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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/28818116/distinct-white-matter-microstructural-abnormalities-and-extracellular-water-increases-relate-to-cognitive-impairment-in-alzheimer-s-disease-with-and-without-cerebrovascular-disease
#1
Fang Ji, Ofer Pasternak, Siwei Liu, Yng Miin Loke, Boon Linn Choo, Saima Hilal, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, Juan Zhou
BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28818092/associations-of-thyroid-hormone-serum-levels-with-in-vivo-alzheimer-s-disease-pathologies
#2
Hyo Jung Choi, Min Soo Byun, Dahyun Yi, Bo Kyung Sohn, Jun Ho Lee, Jun-Young Lee, Yu Kyung Kim, Dong Young Lee
BACKGROUND: The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer's disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. METHODS: This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included (11)C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, (18)F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#3
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28793933/can-cognitive-assessment-really-discriminate-early-stages-of-alzheimer-s-and-behavioural-variant-frontotemporal-dementia-at-initial-clinical-presentation
#4
Sophia Reul, Hubertus Lohmann, Heinz Wiendl, Thomas Duning, Andreas Johnen
BACKGROUND: Neuropsychological testing is considered crucial for differential diagnosis of Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD). In-depth neuropsychological assessment revealed specific dysfunctions in the two dementia syndromes. However, a significant overlap of cognitive impairments exists in early disease stages. We questioned whether a standard neuropsychological assessment at initial clinical presentation can delineate patients with AD versus bvFTD...
August 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28793924/on-the-path-to-2025-understanding-the-alzheimer-s-disease-continuum
#5
REVIEW
Paul S Aisen, Jeffrey Cummings, Clifford R Jack, John C Morris, Reisa Sperling, Lutz Frölich, Roy W Jones, Sherie A Dowsett, Brandy R Matthews, Joel Raskin, Philip Scheltens, Bruno Dubois
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum...
August 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28784164/association-between-chronic-periodontitis-and-the-risk-of-alzheimer-s-disease-a-retrospective-population-based-matched-cohort-study
#6
Chang-Kai Chen, Yung-Tsan Wu, Yu-Chao Chang
BACKGROUND: Although recent short-term cross-sectional studies have revealed that chronic periodontitis (CP) may be a risk factor for increased cognitive impairment in patients with Alzheimer's disease (AD), systematic reviews and long-term longitudinal studies have provided less clear evidence regarding the relationship between CP and AD. Therefore, we conducted a retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan to determine whether patients with CP are at increased risk of developing AD...
August 8, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28764771/sensitivity-of-restriction-spectrum-imaging-to-memory-and-neuropathology-in-alzheimer-s-disease
#7
Emilie T Reas, Donald J Hagler, Nathan S White, Joshua M Kuperman, Hauke Bartsch, Karalani Cross, Richard Q Loi, Akshara R Balachandra, M J Meloy, Christina E Wierenga, Douglas Galasko, James B Brewer, Anders M Dale, Linda K McEvoy
BACKGROUND: Diffusion imaging has demonstrated sensitivity to structural brain changes in Alzheimer's disease (AD). However, there remains a need for a more complete characterization of microstructural alterations occurring at the earliest disease stages, and how these changes relate to underlying neuropathology. This study evaluated the sensitivity of restriction spectrum imaging (RSI), an advanced diffusion magnetic resonance imaging (MRI) technique, to microstructural brain changes in mild cognitive impairment (MCI) and AD...
August 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28764796/anticholinergic-drugs-and-functional-cognitive-impairment-and-behavioral-disturbances-in-patients-from-a-memory-clinic-with-subjective-cognitive-decline-or-neurocognitive-disorders
#8
Virginie Dauphinot, Christelle Mouchoux, Sébastien Veillard, Floriane Delphin-Combe, Pierre Krolak-Salmon
BACKGROUND: Drugs with anticholinergic properties may be associated with various adverse clinical effects. The relationship between the anticholinergic (AC) burden and functional, global cognitive performance and behavior disturbances was assessed among elderly patients. METHODS: A cross-sectional study was conducted between January 2012 and June 2014 in a memory clinic among outpatients living at home and with subjective cognitive decline (SCD) or neurocognitive disorders (NCD)...
