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Biomarker AND Alzheimer's disease

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https://www.readbyqxmd.com/read/29790242/looking-for-trouble-diagnostics-expanding-disease-and-producing-patients
#1
Bjørn Hofmann
Novel tests give great opportunities for earlier and more precise diagnostics. At the same time, new tests expand disease, produce patients, and cause unnecessary harm in overdiagnosis and overtreatment. How can we evaluate diagnostics to obtain the benefits and avoid harm? One way is to pay close attention to the diagnostic process and its core concepts. Doing so reveals 3 errors that expand disease and increase overdiagnosis. The first error is to decouple diagnostics from harm, eg, by diagnosing insignificant conditions...
May 23, 2018: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/29788013/cerebrospinal-fluid-bace1-activity-and-sa%C3%AE-pp%C3%AE-as-biomarker-candidates-of-alzheimer-s-disease
#2
Panagiotis Alexopoulos, Nathalie Thierjung, Timo Grimmer, Marion Ortner, Polychronis Economou, Konstantinos Assimakopoulos, Philippos Gourzis, Antonios Politis, Robert Perneczky
BACKGROUND/AIMS: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. METHODS: BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48)...
May 22, 2018: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/29782824/apoe-%C3%AE%C2%B54-associates-with-hippocampal-volume-learning-and-memory-across-the-spectrum-of-alzheimer-s-disease-and-dementia-with-lewy-bodies
#3
Usman Saeed, Saira S Mirza, Bradley J MacIntosh, Nathan Herrmann, Julia Keith, Joel Ramirez, Sean M Nestor, Qinggang Yu, Jo Knight, Walter Swardfager, Steven G Potkin, Ekaterina Rogaeva, Peter St George-Hyslop, Sandra E Black, Mario Masellis
INTRODUCTION: Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. METHODS: We studied 298 patients (AD = 250, DLB = 48; 38 autopsy confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis...
May 18, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#4
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782318/amyloid-accumulation-and-cognitive-decline-in-clinically-normal-older-individuals-implications-for-aging-and-early-alzheimer-s-disease
#5
Elizabeth C Mormino, Kathryn V Papp
 The aberrant accumulation of the amyloid protein is a critical and early event in the Alzheimer's disease (AD) cascade. Given the early involvement of this pathological process, it is not surprising that many clinically normal (CN) older individuals demonstrate evidence of abnormal Aβ at postmortem examination and in vivo using either CSF or PET imaging. Converging evidence across multiple research groups suggests that the presence of abnormal Aβ among CN individuals is associated with elevated risk of future clinical impairment and cognitive decline...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782317/dementia-research-populations-progress-problems-and-predictions
#6
Sally Hunter, Nadja Smailagic, Carol Brayne
Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782314/a-retrospective-belgian-multi-center-mri-biomarker-study-in-alzheimer-s-disease-remember
#7
Ellis Niemantsverdriet, Annemie Ribbens, Christine Bastin, Florence Benoit, Bruno Bergmans, Jean-Christophe Bier, Roxanne Bladt, Lene Claes, Peter Paul De Deyn, Olivier Deryck, Bernard Hanseeuw, Adrian Ivanoiu, Jean-Claude Lemper, Eric Mormont, Gaëtane Picard, Eric Salmon, Kurt Segers, Anne Sieben, Dirk Smeets, Hanne Struyfs, Evert Thiery, Jos Tournoy, Eric Triau, Anne-Marie Vanbinst, Jan Versijpt, Maria Bjerke, Sebastiaan Engelborghs
BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29780874/the-personalized-alzheimer-s-disease-cortical-thickness-index-predicts-likely-pathology-and-clinical-progression-in-mild-cognitive-impairment
#8
Annie M Racine, Michael Brickhouse, David A Wolk, Bradford C Dickerson
Introduction: An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden. Methods: We calculated a brain-age-adjusted "personalized AD cortical thickness index" (pADi) in mild cognitive impairment patients from the Alzheimer's Disease Neuroimaging Initiative. We performed receiver operating characteristic analysis for discrimination between patients with and without cerebrospinal fluid evidence of AD and logistic regression in an independent sample to determine if a dichotomized pADi predicted conversion to AD dementia...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780873/advances-in-alzheimer-s-imaging-are-changing-the-experience-of-alzheimer-s-disease
