<p dir="ltr">Neurodegenerative diseases are progressive, incurable conditions that affect tens of millions of people worldwide and are characterized by the aggregation of misfolded protein in the brain. Though the precise role of these amyloid aggregates in the onset and progression of these diseases is not clear at this time, there is a pressing need to understand how they form and spread in human disease. In service to these aims, I have conducted three small projects to expand knowledge in this regard. I first investigated the use of thioflavin T, a common amyloid stain, as an affinity reagent for the general purification of amyloid filaments from <i>ex vivo </i>samples, observing strong potential using a relatively simple, inexpensive magnetic bead conjugation technique. I next analyzed the formation of filaments of a truncated recombinant amyloid-beta peptide with residues 1-35, observing a new filament type formed at low pH in the wild-type sequence of this truncated peptide. Finally, I conducted structural studies on amyloid-beta(1-42) filaments prepared under different conditions consistent with traumatic brain injury to observe their effect on amyloid folding. While I found no effect of differential conditions on filament type, the low-resolution structures solved were highly consistent with aggregates found in Alzheimer’s disease patients, presenting a promising way forward for <i>in vitro</i> modeling of amyloid filaments that are true to pathology. In sum, the work here presented advances the concepts of both how amyloid aggregates from patient brains can be best prepared for structural analysis, and the factors underpinning their aggregation at the onset of neurodegenerative disease.</p>

No / OBJECTIVES: To describe ways of coping in people with mild to moderate AD when faced with situations that are challenging to their memory. METHOD: Twenty-four participants (12 with mild and 12 with moderate AD) were presented with a set of seven tasks that were analogues of everyday situations that tax memory. The participants' responses were videotaped and analysed. RESULTS: Participants' coping responses were grouped into seven categories to best reflect the main strategies. Individuals used a significantly greater frequency of effortful problem solving (self-reliance and reliance on carers) (p < 0.01) than other ways of coping. Positive acknowledgement of memory difficulties was used significantly more than negative acknowledgement and defensive coping (concealment and avoidance) (p < 0.01). CONCLUSION: This study used novel methodology of observation of behavioural responses in analogues of everyday situations. The predominance of effortful problem-solving emphasizes the role of the person with AD as an active agent in the management of memory loss. An emphasis in previous literature on defensive coping and denial is counter-balanced by the finding that participants commonly coped by acknowledging their memory impairment.

O efeito da reabilitação neuropsicológica foi verificado em uma amostra de 16 pacientes com diagnóstico de doença de Alzheimer leve e moderado. Após ensaio clínico aberto com rivastigmina por 4 meses, os pacientes foram divididos em três grupos: sessões em grupo, individual e em casa com o cuidador. Os três grupos realizaram o mesmo protocolo de reabilitação, e antes e depois das 22 semanas de tratamento foram avaliados pelos mesmos instrumentos. Os resultados indicaram que as sessões em grupo são mais eficientes para sintomas psiquiátricos; individual para atividades da vida diária; e em casa, dependendo do perfil do paciente e do cuidador, pode ser uma alternativa de tratamento / The effect of a neuropsychological rehabilitation was tested in a sample of 16 patients with mild and moderate Alzheimer disease. After an open trial with rivastigmine for 4 months, they were divided in 3 groups: group sessions, individualized and at home with a caregiver. All 3 groups fulfilled the same rehabilitation protocol, and just before and after the 22 week period of treatment, all patients were evaluated using the same instruments. The results of the study indicated that group session are more effective for psychiatric symptoms, individualized sessions for activities of daily living training and at home training, depending on the patient's and caregiver's profiles, can be an option for treatment of these patients

