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https://www.readbyqxmd.com/read/28445082/the-impact-of-%C3%AE-amyloid-positron-emission-tomography-on-the-diagnostic-and-treatment-decisions-of-dementia-experts
#1
Michael L Ganz, Alie F Tawah, Shien Guo, Abhishek S Chitnis, Hedwig Silies, Barbara Schäuble, Aleksandar Jovalekic, Norman L Foster
AIM: Amyloid positron emission tomography (aPET) measurement of Alzheimer's disease (AD) pathology could improve the accurate diagnosis of cognitive disorders. Appropriate use criteria recommend that only dementia experts order aPET. MATERIALS & METHODS: We surveyed 145 dementia experts about their current approaches to evaluation and treatment and the likely influence of aPET. RESULTS: Experts expected aPET to alter diagnostic procedures and patient management and also increase diagnostic certainty...
April 26, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28444781/constructing-longitudinal-disease-progression-curves-using-sparse-short-term-individual-data-with-an-application-to-alzheimer-s-disease
#2
C A Budgeon, K Murray, B A Turlach, S Baker, V L Villemagne, S C Burnham
In epidemiology, cohort studies utilised to monitor and assess disease status and progression often result in short-term and sparse follow-up data. Thus, gaining an understanding of the full-term disease pathogenesis can be difficult, requiring shorter-term data from many individuals to be collated. We investigate and evaluate methods to construct and quantify the underlying long-term longitudinal trajectories for disease markers using short-term follow-up data, specifically applied to Alzheimer's disease. We generate individuals' follow-up data to investigate approaches to this problem adopting a four-step modelling approach that (i) determines individual slopes and anchor points for their short-term trajectory, (ii) fits polynomials to these slopes and anchor points, (iii) integrates the reciprocated polynomials and (iv) inverts the resulting curve providing an estimate of the underlying longitudinal trajectory...
April 25, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28442348/upregulation-of-neurotrophins-by-s-47445-a-novel-positive-allosteric-modulator-of-ampa-receptors-in-aged-rats
#3
Francesca Calabrese, Elisa Savino, Elisabeth Mocaer, Sylvie Bretin, Giorgio Racagni, Marco A Riva
At molecular levels, it has been shown that aging is associated with alterations in neuroplastic mechanisms. In this study, it was examined if the altered expression of neurotrophins observed in aged rats could be corrected by a chronic treatment with S 47445 (1-3-10mg/kg, p.o.), a novel selective positive allosteric modulator of the AMPA receptors. Both the mRNA and the protein levels of the neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal cortex and hippocampus (ventral and dorsal) of aged rats...
April 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28442284/fitness-fatness-index-and-alzheimer-specific-mortality
#4
Emily Frith, Paul D Loprinzi
OBJECTIVE: We evaluated the specific association between a Fitness Fat Index (FFI) and Alzheimer's-specific mortality among a national sample of the broader U.S. adult population. METHODS: FFI was calculated as cardiorespiratory fitness (CRF) divided by waist-to-height ratio (WHR). Data from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) were used to identify 16,146 participants, ages 20-85. Data from participants in these cycles were linked to death certificate data from the National Death Index...
April 22, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28438466/the-effect-of-n-acetylcysteine-nac-on-human-cognition-a-systematic-review
#5
REVIEW
David R Skvarc, Olivia M Dean, Linda K Byrne, Laura Gray, Stephen Lane, Matthew Lewis, Brisa S Fernandes, Michael Berk, Andrew Marriott
Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a glutathione precursor with potent antioxidant, pro-neurogenesis and anti-inflammatory properties and a favourable safety profile. A systematic review of the literature specifically examining the effect of NAC administration on human cognition revealed twelve suitable articles for inclusion: four examining Alzheimer's disease; three examining healthy participants; two examining physical trauma; one examining bipolar disorder, one examining schizophrenia, and one examining ketamine-induced psychosis...
