coeruleus of DLB patients, the principal site of noradrenaline synthesis...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Susanna Nuvoli, Barbara Palumbo, Simona Malaspina, Giuseppe Madeddu, Angela Spanu
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders...
March 20, 2018: Hellenic Journal of Nuclear Medicine
Ruben Smith, Michael Schöll, Elisabet Londos, Tomas Ohlsson, Oskar Hansson
Mixed pathologies of α-synuclein, β-amyloid and tau are relatively common in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). We therefore wanted to study the retention patterns of18 F-AV-1451 in PD, PD-dementia (PDD), and DLB. To do this 44 healthy controls, 11 non-demented patients with PD, 18 patients with PDD, and six patients with DLB underwent MRI and18 F-AV-1451 PET scanning and cognitive testing. We found that parietal18 F-AV-1451 retention was increased in patients with DLB compared to controls and PD patients, while18 F-AV-1451 uptake was reduced in the substantia nigra in PDD...
March 16, 2018: Scientific Reports
Luis R Peraza, Ruth Cromarty, Xenia Kobeleva, Michael J Firbank, Alison Killen, Sara Graziadio, Alan J Thomas, John T O'Brien, John-Paul Taylor
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias...
March 15, 2018: Scientific Reports
Julia E Gerson, Kathleen M Farmer, Natalie Henson, Diana L Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed
BACKGROUND: We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target...
March 15, 2018: Molecular Neurodegeneration
Po-Chi Chan, Cheng-Yu Wei, Guang-Uei Hung, Pai-Yi Chiu
Objectives: The association of vascular risk factors (VRFs) with incidence of Alzheimer's disease (AD) and vascular dementia (VaD) has been well studied. However, the association between VRFs and non-AD dementia is seldom investigated. In this study, we aim to compare the concurrence of VRFs of Lewy body dementia (LBD) to AD. Materials & Methods: We consecutively enrolled patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and AD, and the prevalence of arterial hypertension, diabetes mellitus, hypercholesterolemia, hyperlipidemia, smoking, and obesity was assessed and compared...
March 2018: Brain and Behavior
Hiroshige Fujishiro, Masato Okuda, Kunihiro Iwamoto, Seiko Miyata, Youta Torii, Shuji Iritani, Norio Ozaki
AIMS: REM sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease / dementia with Lewy bodies. The purpose of this study is to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late-onset psychiatric disorders. METHODS: Study subjects included 19 patients with late-onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward...
March 14, 2018: Psychiatry and Clinical Neurosciences
Ivan Martinez-Valbuena, Irene Amat-Villegas, Rafael Valenti-Azcarate, Maria Del Mar Carmona-Abellan, Irene Marcilla, Maria-Teresa Tuñon, Maria-Rosario Luquin
Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination...
March 13, 2018: Acta Neuropathologica
Emma Robson, Clare Tweedy, Nelson Manzanza, John-Paul Taylor, Peter Atkinson, Fiona Randall, Amy Reeve, Gavin J Clowry, Fiona E N LeBeau
Intracellular accumulation of alpha-synuclein (α-syn) is a key pathological process evident in Lewy body dementias (LBD), including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). LBD results in marked cognitive impairments and changes in cortical networks. To assess the impact of abnormal α-syn expression on cortical network oscillations relevant to cognitive function, we studied changes in fast beta/gamma network oscillations in the hippocampus in a mouse line that over-expresses human mutant α-syn (A30P)...
March 7, 2018: Neuroscience
Morten Gersel Stokholm, Alex Iranzo, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Peter Parbo, Per Borghammer, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Eduardo Tolosa, Nicola Pavese
BACKGROUND: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. METHODS: We studied twenty-one polysomnography-confirmed iRBD patients with18 F-DOPA and11 C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation...
March 6, 2018: Neurobiology of Disease
Kurt A Jellinger, Amos D Korczyn
BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which share many clinical, neurochemical, and morphological features, have been incorporated into DSM-5 as two separate entities of major neurocognitive disorders with Lewy bodies. Despite clinical overlap, their diagnosis is based on an arbitrary distinction concerning the time of onset of motor and cognitive symptoms, namely as early cognitive impairment in DLB and later onset following that of motor symptoms in PDD...
