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Lewy body disease

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https://www.readbyqxmd.com/read/28330542/-lewy-body-dementias
#1
Annemette Løkkegaard, Lise Korbo
Dementia with Lewy bodies and Parkinson disease dementia share the same pathophysiology. Together they are called Lewy body dementias and are the second most common type of dementia. Lewy body dementias receive little attention, and patients are often misdiagnosed, leading to less than ideal management. In this article, diagnostic criteria combined with imaging and other biomarkers as well as current treatment recommendations are summarized, and some of the challenges for the future are outlined. Refinement of diagnosis and clarification of the pathogenesis are required in search for disease-modifying treatments...
March 20, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28329228/gender-differences-in-the-effects-of-cardiovascular-drugs
#2
J Tamargo, G Rosano, W Thomas, J Duarte, A Niessner, J C Kaski, C Cecconi, H Drexel, K Kjeldsen, G Savarese, C Torp-Pedersen, D Atar, B S Lewis, S Agewall
Although sex-specific differences in cardiovascular medicine are well-known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause and pregnancy) and they present differences in drug pharmacokinetics (absorption, distribution, metabolism and excretion) and pharmacodynamics, so that is not rare that they may respond differently to cardiovascular drugs. Furthermore, women are also less often treated with evidence-based drugs thereby preventing optimization of therapeutics for women of all ages, experience more relevant adverse drug reactions than men, and remain under-represented in most clinical trials...
February 28, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/28328536/neurotransmission-systems-in-parkinson-s-disease
#3
Hossein Sanjari Moghaddam, Ameneh Zare-Shahabadi, Farzaneh Rahmani, Nima Rezaei
Parkinson's disease (PD) is histologically characterized by the accumulation of α-synuclein particles, known as Lewy bodies. The second most common neurodegenerative disorder, PD is widely known because of the typical motor manifestations of active tremor, rigidity, and postural instability, while several prodromal non-motor symptoms including REM sleep behavior disorders, depression, autonomic disturbances, and cognitive decline are being more extensively recognized. Motor symptoms most commonly arise from synucleinopathy of nigrostriatal pathway...
March 22, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28324300/%C3%AE-synuclein-and-parkinsonism-updates-and-future-perspectives
#4
REVIEW
Kaie Rosborough, Neha Patel, Lorraine V Kalia
Mutations in the SNCA gene, which encodes the α-synuclein protein, were the first discovered genetic causes of familial parkinsonism with Lewy pathology. To date, six different SNCA missense mutations as well as multiplications are known to cause parkinsonism. For this review, we performed a literature search to identify all published cases of SNCA-related parkinsonism to provide an updated summary of the clinical and neuropathological features of parkinsonism due to SNCA mutations. Familial parkinsonism associated with SNCA is rare, but α-synuclein aggregation is a core feature of sporadic parkinsonism, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28323683/genetic-alzheimer-disease-and-sporadic-dementia-with-lewy-bodies-a-comorbidity-presenting-as-primary-progressive-aphasia
#5
Tereza Picková, Radoslav Matěj, Ondrej Bezdicek, Jiří Keller, Julie van der Zee, Christine Van Broeckhoven, Zsolt Cséfalvay, Robert Rusina
We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes...
March 2017: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
https://www.readbyqxmd.com/read/28322283/susceptibility-to-neurofibrillary-tangles-role-of-the-ptprd-locus-and-limited-pleiotropy-with-other-neuropathologies
#6
L B Chibnik, C C White, S Mukherjee, T Raj, L Yu, E B Larson, T J Montine, C D Keene, J Sonnen, J A Schneider, P K Crane, J M Shulman, D A Bennett, P L De Jager
Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10(-8)) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28321951/transcriptional-network-analysis-in-frontal-cortex-in-lewy-body-diseases-with-focus-on-dementia-with-lewy-bodies
#7
Gabriel Santpere, Paula Garcia-Esparcia, Pol Andres-Benito, Belen Lorente-Galdos, Arcadi Navarro, Isidro Ferrer
The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different co-expressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and down-regulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system, and synapses and neurotransmission (particularly the GABAergic system)...