Chan, Hung Yee. / Thesis submitted in: December 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 121-142). / Abstracts in English and Chinese. / LIST OF TABLES --- p.xi / Chapter CHAPTER 1 --- INTRODUCTION / The Hong Kong context --- p.1 / The research problem --- p.3 / Conclusion --- p.4 / Chapter CHAPTER 2 --- LITERATURE REVIEW / Introduction --- p.6 / Different interpretations of dementia --- p.7 / Experiences of caregivers of older people with dementia --- p.10 / Factors affecting caregiving experiences --- p.15 / Needs of family caregivers --- p.20 / Summary --- p.23 / Chapter CHAPTER 3 --- METHODOLOGY / Introduction --- p.25 / Aim and objectives --- p.25 / Research design --- p.25 / Sampling method --- p.26 / Data collection method --- p.28 / Pilot study --- p.32 / Data analysis --- p.34 / Validity and reliability --- p.37 / Ethical consideration --- p.40 / Summary --- p.41 / Chapter CHAPTER 4 --- RESULTS / Introduction --- p.42 / Demographic characteristics of informants and older people with dementia --- p.43 / Reasons of caregivers for providing home care --- p.45 / Meaning of care --- p.52 / Perceived difficulties in caregiving role --- p.56 / Sources of stress in the caregiving role --- p.59 / Sources of support in caregiving role --- p.62 / Needs of caregivers --- p.65 / Conclusion --- p.69 / Chapter CHAPTER 5 --- DISCUSSION / Introduction --- p.71 / Reason of providing home care --- p.72 / Chinese cultural influences on family caregiving experiences --- p.80 / Perceived difficulties in caregiving roles --- p.91 / Sources of stress --- p.96 / Sources of support in caregiving role --- p.101 / Needs of family caregivers --- p.104 / Conclusion --- p.108 / Chapter CHAPTER 6 --- CONCLUSION / Introduction --- p.110 / Implications to nursing knowledge --- p.110 / Implications to current practice --- p.112 / Limitation of the study --- p.114 / Recommendation to future research areas --- p.116 / Conclusion --- p.118 / REFERENCES --- p.121 / APPENDICES / Chapter Appendix 1 --- "Approval letter from Survey Ethics Committee, CUHK" --- p.143 / Chapter Appendix 2 --- Information letter to informant (English) --- p.144 / Chapter Appendix 3 --- Information letter to informant (Chinese) --- p.145 / Chapter Appendix 4 --- Interview guide --- p.146 / Chapter Appendix 5 --- An example of transcript of interview and preliminary analysis --- p.147 / Chapter Appendix 6 --- Letter of Access --- p.162

O efeito da reabilitação neuropsicológica foi verificado em uma amostra de 16 pacientes com diagnóstico de doença de Alzheimer leve e moderado. Após ensaio clínico aberto com rivastigmina por 4 meses, os pacientes foram divididos em três grupos: sessões em grupo, individual e em casa com o cuidador. Os três grupos realizaram o mesmo protocolo de reabilitação, e antes e depois das 22 semanas de tratamento foram avaliados pelos mesmos instrumentos. Os resultados indicaram que as sessões em grupo são mais eficientes para sintomas psiquiátricos; individual para atividades da vida diária; e em casa, dependendo do perfil do paciente e do cuidador, pode ser uma alternativa de tratamento / The effect of a neuropsychological rehabilitation was tested in a sample of 16 patients with mild and moderate Alzheimer disease. After an open trial with rivastigmine for 4 months, they were divided in 3 groups: group sessions, individualized and at home with a caregiver. All 3 groups fulfilled the same rehabilitation protocol, and just before and after the 22 week period of treatment, all patients were evaluated using the same instruments. The results of the study indicated that group session are more effective for psychiatric symptoms, individualized sessions for activities of daily living training and at home training, depending on the patient's and caregiver's profiles, can be an option for treatment of these patients

Text in English / The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called 'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the question of identifying exclusive neural correlates of aesthetic preference will be raised. Comparing amateurs and experts has revealed the more reduced the cortical activation, the more efficiently it works. Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level. Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)

