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Approved drug treatments for Alzheimer´s disease (AD) are symptomatic and don´t modify the disease course. These include acetylcholinesterase inhibitors (AchI) and N-methyl-D-aspartate receptor antagonist, memantine. Around 20 years ago, these drugs were approved for Alzheimer type Dementia. This wasbased on clinical trials which inclusion criteria were focused on a clinical amnestic AD presentation. At that time, subjects with an atypical AD clinical presentation or biomarkers were not included in the pharmacological trials. New biomarkers that detect amyloid and neurodegeneration have allowed us to evaluate pathological changes compatible with AD. These new advances from aclinical and biomarkers perspective allowed a diagnostic criteria update; going from an exclusively clinical criteria to one that is hybrid: clinical presentation and biomarkers based criteria.New biomarkers facilitate the early diagnosis of AD and other dementias.However, they also generate new challenges and questions regarding the adequate pharmacological treatment.There is a need for clinical trials that evaluate anti-dementia drug's efficacy based on current diagnostic criteria (clinical profile and biomarkers) and new practice guidelines. In addition, regulatory authorities should update ACHI and memantine indications.This will help doctors to prescribe the best possible treatment for this specific population without increasing risks.
Los tratamientos farmacológicos aprobados para la enfermedad de Alzheimer (EA) son sintomáticos y no modifican el curso de la enfermedad. Estos incluyen inhibidores de la acetilcolinesterasa (IACE) y el antagonista del receptor de N-metil-D-aspartato, memantina. Estos medicamentos fueron aprobados para la demencia de tipo Alzheimer (DTA) hace unos 20 años, basándose en ensayos clínicos centrados en la presentación clínica amnésica de la EA sin considerar biomarcadores o presentaciones clínicas atípicas de EA. Los nuevos biomarcadores que detectan amiloide y neurodegeneración nos han permitido evaluar cambios patológicos compatibles con la EA. Estos nuevos avances desde la perspectiva de los biomarcadores y clínicos han llevado a una actualización de los criterios diagnósticos, pasando de criterios exclusivamente clínicos a criterios híbridos: clínicos y basados en marcadores. Estos biomarcadores facilitan el diagnóstico precoz de la EA y otras demencias; sin embargo, a veces generan desafíos y replanteos en relación al tratamiento farmacológico adecuado. Sería útil implementar ensayos clínicos que evalúen la eficacia de los fármacos aprobados para la enfermedad de Alzheimer, en su momento con criterios de demencia tipo Alzheimer en función de los criterios diagnósticos actuales (perfil clínico y biomarcadores). Además, la actualización de la indicación de prescripción de IACE y memantina por parte de las autoridades regulatorias especificando con más detalle la población objetivo ayudaría a prescribir el mejor tratamiento posible a los pacientes sin aumentar los riesgos.
Assuntos
Doença de Alzheimer , Biomarcadores , Humanos , Estudos RetrospectivosRESUMO
Dementia is defined as cognitive impairment in more than one cognitive area and leads to an abnormal degree of impairment in the ability to remember past events. Among mice models of dementia the most used strains are SAMP8 and C57BL/6. There is no reference to characterizing a model of dementia in naturally aged mice of the BALB/c strain, or to the minimum age at which these animals can be used. The aim of this study was the characterization of aged male BALB/ccenp mice as a model of dementia from the evaluation of behavioural, pathological and biochemical markers. One hundred and twenty mice were used and 10 of these were analysed from 8 to 9 months of age, and every 4 months, in a comparative way to young control animals from 4 to 5 months. At the age of 12-13 months there was cognitive impairment in the animals from the Y-maze and object recognition tests and this impairment was maintained at 16-17 months of age. An increase in oxidative damage to proteins in the brains of aged animals was also found in relation to young animals; as well as a decrease in the concentration of triglycerides. At the age of 16-17 months, a significant decrease in the size of the thymus and brain was obtained. We consider that it's a very useful option to use animals 12-13 months of age where there are symptoms of cognitive deficiency, histopathological and biochemical elements characteristic of dementia.
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RESUMEN Se presenta el caso de una paciente femenina de 76 años, estudiada por demencia tipo Alzheimer con trastornos en la esfera conativa y agresividad. El contexto personal y social del paciente, por las características de su enfermedad, especialmente trastornos de conducta, comportamiento agresivo, agitación, irritabilidad, hiperactividad, desinhibición sexual, deambulación errática y reacciones catastróficas, hacen interesante el conocimiento de esta patología, sus implicaciones y el abordaje terapéutico. Por lo expuesto anteriormente se decide realizar esta investigación con el objetivo de describir los desórdenes conativos en la enfermedad de Alzheimer (AU).
