Background: Alzheimer´s disease is the most common dementia illness. In Sweden, about 20 000 – 25 000 people are annually diagnosed with Alzheimer´s disease. Accordingly, this number of diagnosed patients is growing each year and so does the cost of care. The symptoms of dementia are often discovered by family members that eventually takes measures as to support and care for their relatives, when they are no longer in condition to take care of themselves. Aim: The purpose was to describe relatives' experiences of caring for their relatives with Alzheimer's disease at home. Method: This study is based on a general literature review consisting of twelve reliable articles that were identified from the databases CINAHL and PubMed and through a qualitative approach. The selection of articles included in the review were quality checked and analyzed with a qualitative content analysis. Results: Three themes emerged: The need for support and information, impact in daily life and coping with adversity in everyday life. Conclusion: Relatives feel a need for increased understanding and they need support in taking care of their relative. Daily life is adversely affected and the relatives need to develop strategies to cope with adversity in everyday life. / Bakgrund: Alzheimers sjukdom är den vanligaste demenssjukdomen och varje år insjuknar 20 000 till 25 000 personer i Sverige. Antalet insjuknande förväntas öka varje år tillsammans med vårdkostnaderna för sjukdomen. Det är oftast anhöriga som upptäcker symtomen och börjar stödja deras närstående med Alzheimers sjukdom när de inte längre klarar av att ta hand om sig själva. Syfte: Syftet var att beskriva anhörigas upplevelser av att vårda närstående med Alzheimers sjukdom i hemmet. Metod: En allmän litteraturöversikt med en kvalitativ ansats. Tolv originalartiklar identifierades från CINAHL och PubMed. Valda artiklar som inkluderades kvalitetsgranskades och analyserades med en kvalitativ innehållsanalys. Resultat: Det framkom tre teman: behov av stöd och information, påverkan i det dagliga livet samt hantering av motgångar i vardagen. Slutsats: Anhöriga känner ett behov av ökad förståelse och behöver stöd i omvårdnaden. Det dagliga livet påverkas negativt och gör att de anhöriga behöver utveckla strategier för att klara av motgångar i vardagen.

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.

Defects in intracellular transport are implicated in the pathogenesis of Alzheimer’s disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD.

No description available.

Alzheimer s disease is characterized by synaptic alterations and neurodegeneration. Histopathological hallmarks represent amyloidplaques composed of amyloid-beta (Abeta) and neurofibrillary tangles containing hyperphosphorylated tau. To determine whether synaptic changes and neurodegeneration share common pathways we established an ex vivo model using organotypic hippocampal slicecultures from amyloid precursor protein transgenic mice combined with virus-mediated expression of EGFP-tagged tau constructs. Confocal high-resolution imaging, algorithm-based evaluation of spines and live imaging was employed to determine spine changes and neurodegeneration. We report that Abeta but not tau induces spine loss and shifts spine shape from mushroom to stubby through a mechanism involving NMDA receptor (NMDAR), calcineurin and GSK-3beta activation. In contrast, Abeta alone does not cause neurodegeneration but induces toxicity by phosphorylation of wt tau in a NMDAR-dependent pathway. We show thatGSK-3beta levels are elevated in APP transgenic cultures and that inhibiting GSK-3beta activity or use of phosphorylation-blocking tau mutations prevent Abeta-induced toxicity of tau. FTDP-17 tau mutants are differentially affected by Abeta. While R406W tau shows increased toxicity in the presence of Abeta, no change is observed with P301L tau. While blocking NMDAR activity abolishes toxicity of both wt and R406W tau, the inhibition of GSK-3beta only protects against toxicity of wt tau but not of R406W tau induced by Abeta. Tau aggregation does not correlate with toxicity. We propose that Abeta-induced spine pathology and tau-dependent neurodegeneration are mediated by divergent pathways downstream of NMDA receptor activation and suggest that Abeta affects wt and R406W tau toxicity by different pathways downstream of NMDAR activity.

