Background: A family caregiver is a person living close to an individual in need of care. Being a relative of an Alzheimer’s patient involves switching roles from being a family member to a care giver.  Studies have shown that it’s usually spouses and children especially daughters who offer care to their love ones in their homes. Family caregivers are faced with physical, psychological, emotional, social, and financial strain. Aim: The aim of this literature study was to describe the experiences and challenges of family caregivers of people with Alzheimer’s disease. Method: A literature study was conducted, and 11 original articles were selected from the databases PubMed and CINAHL; the selected articles went through a quality analysis with the help of a protocol for quality assessment of qualitative articles. Results: Caregivers viewed their needs as irrelevant and secondary to the needs of the person with dementia. The challenges that come with the role put a lot of strain on the caregiver. Caregivers weren’t prepared to carry out their roles due to lack of support from formal care. A lack of awareness and knowledge about dementia in the community was the leading cause of social stigmatization. Conclusion: With help from formal care, the caregiver doesn’t have to feel like their needs are secondary to their relative’s needs. Nurses, family caregivers and people with Alzheimer's disease are required to work hand in hand in order to achieve their common goal of good health. / Bakgrund: En anhörigvårdare är en familj medlem som vårdar närstående med vårdbehov. Att vara en närstående till en Alzheimers patient innebär att byta roller från att vara familjemedlem till vårdgivare. Studier har visat att det oftast är makar och barn, särskilt döttrar som erbjuder vård till sina närstående i hemmet. Familj vårdgivare står inför fysisk, psykologisk, emotionell, social och ekonomisk belastning. Syfte: Syftet med denna litteraturstudie var att beskriva erfarenheter och utmaningar av familj vårdgivare av personer med Alzheimers sjukdom. Metod: En litteraturstudie genomfördes, 11 original artiklar hämtades från PubMed och CINAHL och genomgick en kvalitetsgranskning med hjälp av en checklista för kvalitativa artiklar. Resultat: Närstående som vårdade den demenssjuke tolkade sina behov som sekundär till den personen med demens. Utmaningarna med rollen la stor belastning på vårdgivaren. Familj vårdgivare var inte beredda att utföra sina roller på grund av brist på stöd från formell vård. Brist på medvetenhet och kunskap om demens i samhället var den främsta orsaken till social stigmatisering. Slutsats: Med hjälp av formell vård behöver närstående inte känna att sina behov är sekundära till närståendes behov. Sjuksköterskor, närstående och personer med Alzheimers sjukdom är skyldiga för att kunna uppnå sitt gemensamma mål för god hälsa.

