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Dementia with lewy bodies

Graham Fairfoul, Lynne I McGuire, Suvankar Pal, James W Ironside, Juliane Neumann, Sharon Christie, Catherine Joachim, Margaret Esiri, Samuel G Evetts, Michal Rolinski, Fahd Baig, Claudio Ruffmann, Richard Wade-Martins, Michele T M Hu, Laura Parkkinen, Alison J E Green
We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results...
October 2016: Annals of Clinical and Translational Neurology
Hye-Jin Park, Kang-Woo Lee, Eun S Park, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
OBJECTIVE: Protein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α-Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho-Ser129 phosphatase...
October 2016: Annals of Clinical and Translational Neurology
Alexandre N Rcom-H'cheo-Gauthier, Amelia Davis, Adrian C B Meedeniya, Dean L Pountney
α-Synuclein (α-syn) aggregates (Lewy bodies) in dementia with Lewy Bodies (DLB) may be associated with disturbed calcium homeostasis and oxidative stress. We investigated the interplay between α-syn aggregation, expression of the calbindin-D28k (CB) neuronal calcium-buffering protein and oxidative stress, combining immunofluorescence double labelling and Western analysis, and examining DLB and normal human cases and a unilateral oxidative stress lesion model of α-syn disease (rotenone mouse). DLB cases showed a greater proportion of CB+ cells in affected brain regions compared to normal cases with Lewy bodies largely present in CB- neurons and virtually undetected in CB+ neurons...
October 13, 2016: Molecular and Cellular Neurosciences
Hirotaka Sekiguchi, Masatsugu Moriwaki, Shuji Iritani, Chikako Habuchi, Youta Torii, Kentaro Umeda, Hiroshige Fujishiro, Mari Yoshida, Kiyoshi Fujita
We herein report the case of a 75-year-old male who had shown many psychiatric symptoms, but whose autopsy disclosed the presence of dementia with Lewy bodies (DLB). When he was 70 years old, the patient had presented with stereotyped behavior, dietary changes, and a decline in social interpersonal conduct in clinical settings, and it was thought that these symptoms were consistent with a behavioral variant of frontotemporal dementia (bvFTD), and he lacked the core features of DLB. Nevertheless, this case was pathologically defined as the limbic type of DLB after he died at the age of 75 years...
October 14, 2016: Clinical Neuropathology
Toshie Manabe, Katsuyoshi Mizukami, Hiroyasu Akatsu, Yoshio Hashizume, Shinji Teramoto, Seiji Nakamura, Koichiro Kudo, Nobuyuki Hizawa
Objective In patients demonstrating dementia with Lewy bodies (DLB), pneumonia is a common complication. However, the prognostic factors for the survival time in DLB with pneumonia have not been investigated by autopsy in patients with neuropathologically confirmed DLB. Methods We conducted a retrospective study of the medical and autopsy reports of 42 patients admitted to a Japanese hospital between 2005 and 2014. The patients were neuropathologically diagnosed as having DLB by post-mortem examinations. We analyzed the effects of various factors on the time from DLB onset to death...
2016: Internal Medicine
Tamara Shiner, Anat Mirelman, Mali Gana Weisz, Anat Bar-Shira, Elissa Ash, Ron Cialic, Naomi Nevler, Tanya Gurevich, Noa Bregman, Avi Orr-Urtreger, Nir Giladi
Importance: Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the development of dementia with Lewy bodies (DLB). These mutations are common among Ashkenazi Jews (AJ) and appear to have an effect on the natural history of the disease. Objectives: To evaluate the clinical and genetic characteristics of an AJ cohort of patients diagnosed with DLB, assess the association of phenotype of DLB with GBA mutations, and explore the effects of these mutations on the clinical course of the disease...
