Bakgrund: Patienter med demenssjukdom har visats erhålla sämre vård i livets slut. Patienterna erhåller bland annat mindre smärtlindring och mindre planering av vården vilket kan resultera i smärtsamma och oönskade livsförlängande åtgärder. Demenssjukdom är ett terminalt tillstånd men patienter med demenssjukdom erhåller sällan palliativ vård, vilket bör främjas. Syfte: Beskriva sjuksköterskors erfarenheter av att vårda patienter med demenssjukdom i livets slutskede.Metod: En litteraturöversikt genomfördes induktivt med kvalitetsgranskade kvalitativa artiklar från åren 2012–2021. Litteratursökningar gjordes i Cinahl, Medline och Scopus. Analysen gjordes med grund i Fribergs analysstruktur i fem steg. Resultat: I resultatet framkom tre teman: Vikten av symtomlindring med två subteman (Att skatta symtom och Att lindra symtom), Vikten av kommunikation med tre subteman (Med patient, Med närstående och Med teamet) och Vikten av en fungerade organisation med tre subteman (Behov av struktur, Behov av tid och Behov av utbildning och kompetens). Kommunikationssvårigheter är hinder för sjuksköterskor i tillhandahållandet av god vård. Närstående kan användas som resurs samtidigt som relationen med närstående kan vara konfliktfylld. Även organisatoriska aspekter har påverkan på vården.Slutsats: Smärta riskerar att bli undervärderat utan användning av smärtskattningsinstrument. Närstående bör involveras i vården även om de inte kan användas som resurs för bibehållande av patientens självbild. Sjuksköterskor och sjuksköterskestudenter behöver mer utbildning för att kunna ge patienter med demenssjukdom god vård i livets slutskede. / Background: Patients with dementia have been shown to receive poorer end-of-life care. Patients receive, among other things, less pain relief and less care planning, which can result in painful and unwanted life-extending interventions. Dementia is a terminal condition but patients with dementia rarely receive palliative care, which should be promoted.Aim: Describe nurses experience of caring for patients with dementia in the end of life. Method: A literature review was performed with an inductive approach and a base in quality reviewed qualitative articles from the years 2012-2021. Searches of articles were made in databases Cinahl, Medline and Scopus. The analysis was based on Friberg’s five step structure of analysis. Result: The results revealed three themes: The importance of symptom relief with two subthemes (Estimating symptoms and Relieving symptoms), The importance of communication with three subthemes (With patient, With relatives and With the team) and The importance of a functioning organization with three subthemes (Need for structure, Need for time and Need for education and competence). Communication difficulties are obstacles for nurses in the provision of good care. Loved ones can be used as resource while the relationship with loved ones can be conflicted. Organizational aspects also have an impact on healthcare.Conclusion: Pain is at risk of being undervalued without the use of pain assessment instruments. Relatives should be involved in care even if they cannot be used as a resource to maintain the patient's self-image. Nurses and nursing students need more training in order to provide patients with dementia with good end-of-life care.

This review is a brief summary of the effects of nicotine on neural plasticity and behavior, with a focus on the preclinical literature and the effects of nicotine on neurotrophic factors. Focus areas include underlying mechanisms of nicotine addiction and the therapeutic potential for nicotine and nicotinic receptor agonists in Parkinson’s disease, Alzheimer’s disease, traumatic brain injury, as well as cutting across these different areas of research with a brief review of the antiinflammatory effects of nicotine. It is clear that agonists at nicotinic receptors have therapeutic potential, but this should be weighed in the context of the effects of nicotine across the brain and its enhancement of neurotrophic factors. Although nicotine may have neuroprotective properties, it is important to keep in mind that these same effects underlie its addictive characteristics.

