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A Computational Model of Arterial Structures: A Relationship to Alzheimer´s DiseaseKristinsdottir, Svava January 2009 (has links)
The role of the cardiovascular system is is to deliver oxygen and nutrients via arteries to the tissues of the body and to remove their waste products through the venous system. Due to certain pathological processes, arteries can be damaged resulting in a reduction of well oxygenated nutrient rich blood delivered to the tissues. Chronic hypoperfusion to the brain has been related to Alzeimer„s disease (AD). AD primarily affects people over 55 years of age, with an average duration of 7-10 years, resulting in death. Currently there are 600 million people in the world aged 60 years and over. This figure is expected to double by 2025 and to reach 2 billions by 2050. Finding a cure for a neurodegenerative disease such as AD would herald a major breakthrough in medical care. Currently AD is being widely investigated, but in order to find a cure, the complete pathophysiology of AD needs to be understood. Physilogical modelling could play a significant role to further develop that understanding. The underlying cause for AD is debated although several genetic loci have been identified for AD. Scientists have also demonstrated a strong connection with cerebral hypoperfusion. This results in tissue oxygen and nutrition deprivation which is a possible causative factor in the development of AD. In this thesis a Simulation model (SM) has been built to produce an arterial tree which resembles a natureal arterial tree. The SM model is based on Schreiner et al´s Constrained Constructive Optimization (CCO) method. The SM model produces a binary tree by choosing a random point in a defined area, and connects it to an exising tree structure, each time forming a new bifurcation. This bifurcation is optimized using the target function total minimum volume of the tree. The main difference between the CCO and SM method is the handling of the constrained areas in which the binary trees are grown within. The CCO method inceases the constrained area each time a segment is added to the tree structure, resulting in
rescaling of the total tree each time. The SM tree utilizes a unit circle for the tree to grow in and uses a scaling factor to retrieve the real values of the tree segments as needed. Two trees were produced using the SM method, containing 250 (T250) and 2000 (T2000) terminals respectively. The segment Radii and length of the T2000 terminal tree was extracted and reorganized to fit the data structure of a zero-dimensional model developed by Alzaidi. This model was used to produce pressure and flow rate results for the T2000 tree. The relative perfusion of the infiltrated area in the T2000 tree was also calculated. This thesis shows a close resemblance between the SM tree and a true arterial tree, both visually and geometrically. The morphometric distribution of radii and length showed a good correlation between the SM tree and previous experimental research. The real values of radii and length found in the T2000 SM tree were found to be of larger radii and shorter length compared to previously reported values in the literature. However the results from the T250 SM tree showed excellent correlation with previous experimental results. The physiological parameters of pressure changes in the SM T2000 tree strongly mimic known in vivo physiological parameters from the human circulation. The flow rate in the tree was larger than expected, but can easily be rectified by changing the initial parameters of the SM program. The perfusion distribution diagram demonstrates a well known in vivo occurrence known as watershed zones which has recently been shown to be strongly associated with pathophysiological changes found on autopsies of brains from Alzheimer‟s patients.
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Charakterisierung von Prädiktoren rapid-progressiver Verläufe des M. Alzheimer / Characterization of predictors for rapid progressive cognitive decline in Alzheimer´s DiseaseBartlau, Thomas 12 July 2016 (has links)
No description available.