Made available in DSpace on 2015-12-06T23:06:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2005 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Objetivo: Este trabalho tem como objetivos avaliar a correlação entre dois instrumentos de avaliação cognitiva. o Mini-exame do estado Mental-grave (MEEM-g) e a Bateria para Comprometimento Grave (SIB), e comparar a Escala Funcional de Atividades Diárias Bristol e sua correlação com o Mini-exame do Estado Mental (MEEM). Nossa hipótese é que o MEEM-g e o SIB apresentam uma melhor correlação com desempenho funcional que o MEEM, em pacientes com demência moderadamente grave a grave. Para isto foi feita uma estratificação entre os desempenhos alcançados através do instrumento MEEM-g, a bateria SIB, o MEEM e a Escala Funcional de Atividades Diárias Bristol. Métodos: Foram avaliados 50 pacientes provenientes do Setor de Neurologia do Comportamento - UNIFESP-EPM - com idade entre 57 e 95 anos (média de 76,84 anos, desvio-padrão de 7.94 anos e mediana de 77,00 anos). Dezesseis (32,0 por cento) eram do sexo masculino e 34 (68,0 por cento) do sexo feminino. O tempo de doença destes pacientes variou de 2 a 10 anos (média de 3,98 anos, desvio-padrão de 1,53 anos e mediana de 4,00 anos) e o tempo de escolaridade de 4 a 15 anos (média de 5,08 anos, desvio-padrão de 2,31 anos e mediana de 4,00 anos). Nestes pacientes foram aplicados os testes MEEM, o MEEM-g, a bateria SIB e para o cuidador, a escala Bristol. Resultados: Embora os achados sejam preliminares e coletados de uma pequena parcela da população em destaque, foi possível observar aspectos de sensibilidade entre o MEEM tradicional e os outros dois instrumentos de avaliação para fases avançadas, sendo que o MEEM-g parece ser ligeiramente mais adequado quando estratificados seus valores e correlacionados com a escala funcional. Conclusões: Os dados deste projeto, precursor em nosso meio, corroboram registros de diversos centros de referência de que é possível seguir acompanhando o paciente demenciado, mesmo em fases avançadas da doença, em relação às avaliações cognitiva e funcional. / Objectives: this research was undertook to study the correlation between two tools for cognitive evaluation, Mini-mental State Examination-severe (MMSE-s) and severe Impairment Battery (SIB) and the Bristol Daily Activities Functional Scale and the correlation between Bristol Scale and the conventional MMSE. Our hypothesis is that the MMSE-s and SIB have a better correlation with functional performance than MMSE in patients with moderately severe to severe dementia. To this end we did a stratification of scores for all the above scales. Methods: 50 patients from the Behavioral Neurology Section – EPM-UNIFESP – were evaluated. Mean age was 76,8 + 7,9 (range 57 to 95) and 32% were males; mean education was 5,0 + 2,3 years (range 4 to 15); mean disease duration was 3,9 + 1,5 years (range 2 to 10). All patients completed all four scales. Results: preliminary results in a small sample drawn from the study group do indicate a difference between the three cognitive scales. SIB and MMSE-s had a better correlation with functional score than MMSE, and MMSE-s had a correlation slightly better than SIB. Conclusions: these data indicate that it is possible a follow up of dementia patients up to severe stage as long as adequate instruments are used. On the other hand, conventional tools like MMSE might not have a correlation with functional status, and thus might not reflect patient’s daily life. / BV UNIFESP: Teses e dissertações

L’objectif de ce travail de thèse était de vérifier l’hypothèse selon laquelle les troubles olfactifs peuvent constituer des marqueurs de la dépression. Tout d’abord, deux études longitudinales ont évalué l’effet du traitement antidépresseur sur les atteintes olfactives et émotionnelles. Deux autres études ont étudié quelles atteintes olfactives peuvent aider à différencier la dépression d’une maladie d’Alzheimer débutante. Les résultats de ce travail ont confirmé la présence de marqueurs olfactifs d’état (pour les aspects hédonique et émotionnel) et de trait (pour les atteintes en rapport avec des capacités cognitives) dans la dépression. Par ailleurs, nos données ont mis en évidence des profils d’altérations différents dans la dépression et la maladie d’Alzheimer débutante, concernanat la mémoire de reconnaissance et l’identification des odeurs, ce qui pourrait aider à différencier ces deux maladies. D’autres travaux devront confirmer l’implication de ces marqueurs dans l’efficacité de la thérapie, le suivi et le diagnostic précoce des patients. / The aim of this study was to test the hypothesis of olfactory deficits as potential markers of depression. Firstly, two longitudinal studies have evaluated the effect of antidepressant treatment on olfactory and emotional alterations. In two other studies, we wanted to investigate which olfactory deficits could differentiate depression and early stage of Alzheimer’s disease. The results have confirmed the presence of state (for hedonic and emotional aspects) and trait (for alterations involving cognitive capacities) olfactory markers of depression. Besides, we have demonstrated two different profiles of alterations in depression and early stage of Alzheimer’s disease, concerning odors’ memory recognition and identification, which could help to discriminate these two diseases. Other investigations are necessary to confirm the implication of these markers in the efficiency of the therapy, the diagnostic and the take care of patients.

