Bakgrund: Alzheimers sjukdom är den tredje vanligaste dödsorsaken i västvärlden idag. Det är en progressiv sjukdom som drabbar hjärnan och därmed påverkar personens kognitiva förmågor. De alzheimersdrabbade blir ofta vårdade i hemmet av sina anhöriga, vilket kan innebära en stor påfrestning för dessa. För att vårdpersonal skall kunna stödja de anhöriga på bästa sätt krävs en förståelse för hur de upplever sin situation. Syfte: Syftet var att belysa anhörigas upplevelser av att leva tillsammans med en person med Alzheimers sjukdom. Metod: En empirisk studie med kvalitativ inriktning gjordes av fyra självbiografier, som analyserades med hjälp av innehållsanalys. Resultat: I resultatet framkom att de anhörigas upplevelser var till största delen negativa. Dock fanns där stunder av glädje och kärlek som gav de anhöriga styrka att kämpa vidare. De upplevde känslor som frustration, ilska, vrede, skuldkänslor och acceptans. Detta pågick i en cykel som ständigt började om. Det var som om de befann sig i ett ekorrhjul och kämpade för att ta sig ur. Slutsats: Sjuksköterskor har en viktig uppgift att fylla. De anhöriga är i en utsatt situation. Att lyssna, förstå och stödja dessa gagnar både de anhöriga och deras partners. / Background: Alzheimer's disease is the third leading cause of death in the western world. It is a progressive disease which affects the brain and the person's cognitive abilities. These people are often cared for at home by their spouses, which may be a great strain for the spouses. For professionals to be able to support the spouses in the best manner requires an understanding of how they are experiencing their situation. Aim: The purpose of this study was to illuminate the spouses´ experiences of living with a person with Alzheimer's disease. Method: An empirical study with qualitative approach was made on four autobiographies. A content analysis was used to analyze the material. Results: The results showed that the spouses´ feelings were mostly negative. However, there were moments of joy and love which gave the relatives strength to keep on fighting. They experienced feelings of frustration, anger, rage, guilt and acceptance. This went on in a repeating cycle. It was as if they were in a treadmill and struggled to get out of. Conclusion: Nurses have an important role to play. The relatives are in a vulnerable position and by listening, understanding and supporting these, it is beneficial not only for them, but also for their partners.

<p>QC 20150922</p>

Immunotherapy for Alzheimer\'s disease has emerged as a promising approach for clearing pathological tau protein conformers. To explore this kind of treatment we tested an active immunization with pseudo-phosphorylated tau fragments in P301L tangle model mice that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer’s disease. We found that an immunization reduces neurodegeneration in α-motor neurons in the spinal cord and slows progression of the tangle-related behavioral phenotype. Performance on behavioral assays correlated with tau pathology at the corresponding spinal cord level. Interestingly, a slowed progression of these tauopathy related characteristics were only seen in mice that received a specific immunization with pseudo-phosphorylated tau fragments, not in animals that received a non-specific activation of the immune system. An immunization witch pseudo-phosphorylated tau fragments may be a valuable therapeutic option in targeting one of the major hallmarks of Alzheimer’s disease and frontotemporal dementia.

Alzheimers sjukdom är mycket vanligt förekommande sett ur både ett internationellt och nationellt perspektiv. Ungefär 90 000 personer har diagnosen Alzheimers i Sverige. För att sjuksköterskan ska kunna ge god och adekvat vård behöver patientens upplevelse av sjukdomen uppmärksammas. Syftet med denna studie var att belysa patientens upplevelse av första fasen vid Alzheimers sjukdom. Studien genomfördes som en litteraturöversikt där tolv vetenskapliga artiklar bearbetades och analyserades för att sedan utgöra resultatet. I resultatet framkom fem teman, bli en främling för sig själv, acceptera och förneka, hantera livet med minnessvårigheter, leva med föreställningen om Alzheimers sjukdom och rädsla för framtiden. Flera personer med Alzheimers upplevde att sjukdomen innebar en stor förändring och en negativ påverkan på deras liv. Personerna utvecklade olika strategier för att hantera livet med sjukdomen. Personer med Alzheimers upplevde brister i mötet med hälso- och sjukvårdspersonal. Framtida forskning bör fokusera på mötet mellan patienten och sjuksköterskan samt patientens upplevelser av erhållen vård för att kunna förbättra vårdinsatserna och sjuksköterskors bemötande. / Alzheimer’s disease has, seen from an international and national perspective, high occurrence. Up to 90 000 people are diagnosed with Alzheimer’s disease in Sweden. It is important to pay attention to the patient’s experience for the nurse to be able to give good and adequate care. The purpose of this study was to highlight patient’s experience in the early stage of Alzheimer’s disease. A literature review was conducted and twelve research articles were processed and analyzed to conclude the result. The result revealed five main themes, to become a stranger in one’s life, acceptance and denial, coping with memory loss in everyday life, living with the idea of Alzheimer’s disease and fear of the future. Several persons with Alzheimer’s felt that the disease meant a big change and had a negative impact on their lives. People with Alzheimer’s developed different strategies to help them cope with the disease. People with Alzheimer’s experienced inadequacies in encounters with health care personnel. Further research should focus on health care encounters in patient perspective and their experience of received care in order to improve health care interventions and nurses’ attitudes.