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Anhörigas upplevelser av att vårda sin partner med demens / Experiences from caring for a demented partnerKarlsson, Michaela January 2013 (has links)
Alzheimer’s disease has increasing effects on the Swedish population. Now, about 90 000 swedes have been diagnosed with the disease. Many of these persons are cared for by someone close to them. The aim of this study is to increase understanding for the situation and experiences of the persons caring for their affected partner and to examine which support they are given by the public sector. It is a qualitative case study where four persons have been interviewed. Previous research concerning experiences, coping strategies and the need for aid is used for reference. The theories chosen for the aim of the study is coping strategies, role theory, social interaction, informal care and informal aid. The results show that the participants have had different experiences of caring for their partners of which stress, anxiety and seeing it as a burden was common. The participants had different coping abilities to master their different situations and over all had good coping strategies. Their need for aid was different but all participants stressed that there is need for support and that this need to be developed. The following conclusions can be drawn from the study. The experiences are different depending on the individual case. It is important for those active within the line of social care to have knowledge about coping strategies in order to give support to those providing care for their kin. All participants experienced a lack of cooperation and information. / Alzheimers sjukdom drabbar Sveriges befolkning i allt större utsträckning. Ungefär 90 000 personer i Sverige har diagnosen. Många av dessa personer vårdas av någon i sin omgivning. Syftet med studien är att få en ökad förståelse för partners som vårdar sin respektive som har Alzheimers sjukdom och vilka upplevelser som förekommer samt att undersöka hur stödet från samhället ser ut. Det är en kvalitativ fallstudie där intervjuer har gjorts med fyra personer. Tidigare forskning har tagits fram som berör upplevelser, olika copingstrategier och behov av stöd. De teorier som valdes för studiens ändamål är copingstrategier, rollteori, social integration, informell omsorg och informell hjälp. Resultatet visar att deltagarna hade olika upplevelser av att vårda varav stress, oro och börda var vanligt. Deltagarna hade olika copingförmågor för att bemästra de olika situationerna och det förekom överlag goda copingstrategier. Behovet av stöd såg olika ut, men deltagarna belyste att det fanns ett behov av stöd samt att stödet behöver utvecklas. Följande slutsatser kan dras av studien. Alla individer har olika upplevelser. Det är viktigt att få kunskap om olika copingstrategier, vilket medför att socialt arbete kan hjälpa dem att hantera olika situationer. Samtliga deltagare upplevde att det saknades samarbete och information.
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Alzheimers sjukdom : Närståendes upplevelser i samband med vården - En studie av självbiografierKarlsson, Sandra, Meholli, Melihate January 2013 (has links)
Background: Alzheimer's disease is a disease that primarily affects the elderly but also younger people. Alzheimer's disease is a type of dementia which means that you get changes in the cerebral cortex and cells gradually die. The disease causes memory loss and things that were obvious before will be difficult for the sufferer. Alzheimer's disease also affects next of kin to a large degree; they will have to take a great responsibility. The next of kin are entitled to support from healthcare. Aim: The aim was to highlight next of kin' experiences of healthcare to their family members with Alzheimer's disease. Method : The study was based on narratives, which in this case means analysis of autobiographies. Five biographies were analyzed in accordance with Dahlborg-Lyckhage Results : Four categories and eleven subcategories emerged which were based on what the next of kin had experienced. The experiences were reflected in four categories: powerlessness, joy in caring, grief and lack of trust. This result shows gaps in knowledge and treatment of relatives. To make it easier for the next of kin caregivers should for example provide information on the course of the disease, get individual support and caregivers should take next of kin seriously. Conclusion : Alzheimer's disease affects the entire family. It is important that nurses take their responsibility by providing information and support to the next of kin so that they can better deal with the situation. The next of kin are an important part of the sufferer's life and have influence for the development of the disease.
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Management pacientů s diagnózou G30 Alzheimerova nemoc / Management of the Patients Diagnosed with G30 Alzheimers DiseaseŠvehlová, Lucie January 2012 (has links)
This thesis describes management of the patients with Alzheimer's disease. I elucidate the issues of Alzheimer's disease. I identify and quantify costs by Cost of Illness from the patient's perspective. I find the level of awareness of the nursing staff on Alzheimer's disease. In conclusion I evaluate results of research.
