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Masoome Salehi, Mohsen Reisi, Leila Ghasisin
Background: The purpose of the study was to analyze naming errors in patients with Alz-heimer's disease in comparison to healthy subjects and determine the underlying cause of naming errors in these patients. Method: In this study, we included 35 healthy elderly subjects, 23 patients with mild Alzheimer's disease, and 23 with moderate Alzheimer's disease. Forty-five images were used to determine the type of naming errors, and to identify the underlying cause of errors, matching an image with a written word was used...
September 2017: Dementia and Geriatric Cognitive Disorders Extra
Nathan L Maris, Dylan Shea, Alissa Bleem, James D Bryers, Valerie Daggett
There has been much interest in synthetic peptides as inhibitors of aggregation associated with amyloid diseases. Of particular interest are compounds that target the cytotoxic soluble oligomers preceding the formation of mature, nontoxic fibrils. This study explores physical and chemical differences between two de novo-designed peptides that share an identical primary structure but differ in backbone chirality at six key positions. We show that the presence of alternating l/d-amino acid motifs dramatically increases aqueous solubility, enforces α-sheet secondary structure, and inhibits aggregation of the β-amyloid peptide implicated in Alzheimer's disease, in addition to neutralizing its cytotoxicity...
February 6, 2018: Biochemistry
S Abushakra, A Porsteinsson, P Scheltens, C Sadowsky, B Vellas, J Cummings, S Gauthier, J A Hey, A Power, P Wang, L Shen, M Tolar
BACKGROUND: Alzheimer's Disease (AD) patients homozygous for the APOE4 allele (APOE4/4) have a distinct clinical and biological phenotype with high levels of beta amyloid (Aβ) pathology and toxic Aβ oligomers. Tramiprosate, an oral agent that inhibits Aβ monomer aggregation into toxic oligomers, was evaluated in two Phase 3 Mild to Moderate AD studies which did not show efficacy in the overall population. Re-analyses of these trials showed the most consistent clinical benefits in APOE4/4 patients...
2017: Journal of Prevention of Alzheimer's Disease
J R Sims, K J Selzler, A M Downing, B A Willis, C D Aluise, J Zimmer, S Bragg, S Andersen, M Ayan-Oshodi, E Liffick, J Eads, A M Wessels, S Monk, J Schumi, J Mullen
Several ongoing clinical development programs are investigating potential disease-modifying treatments for Alzheimer's disease (AD), including lanabecestat (AZD3293/LY3314814). Lanabecestat is a brain-permeable oral inhibitor of human beta-site amyloid (Aβ) precursor protein-cleaving enzyme 1 (BACE1) that reduces Aβ production. As a potent BACE1 inhibitor, lanabecestat significantly reduced soluble Aβ species and soluble amyloid precursor proteins (sAPPβ) in mouse, guinea pig, and dog in a time- and dose-dependent manner...
2017: Journal of Prevention of Alzheimer's Disease
Rafid Mustafa, Jared R Brosch, Gil D Rabinovici, Bradford C Dickerson, Maria C Carrillo, Bradley S Glazier, Sujuan Gao, Martha Tierney, Keith N Fargo, Mary G Austrom, Susan De Santi, David G Clark, Liana G Apostolova
INTRODUCTION: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET). METHODS: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through RESULTS: We received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity...
January 2018: Alzheimer Disease and Associated Disorders
John A Hey, Jeremy Y Yu, Mark Versavel, Susan Abushakra, Petr Kocis, Aidan Power, Paul L Kaplan, John Amedio, Martin Tolar
BACKGROUND: ALZ-801 is an orally available, valine-conjugated prodrug of tramiprosate. Tramiprosate, the active agent, is a small-molecule β-amyloid (Aβ) anti-oligomer and aggregation inhibitor that was evaluated extensively in preclinical and clinical investigations for the treatment of Alzheimer's disease (AD). Tramiprosate has been found to inhibit β-amyloid oligomer formation by a multi-ligand enveloping mechanism of action that stabilizes Aβ42 monomers, resulting in the inhibition of formation of oligomers and subsequent aggregation...
