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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/28100252/a-cognitive-electrophysiological-signature-differentiates-amnestic-mild-cognitive-impairment-from-normal-aging
#1
Juan Li, Lucas S Broster, Gregory A Jicha, Nancy B Munro, Frederick A Schmitt, Erin Abner, Richard Kryscio, Charles D Smith, Yang Jiang
BACKGROUND: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer's disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education...
January 19, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28093088/diagnostic-impact-of-18-f-flutemetamol-pet-in-early-onset-dementia
#2
Marissa D Zwan, Femke H Bouwman, Elles Konijnenberg, Wiesje M van der Flier, Adriaan A Lammertsma, Frans R J Verhey, Pauline Aalten, Bart N M van Berckel, Philip Scheltens
BACKGROUND: Early-onset dementia patients often present with atypical clinical symptoms, hampering an accurate clinical diagnosis. The purpose of the present study was to assess the diagnostic impact of the amyloid-positron emission tomography (PET) imaging agent [(18)F]flutemetamol in early-onset dementia patients, in terms of change in (confidence in) diagnosis and patient management plan. METHODS: This prospective bi-center study included 211 patients suspected of early-onset dementia who visited a tertiary memory clinic...
January 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#3
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28034305/sorl1-gene-plasma-biomarkers-and-the-risk-of-alzheimer-s-disease-for-the-han-chinese-population-in-taiwan
#4
Cheng-Ta Chou, Yi-Chu Liao, Wei-Ju Lee, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: The sortilin-related receptor 1 (SORL1) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer's disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between SORL1 polymorphisms, plasma concentrations of amyloid-beta (Aβ) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan. METHODS: Eight single-nucleotide polymorphisms (SNPs) in SORL1 and the apolipoprotein E gene (APOE) ε4 alleles were genotyped in 798 patients with AD, 157 patients with MCI, and 401 control subjects...
December 30, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27978855/a-digital-enzyme-linked-immunosorbent-assay-for-ultrasensitive-measurement-of-amyloid-%C3%AE-1-42-peptide-in-human-plasma-with-utility-for-studies-of-alzheimer-s-disease-therapeutics
#5
Linan Song, D Richard Lachno, David Hanlon, Adam Shepro, Andreas Jeromin, Dipika Gemani, Jayne A Talbot, Margaret M Racke, Jeffrey L Dage, Robert A Dean
BACKGROUND: Amyloid-β 1-42 peptide (Aβ1-42) is associated with plaque formation in the brain of patients with Alzheimer's disease (AD). Pharmacodynamic studies of AD therapeutics that lower the concentrations of Aβ1-42 in peripheral blood require highly sensitive assays for its measurement. A digital enzyme-linked immunosorbent assay (ELISA) using single molecule array (Simoa) technology has been developed that provides improved sensitivity compared with conventional ELISA methods using the same antibody reagents...
December 15, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27974048/selective-suppression-of-the-%C3%AE-isoform-of-p38-mapk-rescues-late-stage-tau-pathology
#6
Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N Kokiko-Cochran, Saktimayee M Roy, Linda J Van Eldik, D Martin Watterson, Bruce T Lamb, Kiran Bhaskar
BACKGROUND: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer's disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1. METHOD: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice...
December 15, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27964740/lw-afc-a-new-formula-derived-from-liuwei-dihuang-decoction-ameliorates-behavioral-and-pathological-deterioration-via-modulating-the-neuroendocrine-immune-system-in-prp-ha%C3%AE-ppswe-ps1-%C3%AE-e9-transgenic-mice
#7
Jian-Hui Wang, Xi Lei, Xiao-Rui Cheng, Xiao-Rui Zhang, Gang Liu, Jun-Ping Cheng, Yi-Ran Xu, Ju Zeng, Wen-Xia Zhou, Yong-Xiang Zhang
BACKGROUND: Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer's disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1(ΔE9) (APP/PS1) transgenic mouse model of AD. METHODS: After treatment with a novel Liuwei Dihuang formula (LW-AFC), mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Aβ) deposition, and Aβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively...