October 10, 2016: JAMA Neurology
A Sh Chimagomedova, O S Levin
The features of orthostatic hypotension in patients with dementia with Lewy bodies are considered. The early diagnosis of these disorders could prevent adverse conditions (falls and syncopes), improve activities of daily living and quality-of-life. Current approaches to treatment of orthostatic hypotension are analyzed.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
T A Polyakova, O S Levin
AIM: To study a role of cerebral microbleeds (CMB) in the diagnosis of main cerebrovascular and neurodegenerative diseases with cognitive impairment. MATERIAL AND METHODS: CMB were studied in 120 patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and vascular dementia using 1.5T MRI in T2 * gradient echo. An impact of CMB on cognitive functions and the relationship with signs of vascular and neurodegenerative lesions of the brain were studied as well...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Meenakshi Dauwan, Jessica J van der Zande, Edwin van Dellen, Iris E C Sommer, Philip Scheltens, Afina W Lemstra, Cornelis J Stam
INTRODUCTION: The aim of this study was to build a random forest classifier to improve the diagnostic accuracy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and to quantify the relevance of multimodal diagnostic measures, with a focus on electroencephalography (EEG). METHODS: A total of 66 DLB, 66 AD patients, and 66 controls were selected from the Amsterdam Dementia Cohort. Quantitative EEG (qEEG) measures were combined with clinical, neuropsychological, visual EEG, neuroimaging, and cerebrospinal fluid data...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
P S Jairani, P M Aswathy, Srinivas Gopala, Joe Verghese, P S Mathuranath
BACKGROUND: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. METHODS: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138)...
October 6, 2016: Dementia and Geriatric Cognitive Disorders
Yoshihide Takeshita, Nobuto Shibata, Koji Kasanuki, Tomoyuki Nagata, Shunichiro Shinagawa, Nobuyuki Kobayashi, Tohru Ohnuma, Ayako Suzuki, Eri Kawai, Toshiki Takayama, Kenya Nishioka, Yumiko Motoi, Nobutaka Hattori, Kazuhiko Nakayama, Hisashi Yamada, Heii Arai
BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. METHODS: Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls...
October 4, 2016: International Journal of Geriatric Psychiatry
Karen Manoutcharian, Roxanna Perez-Garmendia, Goar Gevorkian
Recombinant antibody fragments are promising alternatives to full-length immunoglobulins and offer important advantages compared with conventional monoclonal antibodies: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity as well as easy and inexpensive large-scale production. Different antibody formats such as single-chain fragment variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in pre-clinical models of cancer as well as infectious and autoimmune diseases and many of them are being tested as therapeutics in clinical trials...
September 30, 2016: Current Neuropharmacology
Bryan D James, Robert S Wilson, Patricia A Boyle, John Q Trojanowski, David A Bennett, Julie A Schneider
Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects...
September 30, 2016: Brain: a Journal of Neurology
Daphné Génier Marchand, Jacques Montplaisir, Ronald B Postuma, Shady Rahayel, Jean-François Gagnon
STUDY OBJECTIVES: Long-term studies in REM sleep behavior disorder (RBD) have shown a high rate of conversion into synucleinopathies. We aimed to prospectively follow up a large cohort of RBD patients to identify cognitive markers for early detection of prodromal dementia. METHODS: Seventy-six idiopathic RBD patients underwent polysomnography and a complete neuropsychological and neurological assessment and were then followed for a mean of 3.6 years. Cognitive characteristics at baseline were compared between patients who remained disease-free and those who developed a synucleinopathy, and between those who developed dementia first and those who developed parkinsonism first...
September 26, 2016: Sleep
Kenichi Nakajima, Masahito Yamada
(123)I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of (123)I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of (123)I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity...
September 2016: Chonnam Medical Journal
Jennifer Whitwell, Jonathan Graff-Radford, Tarun Singh, Daniel Drubach, Matthew Senjem, Anthony Spychalla, Nirubol Tosakulwong, Val J Lowe, Keith Josephs
: Posterior cortical atrophy (PCA) and Dementia with Lewy bodies (DLB) have both been associated with occipital lobe hypometabolism on (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET), while relative sparing of posterior cingulate metabolism compared to precuneus/cuneus (i.e. cingulate island sign) is a feature of DLB. We aimed to determine whether patterns of hypometabolism or the cingulate island sign differed between PCA and DLB. METHODS: Sixteen clinically diagnosed PCA and 13 probable DLB subjects underwent (18)F-FDG PET...
