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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/28212683/evidence-for-benefit-of-statins-to-modify-cognitive-decline-and-risk-in-alzheimer-s-disease
#1
Nophar Geifman, Roberta Diaz Brinton, Richard E Kennedy, Lon S Schneider, Atul J Butte
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28212674/proportion-of-dementia-in-australia-explained-by-common-modifiable-risk-factors
#2
Kimberly Ashby-Mitchell, Richard Burns, Jonathan Shaw, Kaarin J Anstey
BACKGROUND: At present, dementia has no known cure. Interventions to delay onset and reduce prevalence of the disease are therefore focused on risk factor reduction. Previous population attributable risk estimates for western countries may have been underestimated as a result of the relatively low rates of midlife obesity and the lower weighting given to that variable in statistical models. METHODS: Levin's Attributable Risk which assumes independence of risk factors was used to calculate the proportion of dementia attributable to seven modifiable risk factors (midlife obesity, physical inactivity, smoking, low educational attainment, diabetes mellitus, midlife hypertension and depression) in Australia...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28209190/the-effects-of-different-familial-alzheimer-s-disease-mutations-on-app-processing-in-vivo
#3
Steinunn Thordardottir, Anne Kinhult Ståhlbom, Ove Almkvist, Håkan Thonberg, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Caroline Graff
BACKGROUND: Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer's disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. METHODS: In the current cross-sectional study, products of APP processing (e...
February 16, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28193256/unbiased-estimates-of-cerebrospinal-fluid-%C3%AE-amyloid-1-42-cutoffs-in-a-large-memory-clinic-population
#4
Daniela Bertens, Betty M Tijms, Philip Scheltens, Charlotte E Teunissen, Pieter Jelle Visser
BACKGROUND: We sought to define a cutoff for β-amyloid 1-42 in cerebrospinal fluid (CSF), a key marker for Alzheimer's disease (AD), with data-driven Gaussian mixture modeling in a memory clinic population. METHODS: We performed a combined cross-sectional and prospective cohort study. We selected 2462 subjects with subjective cognitive decline, mild cognitive impairment, AD-type dementia, and dementia other than AD from the Amsterdam Dementia Cohort. We defined CSF β-amyloid 1-42 cutoffs by data-driven Gaussian mixture modeling in the total population and in subgroups based on clinical diagnosis, age, and apolipoprotein E (APOE) genotype...
February 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28162091/increased-dementia-risk-predominantly-in-diabetes-mellitus-rather-than-in-hypertension-or-hyperlipidemia-a-population-based-cohort-study
#5
Yen-Chun Fan, Jung-Lung Hsu, Hong-Yi Tung, Chia-Chi Chou, Chyi-Huey Bai
BACKGROUND: The pathophysiology of insulin resistance-induced hypertension and hyperlipidemia might entail differences in dementia risk in cases with hypertension and hyperlipidemia without prior diabetes mellitus (DM). This study investigated whether incident hypertension, incident hyperlipidemia, or both, increased the dementia risk in patients with and without DM. METHODS: A nationwide retrospective cohort study was conducted. The study sample was obtained from the National Health Insurance Research Database...
February 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28153054/interaction-between-personality-traits-and-cerebrospinal-fluid-biomarkers-of-alzheimer-s-disease-pathology-modulates-cognitive-performance
#6
Domilė Tautvydaitė, Deepti Kukreja, Jean-Philippe Antonietti, Hugues Henry, Armin von Gunten, Julius Popp
BACKGROUND: During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition...
February 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28137305/peripheral-apoe-isoform-levels-in-cognitively-normal-apoe-%C3%AE%C2%B53-%C3%AE%C2%B54-individuals-are-associated-with-regional-gray-matter-volume-and-cerebral-glucose-metabolism
#7
Henrietta M Nielsen, Kewei Chen, Wendy Lee, Yinghua Chen, Robert J Bauer, Eric Reiman, Richard Caselli, Guojun Bu
BACKGROUND: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated...
January 30, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28109317/sorting-nexin-4-regulates-%C3%AE-amyloid-production-by-modulating-%C3%AE-site-activating-cleavage-enzyme-1
#8
Na-Young Kim, Mi-Hyang Cho, Se-Hoon Won, Hoe-Jin Kang, Seung-Yong Yoon, Dong-Hou Kim
BACKGROUND: Amyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer's disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet...
January 21, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28100252/a-cognitive-electrophysiological-signature-differentiates-amnestic-mild-cognitive-impairment-from-normal-aging
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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