December 13, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27955707/desire-for-predictive-testing-for-alzheimer-s-disease-and-impact-on-advance-care-planning-a-cross-sectional-study
#8
Meera Sheffrin, Irena Stijacic Cenzer, Michael A Steinman
BACKGROUND: It is unknown whether older adults in the United States would be willing to take a test predictive of future Alzheimer's disease, or whether testing would change behavior. Using a nationally representative sample, we explored who would take a free and definitive test predictive of Alzheimer's disease, and examined how using such a test may impact advance care planning. METHODS: A cross-sectional study within the 2012 Health and Retirement Study of adults aged 65 years or older asked questions about a test predictive of Alzheimer's disease (N = 874)...
December 13, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27931251/conflicting-cerebrospinal-fluid-biomarkers-and-progression-to-dementia-due-to-alzheimer-s-disease
#9
Panagiotis Alexopoulos, Lukas Werle, Jennifer Roesler, Nathalie Thierjung, Lena Sophie Gleixner, Igor Yakushev, Nikolaos Laskaris, Stefan Wagenpfeil, Philippos Gourzis, Alexander Kurz, Robert Perneczky
BACKGROUND: According to new diagnostic guidelines for Alzheimer's disease (AD), biomarkers enable estimation of the individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementia for patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affect the progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF) biomarker constellations on the progression risk of MCI patients...
December 9, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27931245/brain-activation-in-frontotemporal-and-alzheimer-s-dementia-a-functional-near-infrared-spectroscopy-study
#10
Florian G Metzger, Betti Schopp, Florian B Haeussinger, Katja Dehnen, Matthis Synofzik, Andreas J Fallgatter, Ann-Christine Ehlis
BACKGROUND: Frontotemporal dementia is an increasingly studied disease, the underlying functional impairments on a neurobiological level of which have not been fully understood. Patients with the behavioral-subtype frontotemporal dementia (bvFTD) are particularly challenging for clinical measurements such as functional imaging due to their behavioral symptoms. Here, an alternative imaging method, functional near-infrared spectroscopy (fNIRS), is introduced to measure task-related cortical brain activation based on blood oxygenation...
December 8, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27915998/an-update-on-semantic-dementia-genetics-imaging-and-pathology
#11
REVIEW
Ramon Landin-Romero, Rachel Tan, John R Hodges, Fiona Kumfor
Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD...
December 5, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27903289/changes-in-cerebral-glucose-metabolism-after-3%C3%A2-weeks-of-noninvasive-electrical-stimulation-of-mild-cognitive-impairment-patients
#12
Kyongsik Yun, In-Uk Song, Yong-An Chung
BACKGROUND: Mild cognitive impairment (MCI) is a syndrome that disrupts an individual's cognitive function but preserves activities of daily living. MCI is thought to be a prodromal stage of dementia, which disrupts patients' daily lives and causes severe cognitive dysfunction. Although extensive clinical trials have attempted to slow or stop the MCI to dementia conversion, the results have been largely unsuccessful. The purpose of this study was to determine whether noninvasive electrical stimulation of MCI changes glucose metabolism...
December 1, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27884212/angiotensin-converting-enzyme-2-is-reduced-in-alzheimer-s-disease-in-association-with-increasing-amyloid-%C3%AE-and-tau-pathology
#13
Patrick Gavin Kehoe, Steffenny Wong, Noura Al Mulhim, Laura Elyse Palmer, J Scott Miners
BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity...
November 25, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27866472/outcomes-measures-in-a-decade-of-dementia-and-mild-cognitive-impairment-trials
#14
Jennifer Kirsty Harrison, Anna H Noel-Storr, Nele Demeyere, Emma L Reynish, Terry J Quinn
BACKGROUND: In a research study, to give a comprehensive evaluation of the impact of interventions, the outcome measures should reflect the lived experience of the condition. In dementia studies, this necessitates the use of outcome measures which capture the range of disease effects, not limited to cognitive functioning. In particular, assessing the functional impact of cognitive impairment is recommended by regulatory authorities, but there is no consensus on the optimal approach for outcome assessment in dementia research...