Cette thèse vise à nuancer la problématique de la souffrance qui entoure la maladie d’Alzheimer, et notamment celle des malades, des proches et des soignants. Cette souffrance, que nous appelons souffrance Alzheimer, n’est pas uniforme, n’est pas constante, peut arriver à différentes étapes de la maladie chez différents sujets, elle n’est pas toujours liée directement à la maladie d’Alzheimer, même si la maladie peut favoriser son apparition. Cette souffrance Alzheimer n’est pas isolée, elle s’inscrit dans un contexte plus général de la souffrance psychique et sociale. Les réponses possibles afin de la soulager ou diminuer sont multiples : elles peuvent être individuelles (chaque sujet tente, en mesure de ses possibilités de faire face) ou collectives (associations, groupes de paroles), subjectives (la création) ou scientifiques (traitements), ainsi que politiques ou sociétales / This thesis aims to show that the suffering that surrounds Alzheimer’s disease is by no means uniform without nuances. This is especially true for patients, their loved ones and carers. This particular suffering which we have named ‘Alzheimer suffering’ may occur at different stages of the disease in different persons. Neither is it always linked directly to the disease, even if the disease can favour its emergence. Alzheimer suffering is not isolated , being related to an overall context of psychological and social suffering. A number of different solutions to relieve or diminish suffering may be employed. These may be individual (each person does his or her best to cope) or collective (associations, group counselling), subjective (creation) or scientific (treatments) as well as political or societal

Orientador: Wanda Pereira Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-24T01:24:55Z (GMT). No. of bitstreams: 1 Silva_GiseleSilvestreda_M.pdf: 8524593 bytes, checksum: e3f6789232b8b6dc82852428db406fbf (MD5) Previous issue date: 2013 / Resumo: A Doença de Alzheimer (DA) é uma doença neurodegenerativa, que compromete as funções cognitivas. A acetilcolinesterase (AChE), enzima responsável pela hidrólise da acetilcolina (ACh), é um importante alvo para o desenvolvimento de candidatos a fármacos para tratar a DA. A AChE possui dois sítios ligantes: o catalítico e o periférico, envolvidos com a hidrólise da AChE e com o processo de formação de fibrilas do peptídeo b-amilóide, respectivamente. Neste trabalho propusemos a síntese e avaliação biológica de dois híbridos, ambos contendo porção tetraidroacridina baseado na estrutura da tacrina O hibrido I contem uma subunidade indanona baseado na donepezila e o híbrido II contém uma porção anti-inflamatória do ibuprofeno. O híbrido I e o híbrido II comportaram-se como um simples ligante e um híbrido molecular multipotente, respectivamente. Em ambos os casos foram escolhidos híbridos contendo duas unidades metilênicas. Um intermediário tetraidroacridínico contendo um grupo aminoálcool (6), que também se liga ao sítio catalítico da AChE, foi sintetizado a partir do ácido antranílico em uma sequência de três etapas. Todas as tentativas de acoplar este intermediário ao ibuprofeno fracassaram. Face a estes resultados, voltamos nossa atenção para as quinolonas, compostos planares que como a tacrina poderiam interagir com o sítio catalítico da AChE. Assim, nós sintetizamos quatro derivados da 4-quinolona. A síntese envolveu a ciclização catalisada por TFA do aduto de Morita-Baylis-Hillman, derivado do 2-nitrobenzaldeído, levando ao correspondente N-óxido (32). Em seguida, ele foi tratado com hexacarbonilmolibdato para fornecer a 3- carboetoxi-4-quinolona (38) em 33 % de rendimento global. O ácido carboxílico correspondente e derivados N-etilados também foram preparados. O efeito de três destes derivados quinolônicos sobre a atividade da acetilcolinesterase foi estudado. A N-alquil-3- carboetoxi-4-quinolona (40) foi o mais ativo dos derivados (IC50 ~84mmol/L). Estudo de docking molecular corroboraram nossas observações / Abstract: AlzheimerLs disease (AD) is a neurodegenerative pathology, which compromises the cognitive functions. Acetylcholinesterase (AChE) is the enzyme involved in the hydrolysis of neurotransmitter acetylcholine (ACh) and has been highlighted as an important target for the design of drugs to treat AD. AChE has two binding sites: a catalytic site and the peripheral one, which are involved in the acetylcholine hydrolysis and the formation of Ab42 peptide fibrils, respectively. In this work we proposed the synthesis and biological evaluation of two hybrids based on the tacrine structure, both containing portion tetrahydroacridine based on the structure of tacrine. The hybrid I has donepezil moieties and the hybrid II has anti-inflammatory portion. The hybrid I and hybrid II behave as a simple ligand and molecular hybrid, respectively. We have found that linkers with two and three methylene units generate suitable hybrids to bind to the catalytic site of the AChE. A key tetrahydroacridine bearing an amino alcohol function (6) also binds to the catalytic site of the AChE. It was synthesized from anthranilic acid in three steps sequence. All attempts to couple 6 and ibuprofen failed. In view of these results, we turn our attention to other planar structures which could interact with the catalytic site of the AChE. Thus, we synthesized four 4-quinolone derivatives. The synthesis involved a TFA mediated cyclization of the Morita-Baylis-Hillman adduct, derived from 2-nitrobenzaldehyde, leading to the corresponding N-Oxide (32). Then, it was treated with hexacarbonyl molibdate to afford 3-carboethoxy-4-quinolone (38) in 33% overall yield. We have also prepared: the corresponding carboxylic acid and the N-ethyl derivatives. The effect of three of them on the acetylcholinesterase activity was evaluated. The N-alkyl-3-carboethoxy-4- quinolone (40) was the most active (IC50 ~84mmol/L). Molecular docking studies corroborated our observations / Mestrado / Quimica Organica / Mestra em Química