September 29, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Karin Persson, Geir Selbæk, Anne Brækhus, Mona Beyer, Maria Barca, Knut Engedal
BACKGROUND: The dementia syndrome has been regarded a clinical diagnosis but the focus on supplemental biomarkers is increasing. An automatic magnetic resonance imaging (MRI) volumetry method, NeuroQuant® (NQ), has been developed for use in clinical settings. PURPOSE: To evaluate the clinical usefulness of NQ in distinguishing Alzheimer's disease dementia (AD) from non-dementia and non-AD dementia. MATERIAL AND METHODS: NQ was performed in 275 patients diagnosed according to the criteria of ICD-10 for AD, vascular dementia and Parkinson's disease dementia (PDD); the Winblad criteria for mild cognitive impairment; the Lund-Manchester criteria for frontotemporal dementia; and the revised consensus criteria for Lewy body dementia (LBD)...
September 28, 2016: Acta Radiologica
Yu Funahashi, Yuta Yoshino, Kiyohiro Yamazaki, Yoko Mori, Takaaki Mori, Yuki Ozaki, Tomoko Sao, Shinichiro Ochi, Jun-Ichi Iga, Shu-Ichi Ueno
AIM: It is difficult to diagnose dementia with Lewy bodies (DLB) because it exhibits clinical and neuropathological overlap with both Alzheimer's disease (AD) and Parkinson's disease (PD). The α-synuclein protein is a major component of Lewy bodies, and accumulation of α-synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha gene (SNCA) may be involved in DLB pathogenesis. METHODS: We examined DNA methylation rates at 10 CpG sites located in intron 1 of SNCA and SNCA mRNA expression in peripheral leukocytes to compare DLB patients (n = 20; 9 males, 11 females; age = 78...
September 29, 2016: Psychiatry and Clinical Neurosciences
Wolfgang Wrasidlo, Igor F Tsigelny, Diana L Price, Garima Dutta, Edward Rockenstein, Thomas C Schwarz, Karin Ledolter, Douglas Bonhaus, Amy Paulino, Simona Eleuteri, Åge A Skjevik, Valentina L Kouznetsova, Brian Spencer, Paula Desplats, Tania Gonzalez-Ruelas, Margarita Trejo-Morales, Cassia R Overk, Stefan Winter, Chunni Zhu, Marie-Francoise Chesselet, Dieter Meier, Herbert Moessler, Robert Konrat, Eliezer Masliah
Abnormal accumulation and propagation of the neuronal protein α-synuclein has been hypothesized to underlie the pathogenesis of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Here we report a de novo-developed compound (NPT100-18A) that reduces α-synuclein toxicity through a novel mechanism that involves displacing α-synuclein from the membrane. This compound interacts with a domain in the C-terminus of α-synuclein. The E83R mutation reduces the compound interaction with the 80-90 amino acid region of α-synuclein and prevents the effects of NPT100-18A...
September 27, 2016: Brain: a Journal of Neurology
Celia Kun-Rodrigues, Owen A Ross, Tatiana Orme, Claire Shepherd, Laura Parkkinen, Lee Darwent, Dena Hernandez, Olaf Ansorge, Lorraine N Clark, Lawrence S Honig, Karen Marder, Afina Lemstra, Philippe Scheltens, Wiesje van der Flier, Eva Louwersheimer, Henne Holstege, Ekaterina Rogaeva, Peter St George-Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Walter Maetzler, Daniela Berg, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, John Q Trojanowski, Geidy E Serrano, Thomas G Beach, Jordi Clarimon, Alberto Lleó, Estrella Morenas-Rodríguez, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Monica Diez, Pau Pastor, Pentti J Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F Boeve, Ronald C Petersen, Tanis J Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J Cairns, John C Morris, David J Stone, Stuart Pickering-Brown, David Mann, Dennis W Dickson, Glenda M Halliday, Andrew Singleton, Rita Guerreiro, Jose Bras
C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB...
September 2, 2016: Neurobiology of Aging
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