November 21, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27986093/the-societal-costs-of-dementia-in-sweden-2012-relevance-and-methodological-challenges-in-valuing-informal-care
#15
Anders Wimo, Linus Jönsson, Laura Fratiglioni, Per Olof Sandman, Anders Gustavsson, Anders Sköldunger, Lennarth Johansson
BACKGROUND: In this study, we sought to estimate the societal cost of illness in dementia in Sweden in 2012 using different costing approaches to highlight methodological issues. METHODS: We conducted a prevalence-based cost-of-illness study with a societal perspective. RESULTS: The societal costs of dementia in Sweden in 2012 were SEK 62.9 billion (approximately €7.2 billion, approximately US$9.0 billion) or SEK 398,000 per person with dementia (approximately €45,000, approximately US$57,000)...
November 18, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27846868/effect-of-concomitant-use-of-memantine-on-mortality-and-efficacy-outcomes-of-galantamine-treated-patients-with-alzheimer-s-disease-post-hoc-analysis-of-a-randomized-placebo-controlled-study
#16
Klaus Hager, Alan S Baseman, Jeffrey S Nye, H Robert Brashear, John Han, Mary Sano, Bonnie Davis, Henry M Richards
BACKGROUND: A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer's disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome. METHODS: Randomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints...
November 15, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27832826/psychological-behavioral-and-social-effects-of-disclosing-alzheimer-s-disease-biomarkers-to-research-participants-a-systematic-review
#17
S A S A Bemelmans, K Tromp, E M Bunnik, R J Milne, S Badger, C Brayne, M H Schermer, E Richard
BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants...
November 10, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27784332/using-the-affiliate-stigma-scale-with-caregivers-of-people-with-dementia-psychometric-evaluation
#18
Chih-Cheng Chang, Jian-An Su, Chung-Ying Lin
BACKGROUND: In this study, we examined the psychometric properties of the Affiliate Stigma Scale to measure affiliate stigma for caregivers of family members with dementia, a topic scantily covered in the literature. METHODS: Two hundred seventy-one caregivers were recruited. Each completed the Affiliate Stigma Scale, Caregiver Burden Inventory, Taiwanese Depression Questionnaire, Beck Anxiety Inventory, and 28-item World Health Organization Quality of Life questionnaire...
October 26, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27756421/abt-126-monotherapy-in-mild-to-moderate-alzheimer-s-dementia-randomized-double-blind-placebo-and-active-controlled-adaptive-trial-and-open-label-extension
#19
Laura M Gault, Robert A Lenz, Craig W Ritchie, Andreas Meier, Ahmed A Othman, Qi Tang, Scott Berry, Yili Pritchett, Weining Z Robieson
BACKGROUND: Results from a phase 2a study indicated that treatment with the novel α7 nicotinic acetylcholine receptor agonist ABT-126 25 mg once daily (QD) was associated with a trend for improvement in cognition in subjects with mild-to-moderate Alzheimer's dementia (AD). A phase 2b program was designed to evaluate a broader dose range of ABT-126 as monotherapy in subjects with mild-to-moderate AD. The program consisted of a double-blind, placebo and active controlled study of ABT-126 (dose range 25-75 mg) and an open-label extension study (75 mg)...
October 18, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27756387/identifying-biomarkers-of-dementia-prevalent-among-amnestic-mild-cognitively-impaired-ethnic-female-patients
#20
Rinko Grewal, Mona Haghighi, Shuai Huang, Amanda G Smith, Chuanhai Cao, Xiaoyang Lin, Daniel C Lee, Nancy Teten, Angela M Hill, Maj-Linda B Selenica
BACKGROUND: There is a need to investigate biomarkers that are indicative of the progression of dementia in ethnic patient populations. The disparity of information in these populations has been the focus of many clinical and academic centers, including ours, to contribute to a higher success rate in clinical trials. In this study, we have investigated plasma biomarkers in amnestic mild cognitively impaired (aMCI) female patient cohorts in the context of ethnicity and cognitive status...
October 18, 2016: Alzheimer's Research & Therapy
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