<p>Diss. (sammanfattning) Umeå : Umeå universitet, 1980, härtill 5 uppsatser.</p> / digitalisering@umu

Memory dysfunction is common in association with the course of normal aging. Memory dysfunction is also obligatory in age-associated neurological disorders, such as Alzheimer’s disease. However, despite the ubiquitousness of age-related memory decline, several basic questions regarding this entity remain unanswered. The present investigation addressed two such questions: (1) Can individuals suffering from memory dysfunction due to aging and amnesia due to Alzheimer’s disease improve memory performance if contextual support is provided at the time of acquisition of to-be- remembered material or reproduction of to-be-remembered material? (2) Are memory deficits observed in ‘younger’ older adults similar to the deficits observed in ‘older’ elderly subjects, Alzheimer’s disease, and memory dysfunction in younger subjects? The outcome of this investigation suggests an affirmative answer to the first question. Given appropriate support at encoding and retrieval, even densely amnesic patients can improve their memory performance. As to the second question, a more complex pattern emerges. When attentional demands are varied, subjects of varying ages perform qualitatively similar. However, when semantic aspects of the to-be- remembered material are manipulated, age-associated qualitative differences are observed. These qualitative differences show up between older and younger adults, as well as between ‘younger’ and ‘older’ elderly subjects. / <p>Diss. (sammanfattning) Umeå : Univ., 1992, härtill 6 uppsatser</p> / digitalisering@umu

The α7 nicotinic acetylcholine receptor (nAChR) is involved in learning and memory, synaptic plasticity, neuroprotection, inflammation, and presynaptic regulation of neurotransmitter release. Alzheimer’s disease (AD), a neurodegenerative disease characterized by diminished cognitive abilities, memory loss, and neuropsychiatric disturbances, is associated with a loss of nAChRs. Similarly, traumatic brain injury (TBI) may result in long term neurobehavioral changes exemplified by cognitive dysfunction. Deficits in α7 nAChR expression have previously been shown in experimental TBI and may be related to cognitive impairment experienced in patients following TBI. The purpose of this dissertation was to investigate changes in α7 nAChR expression in models of neurodegeneration and determine if allosteric modulation of the nAChR facilitates functional recovery following experimental TBI through changes in nAChRs. Experimental models employed include a transgenic mouse model of AD that overexpresses the amyloid precursor protein (APPswe mice) and the controlled cortical impact injury model of TBI in rats. Quantitative receptor autoradiography using α-[125I]-bungarotoxin and [125I]-epibatidine and in situ hybridization were used to investigate changes in nAChR density and mRNA expression, respectively. In the first study, the effects of aging and β-amyloid on α7 nAChR expression were evaluated in APPswe mice. Hippocampal α7 nAChR density was significantly upregulated in APPswe mice compared to wild-type mice. It is postulated that elevated Aβ levels bind to the α7 nAChR resulting in upregulation. In a second study, galantamine, a medication used in the treatment of AD, was administered subchronically following experimental TBI to determine if treatment could facilitate cognitive recovery and affect nAChR expression. Interestingly, the results indicate TBI interferes with agonist mediated upregulation of nAChRs, and galantamine did not improve function in a behavioral task of learning a memory. In a third study, the regulation of TBI related deficits in α7 nAChRs was examined 48 hours following injury. α7 nAChR deficits occurred with a reduction in α7 mRNA in several hippocampal regions and non-α7 nAChR deficits occurred with a reduction in α4 mRNA in the metathalamus. The results of these studies suggest AD and TBI may involve complex but parallel processes contributing to the regulation of α7 nAChRs.