#9
REVIEW
Shana D Stites, Richard Milne, Jason Karlawish
Neuroimaging is advancing a new definition of Alzheimer's disease (AD). Using imaging biomarkers, clinicians may begin to diagnose the disease by identifying pathology and neurodegeneration in either cognitively impaired or unimpaired adults. This "biomarker-based" diagnosis may allow clinicians novel opportunities to use interventions that either delay the onset or slow the progression of cognitive decline, but it will also bring novel challenges. How will changing the definition of AD from a clinical to a biomarker construct change the experience of living with the disease? Knowledge of AD biomarker status can affect how individuals feel about themselves (internalized stigma) and how others judge them (public stigma)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780869/cross-sectional-and-longitudinal-atrophy-is-preferentially-associated-with-tau-rather-than-amyloid-%C3%AE-positron-emission-tomography-pathology
#10
Brian A Gordon, Austin McCullough, Shruti Mishra, Tyler M Blazey, Yi Su, John Christensen, Aylin Dincer, Kelley Jackson, Russ C Hornbeck, John C Morris, Beau M Ances, Tammie L S Benzinger
Introduction: Structural magnetic resonance imaging is a marker of gray matter health and decline that is sensitive to impaired cognition and Alzheimer's disease pathology. Prior work has shown that both amyloid β (Aβ) and tau biomarkers are related to cortical thinning, but it is unclear what unique influences they have on the brain. Methods: Aβ pathology was measured with [18 F] AV-45 (florbetapir) positron emission tomography (PET) and tau was assessed with [18 F] AV-1451 (flortaucipir) PET in a population of 178 older adults, of which 123 had longitudinal magnetic resonance imaging assessments (average of 5...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29776894/amyloid-pet-in-neurodegenerative-diseases-with-dementia
#11
V Camacho, A Gómez-Grande, P Sopena, D García-Solís, M Gómez Río, C Lorenzo, S Rubí, J Arbizu
Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI)...
May 15, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#12
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772817/computational-convolution-of-seldi-data-for-the-diagnosis-of-alzheimer-s-disease
#13
Destiny E O Anyaiwe, Gautam B Singh, George D Wilson, Timothy J Geddes
Alzheimer's disease is rapidly becoming an endemic for people over the age of 65. A vital path towards reversing this ominous trend is the building of reliable diagnostic devices for definite and early diagnoses in lieu of the longitudinal, usually inconclusive and non-generalize-able methods currently in use. In this article, we present a survey of methods for mining pools of mass spectrometer saliva data in relation to diagnosing Alzheimer's disease. The computational methods provides new approaches for appropriately gleaning latent information from mass spectra data...
May 17, 2018: High-throughput
https://www.readbyqxmd.com/read/29762152/alzheimer-s-disease-neuroimaging
#14
Jennifer L Whitwell
PURPOSE OF REVIEW: The aim of this study was to discuss the contribution of neuroimaging studies to our understanding of Alzheimer's disease. We now have the capability of measuring both tau and beta-amyloid (Aβ) proteins in the brain, which together with more traditional neuroimaging modalities, has led the field to focus on using neuroimaging to better characterize disease mechanisms underlying Alzheimer's disease. RECENT FINDINGS: Studies have utilized tau and Aβ PET, as well as [18F]fluorodeoxyglucose PET, and structural and functional MRI, to investigate the following topics: phenotypic variability in Alzheimer's disease , including how neuroimaging findings are related to clinical phenotype and age; multimodality analyses to investigate the relationships between different neuroimaging modalities and what that teaches us about disease mechanisms; disease staging by assessing neuroimaging changes in the very earliest phases of the disease in cognitively normal individuals and individuals carrying an autosomal dominant Alzheimer's disease mutation; and influence of other comorbidities and proteins to the disease process...