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Pharmacokinetics/Pharmacodynamics and Analysis of the Effect of ??-Amyloid Peptide on Acetylcholine Neurocycle and Alzheimer???s Disease MedicationsAwad, Asmaa January 2013 (has links)
The brain of Alzheimer???s disease (AD) is characterized by accumulations of ??-amyloid peptide aggregates which promote neurodegentartive dysfunction. Comprehensive understanding of the interaction between ??-amyloid aggregates and acetylcholine (ACh) neurocycle is required to uncover the physiological processes related to AD and might result in improving therapeutic approaches for AD. Pharmacokinetics (PK) and pharmacodynamics (PD) techniques were applied to allow predicting the extent of the interaction of certain doses of AD drugs and ??-amyloid inhibitors and levels of ACh as well. Although many researchers focused on the ??-amyloid interactions, the mechanisms by which ??-amyloid affects cholinergic neurons and reduction of ACh are still unclear. The prediction of ACh and drug concentrations in the tissues and body needs an understanding of the physiology and mechanisms of ??-amyloid aggregates processes and their compilation into a mechanistic model
In this work, two hypotheses are proposed to investigate the dynamic behavior of the interaction between ??-amyloid peptide aggregates and cholinergic neurocycle and the possible therapeutic approaches through proposing pharmacokinetic/pharmacodynamics (PK/PD) models to represent the impact of ??-amyloid aggregates in AD. The effect of ??-amyloid peptide aggregates is formulated through incorporating ??- amyloid aggregates into non-linear model for the neurocycle of ACh where the presynaptic neuron is considered as compartment 1 and both synaptic cleft and postsynaptic neurons are considered as compartment 2. In the first hypothesis which is choline leakage hypothesis, ??-amyloid peptide aggregates are considered to be located in the membrane of the presynaptic neuron and create pathways inside the membrane to allow for the intracellular choline to leak outside the cholinergic system. It is observed that ??-amyloid aggregates via the choline leakage hypothesis could cause significant reductions of ACh and choline levels in both compartments. Furthermore, the process rates of ACh synthesis and hydrolysis have been affected negatively by a wide range of ??-amyloid aggregate concentrations. It is found that as the input rate of ??-amyloid aggregates to compartment 1 increases, the loss of choline from compartment 1 increases leading to an increase in the intracellular concentration of ??-amyloid.
In the second hypothesis, ??-amyloid peptide aggregates are proposed to interact with the enzyme ChAT which is responsible for the synthesis of ACh in compartment 1; three different kinetic mechanisms are suggested to account for the interaction between ??-amyloid aggregates and ChAT activity. In the first and second kinetic mechanisms, ??-amyloid aggregate is supposed to attack different species in the enzyme. It is found that there is a significant decrease in the rate of ACh synthesis in compartment 1 and ACh concentrations in both compartments. However, it is observed that there is no effect on choline levels in both compartments, the rate of ACh hydrolysis in compartment 2, pH, and ACh levels in compartment 2. In the third kinetic mechanism, all species in ChAT are attacked by ??-amyloid aggregates; it is observed that at very high input rates of ??-amyloid aggregates, the oscillatory behavior dominates all components of the neurocycle of ACh. The disturbance observed in ACh levels in both compartments explains the harmful effect of the full attack of ??-amyloid aggregates to all species of ChAT. It is found that to contribute significantly in ACh neurocycle, choline leakage hypothesis needs concentration of ??-amyloid aggregates lower than that needed in ChAT activity hypothesis which is in agreement with experimental observations. The significant decrease in ACh levels observed in both choline leakage and loss of ChAT activity hypotheses leads to cognitive loss and memory impairment which were observed in individuals with AD.