ABSTRACT The case of a 76-years-old female patient, studied for Alzheimer-type dementia with disorders in the conative sphere and aggressiveness is presented. The patient´s personal and social context makes it interesting knowing this pathology, its implications and therapeutic approach due to the nature of the illness, especially the behavior disorder, aggressive behavior, agitation, irritability, hyperactivity, sexual disinhibition, erratic wandering and catastrophic reactions. For all the before said, it was decided to make this research with the aim of describing the conative disorders in Alzheimer's disease (AU).
Assuntos
Humanos , Feminino , Idoso , Arteterapia , Tomografia Computadorizada por Raios X , Fatores de Risco , Manifestações Neurocomportamentais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Psicoterapia , Condições Patológicas, Sinais e Sintomas , Sintomas Comportamentais , Transtorno de Comunicação Social , Transtornos do Desenvolvimento da Linguagem , MusicoterapiaRESUMO
Estudio transversal descriptivo, tipo cuantitativo, cuyo objetivo fue identificar el nivel de depresión en una muestra de cuidadores informales de pacientes con Alzheimer, compuesta por 52 sujetos. Se tuvo en cuenta los siguientes criterios de inclusión: ser cuidador informal principal, tener mínimo 3 meses cuidando al enfermo, no recibir ningún tipo de remuneración económica y cuidar pacientes no institucionalizados. Se aplicó el Inventario de Depresión Estado/ Rasgo ( IDER ). Los resultados arrojados indican en la escala total de estado 46,2% y en la subescala de eutimia estado 51,9%, lo cual evidencia una alta presencia de depresión. En la escala total de rasgo se encuentra un total de ausencia de 76,9% y en la subescala de distimia rasgo una ausencia de 88,5%, lo cual indica que no hay relevancia en cuanto el nivel de depresión como rasgo.
Descriptive cross-sectional, quantitative study, aimed to identify the level of depression in a sample of informal caregivers of Alzheimer's patients, composed of 52 subjects. Consideration was given to the following inclusion criteria: primary informal caregiving, with at least 3 months in the care of the patient, with no financial compensation and taking care of non-institutionalized patients. The Depression Inventory (state / trait) IDER , was applied on the sample; The results of the test show a 46.2% in the scale of total state, and a 51.9% in euthymic state subscale, showing also a high incidence of depression. In full scale of trait, there is a total absence of 76.9%, but in the dysthymia subscale, the trait had an absence of 88.5%, therefore, there is no relevance in terms of the level of depression as a trait.
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En el contexto de evaluación de praxias, los gestos pueden clasificarse en tres categorías: transitivos, intransitivos y no familiares. Si bien ha sido reportada la disociación entre los distintos tipos de gestos, es usual que en la evaluación de praxias o en el análisis del desempeño de los pacientes no se consideren por separado estas tres categorías de gestos, o se varíe la definición de ellas. El objetivo del estudio que se informa fue evaluar si en un mismo grupo de pacientes con demencia tipo Alzheimer se encuentran disociaciones entre gestos transitivos, intransitivos y no familiares, previamente descriptas en el rendimiento práxico de pacientes con lesiones focales (González Rothi, Mack, Verfaellie, Brown & Heilman, 1988; Negri et al., 2007). Se evaluaron 50 pacientes con diagnóstico de demencia tipo Alzheimer probable en imitación de praxias (gestos transitivos, gestos intransitivos y gestos no familiares) y uso de objetos. Los estímulos fueron tomados de la batería cognitiva de evaluación de praxias (Politis, 2003). Los gestos eran inicialmente realizados por el examinador, quien mantenía su ejecución durante la imitación del paciente. El grupo con diagnóstico de demencia tipo Alzheimer rindió significativamente peor que el grupo de los controles sanos. En el grupo de pacientes, las cuatro pruebas de praxias correlacionaron entre si. Sin embargo, se hallaron disociaciones en el rendimiento individual de cada paciente en esas mismas pruebas. La disociación entre gestos transitivos, intransitivos y no familiares apoya la posibilidad de que estos diferentes tipos de gestos involucren sistemas de procesamiento distintos.