March 21, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28317651/clinical-validity-of-presynaptic-dopaminergic-imaging-with%C3%A2-123-i-ioflupane%C3%A2-and-noradrenergic-imaging-with-123-i-mibg-in-the-differential-diagnosis-between-alzheimer-s-disease-and-dementia-with-lewy-bodies-in-the-context-of-a-structured-5-phase-development
#8
REVIEW
Ida Sonni, Osman Ratib, Marina Boccardi, Agnese Picco, Karl Herholz, Flavio Nobili, Andrea Varrone
The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of (123)I-ioflupane brain single photon emission tomography and (123)I-MIBG cardiac scintigraphy as imaging BMs for DLB...
April 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28315409/in-vivo-tau-pet-imaging-in-dementia-pathophysiology-radiotracer-quantification-and-a-systematic-review-of-clinical-findings
#9
REVIEW
Benjamin Hall, Elijah Mak, Simon Cervenka, Franklin I Aigbirhio, James B Rowe, John T O'Brien
In addition to the deposition of β-amyloid plaques, neurofibrillary tangles composed of aggregated hyperphosphorylated tau are one of the pathological hallmarks of Alzheimer's disease and other neurodegenerative disorders. Until now, our understanding about the natural history and topography of tau deposition has only been based on post-mortem and cerebrospinal fluid studies, and evidence continues to implicate tau as a central driver of downstream neurodegenerative processes and cognitive decline. Recently, it has become possible to assess the regional distribution and severity of tau burden in vivo with the development of novel radiotracers for positron emission tomography (PET) imaging...
March 14, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28304294/long-term-cognitive-decline-in-dementia-with-lewy-bodies-in-a-large-multicenter-international-cohort
#10
Milica G Kramberger, Bjørn Auestad, Sara Garcia-Ptacek, Carla Abdelnour, Josep Garre Olmo, Zuzana Walker, Afina W Lemstra, Elisabet Londos, Frederic Blanc, Laura Bonanni, Ian McKeith, Bengt Winblad, Frank Jan de Jong, Flavio Nobili, Elka Stefanova, Maria Petrova, Cristian Falup-Pecurariu, Irena Rektorova, Sevasti Bostantjopoulou, Roberta Biundo, Daniel Weintraub, Dag Aarsland
BACKGROUND/OBJECTIVE: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. METHODS: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28300150/s-nitrosylation-of-uchl1-induces-its-structural-instability-and-promotes-%C3%AE-synuclein-aggregation
#11
Roshan Kumar, Deepak K Jangir, Garima Verma, Shashi Shekhar, Pranita Hanpude, Sanjay Kumar, Raniki Kumari, Nirpendra Singh, Neel Sarovar Bhavesh, Nihar Ranjan Jana, Tushar Kanti Maiti
Ubiquitin C-terminal Hydrolase-1 (UCHL1) is a deubiquitinating enzyme, which plays a key role in Parkinson's disease (PD). It is one of the most important proteins, which constitute Lewy body in PD patient. However, how this well folded highly soluble protein presents in this proteinaceous aggregate is still unclear. We report here that UCHL1 undergoes S-nitrosylation in vitro and rotenone induced PD mouse model. The preferential nitrosylation in the Cys 90, Cys 152 and Cys 220 has been observed which alters the catalytic activity and structural stability...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28300069/extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#12
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298266/metabolic-effects-of-inflammation-on-vitamin-a-and-carotenoids-in-humans-and-animal-models
#13
REVIEW
Lewis P Rubin, A Catharine Ross, Charles B Stephensen, Torsten Bohn, Sherry A Tanumihardjo
The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28295599/gender-difference-in-the-association-and-presentation-of-visual-hallucinations-in-dementia-with-lewy-bodies-a-cross-sectional-study
#14
Pai-Yi Chiu, Po-Ren Teng, Cheng-Yu Wei, Chein-Wei Wang, Chun-Tang Tsai
OBJECTIVE: Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). We investigated gender differences in the association and presentation of VHs in DLB. METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on dementia was performed. Cumulative frequency, 1-month frequency, and phenomenology of VHs were summarized and compared between female and male patients with DLB. Gender differences in the factors associated with VHs were investigated in patients with and without hallucinations...