ZIEL Als Ursache für die sporadische Creutzfeldt-Jakob Krankheit wird eine spontane Konfigurationsänderung des Prionproteins diskutiert. Die Annahme der Beeinflussung fehlgefaltete Proteinketten, welche bei neurodegenerativen Erkrankungen wie der Alzheimer Demenz oder Parkinson vorliegen, auf die Entwicklung einer zweiten Proteinfehlfaltung stellen eine mögliche Verbindung zwischen dem Auftreten neurodegenerativer Erkrankungen und Prionerkrankungen her. Das Ziel dieser retrospektiven Untersuchung ist es, die klinischen und diagnostischen Eigenschaften von sCJD-Patienten mit Morbus Parkinson oder Demenz in der Familienanamnese zu analysieren um die Diagnostik verbessern zu können. METHODEN Für die vorliegende Arbeit wurde ein Kollektiv aus 133 Patienten mit sicherer oder wahrscheinliche sCJD mit bekannter Ausprägung am Codon-129 rekrutiert. Bei den Geschwistern, den Eltern oder den Großeltern mütterlicher- oder väterlicherseits lag ein Parkinsonsyndrom oder eine dementielle Erkrankung vor. Gegenüber gestellt wurde diesem eine Kontrollgruppe nach Zuordnung nach Geschlecht, Alter (+/- 5 Jahre) sowie PRnP-Codon 129-Genotyp. Der Schwerpunkt der Arbeit liegt auf der klinischen Symptomatik, den Liquorparametern und den Ergebnissen aus bildgebenden Verfahren wie Elektroenzephalographie, zerebraler Computertomographie und Magnetresonanztomographie. ERGEBNISSE Erstes neurologisches Symptom waren zerebelläre Störungen (Ataxie), psychiatrische und visuelle Störungen, während eine dementielle Entwicklung erst im Verlauf hinzutrat. Beim Fortschreiten der Erkrankung wurden Pyramidenbahnzeichen häufiger und extrapyramidale Störungen deutlich seltener diagnostiziert. Insgesamt fiel vom klinischen Erscheinungsbild häufiger die Gruppe FA-Parkinson auf (beispielsweise häufiges Vorkommen von Antriebsstörungen), während FA-Demenz meist der Kontrollgruppe glich. Mit dem Nachweis von PSWC im EEG in 53 % bei FA-Demenz und 61 % bei FA-Parkinson übertrifft die Sensitivität der EEG-Untersuchung nicht die für die sCJD geltende von 64 % (Steinhoff et al. 2004). Mit einem Nachweis der Proteine 14-3-3 im Liquor in 96 % (FA-Demenz) und 100 % (FA-Parkinson) ergibt sich eine ebenso hohe Sensitivität wie für die sCJD bereits postuliert (94 %, Zerr et al. 2000a). Auch die Sensitivität der NSE ist bei den Patienten dieser Arbeit sehr hoch, während der Liquormarker S100b-Protein bei FA-Parkinson-Patienten deutlich seltener den cut-off-Wert erreicht. Ein CJD-typischer MRT-Befund (hyperintense Basalganglien oder kortikale Signalsteigerung) wurde nur in 52 % bei FA-Demenz und bei 49 % bei FA-Parkinson festgestellt. SCHLUSSFOLGERUNG Schließlich lässt sich festhalten, dass bei diesen Patienten nicht vorwiegend eine Demenz wegweisend zur Diagnose ist, sondern auf das Vorliegen zerebellärer oder psychiatrischer Symptome geachtet werden muss. In der Diagnostik kommt dem EEG mit einer hohen Sensitivität eine große Bedeutung zu, während die MRTUntersuchung weniger wegweisend ist. Bei Morbus Parkinson in der Familie unterstützt die Liquoruntersuchung die Diagnostik nicht so stark, während gerade pathologische Werte des Tau-Proteins und des Amyloid-ß 1-42 bei Patienten mit Demenz in der Familie auf eine sCJD hindeuten.