May 11, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29760644/an-algorithm-for-preclinical-diagnosis-of-alzheimer-s-disease
#15
REVIEW
Tapan K Khan
Almost all Alzheimer's disease (AD) therapeutic trials have failed in recent years. One of the main reasons for failure is due to designing the disease-modifying clinical trials at the advanced stage of the disease when irreversible brain damage has already occurred. Diagnosis of the preclinical stage of AD and therapeutic intervention at this phase, with a perfect target, are key points to slowing the progression of the disease. Various AD biomarkers hold enormous promise for identifying individuals with preclinical AD and predicting the development of AD dementia in the future, but no single AD biomarker has the capability to distinguish the AD preclinical stage...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29758944/the-conundrum-of-gsk3-inhibitors-is-it-the-dawn-of-a-new-beginning
#16
Ratan V Bhat, Ulf Andersson, Shalini Andersson, Laurent Knerr, Udo Bauer, Anna Sundgren Andersson
Spanning over three decades of extensive drug discovery research, the efforts to develop a potent and selective GSK3 inhibitor as a therapeutic for the treatment of type 2 diabetes, Alzheimer's disease (AD), bipolar disorders and cancer have been futile. Since its initial discovery in 1980 and subsequent decades of research, one cannot underscore the importance of the target and the promise of a game changing disease modifier. Several pharmaceutical companies, biotech companies, and academic institutions raged in a quest to unravel the biology and discover potent and selective GSK3 inhibitors, some of which went through clinical trials...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758942/lost-in-translation-finding-our-way-to-effective-alzheimer-s-disease-therapies
#17
Joseph Quinn
Efforts over the past two decades to develop effective disease-modifying treatments for Alzheimer's disease have been disappointing, while parallel efforts in another chronic neurologic disease, multiple sclerosis, have been remarkably productive. In an effort to advance development of therapeutics for Alzheimer's disease, these two fields are contrasted in terms of the utility of animal models, definition of study populations, and utility of biomarkers. Possible solutions are suggested, and the review concludes with description of some active peer-reviewed, publicly funded clinical studies which address some of the identified weaknesses in past clinical trials for age-related dementia...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758941/from-cerebrospinal-fluid-to-blood-the-third-wave-of-fluid-biomarkers-for-alzheimer-s-disease
#18
Henrik Zetterberg, Kaj Blennow
The past five years have seen an enormous development in the field of fluid biomarkers for Alzheimer's disease (AD) and related disorders. The proteins that constitute the foundation for the cerebrospinal fluid (CSF) tests for the classical AD pathologies are now being explored as potential blood-based biomarkers, thanks to the recent implementation of ultrasensitive measurement technologies in academic and clinical laboratories worldwide. The current blood-derived data are still less clear than those obtained using CSF as the sample type, but independent research suggests that there are biomarker signals in blood that relate to plaque and tangle pathologies in AD, which are relevant to explore further...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758940/self-reported-physical-activity-is-associated-with-tau-burden-measured-by-positron-emission-tomography
#19
Belinda M Brown, Stephanie R Rainey-Smith, Vincent Dore, Jeremiah J Peiffer, Samantha C Burnham, Simon M Laws, Kevin Taddei, David Ames, Colin L Masters, Christopher C Rowe, Ralph N Martins, Victor L Villemagne
Numerous animal studies have reported exercise reduces the accumulation of Alzheimer's disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758232/a-review-of-brain-insulin-signaling-in-mood-disorders-from-biomarker-to-clinical-target
#20
REVIEW
Thanh Thanh L Nguyen, Lily C Chan, Kristin Borreginne, Rajas P Kale, Chunling Hu, Susannah J Tye
Patients with mood disorders are at increased risk for metabolic dysfunction. Co-occurrence of the two conditions is typically associated with a more severe disease course and poorer treatment outcomes. The specific pathophysiological mechanisms underlying this bidirectional relationship between mood and metabolic dysfunction remains poorly understood. However, it is likely that impairment of metabolic processes within the brain play a critical role. The insulin signaling pathway mediates metabolic homeostasis and is important in the regulation of neurotrophic and synaptic plasticity processes, including those involved in neurodegenerative diseases like Alzheimer's...
May 11, 2018: Neuroscience and Biobehavioral Reviews
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