Introduction : Ces dernières années, les auteurs se sont attachés à créer une théorie générale de la problématique de la relation d’aide afin de mettre en évidence l’importance de la place occupée par les familles auprès du sujet âgé souffrant de la maladie d’Alzheimer. Il peut toutefois être intéressant de replacer l’aidant dans sa singularité de sujet affecté par d’autres questionnements que ceux relatifs à l’aide, afin de déterminer les facteurs influençant son vécu. Problématique : Dans quelle mesure la personnalité, les représentations du vieillissement, le lien de parenté et la qualité des relations passées vont influencer le vécu du rôle d’aidant principal d’un parent ou conjoint âgé en perte d’autonomie psychique, que ce dernier réside à domicile ou en institution ? Objectifs : Dans un premier temps, ce travail a pour objectif, d’établir les relations entre les différentes dimensions du vécu de l’aidant familial (difficultés, satisfactions et stratégies). Il se propose ensuite d’étudier l’influence sur ce vécu du lien de parenté et de l’entrée en institution d’une part, et de la personnalité (modèle en Cinq dimensions) et des représentations de la vieillesse d’autre part. Méthodologie : Pour ce faire, nous avons mené une étude auprès de 113 participants, dont 80 enfants et 33 conjoints. La première moitié accompagnait un proche à son domicile, la seconde en institution. Dans une première partie de l’étude, les participants ont rempli un questionnaire sociodémographique accompagné d’échelles évaluant la qualité des relations passées (QRASA), le fardeau (ZBI), les difficultés (CADI), satisfactions ressenties (CASI) et stratégies utilisées (CAMI) dans la relation d’aide, la personnalité (NEO PI-R) et la dépression (BDI). Dans un second temps, dix-sept participants ont été vus en entretien semi-directif afin d’appréhender qualitativement leur expérience d’aidant, les relations qu’ils entretiennent avec la personne accompagnée ainsi que leurs représentations de la vieillesse. Résultats : Les résultats de cette étude montrent que les difficultés, satisfactions ressenties et stratégies utilisées dans la relation d’aide sont liées entre elles, créant un équilibre nécessaire pour que l’aidant familial puisse investir son rôle. Cet équilibre est influencé aussi bien par des facteurs situationnels (lieu de résidence de la personne malade), relationnels (qualité des relations avec la personne accompagnée) que personnels (personnalité et représentations liées au vieillissement). Conclusion : Les implications en termes d’accompagnement et de prévention auprès de cette population sont discutées. / Introduction: Over the past years, authors have proposed a general theory of the caregiving relationship in order to highlight the importance of the place occupied by the families, who have an elderly relative suffering from Alzheimer's disease. However, it may be interesting to consider the caregiver with all his specificities, and as an individual affected by other problems than only the caregiving. We wonder to what extent the personality of a caregiver, the representations of the ageing process, the family relationship and the quality of the past relationships can influence the experience of caregiving. The studied caregivers were children or spouses of a patient losing his psychic autonomy, living at home or in an institution. Methods: We realized a study with 113 subjects (80 children and 33 spouses of an Alzheimer’s patient). Half of the patients were living at home and the other half in an institution. First, all caregivers filled a socio-demographic questionnaire and different clinical scales, assessing: the quality of the passed relationships (QRASA) ; the burden (ZBI) ; the difficulties (CADI ), satisfactions (CASI ) and strategies they used (CAMI) in the caregiving situations ; the personality (NEO PI-R) and the depression (BDI ). Second, 17 subjects have been seen in a semi-structured interview in order to qualitatively assess their experience of the caregiving, the past and present relationship they have with their parent or spouse. Results: The results of this study showed that the difficulties, the satisfactions which are experienced, and the strategies which are used in the caregiving relation are linked together. A balance between these variables is required for the family caregiver to invest his role. This balance is influenced by situational factors (the place where the patient lives), relational factors (the quality of the present and past relationship with the patient) as well as personal factors (personality and representations linked to the ageing process). Conclusion: The implications in terms of support and prevention for this population of caregivers are discussed.

Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B2, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the protective effects of FMN and FAD, while knockdown of the mitochondrial unfolded protein response factors ubl-5 or atfs-1 also blocked the protective effects. Therefore, vitamin B2 supplementation could lead to the activation of conserved signaling pathways in humans to delay the onset and progression of neurodegenerative diseases such as AD.

Discovery of Novel Serum Biomarkers for Diagnosing and Staging Alzheimer’s DiseaseDipti Jigar ShahDepartment of Chemistry and Biochemistry, BYUDoctor of PhilosophyAlzheimer’s disease (AD) is an untreatable neurologic disease affecting more than 5 million Americans, most over 60 years of age. Protein plaques and neurofibrillary tangles typify AD brain pathology and are thought to cause the progressive dementia and brain shrinkage observed in AD. Currently there are no methods to diagnose the disease at a time before damage becomes irreversible.Biochemical tests for AD using cerebrospinal fluid analysis or neuroimaging are not yet sufficiently sensitive and specific, and they are invasive. This points to a need for a more easily applied and more sensitive diagnostic test. Although the gross anatomical changes are localized to the brain, AD is likely to involve changes throughout the body. As a result of this, changes in the abundance of certain biomolecules present in the circulation system are likely to occur. Consequently, a serum proteomics approach able to measure such changes, when applied to AD, would likely find quantitative changes in relevant molecules that can help diagnose the disease correctly, ideally early in the disease process. The goal of this work was to discover and validate novel diagnostic serum biomarkers for AD. For biomarker discovery and validation, we used a novel serum proteomics approach involving reversed phase capillary-liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry. Our samples were protein depleted, which helped us survey low molecular weight species in the serum without ion suppression from larger proteins like albumin. We were able to observe more than 8000 molecular species in a single run. The overall project was comprised of four studies: (i) discovery of novel potential serum AD markers, (ii) blinded validation of diagnostically promising biomarkers found in the initial study, with their further chemical identification, (iii) exploring gender-based serum AD biomarkers, and (v) discovery of biomarkers that distinguish early versus moderate stage AD. In the first study, the approach found 38 significant (p < 0.05) biomarkers and 21 near significant (p = 0.05 to 0.099) biomarkers. On using the forward selection approach, we built multi-marker panels with specificities and sensitivities higher than 80%.The second study reports on a blinded validation study that was performed on a new set of serum samples. We focused on the 13 most promising AD biomarkers found as part of the initial study. We successfully validated 4 of these biomarkers that showed highly significant statistical p-values. As part of this study, research was conducted to identify these 4 biomarkers, which was accomplished using tandem mass spectrometry with fragmentation experiments. The third study used data from the initial study but looked at gender specific biomarkers. We found 31 significant and near significant serum AD biomarkers for women, 16 for men, and 25 that were gender independent. Multi-marker panels of AD biomarkers for women or men had sensitivities of >60% and specificities >85%.In the fourth study, cases with moderate AD were compared to cases with very mild or mild AD to find novel biomarkers that could be used for staging. We found 44 significant and near significant biomarkers that were quantitatively different between mild and severe AD. In conclusion, we were successful in accomplishing the goal of this work of finding, validating and identifying novel serum biomarkers that diagnose AD.