La preuve de concept d‟une approche theranostique pour la Maladie de Alzheimer basée sur les nanotechnologies a été explorée. Des nouvelles nanoparticules polymeriques fluorescentes on été conçus, et leur internalisation et aptitude à traverser un nouveau modèle in vitro de barrière hémato-encéphalique humaine on été étudiées en détails. Une petite librairie de nanoparticules polymerique a été préparés, et leur capacité de capturer le peptide β-Amyloïde1-42, considéré comme une des principales causes de la dégénérescence neuronale, a été évaluées et quantifiées en utilisant une méthode expressément conçus. / The proof of concept of an original nanotechnology-based theranostic approach for Alzheimer‟s disease has been explored. Novel fluorescently tagged nanoparticles have been designed and employed for internalization and transcytosis studies across a recently developed human in vitro blood-brain barrier model. A small library of polymeric nanoparticles have been designed and their ability to capture the Amyloid β1-42 peptide, considered one of the causes of the Alzheimer‟s disease, has been investigated and quantified using an on purpose designed method.

A doença de Alzheimer (DA) é a doença degenerativa cerebral adquirida mais comum e a principal causa de demência nos paises ocidentais. Sua fisiopatologia pode envolver anormalidades neuronais além do processo inflamatório. As infecções odontogênicas são frequentes nestes doentes, e são importantes causas de dor e inflamação crônicas. Os objetivos desta pesquisa foram avaliar as características odontológicas e de dor orofacial de doentes com DA leve comparados aos controles, e verificar aspectos cognitivos, funcionais e emocionais após o tratamento das infecções odontogênicas presentes. Foram avaliados 29 doentes e 30 controles, sendo que os doentes foram tratados e reavaliados posteriormente em dois momentos (após um mês e após seis meses). Foram utilizados os seguintes instrumentos de avaliação: ficha clínica da Equipe de Dor Orofacial; Critérios de diagnóstico em Pesquisa para Disfunção Temporomandibular; questionário de dor McGill; qualidade de vida relacionada à saúde oral (OHIP); avaliação clínica periodontal; índice CPOD-d; índice de placa OLeary; Mini-Exame do Estado Mental (MEEM); escala funcional de Pfeffer. No grupo de estudo, houve maior prevalência de dor orofacial (20,7%, P<0,001), alterações nas articulações temporomandibulares (P<0,05), e infecção periodontal (P=0,002). Após o tratamento, a dor diminuiu (P=0,014), assim como as limitações mandibulares (P=0,011) e os índices periodontais (P<0,05), havendo melhora na qualidade de vida (P=0,009), índice funcional (P=0,001) e índice cognitivo (P=0,048). Como conclusão, a dor orofacial e infecções odontogênicas foram mais comuns em idosos com DA leve do que em idosos saudáveis e seu tratamento resultou em melhora funcional desses indivíduos / Alzheimer\'s disease (AD) is the most common acquired cerebral degeneration and the main cause of dementia in Western countries. Its physiopathology involves neuronal abnormalities and an inflammatory process. Dental infections are frequent in these patients, and important causes of pain and chronic inflammation. The objectives of this research were to evaluate the dental characteristics and orofacial pain of patients with mild AD compared to controls, and to verify cognitive, functional and emotional aspects after the treatment of present oral infections. Twenty-nine patients (29) and 30 controls were evaluated, and the patients were treated and reevaluated in two moments (after one month and after six months). The following instruments were used: clinical questionnaire (Clinical Questionnaire of Orofacial Pain); Research Diagnostic Criteria for Temporomandibular Disorders; McGill Pain Questionnaire; Oral Health Impact Profile (OHIP); periodontal clinical evaluation; DMFT; Plaque index of O´Leary; Mini-Mental State Exam; functional scale of Pfeffer. In the study group, there was a higher prevalence of orofacial pain (20.7%, P<0.001), articular abnormalities at temporomandibular joints (P<0.05) and periodontal infections (P=0,002). After the treatment, the pain reduced (P=0,014), as well as mandibular limitations (P=0.011) and periodontal indexes (P<0.05), and there was an improvement in quality of life (P=0.009), functional index (P<0.001) and cognition (P=0.048). In conclusion, orofacial pain and periodontal infections were more common in patients with mild AD than in healthy subjects and their treatment resulted in better functionality of them

