Wilson's disease (WD), bepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene, and is characterised by abnormal metabolism and deposition of copper in the liver, brain and other organs. The main aim of this thesis was to investigate the occurrence of psychopathology, as well as personality traits and neuropsychological function in Swedish patients with treated WD. The research subjects were 29 patients with confirmed WD, investigated at the Department of Internal Medicine at Uppsala University Hospital between 1996 and 2000. The treated WD patients showed prominent psychopathology as determined by the Comprehensive Psychopathological Rating Scale. The spectrum of psychopathological symptoms is not typical of classic psychiatric syndromes, and includes symptoms from Anxiety, Depression and Obsessive-Compulsive disorders as well as Negative Symptoms. In self-assessment, the WD patients tended to underestimate the presence of psychopathological symptoms. The treated WD patients differed in their sleep pattern from the control group, as measured with the Uppsala Sleep Inventory. The spectrum of self-reported symptoms suggests an altered REM sleep function. The treated WD patients had significant deviations in personality traits, especially in aggressivity-hostility related scales and Psychic anxiety, compared to healthy controls, as measured with the Karolinska Scales of Personality. The deviations were not related to age, age at onset or duration of WD. The treated WD patients displayed a specific profile of moderate neuropsychological impairment, as determined by the Automated Psychological Test battery. Finally, an attempt was made to search for, possible genotype-phenotype relationships in some ATP7B mutations.

The present study assessed olfactory and cognitive abilities in two strains of Alzheimer’s disease (AD) model mice and in healthy control mice over a four month time period. To this end an operant conditioning paradigm using an automated olfactometer and a spatial learning test with non-olfactory cues were employed and data on olfactory learning and memory, discrimination, and sensitivity as well as spatial learning and memory were collected. The mice were between 6 to 7 month old at the beginning of the study and 9 to 10 months old at the end of the data collection, that is, in the age range when the animals are supposed to display marked neuroanatomical changes typical of AD. The results demonstrate that there were no systematic differences in olfactory performance and spatial learning and memory abilities of AD model mice and the control mice up to the age they were tested. Further, there was no indication of an age-related decline in performance in any of the mouse strains across the testing period. Several reasons might account for the observed lack of difference in olfactory and cognitive performance between the mouse strains tested here: the AD model mice might not develop amyloid plaques and neurofibrillary tangles at all or they might develop them later than stated by the supplier. Alternatively, the AD model mice may have developed AD-typical neuroanatomical changes but these do not, or not yet, affect their olfactory performance and/or spatial learning and memory capabilities. Ongoing data collection will help to evaluate which of these explanations holds true.

Befolkningen i dagens samhälle blir allt äldre. Många individer drabbas av någon typ av demens, exempelvis Alzheimers sjukdom, då denna sjukdom är starkt knuten till hög ålder. En demenssjukdom för med sig många svårigheter, däribland drabbas minne, språk samt kommunikation. I Sverige idag finns många yrkesgrupper representerade kring den som har insjuknat i demens men sällan finns någon som har djupgående kunskaper om de språkliga och kommunikativa svårigheter som en individ, till följd av sjukdomen får. I början av Alzheimers sjukdom är de språkliga förändringarna knappt märkbara men med tiden tilltar de språkliga svårigheterna. Den yrkesgrupp som har särskild kompetens inom området språk- och kommunikationsstörningar är logopeder. Syftet med föreliggande arbete var att undersöka hur den svenska logopedens arbete kan te sig idag vad gäller arbetet med personer med demens. Syftet var också att kartlägga några av de i litteraturen beskrivna metoder gällande språklig kognitiv intervention av personer med demens. Resultatet visade att få logopeder arbetar med kommunikationsproblem vid demens i Sverige idag men det finns dock goda exempel där logopeden är involverad både i utredningsarbetet för en diagnos samt i rådgivning till den drabbade och de anhöriga. Resultatet visade också att det i litteraturen finns metoder både för direkt och indirekt intervention gällande denna patientgrupp. Några av de metoder som svenska logopeder redan idag använder, såsom exempelvis Supported Conversation for Adults with Aphasia, (SCATM ) eller Alternativ och Kompletterande Kommunikation (AKK) kanske går att använda i arbetet med individer med demens. Slutsatsen är att det är få logopeder som arbetar inom den svenska demensvården och att det finns arbetsmetoder beskrivna i litteraturen, både för direkt samt indirekt intervention, som kan användas av logopeder vid arbete med personer med demens/Alzheimers sjukdom. Metoder som Spaced Retrieval training (SR-träning), Reminiscence samt ?The Breakfast Club? är exempel på metoder som är evidensbaserade. För att fortsätta utveckla metoder och utvärdera dess effekt på individer med demens, behövs vidare studier både kring de idag befintliga arbetsmetoderna, samt ett utprövande av nya. / The population in today´s society is getting older. A lot of people suffer from some kind of dementia, including Alzheimer´s disease, as this disease is strongly associated with old age. Dementia brings many difficulties, including difficulties with memory, language and communication. Many professions are represented around the person with dementia in Sweden today, however there is rarely any professional person with a thorough knowledge of the language and communication difficulties which the sick individual gets. In early Alzheimer´s disease the linguistic changes are barely noticeable, but as the disease gets worse, major linguistic difficulties will show. The occupational group that is already in the field of language and communication disorders is the speech therapist. The purpose of this study was to identify the Swedish speech therapists work today regard working with people with dementia and to map some of the methods described in the literature concerning cognitive communicative intervention of people with dementia. The results of this study showed, that few speech therapists are working with people with communication problems of dementia in Sweden today. There are still good examples though, where the speech therapist is involved in both diagnosing and advising the person with dementia and their relatives. The results also showed that in the literature there are methods for both direct and indirect interventions regarding this patient group. Perhaps some of the methods that Swedish speech therapists use today, like Supported Conversation for Adults with Aphasia (SCATM ) or Augmentative and Alternative Communication (AAC) can be used with patients with dementia. The conclusion is that there are few speech therapists that exist in the Swedish dementia care and that there are methods for working with this group of patients described in the literature, both for direct and indirect interventions, which can be used by speech therapists when working with people with dementia/Alzheimer´s disease. Spaced Retrieval training (SR-training), Reminiscence and “The Breakfast Club” are examples of some evidence based methods. To continue to develop methods and to assess its effect on people with dementia, further studies are needed both on the currently existing methods as well as testing of new ones.