L’atrophie corticale postérieure (ACP) est un syndrome clinique assez rare d’apparition insidieuse et d’évolution progressive amenant des difficultés visuelles complexes, associées à une atrophie prédominant dans les régions corticales postérieures, en dépit d’une relative préservation des autres sphères de la cognition. Cependant, cette forme atypique de démence demeure encore mal caractérisée en début d’évolution. L’objectif principal de ce projet est de mieux caractériser sur le plan neuropsychologique l’ACP en début d’évolution. Une étude de cas neuropsychologique approfondie a été réalisée chez un patient de 63 ans atteint d’une ACP débutante (M.T.) présentant initialement des plaintes au niveau de la perception visuelle. Une batterie exhaustive de tests neuropsychologiques a été administrée afin d’évaluer l’ensemble des fonctions cognitives. Une évaluation fonctionnelle en ergothérapie a également été réalisée afin d’évaluer l’ampleur des difficultés dans les activités de la vie quotidienne, ainsi qu’une IRM anatomique haute résolution (3 Teslas). Les résultats de l’évaluation neuropsychologique ont mis en évidence des difficultés relativement sélectives à traiter de l’information visuelle spatiale tridimensionnelle, suggérant sur le plan clinique une atteinte de la voie dorsale. Les résultats de l’imagerie par résonance magnétique (IRM) ont mis en évidence une atrophie prédominant dans la région pariétale, surtout dans l’hémisphère droit, corroborant ainsi les atteintes sur le plan neuropsychologique. Cette étude dans son ensemble contribue à mieux documenter la nature des atteintes cognitives, fonctionnelles et cérébrales dans un syndrome progressif rare. / Posterior cortical atrophy (PCA) is an insidious, rare and progressive clinic syndrome which causes complex visual difficulties, associated with atrophy predominating in posterior cortical areas, despite a relative preservation in other cognitive domains. This unusual type of dementia has been poorly characterized in the very early stage of the disease from a neuropsychological standpoint. The main goal of this project is to better characterize PCA from a neuropsychological and functional perspective in the very early stage of the disease, through a very detailed single case study of a 63 years old patient who presented with slowly progressive difficulties in visual perception. A detailed neuropsychological assessment of patient M.T. was carried out in order to assess his abilities in different cognitive domains. A functional evaluation of his activities of daily living was also carried out. The results of the neuropsychological assessment revealed specific difficulties in processing three-dimensional, visuospatial information, suggesting lesions to the occipitoparietal pathway (dorsal stream). M.T. carried out a high-resolution 3T anatomical MRI, which revealed bi-parietal atrophy, predominating in the right hemisphere. This study helps better documenting the nature of neuropsychological, functional, and neuroanatomical deficits in the very early stage of PCA.

La Maladie d’Alzheimer est caractérisée par la formation de dégénérescences neurofibrillaires, constituées de protéine Tau anormalement hyperphosphorylée et agrégée. De nombreuses études traitent de possibles stratégies thérapeutiques basées sur l’inhibition de cette polymérisation, et présentent les effets bénéfiques de certaines molécules dont les polyphénols, mais les résultats obtenus jusque là, manquent de données au niveau moléculaire. Ainsi, après avoir synthétisé, une banque de polyphénols de structures différentes, et 3 peptides représentatifs de la région P de phosphorylation de Tau, c’est en suivant une stratégie combinant la RMN et la modélisation moléculaire, que nous avons évalué les paramètres dynamiques du complexe formé. Ce projet nous a apporté des informations en termes d’affinité, et de relations structure/activité et ainsi, de mieux appréhender les mécanismes d’interactions intervenant dans l’agrégation de Tau par les polyphénols. / Alzheimer's disease is characterized by the formation of neurofibrillary tangles constituted by abnormally hyperphosphorylated and aggregated Tau protein. Many studies deal with potential therapeutic strategies based on the inhibition of this polymerization, and show the beneficial effects of some molecules like polyphenols, but the obtained so far results show a lack of data at the molecular level. Thus, after the synthesis of, a library of polyphenols with different structures, and 3 representative peptides of the P2 phosphorylation Tau region, by following a strategy combining NMR and molecular modeling, we have evaluated dynamic parameters of the formed complex. This project has provided us informations in terms of affinity, and structure / activity relationships, and leading us to a better understanding of the mechanisms led to better understand the mechanisms involved in the aggregation Tau inhibition phenomena by polyphenols.