March 6, 2018: BMC Medicine
Viorica Chelban, Ekawat Vichayanrat, Lucia Schottlaende, Valeria Iodice, Henry Houlden
The discovery of genetic links between alpha-synuclein and PD has opened unprecedented opportunities for research into a new group of diseases, now collectively known as synucleinopathies. Autonomic dysfunction, including cardiac sympathetic denervation, has been reported in familial forms of synucleinopathies that have Lewy bodies at the core of their pathogenesis. SNCA mutations and multiplications, LRRK2 disease with Lewy bodies as well as other common, sporadic forms of idiopathic PD, MSA, pure autonomic failure, and dementia with Lewy bodies have all been associated with dysautonomia...
March 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Jose-Alberto Palma, Horacio Kaufmann
Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully...
March 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Nicolaas I Bohnen, Michel J Grothe, Nicola J Ray, Martijn L T M Müller, Stefan J Teipel
Purpose of review: Although the cholinergic hypothesis of dementia provided a successful paradigm for the development of new drugs for dementia, this hypothesis has waned in popularity. Cholinergic brain imaging may provide novel insights into the viability of this hypothesis. Recent findings: Cholinergic receptor and forebrain volumetric studies suggest an important role of the cholinergic system in maintaining brain network integrity that may deteriorate with cognitive decline in Alzheimer disease (AD) and Lewy body disorders (LBD)...
March 2018: Current Geriatrics Reports
Madhavi Tripathi, Atin Kumar, Chandrasekhar Bal
Neuroimaging (NI) in Parkinson's disease (PD) includes functional techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT), and morphological imaging using magnetic resonance imaging (MRI) and transcranial sonography to probe different aspects of the neurobiology of PD. Changes in neurotransmitters in various regions of the brain and their influence on brain networks is the basis for the motor symptoms of PD which are interrogated by NI. The recent Movement Disorders Society Clinical Diagnostic Criteria for PD (MDS-PD) have included the results of a few of these neuroimaging techniques to serve as single supportive criteria or absolute exclusion criteria for the diagnosis of PD...
March 2018: Neurology India
Esteban Luna, Samantha C Decker, Dawn M Riddle, Anna Caputo, Bin Zhang, Tracy Cole, Carrie Caswell, Sharon X Xie, Virginia M Y Lee, Kelvin C Luk
The accumulation of misfolded α-synuclein (aSyn) and neuron loss define several neurodegenerative disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the precise relationship between pathology and neurotoxicity and why these processes disproportionately affect certain neuron subpopulations are poorly understood. We show here that Math2-expressing neurons in the hippocampal Cornu ammonis (CA), a region significantly affected by aSyn pathology in advanced PD and DLB, are highly susceptible to pathological seeding with pre-formed fibrils (PFFs), in contrast to dentate gyrus neurons, which are relatively spared...
March 3, 2018: Acta Neuropathologica
Lasse Reimer, Louise Buur Vesterager, Cristine Betzer, Jin Zheng, Lærke Dalsgaard Nielsen, Rikke Hahn Kofoed, Louise Berkhoudt Lassen, Ulrik Bølcho, Søren Riis Paludan, Karina Fog, Poul Henning Jensen
Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy comprise a group of neurodegenerative diseases termed synucleinopathies. Synucleinopathie are, characterized by presence of inclusion bodies in degenerating brain cells which contain aggregated α-synuclein phosphorylated on Ser129. Although the inflammation-associated serine-threonine kinase, PKR (EIF2AK2), promotes cellular protection against infection, we demonstrate a pro-degenerative role of activated PKR in an α-synuclein-dependent cell model of multiple system atrophy, where inhibition and silencing of PKR decrease cellular degeneration...
March 1, 2018: Neurobiology of Disease
Jennifer G Goldman, Samantha K Holden, Irene Litvan, Ian McKeith, Glenn T Stebbins, John-Paul Taylor
Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology...
February 28, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Ana Gámez-Valero, Alex Iranzo, Monica Serradell, Dolores Vilas, Joan Santamaria, Carles Gaig, Ramiro Álvarez, Aurelio Ariza, Eduardo Tolosa, Katrin Beyer
INTRODUCTION: Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their presence shortens the time to conversion to clinically-defined LBD. METHODS: All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method...
February 21, 2018: Parkinsonism & related Disorders
Sygrid van der Zee, Yannick Vermeiren, Erik Fransen, Debby Van Dam, Tony Aerts, Marleen J Gerritsen, Jacoba M Spikman, Teus van Laar, Peter P De Deyn
BACKGROUND: Lewy body disorders, including Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), are characterized by profound central and peripheral monoaminergic dysfunction. OBJECTIVE: To investigate whether these alterations depend on dementia status, we measured cerebrospinal fluid (CSF) and serum monoamine and metabolite levels across subgroups of the cognitive spectrum, and evaluated their marker potential afterwards...
2018: Journal of Parkinson's Disease
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