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In the literature, the experience of ‘care’ and ‘caregiving’ has been well documented and widely researched. Caregivers are recognized as people (family and friends) who provide unpaid substantial care for family members. Over time, research has increased awareness of caregivers as a distinct social group and has also contributed to caregiving being a widely recognized social issue. However, despite this increased awareness and continued concern for caregivers, much of the literature focuses on adult caregivers. As a result, the experiences of other caregiving populations, such as the youth and young adults, continues to be overlooked and underrepresented. Therefore, there is a need to explore and understand the unique experience of this population and how they give meaning to their experiences. Young caregivers (YCs) are children (5-18) and young adults (18-25) who provide substantial (unpaid) care for a family member who has an illness or disability (Stamatopoulos, 2016). Research on this population is scant and there exists many notable gaps in the literature in terms of diversity, age-based differences, programming and best practices for intervention. More specifically, there is a gap in understanding the experiences of young caregivers who are affected by progressive and incurable chronic brain diseases such as Alzheimer’s Disease or a Related Dementia. As such, this dissertation explores the experiences of YACs affected by ADRD, in terms of their personal experiences with ADRD (knowledge, dementia care and care practices), perceptions of their caregiving role and how they navigate the caregiving role. It builds on scholarship on young caregivers to broaden existing knowledge by using a phenomenological approach, known as Interpretive Phenomenological Analysis, to explore their caregiving experiences and the meaning they give to these experiences in-depth (n=12). It also aims to challenge the dominant assumptions about young caregivers by giving voice to this population by situating the young caregivers as the experts in their own lives. Findings indicate that the caregiving experience for YACs is complex, and situated within a larger socio-political context, which impacts the overall experience of care. Overall, the findings contribute to knowledge on the experiences of care among YACs and highlight the need for more inclusive research and practices on addressing caregiving among this group. / Dissertation / Candidate in Philosophy / This dissertation explores the lived experiences of young adult caregivers (YACs) caring for an older adult with Alzheimer’s Disease or a Related Dementia. Research on this group of caregivers is limited, particularly YACs (ages 18-25) who provide substantial (unpaid) caregiving for an older adult affected by Alzheimer’s or a Related Dementia. Therefore, a key aim of this research is to generate awareness and shed light on the nature of caregiving as experienced by this overlooked population of caregivers. As such, this dissertation aims to understand how young caregivers give meaning to, interpret and make sense of their caregiving experience. To understand the caregiving experience of YACs, I conducted interviews with 12 YACs from Canada and the United States and analyzed their perspectives in detail. The findings shed light on the many factors that shape the caregiving experiences. In addition, the findings show that more research is needed to understand the differences amongst young caregivers to better support their needs. In general, the research can contribute to existing knowledge on young adult caregivers, as well as relevant programs and policies.

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

Alzheimer’s disease (AD) drugs in therapy are limited to acetylcholine esterase inhibitors and memantine. Newly developed drugs against a single target structure have an insufficient effect on symptomatic AD patients. Results: Novel aromatically anellated pyridofuranes have been evaluated for inhibition of AD-relevant protein kinases cdk1, cdk2, gsk-3b and Fyn. Best activities have been found for naphthopyridofuranes with a hydroxyl function as part of the 5-substituent and a hydrogen or halogen substituent in the 8-position. Best results in nanomolar ranges were found for benzopyridofuranes with a 6-hydroxy and a 3-alkoxy substitution or an exclusive 6-alkoxy substituent. Conclusion: First lead compounds were identified inhibiting two to three kinases in nanomolar ranges to be qualified as an innovative approach for AD multitargeting.

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