Syftet med litteraturstudien var att undersöka förekomsten av karies och parodontit hos personer med Morbus Crohn. Metoden som användes var en allmän litteraturstudie. Materialet till litteraturstudien samlades in genom sökning i databaserna Cinahl, PubMed och ScienceDirect. De sökord som användes vid litteratursökningen i samtliga databaser var ”caries”, ”Crohn’s disease”, ”periodontal disease” och ”periodontitis”. Vetenskapliga artiklar som fick ingå i litteraturstudien begränsades till ”English”, ”humans” och ”title/abstract” alternativt ”abstract/title/keywords”. Litteraturstudiens resultat baserades på en sammanställning av resultaten från tolv vetenskapliga artiklar. Tio av de vetenskapliga artiklarna berörde förekomst av karies hos personer med Morbus Crohn och i sju av dem redovisades att en signifikant förhöjd förekomst av karies fanns hos dessa personer. Tre av de tio vetenskapliga artiklarna redogjorde för att det fanns en förhöjd förekomst av karies hos personer med Morbus Crohn men det framgick inte om den var signifikant eller ej. Fem av de tolv vetenskapliga artiklarna berörde förekomst av parodontit hos personer med Morbus Crohn och i fyra av dem redovisades att en signifikant förhöjd förekomst av parodontit fanns hos dessa personer. Den kvarvarande vetenskapliga artikeln som berörde förekomst av parodontit hos personer med Morbus Crohn redogjorde för att det inte fanns en liten men inte signifikant förhöjd förekomst av parodontit hos dessa personer. Tre av de tolv vetenskapliga artiklarna berörde både förekomst av karies och parodontit hos personer med Morbus Crohn. Slutsatsen med litteraturstudien är att personer med Morbus Crohn verkar ha ökad förekomst av karies och parodontit. / The aim of the study was to investigate the occurrence of dental caries and periodontitis in people with Crohn’s disease. The method that was used in this study was a general literature review. The material for the literature review was collected by searching in the databases Cinahl, PubMed and ScienceDirect. The keywords that were used in the searches in all of the databases were ”caries”, ”Crohn’s disease”, ”periodontal disease” and ”periodontitis”. The scientific articles that were included in the literature review were limited to ”English”, ”humans” and ”title/abstract” alternatively ”abstract/title/keywords”. The result of the literature review was based on a compilation of the results from twelve scientific articles. Ten of the twelve scientific articles concerned the occurrence of dental caries in people with Crohn’s disease and seven of them reported a significantly elevated prevalence of dental caries in these individuals. Three of the ten scientific articles reported that there was an elevated incidence of dental caries in people with Crohn’s disease but they did not show whether the elevated incidence was significant or not. Five of the twelve scientific articles concerned the occurrence of periodontitis in people with Crohn’s disease and four of them reported a significantly elevated prevalence of periodontitis in these individuals. The remaining scientific article that concerned the occurrence of periodontitis in people with Crohn’s disease reported that there was a slightly but no significantly elevated prevalence of periodontitis in people with Crohn’s disease. Three of the twelve scientific articles concerned both the occurrence of dental caries and periodontitis in people with Crohn’s disease. The conclusion of the literature review is that people with Crohn’s disease seems to have elevated occurrence of dental caries and periodontitis.