March 13, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28291240/testosterone-levels-in-pre-menopausal-women-are-associated-with-nonalcoholic-fatty-liver-disease-in-midlife
#15
Monika Sarkar, Melissa Wellons, Marcelle I Cedars, Lisa VanWagner, Erica P Gunderson, Veeral Ajmera, Laura Torchen, David Siscovick, J Jeffrey Carr, James G Terry, Mary Rinella, Cora E Lewis, Norah Terrault
OBJECTIVES: Young women with hyperandrogenism have high risk of metabolic co-morbidities, including increased risk of nonalcoholic fatty liver disease (NAFLD). Whether testosterone (the predominant androgen) is associated with NAFLD independent of metabolic co-factors is unclear. Additionally, whether testosterone confers increased risk of NAFLD in women without hyperandrogenism is unknown. METHODS: Among women in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether free testosterone levels measured at Year 2 (1987-1988) were associated with prevalent NAFLD at Year 25 (2010-2011) (n=1052)...
March 14, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28289780/multifaceted-interaction-of-bone-muscle-lifestyle-interventions-and-metabolic-and-cardiovascular-disease-role-of-osteocalcin
#16
REVIEW
I Levinger, T C Brennan-Speranza, A Zulli, L Parker, X Lin, J R Lewis, B B Yeap
Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e...
March 13, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28285306/extremely-low-prevalence-of-amyloid-positron-emission-tomography-positivity-in-parkinson-s-disease-without-dementia
#17
Kyoko Mashima, Daisuke Ito, Masashi Kameyama, Takashi Osada, Hajime Tabuchi, Yoshihiro Nihei, Takahito Yoshizaki, Eri Noguchi, Mariko Tanikawa, Takashi Iizuka, Yugaku Date, Yuji Ogata, Tadaki Nakahara, Yu Iwabuchi, Masahiro Jinzaki, Koji Murakami, Norihiro Suzuki
BACKGROUND: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain β amyloid (Aβ) burden begins and progresses. Our study aimed to determine the prevalence of Aβ deposition in PD without dementia using amyloid PET...
March 11, 2017: European Neurology
https://www.readbyqxmd.com/read/28282814/the-synucleinopathies-twenty-years-on
#18
Michel Goedert, Ross Jakes, Maria Grazia Spillantini
In 2017, it is two hundred years since James Parkinson provided the first complete clinical description of the disease named after him, fifty years since the introduction of high-dose D,L-DOPA treatment and twenty years since α-synuclein aggregation came to the fore. In 1998, multiple system atrophy joined Parkinson's disease and dementia with Lewy bodies as the third major synucleinopathy. Here we review our work, which led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp-Lantos bodies, as well as what has happened since...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28282807/radiological-pathological-correlation-in-alzheimer-s-disease-systematic-review-of-antemortem-magnetic-resonance-imaging-findings
#19
Caroline Dallaire-Théroux, Brandy L Callahan, Olivier Potvin, Stephan Saikali, Simon Duchesne
BACKGROUND: The standard method of ascertaining Alzheimer's disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these etiologies and provide a diagnosis in vivo. OBJECTIVE: We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD...
March 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28279643/follistatin-gene-therapy-for-sporadic-inclusion-body-myositis-improves-functional-outcomes
#20
Jerry R Mendell, Zarife Sahenk, Samiah Al-Zaidy, Louise R Rodino-Klapac, Linda P Lowes, Lindsay N Alfano, Katherine Berry, Natalie Miller, Mehmet Yalvac, Igor Dvorchik, Melissa Moore-Clingenpeel, Kevin M Flanigan, Kathleen Church, Kim Shontz, Choumpree Curry, Sarah Lewis, Markus McColly, Mark J Hogan, Brian K Kaspar
Sporadic inclusion body myositis, a variant of inflammatory myopathy, has features distinct from polymyositis/dermatomyositis. The disease affects men more than women, most commonly after age 50. Clinical features include weakness of the quadriceps, finger flexors, ankle dorsiflexors, and dysphagia. The distribution of weakness is similar to Becker muscular dystrophy, where we previously reported improvement following intramuscular injection of an isoform of follistatin (FS344) by AAV1. For this clinical trial, rAAV1...
March 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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