Cardiovascular Damage in Alzheimer Disease: Autopsy Findings From the Bryan ADRC

Autopsy information on cardiovascular damage was investigated for pathologically confirmed Alzheimer disease (AD) patients (n = 84) and non-AD control patients (n = 60). The 51 relevant items were entered into a grade-of-membership model to describe vascular damage in AD. Five latent groups were identified “I: early-onset AD,” “II: controls, cancer,” “III: controls, extensive atherosclerosis,” “IV: late-onset AD, male,” and “V: late-onset AD, female.” Expectedly, Groups IV and V had elevated APOE ϵ4 frequency. Unexpectedly, there was limited atherosclerosis and frequent myocardial valve and ventricular damage. The findings do not indicate a strong relationship between atherosclerosis and AD, although both are associated with the APOE ϵ4. Instead, autopsy findings of extensive atherosclerosis were associated with possible, not probable or definite AD, and premature death. They are consistent with the hypothesis that brain hypoperfusion contributes to dementia, possibly to AD pathogenesis, and raise the possibility that the APOE allele ϵ4 contributes directly to heart valve and myocardial damage

Event-Related Functional Magnetic Resonance Imaging Changes during Relational Retrieval in Normal Aging and Amnestic Mild Cognitive Impairment

The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course

Washington University Record, April 7, 1994

https://digitalcommons.wustl.edu/record/1649/thumbnail.jp

Event-Related Functional Magnetic Resonance Imaging Changes during Relational Retrieval in Normal Aging and Amnestic Mild Cognitive Impairment

Abstract The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 886-897

Papel do fisioterapeuta nos cuidados paliativos

Relatório de Prática Clínica apresentado à Escola Superior de Saúde Dr. Lopes Dias do Instituto Politécnico de Castelo Branco para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Cuidados Paliativos.Este relatório insere-se no 2º ano do Mestrado em Cuidados Paliativos da Escola Superior de Saúde Dr. Lopes Dias, do Instituto Politécnico de Castelo Branco e tem como finalidade descrever o percurso desenvolvido no 3º semestre do Mestrado, como requisito à obtenção do nível de mestre em Cuidados Paliativos. Durante o processo de formação da prática clínica, devem ser adquiridas competências ao nível do saber agir profissional e responsável, reconhecido pelos outros; ao nível da mobilização e integração de conhecimentos, recursos e habilidades, num contexto profissional determinado. A unidade curricular de prática clinica teve uma duração de 300 horas, das quais 100 horas foram realizadas no serviço onde desempenho funções, através da realização de um projeto de intervenção/formação. As restantes 200 horas foram realizadas numa Unidade de Cuidados Continuados e Paliativos. A Fisioterapia e os Cuidados Paliativos surgem como duas partes integrantes do tratamento multidisciplinar a doentes com doença crónica avançada, uma vez que partilham objetivos e abordagens terapêuticas, ambos possuem um modelo multidisciplinar de atendimento, que visa melhorar os níveis de função e conforto do doente. Contudo, a reabilitação de doentes paliativos tem recebido pouca atenção, existindo pouca evidência para apoiar a sua eficácia. Apesar da escassa evidência, o fisioterapeuta desempenha um papel importante na equipa de Cuidados Paliativos intervindo numa grande variedade de situações. A prestação de um serviço de fisioterapia especializado resulta em níveis elevados de funcionalidade, qualidade de vida e satisfação do doente. Porém este tipo de doentes representa muitas vezes um desafio na atuação do fisioterapeuta e a sua complexidade requer formação específica. Deste modo para integrar uma equipa de Cuidados Paliativos, é necessário que o fisioterapeuta possua formação específica quer pela elevada componente psicológica, quer pelas necessidades especiais destes doentes. Após perceber a filosofia dos Cuidados Paliativos e a importância da fisioterapia nas suas equipas, foi delineado um projeto de intervenção que teve como principal objetivo demonstrar que a prática paliativa não é exclusiva dos serviços de Cuidados Paliativos e pode ser transposta para outros serviços. Embora realizado num serviço pequeno e com uma amostra reduzida de profissionais, verificou-se que os princípios dos Cuidados Paliativos podem ser aplicados num serviço de Medicina Física e de Reabilitação.ABSTRACT: This report is part of the second year of the Master in Palliative Care of the Escola Superior de Saúde Dr. Lopes Dias, Instituto Politécnico de Castelo Branco and aims to describe the journey developed in the third semester, as a requirement to obtain Master’s degree. During the formation process of clinical practice, should be acquired skills at the level of know to act professional and responsible, recognized by others and mobilization and integration of knowledge, resources and skills, in a professional specific context. The curricular unit of clinical practice had a duration 300 hours, of which 100 hours were performed in my workplace, by conducting an intervention/training project. The remaining 200 hours were performed in a Unidade de Cuidados Continuados e Paliativos. Physical Therapy and Palliative Care emerge as two integral parts of the multidisciplinary treatment in patients with advanced chronic disease, since they share goals and therapeutic approaches, both have a multidisciplinary model of care, which aims to improve levels of function and patient comfort. However, the rehabilitation of palliative patients has received little attention, and there is little evidence to support its effectiveness. Despite limited evidence, the physical therapist plays an important role in the Palliative Care team by intervening in a variety of situations. The provision of a specialized physiotherapy service results in high levels of functionality, quality of life and patient satisfaction. But these types of patients is often a challenge in the physiotherapist performance and its complexity requires a specific training. In this way to integrate a palliative care team, it’s necessary that physical therapists have specific training either by high psychological component, either by the special needs of these patients. After realizing the philosophy of Palliative Care and the importance of Physical Therapy in their teams, we designed an intervention project that aims to demonstrate that palliative practice is not unique to the Palliative Care services and can be applied to other services. Although performed in a small service with a small sample of professionals, it was found that the principles of Palliative Care can be applied in a Physiotherapy service