August 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28764767/monoamine-oxidase-b-is-elevated-in-alzheimer-disease-neurons-is-associated-with-%C3%AE-secretase-and-regulates-neuronal-amyloid-%C3%AE-peptide-levels
#9
Sophia Schedin-Weiss, Mitsuhiro Inoue, Lenka Hromadkova, Yasuhiro Teranishi, Natsuko Goto Yamamoto, Birgitta Wiehager, Nenad Bogdanovic, Bengt Winblad, Anna Sandebring-Matton, Susanne Frykman, Lars O Tjernberg
BACKGROUND: Increased levels of the pathogenic amyloid β-peptide (Aβ), released from its precursor by the transmembrane protease γ-secretase, are found in Alzheimer disease (AD) brains. Interestingly, monoamine oxidase B (MAO-B) activity is also increased in AD brain, but its role in AD pathogenesis is not known. Recent neuroimaging studies have shown that the increased MAO-B expression in AD brain starts several years before the onset of the disease. Here, we show a potential connection between MAO-B, γ-secretase and Aβ in neurons...
August 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28764750/risk-of-head-and-traumatic-brain-injuries-associated-with-antidepressant-use-among-community-dwelling-persons-with-alzheimer-s-disease-a-nationwide-matched-cohort-study
#10
Heidi Taipale, Marjaana Koponen, Antti Tanskanen, Piia Lavikainen, Reijo Sund, Jari Tiihonen, Sirpa Hartikainen, Anna-Maija Tolppanen
BACKGROUND: Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease. METHODS: A matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort...
August 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28750675/differential-role-of-csf-fatty-acid-binding-protein-3-%C3%AE-synuclein-and-alzheimer-s-disease-core-biomarkers-in-lewy-body-disorders-and-alzheimer-s-dementia
#11
Davide Chiasserini, Leonardo Biscetti, Paolo Eusebi, Nicola Salvadori, Giulia Frattini, Simone Simoni, Naomi De Roeck, Nicola Tambasco, Erik Stoops, Hugo Vanderstichele, Sebastiaan Engelborghs, Brit Mollenhauer, Paolo Calabresi, Lucilla Parnetti
BACKGROUND: Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB) share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may help the characterization of these diseases, improving the differential diagnosis. We evaluated the diagnostic performance of five CSF biomarkers across a well-characterized cohort of patients diagnosed with AD, DLB, PDD, and Parkinson's disease (PD). METHODS: A total of 208 patients were enrolled in 3 European centers...
July 28, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28750690/increased-a%C3%AE-42-%C3%AE-7-like-nicotinic-acetylcholine-receptor-complex-level-in-lymphocytes-is-associated-with-apolipoprotein-e4-driven-alzheimer-s-disease-pathogenesis
#12
Hoau-Yan Wang, Caryn Trocmé-Thibierge, Andres Stucky, Sanket M Shah, Jessica Kvasic, Amber Khan, Philippe Morain, Isabelle Guignot, Eva Bouguen, Karine Deschet, Maria Pueyo, Elisabeth Mocaer, Pierre-Jean Ousset, Bruno Vellas, Vera Kiyasova
BACKGROUND: The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS: Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)42-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ42-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes...
July 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28750682/behavioural-and-neuroanatomical-correlates-of-auditory-speech-analysis-in-primary-progressive-aphasias
#13
Chris J D Hardy, Jennifer L Agustus, Charles R Marshall, Camilla N Clark, Lucy L Russell, Rebecca L Bond, Emilie V Brotherhood, David L Thomas, Sebastian J Crutch, Jonathan D Rohrer, Jason D Warren
BACKGROUND: Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. METHODS: We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters-temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)-in sequences of spoken syllables...
July 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28747210/the-medical-food-souvenaid-affects-brain-phospholipid-metabolism-in-mild-alzheimer-s-disease-results-from-a-randomized-controlled-trial
#14
Anne Rijpma, Marinette van der Graaf, Marieke M Lansbergen, Olga Meulenbroek, Aysun Cetinyurek-Yavuz, John W Sijben, Arend Heerschap, Marcel G M Olde Rikkert
BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. METHODS: Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study...