Introdução: O envelhecimento populacional traz desafios, como os prejuízos de funcionalidade em tarefas rotineiras, decorrentes de condições crônicas de saúde, como a demência da doença de Alzheimer (DA). Para elaborar propostas de intervenção adequadas ao portador de DA e a sua família, a funcionalidade deve ser avaliada. O Routine Task Inventory - Expanded (RTI-E) é uma avaliação que permite avaliar o desempenho em ABVD, AIVD, Comunicação e Preparo para o Trabalho a partir da perspectiva do paciente, do cuidador e do terapeuta. Objetivo: Traduzir, adaptar transculturalmente, medir a fidedignidade e a validade da versão brasileira do RTI-E para avaliar a funcionalidade em idosos com DA. Métodos: Realizou-se a tradução e adaptação transcultural do instrumento. Utilizou-se o coeficiente ? de Chronbach para avaliar a consistência interna. A fidedignidade entre avaliadores do RTI-E foi obtida por CCI. A validade de conteúdo foi obtida por validade convergente (correlacionando a avaliações cognitivas e funcionais) e divergente (correlação com HAM-D). A validade de critério foi obtida por validade concorrente. Resultados: Foram avaliados 85 sujeitos, divididos em 42 sujeitos grupo DA (CDR=1 ou 2) e 43 sujeitos grupo controle (CDR=0) e seus pares. Obteve-se a tradução e adaptação transcultural do RTI-E, aprovada pela autora. O RTI-E demonstrou consistência interna elevada em cada escala analisada, sendo o valor mais alto em AIVD obtida por relato do cuidador (?=0,966) e alta fidedignidade entre avaliadores. O instrumento mostrou validade convergente em relação a medidas cognitivas, sendo a maior correlação encontrada em AIVD, relato cuidador (r=0,912, comparado a CAMCOG e r=0,911, comparado a MEEM). Em relação a medidas funcionais, a correlação foi muito forte em relato do cuidador (AIVD X Lawton [r= 0,917]) e em observação do terapeuta (AIVD X DAFS-Br [r=0,911]). As escalas por autorrelato mostram correlações fracas ou insignificantes. O RTI-E mostrou-se capaz de discriminar sujeitos com DA e sem DA, calculando-se áreas sob a curva ROC. Obteve-se pontos de corte variando conforme cada escala. A maior precisão (98,82%) foi encontrada em AIVD, relato cuidador, com sensibilidade 100% e especificidade 97,67%, para ponto de corte 5,26, porém, observando-se todos os valores, nota-se que o RTI-E mostra-se um instrumento mais específico do que sensível. Conclusão: Obteve-se uma versão final adaptada ao nosso meio, aprovada pela autora. O instrumento mostrou-se válido e fidedigno para avaliar a funcionalidade de idosos com DA, oferencendo informações importantes para planejamento de intervenções / Background: Population aging presents challenges, such as functional impairment in routine tasks, due to chronic health conditions, like dementia of Alzheimer\'s disease (AD). In order to design appropriate intervention programs for the AD and his / her family, functionality should be evaluated. The Routine Task Inventory - Expanded (RTI-E) is an assessment that allows evaluating the performance in AVD, IADL, Communication and Working Readiness from the perspective of the patient, the caregiver and the therapist. Objective: To translate, cross-culturally adapt, measure the reliability and validity of the Brazilian version of RTI-E to evaluate the functionality in the elderly with AD dementia compared to the elderly without cognitive impairment. Methods: Translation and cross-cultural adaptation of the instrument was carried out, aiming to maintain semantic and conceptual equivalence to the original. The Chronbach\'s ? coefficient was used to evaluate the internal consistency and interrater reliability was obtained by ICC. Content validity was obtained by convergent validity (correlation with cognitive and functional assessments) and divergent (correlation with HAM-D). Criterion validity was obtained by concurrent validity. Results: There were 85 subjects, divided into 42 subjects, AD group (CDR = 1 or 2) and 43 control group subjects (CDR = 0) and their peers. Translated and cross-culturally adapted version of the RTI-E, approved by the author, was achieved. The RTI-E demonstrated high internal consistency in each analyzed scale, being the highest value in AIVD obtained by a caregiver report (alpha = 0.966) and high interrater reliability. The instrument showed convergent validity in relation to cognitive measures, the highest correlation was found in AIVD, caregiver report (r = 0.912, compared to CAMCOG and r = 0.911, compared to MMSE). About functional measures, the correlation was very strong in caregiver\'s report (AIVD X Lawton [r = 0.917]) and in therapist\'s observation (AIVD X DAFS-Br [r = 0.911]). Self-report scales showed weak or insignificant correlations. RTI-E was able to discriminate between subjects with AD and controls. Cut-off points were obtained varying according to each scale. The highest precision (98.82%) was found in AIVD, a caregiver report, with 100% sensitivity and 97.67% specificity, for cut-off point 5,26. However, observing all values, RTI-E shows to be more specific than sensitive. Conclusion: A final version adapted to our culture, approved by the author was obtained. The instrument was valid and reliable to evaluate the functionality of the elderly with AD, offering important information for planning interventions