Background: Alzheimer´s disease is a so-called degenerative dementia in which brain cells gradually degenerate and die. The disease causes memory disorders and the trait of character disappears. Alzheimer´s disease also affects the related parties that may take a great responsibility. Related caregivers are entitled to support from healthcare. Aim: The aim of the study was to describe the experiences of being related when caring for a person suffering from Alzheimer´s disease. Method: The study was based on narratives, which in this case means analysis of autobiographies. Six books were analyzed in accordance with Dahlborg-Lyckhage. Results: Three themes and nine sub-themes were developed. The related experienced several emotions. The feelings are reflected in three themes; anxiety, new life and powerlessness. Fear and anxiety were feelings that were there constantly. The new life led to a role change and aroused feelings of sorrow and loneliness. There were times when the related felt powerless. Anger, irritation, guilt and shame were experiences which they could not control. Conclusion: Alzheimer´s disease affects the entire family. The burden of the related caregiver can lead to illness. It is important that nurses take their responsibility by providing information and support the related so that he or she can better deal with the situation.

Alzheimers sjukdom är vanlig sjukdom i Sverige och övriga världen där symptombilden har en negativ inverkan på personens livssituation. Syftet med studien var att belysa vilka positiva effekter fysisk aktivitet har hos patienter med Alzheimers sjukdom. Studien genomfördes som en litteraturstudie och var grundad på 15 vetenskapliga artiklar. Resultatet indelades i tre huvudkategorier, påverkan på sinnesstämning, förbättrade kognitiva funktioner och förbättrad fysisk förmåga. Genom att utöva fysisk aktivitet förbättrades sinnesstämningen hos patienterna vilket visade sig genom att de blev mindre rastlösa, agiterade och oroliga. Psykofarmakaförbrukningen reducerades och patienterna kände sig mindre nedstämda efter att ha deltagit i fysiska övningar. Den kognitiva funktionen hos patienterna förbättrades, likaså förmågan att utföra den allmänna dagliga livsföringen. Genom fysisk träning blev patienterna rörligare, flexiblare, starkare, snabbare och de fick bättre balans. Resultatet visade att utövandet av fysisk aktivitet har olika positiva effekter hos patienter med Alzheimers sjukdom. Vidare forskning skulle kunna inrikta sig på vilken betydelse regelbunden träning har för att uppnå en positiv effekt av träningen. Patienter med Alzheimers sjukdom har lika stort behov av fysisk aktivitet som övriga befolkningen, det är därför betydelsefullt att patienternas behov av aktivitet uppmärksammas av sjuksköterskan. / Alzheimer´s disease is a common disease in Sweden and in rest of the world. The symptoms have a negative impact on the person's life situation. The purpose of this study was to investigate the positive impact of physical activity in patients with Alzheimer's disease. The study was conducted as a literature review and was based on 15 scientific articles. The results were divided into three main categories, the effect on mood, improved cognitive function and improved physical ability. The patients’ moods were improved by participation in physical activities and they became less restless, agitated and anxious. The consumption of psychotropic drugs was reduced and the patients felt less depressed after taking part in physical exercises. The cognitive function of patients improved, likewise the ability to perform the activities of daily living. The patients who participated in physical exercises became more mobilized, more flexible, stronger, faster, and they improved their balance. The results showed that physical activity has different positive impacts on patients with Alzheimer´s disease. Additional research could focus on what impact adherence has for achieving a positive effect of physical activity. Patients with Alzheimer’s disease have equal needs of physical activity as other people, therefore it´s important that nurses are aware of the patients’ needs for activity.