March 2018: Clinical Pharmacokinetics
Astrid M Hooghiemstra, Anne Suzanne Bertens, Anna E Leeuwis, Esther E Bron, Michiel L Bots, Hans-Peter Brunner-La Rocca, Anton J M de Craen, Rob J van der Geest, Jacoba P Greving, L Jaap Kappelle, Wiro J Niessen, Robert J van Oostenbrugge, Matthias J P van Osch, Albert de Roos, Albert C van Rossum, Geert Jan Biessels, Mark A van Buchem, Mat J A P Daemen, Wiesje M van der Flier
BACKGROUND: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice...
2017: Cerebrovascular Diseases Extra
Georgios Efthymiou, Efthymios Dardiotis, Christos Liaskos, Emmanouela Marou, Vana Tsimourtou, Eirini I Rigopoulou, Thomas Scheper, Alexandros Daponte, Wolfgang Meyer, Lazaros I Sakkas, Georgios Hadjigeorgiou, Dimitrios P Bogdanos
To assess whether Helicobacter pylori (Hp) antibody (ab) reactivity against individual Hp antigens is pathogenetically relevant to multiple sclerosis (MS), we systematically investigated prevalence and clinical significance of abs against 14 immunodominant and subdominant Hp antigens by ELISA and immunoblotting in 139 consecutive MS patients with relapsing-remitting (RRMS, n = 102) or secondary progressive (SPMS, n = 37). Sera from 39 patients with Parkinson's disease (PD), 21 with Alzheimer's disease (ALZ) and 68 healthy controls (HCs), were also tested...
August 11, 2017: Scientific Reports
Orkid Coskuner, Vladimir N Uversky
Our recent studies show that the single Tyr residue in the sequence of amyloid-β42 (Aβ42 ) is reactive toward various ligands, including metals and adenosine trisphospate (see: Coskuner , O. J. Biol. Inorg. Chem. 2016 , 21 , 957 - 973 and Coskuner , O. ; Murray , I. V. J. J. Alzheimer's Dis. 2014 , 41 , 561 - 574 ). However, the exact role of Tyr in the structures of Aβ42 remains unknown. To fill this gap, here we analyzed the role of Tyr and the impact of the Tyr10Ala mutation on the structural ensemble of Aβ42 ...
June 26, 2017: Journal of Chemical Information and Modeling
Petr Kocis, Martin Tolar, Jeremy Yu, William Sinko, Soumya Ray, Kaj Blennow, Howard Fillit, John A Hey
BACKGROUND: Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease...
June 2017: CNS Drugs
Tzeyu L Michaud, Dejun Su, Mohammad Siahpush, Daniel L Murman
BACKGROUND: It remains unclear how demographic and clinical characteristics are related to the risk of incident mild cognitive impairment (MCI) by its subtypes. Moreover, the contribution of the subtypes of incident MCI to the progression to dementia remains puzzling. METHODS: We used data collected by the National Alzheimer Coordinating Center. Our analysis sample included cognitively normal subjects at baseline. The associations were examined using competing-risks survival regression models and Cox proportional hazards models...
January 2017: Dementia and Geriatric Cognitive Disorders Extra
Babak Tousi, Cheryl Kanetsky, Nancy Udelson
Currently, there is not enough time or staff in the physician's office to provide education about Alzheimer's disease for newly diagnosed patients and their family members. The Alzheimer's Association Cleveland Area Chapter has implemented a novel approach for individuals to connect to helpful information about Alzheimer's disease and related dementias while at the physician's office. This project is being piloted at two memory assessment clinics of The Cleveland Clinic as a way to give assessment center staff the opportunity to connect families right away with the free support services available at the Association...