Role of Cerebrovascular Cells in Tau Processing Following Traumatic Brain Injury

Repetitive exposure to mild traumatic brain injuries (r-mTBI) sustained through the participation in contact sports can lead to chronic post-concussive symptoms and the development of neurodegenerative diseases such as Alzheimer’s disease and Chronic Traumatic Encephalopathy (CTE). A primary hallmark of CTE is the accumulation of pathogenic tau in neurons and astrocytes that surround small blood vessels in the brain. Chronic exposure to r-mTBI leads to elevated levels of extracellular tau and pathogenic tau accumulation in neurons, ultimately resulting in neuronal death. While the mechanisms responsible for pathogenic tau elimination from the brain are unclear, our prior work demonstrated that cells associated with the cerebrovasculature can interact with extracellular tau and may contribute to the removal of extracellular tau from the brain. In this thesis, I examined the mechanisms through which the cerebrovascular cells eliminate extracellular tau from the brain and how those processes are impacted by r-mTBI. I demonstrated that brain vascular mural cells (pericytes and smooth muscle cells) progressively degenerate following exposure to r-mTBI consistent with what is observed in individuals with AD. This mural cell dysfunction impairs the ability of the cerebrovessels to interact with tau. Furthermore, I found that the cerebrovasculature can eliminate extracellular tau from the brain through caveolae-mediated endothelial transcytosis, which is impaired following chronic exposure to r-mTBI. The diminished tau transit across the blood-brain barrier following brain injury may be a contributing factor in the pathogenic tau accumulation observed in CTE. A significant genetic risk factor for neurodegenerative diseases including AD and CTE is possession of the E4 isoform of Apolipoprotein E (ApoE). Astrocytes are the predominant source of ApoE in the brain, though there is very little understanding regarding their interactions with extracellular tau, particularly after exposure to head trauma. While the ApoE4 isoform has been associated with increased tau accumulation and cerebrovascular dysfunction after TBI, investigations into these associations are limited. The current studies found that while astrocytes internalize and release tau back into the extracellular space under normal conditions, these processes become dysfunctional following r-mTBI leading to astrocytic tau accumulation, which is further exacerbated by the ApoE4 isoform. In summary, I identified the factors responsible for the elimination of extracellular tau across the BBB, which are impaired after head trauma. Therapeutic interventions that restore these processes may ameliorate the chronic accumulation of tau associated with neurodegenerative disease. These findings may be particularly important for individuals with the ApoE4 isoform, who are more susceptible to the pathophysiological sequelae of tau accumulation, particularly after exposure to r-mTBI

Deficiency of α-1-antitrypsin influences systemic iron homeostasis

Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology), Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals) were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP). Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES). Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative) relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively) with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1-antitrypsin deficiency, serpins, proteinase inhibitor proteins, ferritin, transferri