Lead (Pb) is one of the most well known toxic heavy metals in human beings and animals, which leads to toxic neurological disorders, cognitive problems, learning and memory disabilities. Epidemiological studies revealed that chronic lead exposure is one of the environmental risk factors which may cause Alzheimer¡¦s Disease, which were speculated for the observation of cellular necrosis, apoptosis, and £]-amyloid deposition frequently occuring altogether after chronic lead exposure. Recent studies have shown that the £]-amyloid formed during autophagic turnover of APP-rich organelles supplied by both autophagy and endocytosis. Therefore, we will conduct the new perspective for studying the possible role of autophagy on amyloidogensis disorders after lead exposure. SH-SY5Y human neuroblastoma cells, used in this study, were differentiated to a neuronal phenotype by retinoic acid (RA) to the culture medium at 10 £gM for 1, 2, 3 and 4 days. Doses of lead acetate with of lead acetate were 5 £gM and applied to the neuronal culture and then cell viability measurement by MTT assay. The apoptotic effect of non-differentiation and differentiation neuroblastoma cells after lead exposure was determined by cleaved DNA fragments. Furthermore, APP, intracellular A£]1-40 and A£]1-42 expression were quantified by Real-time PCR and ELISA, respectively. The autophagy process and variation of total and phosphorylated mammalian target of rapamycin (mTOR) forms were determined after lead exposure in non-differentiation and differentiation neuroblastoma cells by western blot. The results indicate that lead exposure enhances autophagy response in both non-differentiation and differentiation SH-SY5Y cells, which might cause neuronal apoptosis associated with £]-amyloidgenesis. Otherwise, lead exposure resulted in the inhibition of mTOR signaling, which correlated with the autophagic process. Besides, in our studies, non-differentiated cells exhibited more toxic vulnerability than RA induced differentiated neuron is congruous to previous finding that lead exposure during fetal development might be a potential risk factor for AD in the adulthood.

<p> <p>&nbsp / </p> </p> <p align="left">This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon&rsquo / s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy.</p>

Bakgrund: Ungefär 100 000 människor i Sverige beräknas lida av Alzheimers sjukdom. Vanliga symtom är minnesförlust och nedsatt inlärningsförmåga. Vården av de med Alzheimers sjukdom sker ofta i hemmet av en närstående. Dessa närstående får inte tillräckligt med information och deras livskvalitet blir sämre. Det är därför viktigt att vårdpersonalen kar kunskap om de upplevelser som de närstående vårdarna har för att kunna stötta dem. Syfte: Syftet med denna litteraturstudie var att belysa upplevelser av att vårda en närstående med diagnosen Alzheimers sjukdom. Metod: I denna litteraturstudie har nio empiriska studier kvalitetsgranskats och analyserats utifrån en analysmetod med grund i metasyntes. De databaser som använts är; Cinahl, PubMed och PsycInfo. Resultat: Analysen gav 5 kategorier och 14 subkategorier. De fem kategorierna var; 1) Vårdarrollen. 2) Vårdandets positiva aspekter. 3) Diagnosens negativa konsekvenser. 4) Stöd och hjälp. 5) Det oundvikliga beslutet. Konklusion: Resultatet visar på att de som vårdar en närstående med Alzheimers sjukdom kan uppleva såväl ökad närhet som en känsla av förlust vilket är något som vårdpersonal bör vara uppmärksam på för att kunna stötta. Mer information genom sjukdomsförloppet var nödvändigt. Personcentrerad omvårdnad behövdes till följd av de skilda upplevelserna hos de närstående. Nyckelord: Närstående, upplevelse, Alzheimers sjukdom, omvårdnad.

Die Alzheimer-Demenz drängt immer mehr in den Fokus unserer Gesellschaft, doch ihre Pathophysiologie ist bisher nicht vollständig verstanden. Seit einigen Jahren ist das Enzym Glutaminylzyklase (QC) als wichtiger Katalysator der Bildung von Pyroglutamat-ß-Amyloid Inhalt intensiver Forschung. Zielsetzung dieser Arbeit war es, die Expression der QC, welche bisher nur in Neuronen nachgewiesen wurde, in Astrozyten und Mikrogliazellen zu untersuchen. Da Gliazellen einen wichtigen Faktor der pathologischen Veränderungen neurodegenerativer Erkrankungen ausmachen, stellt sich die Frage nach ihrer kausalen Beteiligung an Prozessen, die zur Entstehung der Alzheimer-Demenz beitragen können. Für diese Studie wurden zwei Modelle gewählt, die zu einer spezifischen Aktivierung von Astrozyten und Mikrogliazellen als Reaktion auf eine Schädigung von Neuronen führten, zum einen nach Schädigung cholinerger Neurone durch das Neurotoxin 192-IgG-Saporin, zum anderen nach temporärer Okklusion der Arteria cerebri media. Die aktivierten Astrozyten zeigten eine deutliche Expression der QC, welche hingegen bei ruhenden Astrozyten im gesunden Gewebe nicht nachweisbar war, so dass von einer Hochregulation der Expression bei Aktivierung der Zellen ausgegangen werden kann. Weiterhin konnte die QC in Mikrogliazellen, die sich im phagozytierenden Stadium befinden, dargestellt werden. Diese Arbeit soll dazu beitragen die Zusammenhänge zwischen einer Aktivierung von Gliazellen nach einem Schädigungsereignis, wie zum Beispiel einer Ischämie bei Verschluss eines cerebralen Gefäßes, und der Entwicklung einer Alzheimer-Demenz aufzuklären.