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Alzheimers disease treatment

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https://www.readbyqxmd.com/read/28550260/living-alone-with-alzheimer-s-disease-data-from-svedem-the-swedish-dementia-registry
#1
Pavla Cermakova, Maja Nelson, Juraj Secnik, Sara Garcia-Ptacek, Kristina Johnell, Johan Fastbom, Lena Kilander, Bengt Winblad, Maria Eriksdotter, Dorota Religa
BACKGROUND: Many people with Alzheimer's disease (AD) live alone in their own homes. There is a lack of knowledge about whether these individuals receive the same quality of diagnostics and treatment for AD as patients who are cohabiting. OBJECTIVES: To investigate the diagnostic work-up and treatment of community-dwelling AD patients who live alone. METHODS: We performed a cross-sectional cohort study based on data from the Swedish Dementia Registry (SveDem)...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550255/sembragiline-in-moderate-alzheimer-s-disease-results-of-a-randomized-double-blind-placebo-controlled-phase-ii-trial-mayflower-road
#2
Stephane Nave, Rachelle S Doody, Mercè Boada, Timo Grimmer, Juha-Matti Savola, Paul Delmar, Meike Pauly-Evers, Tania Nikolcheva, Christian Czech, Edilio Borroni, Benedicte Ricci, Juergen Dukart, Marie Mannino, Tracie Carey, Emma Moran, Inma Gilaberte, Nicoletta Milani Muelhardt, Irene Gerlach, Luca Santarelli, Susanne Ostrowitzki, Paulo Fontoura
BACKGROUND: Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD). OBJECTIVE: To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD. METHODS: In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks...
May 26, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550249/avn-492-a-novel-highly-selective-5-ht6r-antagonist-preclinical-evaluation
#3
Alexandre V Ivachtchenko, Ilya Okun, Vladimir Aladinskiy, Yan Ivanenkov, Angela Koryakova, Ruben Karapetyan, Oleg Mitkin, Ramiz Salimov, Andrey Ivashchenko
Discovery of 5-HT6 receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer's disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT6R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT6R (Ki = 91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki = 170 nM). Thus, the compound displayed great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550248/cd44-splice-variants-as-potential-players-in%C3%A2-alzheimer-s-disease-pathology
#4
Elhanan Pinner, Yaron Gruper, Micha Ben Zimra, Don Kristt, Moshe Laudon, David Naor, Nava Zisapel
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, deposition of amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles, and neuronal cell death. Neuroinflammation is commonly believed to participate in AD pathogenesis. CD44 is an inflammation-related gene encoding a widely-distributed family of alternatively spliced cell surface glycoproteins that have been implicated in inflammation, metastases, and inflammation-linked neuronal injuries. Here we investigated the expression patterns of CD44S (which does not contain any alternative exon) and CD44 splice variants in postmortem hippocampal samples from AD patients and matched non-AD controls...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550244/apoe-%C3%AE%C2%B54-modulation-of-training-outcomes-in-several-cognitive-domains-in-a-sample-of-cognitively-intact-older-adults
#5
Ramón López-Higes, Inmaculada C Rodríguez-Rojo, José M Prados, Pedro Montejo, David Del-Río, María Luisa Delgado-Losada, Mercedes Montenegro, David López-Sanz, Ana Barabash
BACKGROUND: Most research points to the ɛ4 allele of the apolipoprotein E (APOE) gene as the most recognizable genetic risk factor associated with Alzheimer's disease pathogenesis. It has been also suggested that the APOEɛ4 allele has a negative influence on cognitive functioning, which begins long before cognitive impairment becomes manifest. However, still, little is known about the APOEɛ4 interaction with cognitive intervention programs. OBJECTIVE: The main goal of this study was to explore whether there was a differential APOE genotype modulation effect after cognitive training in different domains, such as language comprehension, executive functions, and memory...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550243/apomorphine-therapy-for-neuronal-insulin-resistance-in-a-mouse-model-of-alzheimer-s-disease
#6
Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T Yanagihara, Kyoko M Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira
Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28549949/recent-advancements-in-liposomes-targeting-strategies-to-cross-blood-brain-barrier-bbb-for-the-treatment-of-alzheimer-s-disease
#7
REVIEW
Mukta Agrawal, Ajazuddin, Dulal K Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli...