Apraxia is classically defined as a difficulty or inability to imitate gestures, produce pantomimes of tool's use, or make gestures to verbal command. In apraxia assessment, gestures can be classified in transitives, intransitives, and non-familiars. The movements are classified according to the purpose of the motor act: if involves manipulation of an object, if serves to communicate ideas or feelings, or if it lack of any practical or symbolical value. Whilst the selective impairment for the processing of transitive gestures was widely reported, a deficit restricted to intransitive gestures was reported only exceptionally. Although it has been reported dissociation between different types of gestures, is usual in apraxia assessment that these three categories of gestures don't be considered separately or that varies the definition of these categories. The aim of this study was verify the presence of dissociations between transitives, intransitives, and non-familiars gestures in a same group of patients with Alzheimer-type dementia, that was previously described in the praxias performance of patients with focal lesions (González Rothi, Mack, Verfaellie, Brown, & Heilman, 1988; Negri et al., 2007). It was assessed imitation of transitives, intransitives and non-familiar gestures, and the use of objects, in 50 patients of the Neurology Department of Eva Perón Hospital (Buenos Aires -Argentina) diagnosed with probable Alzheimer-type dementia, under the diagnostic criteria of NINCDS - ADRDA. The Alzheimer-type dementia group performed the tasks significantly worse than healthy controls. 72% showed deficit in the per formance of at least one of the praxis battery tests. In Alzheimer-type dementia group, each praxis subtest are significantly and positively correlated with the others. However, there were dissociations in the performances at the single-case level analysis. One patient (Case 3) showed a selective deficit in imitation of intransitives gestures, while retaining the imitation of transitives gestures and non-familiar gestures; five patients (Cases 16, 23, 31, 45, and 46) showed an exclusively impairment in the imitation of transitives gestures while retaining the imitation of intransitives gestures and non-familiar gestures; and five patients (Cases 2, 6, 12, 14, and 29) showed a deficit only in the imitation of non-familiar gestures, while retaining the imitation of transitives and intransitives gestures. The dissociation between transitives, intransitives, and non-familiar gestures supports the possibility that these different types of gestures implicate different processing systems. The presence of double dissociations points out that the processes underlying each task, at least, are partially independent, and can be affected in a differentiated way. The finding of alterations in the three types of gestures questions the hypothesis that ideomotor apraxia is a disorder in the representations underlying transitives gestures (Buxbaum et al., 2005). The double dissociation found in theimitation of familiar gestures and non-familiar gestures provides new evidence for a non-lexical path, exclusive for imitating non-familiar gestures (González Rothi, Ochipa, & Heilman, 1991) and contradicts the model of ideomotor apraxia that propose a common substrate for lexical path and non-lexical pathway, linked to body schema (Buxbaum, Giovannetti, & Libon, 2000). The results of this work show the value of the study of multiple cases for the validation of cognitive models in patients with brain injuries. It is transcendent the systematic exploration and analysis of the different types of gestures in apraxic patients, in theoretical terms and with a view to developing clinical advantages in identifying and potentially rehabilitate apraxia.
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Introducción: El Grupo de Neurociencias de Antioquia utiliza como protocolo de evaluación cognitiva la batería cognitiva del CERAD. Objetivo: Validar una serie de pruebas neuropsicológicas utilizadas para el diagnóstico de enfermedades neurodegenerativas en una población colombiana. Procedimiento: La muestra estuvo conformada por 848 participantes. Además 151 personas con demencia de Tipo Alzheimer (DTA) y 36 con Deterioro Cognitivo Leve (DCL). Resultados: Para los dominios cognoscitivos evaluados se encontraron coeficientes de consistencia superiores a 0.70. La confiabilidad test-retest presentó coeficientes de correlación intraclase mayores a 0.70. Entre grupos se encontraron diferencias estadísticamente significativas (p<0.05). Se encontraron correlaciones de moderadas a altas entre las pruebas neuropsicológicas y las escalas que miden severidad de la demencia y la funcionalidad. Discusión: Las pruebas utilizadas son útiles para la evaluación de las enfermedades neurodegenerativas, la comunidad científica podrá contar con normas ajustadas a los factores sociodemográficos característicos de nuestra población y otras que presenten características similares a esta población colombiana.
Introduction: Antioquia Neurosciences Group used as a cognitive assessment protocol, the CERAD cognitive battery. Objective: To validate a series of neuropsychological tests used for diagnosis of neurodegenerative disease in a Colombian population. Procedure: The sample consisted of 848 participants. In addition 151 people with dementia of Alzheimer type (DAT) and 36 with mild cognitive impairment (MCI). Results: For the cognitive domains assessed by this protocol consistency coefficients were above 0.70. The test-retest reliability intraclass correlation coefficients showed greater than 0.70. Between groups differences were statistically significant (p <0.05). We found moderate to high correlations between neuropsychological tests and scales that measure severity of dementia and functionality. Discussion: The tests used are useful for the evaluation of neurodegenerative diseases, the scientific community may have rules tailored to the sociodemographic characteristics of our population and that may be useful in populations that have similar characteristics to this Colombian population.