A Escala de Avaliação de Demência (Dementia Rating Scale -DRS), proposta por Steven Mattis (1988), tem sido bastante utilizada na avaliação de pacientes com demência tanto na atividade clínica como na pesquisa. Consiste de 5 subescalas: Atenção, Iniciativa/Perseveração, Construção, Conceituação e Memória. Neste estudo, a Escala de Avaliação de Demência foi aplicada em 56 pacientes com doença de Alzheimer com demência de intensidade leve; 55 pacientes com diagnóstico de comprometimento cognitivo leve; e, 60 indivíduos controles. Na diferenciação entre pacientes com doença de Alzheimer e controles a nota de corte de < 128 demonstrou 90,0% de sensibilidade e 89,3 % de especificidade; e, entre pacientes com doença de Alzheimer e comprometimento cognitivo leve, a nota de corte foi < 123 com sensibilidade de 78,2% e 76,8% de especificidade. Na diferenciação entre pacientes com comprometimento cognitivo leve e controles, a nota de corte foi de < 134 com 73,3% de sensibilidade e 72,7% de especificidade. A DRS demonstrou ser um instrumento com boa acurácia diagnóstica na discriminação entre pacientes com doença de Alzheimer de intensidade leve e indivíduos controles. A DRS também foi capaz de diferenciar entre pacientes com comprometimento cognitivo leve de controles, e pacientes com comprometiemnto cognitivo leve de pacientes com doença de Alzheimer de intensidade leve. As subescalas Memória e Iniciativa/Perseveração demonstraram maior acurácia diagnóstica em todas as situações analisadas quando comparadas às demais subescalas. / The Dementia Rating Scale (DRS), proposed by Steven Mattis (1988), it has been very used to assess patients with dementia both in clinical practice and research. Consists of 5 subscales: Attention, Initiation/Perseveration, Construction, Conceptualization and Memory. The Dementia Rating Scale was applied to 56 patients with Alzheimer´s disease, witha dementia of mild intensity; 55 patients with diagnosis of mild cognitive impairment; and, 60 controls. Between patients with Alzheimer´s disease and controls the cutoff score of <128 showed a 90.0% of sensitivity and 89.3% of specificity; and, between patients with Alzheimer´s disease and mild cognitive impairment, the cutoff score was <123 with sensitivity of 78.2% e 76.8% of specificity. In the analysis between patients with mild cognitive impairment and controls, the cutoff score was <134 with 73.3% of sensitivity and 72.7% of specificity. The Dementia Rating Scale showed to be a instrument with good diagnostic accuracy in the discrimination between patients with mild Alzheimer´s disease and controls. The Dementia Rating Scale also was able to discriminated between patients mild cognitive impairment and controls, and between patients with mild cognitive impairment and mild Alzheimer´s disease. The Memory and Initiation/Perseveration subscales showed good diagnostic accuracy in all analysed situations.