May 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28549891/synthesis-and-pharmacological-evaluation-of-novel-chromone-derivatives-as-balanced-multifunctional-agents-against-alzheimer-s-disease
#8
Fan Li, Jia-Jia Wu, Jin Wang, Xue-Lian Yang, Pei Cai, Qiao-Hong Liu, Ling-Yi Kong, Xiao-Bing Wang
In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12μM for hMAO-A and 0.816μM for hMAO-B), moderate inhibition of Aβ aggregation (75...
May 17, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28549745/-anti-ageing-therapies-in-alzheimer-s-disease
#9
Gara S Alonso Abreu, José M Brito Armas, Rafael Castro Fuentes
Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor...
May 23, 2017: Revista Española de Geriatría y Gerontología
https://www.readbyqxmd.com/read/28549481/late-onset-alzheimer-s-disease-genetics-implicates-microglial-pathways-in-disease-risk
#10
REVIEW
Anastasia G Efthymiou, Alison M Goate
Alzheimer's disease (AD) is a highly heritable complex disease with no current effective prevention or treatment. The majority of drugs developed for AD focus on the amyloid cascade hypothesis, which implicates Aß plaques as a causal factor in the disease. However, it is possible that other underexplored disease-associated pathways may be more fruitful targets for drug development. Findings from gene network analyses implicate immune networks as being enriched in AD; many of the genes in these networks fall within genomic regions that contain common and rare variants that are associated with increased risk of developing AD...
May 26, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28546539/microbiota-modulation-counteracts-alzheimer-s-disease-progression-influencing-neuronal-proteolysis-and-gut-hormones-plasma-levels
#11
Laura Bonfili, Valentina Cecarini, Sara Berardi, Silvia Scarpona, Jan S Suchodolski, Cinzia Nasuti, Dennis Fiorini, Maria Chiara Boarelli, Giacomo Rossi, Anna Maria Eleuteri
Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer's disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28545202/memantine-inhibits-degradation-of-the-articular-cartilage-extracellular-matrix-induced-by-advanced-glycation-end-products-ages
#12
Jijun Zhao, Yinghao Yu, Zhaofeng Wu, Ling Wang, Wei Li
The accumulation of inflammation and cartilage damage induced by advanced glycation end products (AGEs) are important hallmarks of osteoarthritis (OA). Memantine is a clinically licensed drug used for the treatment of moderate and severe Alzheimer's disease. To date, little information has been reported regarding the effects of memantine on cartilage destruction. In this study, we investigated the protective effects of memantine on AGE-induced degradation of collagen II and aggrecans in human SW1353 chondrocytes...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28544981/synthesis-and-in%C3%A2-vitro-evaluation-of-new-fluorinated-quinoline-derivatives-with-high-affinity-for-pde5-towards-the-development-of-new-pet-neuroimaging-probes
#13
Jianrong Liu, Aurélie Maisonial-Besset, Barbara Wenzel, Damien Canitrot, Ariane Baufond, Jean-Michel Chezal, Peter Brust, Emmanuel Moreau
The increasing incidence of Alzheimer's disease (AD) worldwide is a major public health problem. Current treatments provide only palliative solutions with significant side effects. Therefore, new efficient treatment options and novel early diagnosis tools are urgently needed. Recently, strong pre-clinical evidences suggested that phosphodiesterase 5 (PDE5) may be clinically relevant both as biomarker and drug-target in AD. In this study, we intended to develop a new radiofluorinated tracer for the visualisation of PDE5 in brain using PET imaging...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28542068/reduced-cortical-excitatory-synapse-number-in-apoe4-mice-is-associated-with-increased-calcineurin-activity
#14
Aidan L Neustadtl, Charisse N Winston, Maia Parsadanian, Bevan S Main, Sonia Villapol, Mark P Burns
Synaptic loss is a symptom of Alzheimer's disease (AD) that is associated with the onset of cognitive decline and the loss of executive function. The strongest genetic risk factor for AD is the APOE4 allele, which results in both a greater risk of developing AD as well as an earlier age of onset of AD. Dendritic spines, the anatomical substrate of the excitatory synapse, are reduced in the cortex of humanized APOE4 mice but the reason for this synaptic decline is unknown. Calcineurin, a calcium/calmodulin dependent phosphatase, is a mediator of dendritic spine retraction...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28541924/characterizing-highly-benefited-patients-in-randomized-clinical-trials
#15
Vivek Charu, Paul B Rosenberg, Lon S Schneider, Lea T Drye, Lisa Rein, David Shade, Constantine G Lyketsos, Constantine E Frangakis
Physicians and patients may choose a certain treatment only if it is predicted to have a large effect for the profile of that patient. We consider randomized controlled trials in which the clinical goal is to identify as many patients as possible that can highly benefit from the treatment. This is challenging with large numbers of covariate profiles, first, because the theoretical, exact method is not feasible, and, second, because usual model-based methods typically give incorrect results. Better, more recent methods use a two-stage approach, where a first stage estimates a working model to produce a scalar predictor of the treatment effect for each covariate profile; and a second stage estimates empirically a high-benefit group based on the first-stage predictor...