February 2017: American Journal of Alzheimer's Disease and Other Dementias
Gvido Cebers, Robert C Alexander, Samantha Budd Haeberlein, David Han, Ronald Goldwater, Larry Ereshefsky, Tina Olsson, Naidong Ye, Laura Rosen, Muir Russell, Justine Maltby, Susanna Eketjäll, Alan R Kugler
AZD3293 (LY3314814) is a promising new potentially disease-modifying BACE1 (β-secretase) inhibitor in Phase III clinical development for the treatment of Alzheimer's disease. Reported here are the first two Phase I studies: (1) a single ascending dose study evaluating doses of 1-750 mg with a food-effect component (n = 72), and (2) a 2-week multiple ascending dose study evaluating doses of 15 or 50 mg once daily (QD) or 70 mg once weekly (QW) in elderly subjects (Part 1, n = 31), and 15, 50, or 150 mg QD in patients with mild to moderate Alzheimer's disease (Part 2, n = 16)...
2017: Journal of Alzheimer's Disease: JAD
Alze Pereira Dos Santos Tavares, Carolina Paparelli, Carolina Sassaki Kishimoto, Silvia Avo Cortizo, Karen Ebina, Mariana Sarkis Braz, Sandra Regina Gonçalves Mazutti, Marcio José Cristiano Arruda, Bárbara Antunes
BACKGROUND: Gathering clinical evidence data on patients' palliative care needs is paramount to identify changes in outcomes over time and maintaining on-going quality improvement. Implementation of patient-centred outcome measures has been widely recommended. The routine use of these instruments in daily practice is challenging and not widespread. AIM: To implement a patient-centred outcome measure in daily practice and fulfil one quality indicator: improve pain during the 72 h after admission, in at least 75% of patients...
March 2017: Palliative Medicine
Masoud Soheili, Mostafa Rezaei Tavirani, Mahmoud Salami
OBJECTIVES: Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area...
November 2015: Iranian Journal of Basic Medical Sciences
Yuhai Zhao, Peter N Alexandrov, Walter J Lukiw
Overview- One hundred and ten years since its first description Alzheimer's disease (AD) still retains its prominent status: (i) as the industrialized world's number one cause of age-related intellectual impairment and cognitive decline; (ii) as this country's most rapidly expanding socioeconomic and healthcare concern; and (iii) as an insidious, progressive and lethal neurological disorder of the human central nervous system (CNS) for which there is currently no adequate treatment or cure (Alzheimer, 1991; Alzheimer et al...
2016: Frontiers in Neuroscience
Rebecca Davis, Jennifer Ohman
AIM: To report a study protocol that examines the impact of adding salient cues in a virtual reality simulation of a senior residential building on wayfinding for older adults with and without Alzheimer's disease. BACKGROUND: An early symptom of Alzheimer's disease is the inability to find one's way (wayfinding). Senior residential environments are especially difficult for wayfinding. Salient cues may be able to help persons with Alzheimer's disease find their way more effectively so they can maintain independence...
July 2016: Journal of Advanced Nursing
David T Liebers, Mehdi Pirooznia, Fayaz Seiffudin, Katherine L Musliner, Peter P Zandi, Fernando S Goes
Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years...
July 2016: Schizophrenia Bulletin
K Kremeike, C Juergens, H Alz, D Reinhardt
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of paediatric cancer. Maintenance therapy as last treatment phase includes oral chemotherapy with methotrexate (MTX) and mercaptopurine (6-MP), self- or parent-administered at home, given for about 1 ½ years, and qualified as decisive for an optimum therapy outcome. The aim of our study was to analyze factors influencing the adherence of patients with ALL undergoing maintenance therapy and their families. METHODS: A multi-method study was undertaken between 11/2011 and 10/2014 with patients surveyed by the Hannover Medical School outpatient clinic, including a questionnaire survey and qualitative interviews with parents as well as blood samples of the patients...
November 2015: Klinische Pädiatrie
G O André, W R Politano, S Mirza, T R Converso, L F C Ferraz, L C C Leite, M Darrieux
Streptococcus pneumoniae is a common colonizer of the human nasopharynx, which can occasionally spread to sterile sites, causing diseases such as otitis media, sinusitis, pneumonia, meningitis and bacteremia. Human apolactoferrin (ALF) and lysozyme (LZ) are two important components of the mucosal innate immune system, exhibiting lytic effects against a wide range of microorganisms. Since they are found in similar niches of the host, it has been proposed that ALF and LZ could act synergistically in controlling bacterial spread throughout the mucosa...
December 2015: Microbial Pathogenesis
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