July 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28709449/a-novel-alzheimer-s-disease-drug-candidate-targeting-inflammation-and-fatty-acid-metabolism
#15
Daniel Daugherty, Joshua Goldberg, Wolfgang Fischer, Richard Dargusch, Pamela Maher, David Schubert
BACKGROUND: CAD-31 is an Alzheimer's disease (AD) drug candidate that was selected on the basis of its ability to stimulate the replication of human embryonic stem cell-derived neural precursor cells as well as in APPswe/PS1ΔE9 AD mice. To move CAD-31 toward the clinic, experiments were undertaken to determine its neuroprotective and pharmacological properties, as well as to assay its therapeutic efficacy in a rigorous mouse model of AD. RESULTS: CAD-31 has potent neuroprotective properties in six distinct nerve cell assays that mimic toxicities observed in the old brain...
July 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28709448/no-added-diagnostic-value-of-non-phosphorylated-tau-fraction-p-taurel-in-csf-as-a-biomarker-for-differential-dementia-diagnosis
#16
Joery Goossens, Maria Bjerke, Hanne Struyfs, Ellis Niemantsverdriet, Charisse Somers, Tobi Van den Bossche, Sara Van Mossevelde, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Johan Goeman, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ1-42, t-tau, and p-tau181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-taurel), may improve differential dementia diagnosis. The goal of this study is to investigate if p-taurel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. METHODS: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls...
July 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28673336/cerebrospinal-fluid-biomarkers-for-alzheimer-s-and-vascular-disease-vary-by-age-gender-and-apoe-genotype-in-cognitively-normal-adults
#17
Ge Li, Jane B Shofer, Eric C Petrie, Chang-En Yu, Charles W Wilkinson, Dianne P Figlewicz, Andrew Shutes-David, Jing Zhang, Thomas J Montine, Murray A Raskind, Joseph F Quinn, Douglas R Galasko, Elaine R Peskind
BACKGROUND: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults. METHODS: CSF amyloid beta1-42 (Aβ42), phospho-tau-181 (p-tau181), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100...
July 3, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655351/digitally-translated-self-administered-gerocognitive-examination-esage-relationship-with-its-validated-paper-version-neuropsychological-evaluations-and-clinical-assessments
#18
Douglas W Scharre, Shu Ing Chang, Haikady N Nagaraja, Nicole E Vrettos, Robert A Bornstein
BACKGROUND: The original paper Self-Administered Gerocognitive Examination (SAGE) is a valid and reliable cognitive assessment tool used to identify individuals with mild cognitive impairment (MCI) or early dementia. We evaluated identical test questions in a digital format (eSAGE) made for tablet use with the goals of calibrating it against SAGE and establishing its association with other neuropsychological tests and clinical assessments of cognitive impairment. METHODS: Subjects aged 50 and over who had taken SAGE were recruited from community and clinic settings...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655349/oligomeric-tau-targeted-immunotherapy-in-tg4510-mice
#19
Sulana Schroeder, Aurelie Joly-Amado, Ahlam Soliman, Urmi Sengupta, Rakiz Kayed, Marcia N Gordon, David Morgan
BACKGROUND: Finding ways to reverse or prevent the consequences of pathogenic tau in the brain is of considerable importance for treatment of Alzheimer's disease and other tauopathies. Immunotherapy against tau has shown promise in several mouse models. In particular, an antibody with selectivity for oligomeric forms of tau, tau oligomer monoclonal antibody (TOMA), has shown rescue of the behavioral phenotype in several murine models of tau deposition. METHODS: In this study, we examined the capacity of TOMA to rescue the behavioral, histological, and neurochemical consequences of tau deposition in the aggressive Tg4510 model...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655344/prevention-of-dendritic-and-synaptic-deficits-and-cognitive-impairment-with-a-neurotrophic-compound
#20
Narjes Baazaoui, Khalid Iqbal
BACKGROUND: The use of neurotrophic factors to treat Alzheimer's disease (AD) is hindered by their blood-brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases to make it druggable...
June 27, 2017: Alzheimer's Research & Therapy
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