Le vieillissement des populations est corrélé à l’augmentation des pathologies neurodégénératives liées à l’âge, plus particulièrement la maladie d’Alzheimer. La recherche de marqueurs précoces de la maladie ainsi que l’élaboration de nouvelles stratégies thérapeutiques constituent un enjeu de taille. Parmi les mécanismes moléculaires de la formation des plaques amyloïdes actuellement explorés, les formes oligomériques tronquées de peptide amyloïde (Aß), notamment le peptide Aß3(?pE)??42? retrouvé à des stades précoces de la maladie, joueraient un rôle déterminant. Ces travaux de thèse ont permis de montrer, dans un premier temps, que l’injection intracérébrale de ce peptide chez la souris entraîne des altérations de la mémoire de travail et des capacités d’apprentissage, associées à une accumulation d’espèces réactives dérivées de l’oxygène dans des régions cérébrales spécifiques (hippocampe et bulbes olfactifs) de ces animaux. Des essais menés in vitro sur des cultures primaires de neurones de souris montrent leur implication dans les voies apoptotiques impliquant l’activation des caspases et la cascade métabolique de l’acide arachidonique. La seconde étape de ces travaux a constitué en l’étude des effets protecteurs d’un peptide antiapoptotique d’origine endogène, l’humanine (HN) et son variant S14G (HNG). In vitro, un effet protecteur de ces peptides a été mesuré après traitement de neurones en culture par le peptide A[bêta]3?(pE)42.??? Les résultats les plus marquants résident dans les observations faites in vivo : en effet, ces peptides inhibent l’effet délétère de l’injection intracérébroventriculaire du peptide Aß3?(pE??)42?? en restaurant les performances mnésiques des animaux dans les tests comportementaux. A la lumière de ces résultats, les peptides HN pourraient constituer de nouveaux outils thérapeutiques dans le traitement ou la prévention des dommages cellulaires précoces liés à la présence des oligomères solubles du peptide Aß / Aging of population is correlated to the increase of neurodegenerative disease, more particularly Alzheimer disease. Defining early diagnostic markers and new therapeutic strategies are highly relevant. Among the molecular pathways which are currently developed, N-terminal-truncated forms of amyloid-ß (Aß) peptide have been recently suggested to play a pivotal role in the disease. Among them, Aß3(?pE)42 ?peptide is the dominant Aß species in amyloid plaques. We first investigated the effects of soluble oligomeric Aß3(pE) 42 after intracerebroventricular injection on mice learning capacities and the molecular mechanisms of in vitro neurotoxicity. Mice injected with soluble Aß3(pE) 42 displayed impaired spatial working memory and delayed memory acquisition. These cognitive alterations were associated with free radical overproduction in hippocampus and olfactory bulbs. In vitro, Aß3(pE) 42 oligomers induced a redox-sensitive neuronal apoptosis involving caspase activation and an arachidonic acid-dependent pathway. The second goal of this work was to investigate the protective effects of the apoptosis rescue endogenous peptide humanin (HN) and its S14G mutant (HNG). In vitro, we measured their inhibitory effect on neuronal death and apoptotic events resulting from soluble Ab oligomer treatment. What’s of particular interest is the in vivo restoration of soluble Aß3(pE) 42 oligomer-induced mnesic impairment. Thus, HN peptides might serve as new drug candidates for treatment or prevention of early cellular damages linked to soluble A[bêta] oligomers

The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called 'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the question of identifying exclusive neural correlates of aesthetic preference will be raised. Comparing amateurs and experts has revealed the more reduced the cortical activation, the more efficiently it works. Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level. Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)