April 21, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#6
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28436391/prediction-of-conversion-to-alzheimer-s-disease-with-longitudinal-measures-and-time-to-event-data
#7
Kan Li, Wenyaw Chan, Rachelle S Doody, Joseph Quinn, Sheng Luo
BACKGROUND: Identifying predictors of conversion to Alzheimer's disease (AD) is critically important for AD prevention and targeted treatment. OBJECTIVE: To compare various clinical and biomarker trajectories for tracking progression and predicting conversion from amnestic mild cognitive impairment to probable AD. METHODS: Participants were from the ADNI-1 study. We assessed the ability of 33 longitudinal biomarkers to predict time to AD conversion, accounting for demographic and genetic factors...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435853/preclinical-alzheimer-s-disease-and-longitudinal-driving-decline
#8
Catherine M Roe, Ganesh M Babulal, Denise M Head, Sarah H Stout, Elizabeth K Vernon, Nupur Ghoshal, Brad Garland, Peggy P Barco, Monique M Williams, Ann Johnson, Rebecca Fierberg, M Scot Fague, Chengjie Xiong, Elizabeth Mormino, Elizabeth A Grant, David M Holtzman, Tammie L S Benzinger, Anne M Fagan, Brian R Ott, David B Carr, John C Morris
INTRODUCTION: Links between preclinical AD and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs. METHODS: 104 OAs (65+ years) with normal cognition took part in biomarker measurements, a road test, clinical and psychometric batteries and self-reported their driving habits. RESULTS: Higher values of CSF tau/Aβ42 and ptau181/Aβ42 ratios, but not uptake on PIB amyloid imaging (p=...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28434642/-late-life-depression-or-prodromal-alzheimer-s-disease-which-tools-for-the-differential-diagnosis
#9
A-I Gasser, V Salamin, S Zumbach
INTRODUCTION: Depression and Alzheimer's disease are both very frequent in elderly people. Cognitive deficits are the hallmark of Alzheimer's disease, but they are also common in depressed elderly people who often present cognitive deficits such as memory, attention and executive function problems. On the other hand, people with early Alzheimer's disease demonstrate emotional and behavioral disorders generally encountered in depression such as loss of energy, apathy, mood disorder, and irritability...
April 20, 2017: L'Encéphale
https://www.readbyqxmd.com/read/28433262/primary-motor-cortex-alterations-in-alzheimer-disease-a-study-in-the-3xtg-ad-model
#10
E Orta-Salazar, A I Feria-Velasco, S Díaz-Cintra
INTRODUCTION: In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD...
April 19, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28433113/wilson-disease-brain-pathology
#11
Aurélia Poujois, Jacqueline Mikol, France Woimant
In Wilson disease (WD), brain cellular damage is thought to be due to copper deposition. Striatal lesions are the most characteristic lesions found in the brain of patients with neurologic symptoms, as emphasized in the initial reports of S.A.K. Wilson. WD brain lesions can be more diffuse, including in the pons, midbrain, thalamus, dentate nucleus, and, less frequently, corpus callosum and cortex. In rare cases, extensive cortical-subcortical lesions have been reported. Increased cellularity is noted in the lesions due to the proliferation of modified astrocytes named Alzheimer types of glia and specific cells, called Opalski cells, that are characteristic of WD...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28432784/contributions-of-imprecision-in-pet-mri-rigid-registration-to-imprecision-in-amyloid-pet-suvr-measurements
#12
Christopher G Schwarz, David T Jones, Jeffrey L Gunter, Val J Lowe, Prashanthi Vemuri, Matthew L Senjem, Ronald C Petersen, David S Knopman, Clifford R Jack
Quantitative measurement of β-amyloid from amyloid PET scans typically relies on localizing target and reference regions by image registration to MRI. In this work, we present a series of simulations where 50 small random perturbations of starting location and orientation were applied to each subject's PET scan, and rigid registration using spm_coreg was performed between each perturbed PET scan and its corresponding MRI. We then measured variation in the output PET-MRI registrations and how this variation affected the resulting SUVR measurements...
