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https://www.readbyqxmd.com/read/28100023/frontotemporal-lobar-degeneration-pathogenesis-pathology-and-pathways-to-phenotype
#1
REVIEW
David Ma Mann, Julie S Snowden
Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There are three major associated clinical syndromes, behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA); three principal histologies, involving tau, TDP-43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations...
January 18, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28099631/associations-of-cerebrovascular-metabolism-genotypes-with-neuropsychiatric-symptoms-and-age-at-onset-of-alzheimer-s-disease-dementia
#2
Fabricio F de Oliveira, Elizabeth S Chen, Marilia C Smith, Paulo H Bertolucci
Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121...
January 12, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28099083/update-on-alzheimer-s-disease-therapy-and-prevention-strategies
#3
W Vallen Graham, Alessandra Bonito-Oliva, Thomas P Sakmar
Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28093855/typical-and-atypical-appearance-of-early-onset-alzheimer-s-disease-a-clinical-neuroimaging-and-neuropathological-study-symposium-fundamentals-learned-from-diversity-among-typical-and-atypical-appearances
#4
Shinobu Kawakatsu 川勝 忍, Ryota Kobayashi, Hiroshi Hayashi
The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia...
January 17, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28093491/early-microgliosis-precedes-neuronal-loss-and-behavioural-impairment-in-mice-with-a-frontotemporal-dementia-causing-chmp2b-mutation
#5
Emma L Clayton, Renzo Mancuso, Troels Tolstrup Nielsen, Sarah Mizielinska, Holly Holmes, Nicholas Powell, Frances Norona, Jytte Overgaard Larsen, Carmelo Milioto, Katherine M Wilson, Mark F Lythgoe, Sebastian Ourselin, Jörgen E Nielsen, Peter Johannsen, Ida Holm, John Collinge, A Frej, Peter L Oliver, Diego Gomez-Nicola, Adrian M Isaacs
Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD...
January 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087828/tdp-43-pathology-and-memory-impairment-in-elders-without-pathologic-diagnoses-of-ad-or-ftld
#6
Sukriti Nag, Lei Yu, Robert S Wilson, Er-Yun Chen, David A Bennett, Julie A Schneider
OBJECTIVE: To investigate the association of TAR DNA-binding protein 43 (TDP-43) pathology with memory, other cognitive domains, and dementia in community-dwelling elders without pathologic diagnoses of Alzheimer disease (AD) or frontotemporal lobar degeneration (FTLD). METHODS: Of 1,058 autopsied participants, 343 (32.4%) did not have pathologic diagnoses of AD or FTLD. Diagnosis of dementia was based on clinical evaluation and cognitive performance tests, which were used to create summary measures of global cognition and of 5 cognitive domains...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28077166/threonine-175-a-novel-pathological-phosphorylation-site-on-tau-protein-linked-to-multiple-tauopathies
#7
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/28068866/cognitive-abnormalities-and-cerebral-perfusion-defects-in-a-community-dwelling-cohort-of-elderly-men-with-mmse-within-the-normal-range
#8
Lena André-Petersson, Ola Thorsson, Arkadiusz Siennicki-Lantz
OBJECTIVES: Mini Mental State Examination's (MMSE's) sensitivity in its upper level is questioned, hence we investigated cognitive abnormalities and defects in regional cerebral blood flow (rCBF) in elderly with MMSE scores ≥24. METHODS: One hundred and four men at age 81 with MMSE scores ≥24 (mean 28.4 ± 1.7), no dementia or stroke, were examined with neuropsychological test battery, and their rCBF was estimated using (99mTc)-HMPAO SPECT. RESULTS: MMSE was very sparsely correlated with rCBF...
January 9, 2017: Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition
https://www.readbyqxmd.com/read/28063896/clinical-correlation-of-abnormal-findings-on-magnetic-resonance-elastography-in-idiopathic-normal-pressure-hydrocephalus
#9
Avital Perry, Christopher S Graffeo, Nikoo Fattahi, Mona M ElSheikh, Nealey Cray, Arvin Arani, Richard L Ehman, Kevin J Glaser, Armando Manduca, Fredric B Meyer, John Huston
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible following ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. OBJECTIVE: We studied iNPH patients using MRE prior to shunting, compared them to normal controls, and analyzed associations between MRE findings and clinical features, as a pilot assessment of MRE in iNPH...