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment. The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass spectrometry (MS) is an ideal tool for lipidomics allowing detection, quantification and structural elucidation [6]. Coupling of a mass spectrometer to a chromatographic system, such as gas chromatograph (GC), allows the separation of fatty acid methyl esters analytes prior to analysis [7]. The research investigations that comprise this dissertation are divided into three interrelated projects. The first project involved the analysis of composition and structure of Clostridium thermocellum membranes from wild-type and ethanol-adapted strains in response to adaptation of cultures to growth in ethanol. The hypothesis being that adaptation of cultures to growth in ethanol would result in compensatory change to the membrane composition. Rat mitochondrial fatty acid profiles isolated from brain, liver, kidney and heart tissues were compared. The hypothesis being that differences in cellular environments found among various tissues would be reflected in the mitochondrial membrane composition. These data support the concept that variations to the lipid content of neurological mitochondria may increase susceptibility to the products of oxidative stress. Lastly, changes in neurological mitochondria as a function of Alzheimer’s disease progression were studied. The hypothesis being that changes to the mitochondrial lipidome would be significantly reflected during advanced stages of AD, in addition to being more prevalent in regions displaying greater pathology. The three interrelated projects increased our understanding of the boundaries established by the concept of homeoviscous adaptation. Project specific hypotheses were supported by data obtained from these investigations.

Previous studies from our laboratory and others show a significant increase in levels of both nuclear and mitochondrial DNA and RNA oxidation in vulnerable brain regions in the progression of Alzheimer’s disease (AD). Although total DNA oxidation is increased in AD it remains unclear whether oxidative damage is widespread throughout the genome or is concentrated to specific genes. To test the hypothesis that specific genes are more highly oxidized in the progression of AD, we propose to quantify the percent oxidative damage in genes coding for proteins shown to be altered in the progression of AD using quantitative/real-time polymerase chain reaction (qPCR/ RT-PCR). To further test the hypothesis that diminished DNA repair capacity in the progression of AD contributes to increased DNA oxidation we will use custom PCR arrays and qPCR, Western blot analysis and activity assays to quantify changes in enzymes involved in base excision repair (BER). In order to carry out these studies tissue specimens from superior and middle temporal gyri (SMTG) and inferior parietal lobe (IP), as well as, a non-vulnerable region, the cerebellum (CER) will be analyzed from normal control (NC) subjects and subjects throughout the progression of AD including those with preclinical AD (PCAD), mild cognitive impairment (MCI), and late stage AD (LAD). We will also analyze specimens from diseased control subjects (DC; Frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB)) to determine if the changes we observe in AD are specific.

Mitochondria are essential for promoting cell survival and growth through aerobic metabolism and energy production. Mitochondrial function is typically analyzed using mitochondria freshly isolated from tissues and cells because they yield tightly coupled mitochondria, whereas those from frozen tissue can consist of broken mitochondria and membrane fragments. A method, utilizing a well-characterized cryoprotectant such as dimethyl sulfoxide (DMSO), is described. Such mitochondria show preserved structure and function that presents us with a possible strategy to considerably expand the time-frame and the range of biochemical, molecular and metabolic studies that can be performed without the constraints of mitochondrial longevity ex vivo. Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) mainly through oxidative stress and altered metabolism. Mitochondria are isolated from post-mortem brain samples from selective regions of AD and control patients and, utilizing the cryopreservation strategy, analyzed for respiration and oxidative damage. While we did not observe increases in free radicals, we did observe decreased respiration and increases in oxidative damage markers in AD patients, suggesting a role for oxidative stress in mitochondrial dysfunction. While in the mitochondria, calcium (Ca2+) increases free radical generation by processes not completely understood. A new isoform of nitric oxide synthase (mtNOS) has been isolated and localized to mitochondria; though its existence and physiological role is debated. Nitric oxide synthase (NOS), when activated by Ca2+, produces nitric oxide (NO•) that can interact with ROS producing various reactive nitrogen species (RNS). These highly reactive radical species can damage DNA, proteins and lipids, ultimately resulting in cell death via apoptosis or necrosis. The current research is aimed at understanding the role of Ca2+ and NOS in oxidative stress leading to mitochondrial dysfunction. We observed a significant reduction in mitochondrial respiration with increasing doses of calcium. We also observed NOS enzyme activity and detected NOS protein in the purified mitochondrial fraction. Lastly, we were also able to show that Ca2+ increased the levels of free radicals and changes in oxidative damage markers. These results suggest the presence of NOS in mitochondria that could play a role in Ca2+ induced mitochondrial dysfunction and potentially leading to cell death as relevant to aging and neurodegenerative diseases.