April 22, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28432674/partial-volume-correction-of-brain-pet-studies-using-iterative-deconvolution-in-combination-with-hypr-denoising
#13
Sandeep S V Golla, Mark Lubberink, Bart N M van Berckel, Adriaan A Lammertsma, Ronald Boellaard
BACKGROUND: Accurate quantification of PET studies depends on the spatial resolution of the PET data. The commonly limited PET resolution results in partial volume effects (PVE). Iterative deconvolution methods (IDM) have been proposed as a means to correct for PVE. IDM improves spatial resolution of PET studies without the need for structural information (e.g. MR scans). On the other hand, deconvolution also increases noise, which results in lower signal-to-noise ratios (SNR). The aim of this study was to implement IDM in combination with HighlY constrained back-PRojection (HYPR) denoising to mitigate poor SNR properties of conventional IDM...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#14
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28428346/sugar-and-artificially-sweetened-beverages-and-the-risks-of-incident-stroke-and-dementia-a-prospective-cohort-study
#15
Matthew P Pase, Jayandra J Himali, Alexa S Beiser, Hugo J Aparicio, Claudia L Satizabal, Ramachandran S Vasan, Sudha Seshadri, Paul F Jacques
BACKGROUND AND PURPOSE: Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. METHODS: We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men)...
April 20, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28427941/elongation-affinity-activation-barrier-and-stability-of-a%C3%AE-42-oligomers-fibrils-in-physiological-saline
#16
Roberto A Rodriguez, Liao Y Chen, Germán Plascencia-Villa, George Perry
Amyloid-beta (Aβ) peptides, Aβ40 and the more neurotoxic Aβ42, have been the subject of many research efforts for Alzheimer's disease. In two recent independent investigations, the atomistic structure of Aβ42 fibril has been clearly established in the S-shaped conformation consisting of three β-sheets stabilized by salt bridges formed between the Lys28 sidechain and the C-terminus of Ala42. This structure distinctively differs from the long-known structure of Aβ40 in the β-hairpin shaped conformation consisting of two β-sheets...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427114/h-lifestyle-use-of-drugs-by-healthy-people-for-enhancing-cognition-creativity-motivation-and-pleasure
#17
REVIEW
L-S Camilla d'Angelo, George Savulich, Barbara J Sahakian
Today there is continued, and in some cases growing, availability of psychoactive substances, including treatments for mental health disorders such as cognitive enhancers, which can enhance or restore brain function, but also 'recreational' drugs such as novel psychoactive substances (NPS). The use of psychoactive drugs has both benefits and risks: whilst new drugs to treat cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have great benefits for many patient groups, the increasing ease of accessibility to recreational NPS and the increasing lifestyle use of cognitive enhancers by healthy people means that the effective management of psychoactive substances will be an issue of increasing importance...
April 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#18
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28424864/loss-of-chromosome-y-loy-in-blood-cells-is-associated-with-increased-risk-for-disease-and-mortality-in-aging-men
#19
REVIEW
Lars A Forsberg
Recent discoveries have shown that harboring cells without the Y chromosome in the peripheral blood is associated with increased risk for all-cause mortality and disease such as different forms of cancer, Alzheimer's disease, as well as other conditions in aging men. In the entire world, the life expectancy of men is shorter compared to women, a sex difference that has been known for centuries, but the underlying mechanism(s) are not well understood. As a male-specific genetic risk factor, an increased risk for pathology and mortality associated with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that men on average live shorter lives compared to women...
April 19, 2017: Human Genetics
https://www.readbyqxmd.com/read/28424614/relationship-between-cognitive-and-sleep-wake-variables-in-asymptomatic-offspring-of-patients-with-late-onset-alzheimer-s-disease
#20
Carolina Abulafia, Bárbara Duarte-Abritta, Mirta F Villarreal, María S Ladrón-de-Guevara, Celeste García, Geraldine Sequeyra, Gustavo Sevlever, Leticia Fiorentini, Karl-Jürgen Bär, Deborah R Gustafson, Daniel E Vigo, Salvador M Guinjoan
Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature...
2017: Frontiers in Aging Neuroscience
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