January 4, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28059782/differential-hemispheric-predilection-of%C3%A2-microstructural-white-matter-and%C3%A2-functional-connectivity-abnormalities-between-respectively-semantic-and%C3%A2-behavioral-variant-frontotemporal-dementia
#10
Rozanna Meijboom, Rebecca M E Steketee, Leontine S Ham, Aad van der Lugt, John C van Swieten, Marion Smits
Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28052883/association-of-dietary-cholesterol-and-egg-intakes-with-the-risk-of-incident-dementia-or-alzheimer-disease-the-kuopio-ischaemic-heart-disease-risk-factor-study
#11
Maija Pt Ylilauri, Sari Voutilainen, Eija Lönnroos, Jaakko Mursu, Heli Ek Virtanen, Timo T Koskinen, Jukka T Salonen, Tomi-Pekka Tuomainen, Jyrki K Virtanen
BACKGROUND: There is little information about the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with the risk of cognitive decline in general populations or in carriers of apolipoprotein E ɛ4 (APO-E4), a major risk factor for dementia. OBJECTIVE: We investigated the associations of cholesterol and egg intakes with incident dementia, Alzheimer disease (AD), and cognitive performance in middle-aged and older men from Eastern Finland...
January 4, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28038340/spatio-temporal-and-kinematic-gait-analysis-in-patients-with-frontotemporal-dementia-and-alzheimer-s-disease-through-3d-motion-capture
#12
Rosaria Rucco, Valeria Agosti, Francesca Jacini, Pierpaolo Sorrentino, Pasquale Varriale, Manuela De Stefano, Graziella Milan, Patrizia Montella, Giuseppe Sorrentino
Alzheimer's disease (AD) and behavioral variant of Frontotemporal Dementia (bvFTD) are characterized respectively by atrophy in the medial temporal lobe with memory loss and prefrontal and anterior temporal degeneration with dysexecutive syndrome. In this study, we hypothesized that specific gait patterns are induced by either frontal or temporal degeneration. To test this hypothesis, we studied the gait pattern in bvFTD (23) and AD (22) patients in single and dual task ("motor" and "cognitive") conditions...
December 21, 2016: Gait & Posture
https://www.readbyqxmd.com/read/28035933/frontal-lobe-function-correlates-with%C3%A2-one-year-incidence-of-urinary-incontinence-in-elderly-with-alzheimer-disease
#13
Taiki Sugimoto, Masaki Yoshida, Rei Ono, Shunsuke Murata, Naoki Saji, Shumpei Niida, Kenji Toba, Takashi Sakurai
BACKGROUND: Urinary incontinence (UI) is frequently observed in patients with Alzheimer's disease (AD). Although previous works highlight the association between frontal lobe-related function and UI, causal relationship is unclear. OBJECTS: To clarify the longitudinal association between frontal lobe function and the incidence of UI at 1 year in patients with AD. METHODS: The subjects were 215 continent AD patients who attended the Memory Clinic of the National Center for Geriatrics and Gerontology of Japan during the period from March 2011 to December 2014...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28031997/cortical-asymmetry-in-parkinson-s-disease-early-susceptibility-of-the-left-hemisphere
#14
Daniel O Claassen, Katherine E McDonell, Manus Donahue, Shiv Rawal, Scott A Wylie, Joseph S Neimat, Hakmook Kang, Peter Hedera, David Zald, Bennett Landman, Benoit Dawant, Swati Rane
BACKGROUND AND PURPOSE: Clinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left-lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well-characterized cohort of PD patients...
December 2016: Brain and Behavior
https://www.readbyqxmd.com/read/28030474/therapeutic-benefits-of-the-methyl-donor-s-adenosylmethionine-sam-on-nerve-injury-induced-mechanical-hypersensitivity-and-cognitive-impairment-in-mice
#15
Stéphanie Grégoire, Magali Millecamps, Lina Naso, Sonia Do Carmo, A Claudio Cuello, Moshe Szyf, Laura S Stone
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Co-morbid conditions including anxiety, depression and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex six months following induction of neuropathic pain using the Spared Nerve Injury (SNI) model...