A one-compartment drug PK/PD model is proposed to investigate a therapeutic approach for inhibiting ??-amyloid aggregation via choline leakage hypothesis where the maximum feed rate of ??-amyloid (KL2 = 1) is considered. The drug is assumed to interact with the tissues of the presynaptic neurons where ??-amyloid aggregates are located. The PK/PD model is built based on the effect of ??-amyloid aggregates via choline leakage hypothesis where the maximum feed rate of ??-amyloid aggregates is considered. The dynamic behavior of all concentrations of ??-amyloid aggregates, choline, ACh, acetate, and pH in both compartments in addition to the rate of ACh synthesis in compartment 1 and ACh hydrolysis are investigated by monitoring the impacts of the drug on ??-amyloid aggregates and cholinergic neurocycle over a wide range of the input drug dosage. The PK/PD model is able to predict the reduction in levels of ??-amyloid aggregates and the increase in choline and ACh, in both compartments as well as both rates of ACh synthesis and hydrolysis catalyzed. The parameters of the PK/PD model such as maximum concentration (Cmax), maximum time (Tmax), area under the curve (AUC), and maximum effect (Emax) were investigated. It was found that it takes a longer time (Tmax) (3-5 h) to reach Emax as the drug dose increases. Furthermore, AUC was found to increase with increasing drug dosage. The results of the current work show that drugs / therapeutic agents inhibiting ??- amyloid aggregation in the brain represent a likely successful therapeutic approach to give systematic highlights to develop future trials, new diagnostic techniques, and medications for AD. This study is helpful in designing PK and PD and developing experimental animal models to support AD drug development and therapy in the future.
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Hook proteinsHerrmann, Lydia, Wiegmann, Caspar, Arsalan-Werner, Annika, Hilbrich, Isabel, Jäger, Carsten, Flach, Katharina, Suttkus, Anne, Lachmann, Ingolf, Arendt, Thomas, Holzer, Max 23 March 2015 (has links) (PDF)
Defects in intracellular transport are implicated in the pathogenesis of Alzheimer’s disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD.
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In Vitro and In Vivo Studies on Antibodies - N-terminally Truncated Abeta in the 5XFAD Mouse ModelRichard, Bernhard Clemens 07 May 2015 (has links)
No description available.
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Analysis of protein SUMOylation and its role in Alzheimer's disease using mouse modelsStankova, Trayana 02 February 2017 (has links)
No description available.
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Alzheimers sjukdom : Att vara anhörig / Alzheimer`s disease : To be a relativeCarlstrand, Johanna, Thorén, Annika January 2017 (has links)
Alzheimers sjukdom ökar stadigt och beräknas ha stigit till det dubbla år 2050. När en närstående drabbas utav Alzheimers sjukdom förändras även livet för den anhörige. Som sjuksköterska är det av stor vikt att ha kännedom om det för att på bästa sätt ge den anhörige den information och det stöd som behövs. Att involvera den anhörige i den sjukes vård är av stor vikt för att få en så optimal vård som möjligt. Syftet var att belysa anhörigas upplevesle av att leva med en person med Alzheimers sjukdom. Studien genomfördes som en litteraturstudie där tio vetenskapliga artiklar kvalitetsgranskades, analyserades och kodades. Kodningen resulterade i sex olika kategorier. Resultatet visar på att den anhöriges liv vänds upp och ner när en närstående drabbas utav Alzheimers sjukdom. Behovet av information gällande Alzheimers sjukdom och stöd i form av olika vårdinsatser under hela sjukdomsprocessen är stort. Sjuksköterskan efterlyser fler verktyg och mer kunskap om Alzheimers sjukdom för att kunna ge en optimal vård. Det här styrktes av att de anhöriga kände sig dåligt förberedda på att ge vård på grund av kunskapsbristen. / Alzheimer´s disease is growing steadily and is expected to have risen to the double by 2050. When a loved one is affected by Alzheimer´s disease it also changes the lives of the relative. As a nurse, it is very important to be aware of this to be able to give the relative information and the necessary support in the best way. Involving the relative in the care of the loved one´s health is very important to get as optimal care possible. The aim was to highlight the relative`s experience of living with a person with Alzheimers´s disease. The study was conducted as a literature review of ten scientific articles, the articles were reviewed, analyzed and coded. The coding resulted i six different categories. The results show that the relative´s life is turned up side down when a loved one is suffering from Alzheimer´s disease. The need of information about Alzheimer´s diease and support of various health care initiatives throughout the disease process is big. The nurse calls for more tools and more knowledge about Alzheimer´s disease in order to provide optimal care. This was strengthened when the relatives felt ill-prepared to provide care because the lack of knowledge.
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