Orientador: Meire Cachioni / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T03:03:58Z (GMT). No. of bitstreams: 1 Lopes_LaisdeOliveira_M.pdf: 2003500 bytes, checksum: d72be147c3b29dfc875042acb3e7f7ea (MD5) Previous issue date: 2013 / Resumo: Objetivo: Investigar o impacto de um programa psicoeducacional dirigido a cuidadores familiares de idosos com Doença de Alzheimer (DA) a partir das avaliações desses cuidadores sobre o seu bem-estar subjetivo e sobre os ônus e benefícios do cuidado. Método: Trata-se de um estudo quase experimental. Foram utilizados os seguintes instrumentos: ficha de caracterização sociodemográfica do participante; roteiro para avaliar o contexto do cuidado; Escala de Satisfação Geral com a Vida; Escala de Satisfação Geral com a Vida Referenciada a Domínios; Inventário de Ônus e Benefícios associados ao Cuidado; Escala de Afetos Positivos e Afetos Negativos e Escala de Depressão Geriátrica. Tais instrumentos foram aplicados em 21 cuidadores antes e após a intervenção, composta por 15 sessões. Resultados: A intervenção apresentou impacto positivo sobre o bem-estar subjetivo, sobre as variáveis de satisfação geral com a vida, satisfação com o envolvimento social e equilíbrio entre afetos positivos e afetos negativos. Em relação ao ônus e aos benefícios percebidos, houve aumento de respostas nos domínios psicológico positivo e social positivo após a participação na intervenção. Conclusão: A intervenção psicoeducacional investigada apresentou um impacto positivo no bem-estar subjetivo em relação às variáveis de satisfação geral com a vida, satisfação com o envolvimento social e equilíbrio entre afetos positivos e afetos negativos. Além disso, os dados desse estudo mostraram que intervenções psicoeducacionais podem contribuir para o aumento de benefícios psicológicos e sociais em relação ao contexto do cuidado. É importante considerar as peculiaridades das diferentes etapas de vida em que o cuidador está vivendo, bem como a faixa etária, a renda, o gênero, as relações de parentesco e o tempo de cuidado, para que o desenvolvimento das intervenções atinja o objetivo proposto / Abstract: Objective: To investigate the impact of a psychoeducational program aimed at family caregivers of elders with Alzheimer's disease (AD) in relation to assessments of these caregivers about their subjective well-being and about the benefits and burdens of care. Method: This was a quasi-experimental study. The following instruments were used: plug sociodemographic characteristics of the participant; script to evaluate the context of care; General Satisfaction with Life Scale; General Satisfaction with Life Referenced to Domains Scale; Inventory of Burden and Benefits of the Care; The Positive and Negative Affects Scale, and the Geriatric Depression Scale. These instruments were applied in 21 caregivers before and after the intervention, consisting of 15 sessions. Results: The intervention investigated showed a positive impact on subjective well-being in relation to variables of overall satisfaction with life, satisfaction with social involvement and balance between positive and negative effect. Regarding the perceived burden and benefits, there was an increase of positive responses in the psychological and social impact after the participation in the intervention. Conclusion: The investigated psychoeducational intervention had a positive impact on subjective well-being in relation to variables of overall satisfaction with life, satisfaction with social involvement and balance between positive and negative effect. Furthermore, the data from this study showed that psychoeducational interventions can contribute to increased psychological and social benefits in relation to the context of care. It is important to consider the peculiarities of the different stages of life in which the caregiver is living, as well as age, income, gender, kinship relations and time of care, so the development of interventions achieve the proposed objective / Mestrado / Gerontologia / Mestra em Gerontologia