May 20, 2017: International Journal of Biostatistics
https://www.readbyqxmd.com/read/28540646/the-molecular-mechanism-of-glucagon-like-peptide-1-therapy-in-alzheimer-s-disease-based-on-a-mechanistic-target-of-rapamycin-pathway
#16
Lin Li
The mechanistic target of rapamycin (mTOR) is an important molecule that connects aging, lifespan, energy balance, glucose and lipid metabolism, and neurodegeneration. Rapamycin exerts effects in numerous biological activities via its target protein, playing a key role in energy balance, regulation of autophagy, extension of lifespan, immunosuppression, and protection against neurodegeneration. There are many similar pathophysiological processes and molecular pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), and pharmacologic agents used to treat T2DM, including glucagon-like peptide-1 (GLP-1) analogs, seem to be beneficial for AD...
May 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28540600/microglial-interferon-signaling-and-white-matter
#17
Ashley McDonough, Richard V Lee, Jonathan R Weinstein
Microglia, the resident immune cells of the CNS, are primary regulators of the neuroimmune response to injury. Type I interferons (IFNs), including the IFNαs and IFNβ, are key cytokines in the innate immune system. Their activity is implicated in the regulation of microglial function both during development and in response to neuroinflammation, ischemia, and neurodegeneration. Data from numerous studies in multiple sclerosis (MS) and stroke suggest that type I IFNs can modulate the microglial phenotype, influence the overall neuroimmune milieu, regulate phagocytosis, and affect blood-brain barrier integrity...
May 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28539894/modulation-of-brain-activity-with-noninvasive-transcranial-direct-current-stimulation-tdcs-clinical-applications-and-safety-concerns
#18
REVIEW
Haichao Zhao, Lei Qiao, Dongqiong Fan, Shuyue Zhang, Ofir Turel, Yonghui Li, Jun Li, Gui Xue, Antao Chen, Qinghua He
Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28539885/intranasal-insulin-prevents-anesthesia-induced-cognitive-impairment-and-chronic-neurobehavioral-changes
#19
Yanxing Chen, Chun-Ling Dai, Zhe Wu, Khalid Iqbal, Fei Liu, Baorong Zhang, Cheng-Xin Gong
General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM) 2-6 days after anesthesia exposure, in aged (17-18 months old) wild-type (WT) mice and in adult (7-8 months old) 3xTg-AD mice (a triple transgenic mouse model of Alzheimer's disease (AD)), but not in adult WT mice...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28539682/the-human-body-as-an-energetic-hybrid-new-perspectives-for-chronic-disease-treatment
#20
REVIEW
Michał Gajewski, Przemysław Rzodkiewicz, Sławomir Maśliński
Inflammatory response is accompanied by changes in cellular energy metabolism. Proinflammatory mediators like plasma C-reactive protein, IL-6, plasminogen activator inhibitor-1, TNF-α or monocyte chemoattractant protein-1 released in the site of inflammation activates immune cells and increase energy consumption. Increased demand for energy creates local hypoxia and lead in consequence to mitochondrial dysfunction. Metabolism of cells is switched to anaerobic glycolysis. Mitochondria continuously generate free radicals that what result in imbalance that causes oxidative stress, which results in oxidative damage...
2017: Reumatologia
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