December 22, 2016: Pain
https://www.readbyqxmd.com/read/28017247/clinical-characteristics-of-parkinsonism-in-frontotemporal-dementia-according-to-subtypes
#16
Hee Kyung Park, Kee Hyung Park, Bora Yoon, Jae-Hong Lee, Seong Hye Choi, Jee H Joung, Soo Jin Yoon, Byeong C Kim, Seung Hyun Kim, Eun-Joo Kim, Duk L Na, Kyung Won Park
BACKGROUND: We investigated the prevalence of parkinsonism in frontotemporal dementia (FTD) subtypes and the cognitive and behavioral differences between FTD with and without parkinsonism in a well-structured, prospective cohort. METHODS: One hundred and ninety-one FTD patients were enrolled and all patients underwent comprehensive neurological evaluations, neuropsychological tests, and the Unified Parkinson's Disease Rating Scale. RESULTS: The prevalence of parkinsonism was 38...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28017230/longitudinal-study-of-cognitive-and-cerebral-metabolic-changes-in-parkinson-s-disease
#17
Toru Baba, Yoshiyuki Hosokai, Yoshiyuki Nishio, Akio Kikuchi, Kazumi Hirayama, Kyoko Suzuki, Takafumi Hasegawa, Masashi Aoki, Atsushi Takeda, Etsuro Mori
OBJECTIVE: To investigate the cortical metabolic alterations that precedes longitudinal cognitive decline in Parkinson's disease (PD). METHODS: We analyzed the data of 46 PD patients who did not have dementia at baseline and completed 3-year follow-up. Based on the results of general cognitive, memory and visuospatial tests, patients were classified into cognitively normal PD (PD-CogNL), PD with mild cognitive impairment (PD-MCI), and PD dementia (PDD). The regional cerebral glucose metabolism at rest was measured using (18)F-fluorodeoxyglucose positron emission tomography...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28012952/frontotemporal-dementia-as-the-presenting-phenotype-of-p-a53t-mutation-carriers-in-the-alpha-synuclein-gene
#18
Anastasia Bougea, Christos Koros, Maria Stamelou, Athina Simitsi, Nikolaos Papagiannakis, Roubina Antonelou, Dimitra Papadimitriou, Marianthi Breza, Konstantinos Tasios, Stella Fragkiadaki, Xenia Geronicola Trapali, Mara Bourbouli, Georgios Koutsis, Sokratis G Papageorgiou, Elisabeth Kapaki, George P Paraskevas, Leonidas Stefanis
INTRODUCTION: The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinson's disease (PD). METHODS: Here, we describe two apparently unrelated cases of p.A53T (G209A) SNCA mutation carriers with an atypical initial manifestation and disease course. Moreover, cerebrospinal fluid (CSF) levels of tau, p-tau and amyloid Aβ42 were measured in these patients and in an additional cohort of 5 symptomatic and 2 asymptomatic p...
December 6, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27995069/longitudinal-imaging-in-c9orf72-mutation-carriers-relationship-to-phenotype
#19
Mary Kay Floeter, Devin Bageac, Laura E Danielian, Laura E Braun, Bryan J Traynor, Justin Y Kwan
Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotypes, but it is uncertain whether different phenotypes have a common genotype-associated imaging signature. To address this question, 27 unrelated C9orf72 expansion mutation carriers (C9 +) with varied phenotypes, 28 age-matched healthy controls and 22 patients with sporadic ALS (sALS) underwent 3T MRI scanning and clinical phenotyping...
2016: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27984680/mitochondrial-activity-in-the-frontal-cortex-area-8-and-angular-gyrus-in-parkinson-s-disease-and-parkinson-s-disease-with-dementia
#20
Paula Garcia-Esparcia, Anusha Koneti, M Cruz Rodríguez-Oroz, Belen Lago, José Antonio Del Rio, Isidro Ferrer
Altered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression, and clinical symptoms such as the presence or absence of dementia. RT-qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism-related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle-aged individuals (MA), and those with incidental PD (iPD), long-lasting PD with parkinsonism without dementia (PD) and long-lasting PD with dementia (PDD)...
December 16, 2016: Brain Pathology
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