Excerpt: Yes, but the extent of the benefit is unclear.

In February 2012, the FDA issued safety label changes and monitoring requirements for statin therapy. A risk of cognitive impairment was noted, although evidence was largely based on observational data, including case reports. In 2014, the National Lipid Association's safety task force found that evidence does not support cognitive decline as a classwide effect for statins. Some evidence has shown that statins may actually have beneficial effects on cognition. This article discusses management of statin therapy in patients with cardiovascular risk who may experience cognitive decline or have cognitive impairment, such as Alzheimer disease.

In neurologic disorders, there are progressive losses in regional brain structural integrity, circuitry, and neuronal process that threaten individuals' ability to express functional capacity at several levels of severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome forms the basis of clinical staging and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, of the disease state with certain associated epidemiological, biological, and genetic characteristics. The investigation of epigenetics and biomarkers is intrinsic to any analysis of the progressive nature of the neurogenerative disorders, in the present account disorders relating to Alzheimer's disease, Parkinson's disease, depression, and diabetes.

The genome-wide association study (GWAS) approach has identified novel loci for a variety of complex diseases. However, for most of these disorder much of the heritability is not explained by this approach, which focuses on identifying common variants that are associated with disease risk. The unexplained heritability may be due to genetic or phenotypic heterogeneity or the influence of rare variants. The motivation behind this thesis was to uncover the unexplained heritability by applying joint analyses of sets of variants (gene-based association test) and multiple disease-related phenotypes (called multivariate gene-based association test). First, we evaluated multivariate gene-based methods for detecting association of common genetic variants with correlated phenotypes. An extensive simulation study showed that the method combining the MultiPhen and GATES software performed best for most tested scenarios especially when correlations among phenotypes are relatively low. We developed a new multivariate gene-based test using rare variants called VEMPHAS. A simulation study using VEMPHAS showed that this method correctly controls for type I error in all tested scenarios. We applied VEMPHAS to analysis of various phenotypes related to Alzheimer disease (AD) and found suggestive association (P < 4.15x10-6) with the gene TRIM22, which has been identified in a previous sequencing study of AD onset in PSEN1/2 mutation carriers. We also developed software with a graphical user interface which is designed for integrating information from different types of data sources including genetic data (from GWAS or sequencing), expression data (from RNA-Seq), and protein structures (from protein data banks). This software has several features including 1) testing associations between genetic variants and gene expressions; 2) locating amino acids, encoded by the variants, in a protein structure; and 3) retrieving genetic locations (chromosome and base pair positions) of amino acids of interest in the protein structure. The last feature can be applied for prioritizing coding variants for gene-based association testing. The methods and strategies developed for this dissertation project can effectively uncover a portion of the remaining heritability of complex diseases that is unexplained by traditional GWAS approaches.