Alzheimer's Disease

Following an analysis of the state of investigations and clinical outcomes in the Alzheimer's research field, I argue that the widely-accepted 'amyloid cascade' mechanistic explanation of Alzheimer's disease appears to be fundamentally incomplete. In this context, I propose that a framework termed 'principled mechanism' (PM) can help with remedying this problem. First, using a series of five 'tests', PM systematically compares different components of a given mechanistic explanation against a paradigmatic set of criteria, and hints at various ways of making (...) the mechanistic explanation more 'complete'. These steps will be demonstrated using the amyloid explanation, and its missing or problematic mechanistic elements will be highlighted. Second, PM makes an appeal for the discovery and application of 'biological principles' (BPs), which approximate ceteris paribus laws and are operative at the level of a biological cell. As such, although thermodynamic, evolutionary, ecological and other laws or principles from chemistry and the broader life sciences could inform them, BPs should be considered ontologically unique. BPs could augment different facets of the mechanistic explanation but also allow further independent nomological explanation of the phenomenon. Whilst this overall strategy can be complementary to certain 'New Mechanist' approaches, an important distinction of the PM framework is its equal attention to the explanatory utility of biological principles. Lastly, I detail two hypothetical BPs, and show how they could each inform and improve the potentially incomplete mechanistic aspects of the amyloid explanation and also how they could provide independent explanations of the cellular features associated with Alzheimer's disease. (shrink)

One goal of this paper is to argue that autobiographical memories are extended and distributed across embodied brains and environmental resources. This is important because such distributed memories play a constitutive role in our narrative identity. So, some of the building blocks of our narrative identity are not brain-bound but extended and distributed. Recognising the distributed nature of memory and narrative identity, invites us to find treatments and strategies focusing on the environment in which dementia patients are situated. A second (...) goal of this paper is to suggest various of such strategies, including lifelogging technologies such as SenseCams, life story books, multimedia biographies, memory boxes, ambient intelligence systems, and virtual reality applications. Such technologies allow dementia patients to remember their personal past in a way that wouldn’t be possible by merely relying on their biological memory, in that way aiding in preserving their narrative identity and positively contributing to their sense of well-being. (shrink)

Brain-related diseases are among the most difficult diseases due to their sensitivity, the difficulty of performing operations, and their high costs. In contrast, the operation is not necessary to succeed, as the results of the operation may be unsuccessful. One of the most common diseases that affect the brain is Alzheimer’s disease, which affects adults, a disease that leads to memory loss and forgetting information in varying degrees. According to the condition of each patient. For these reasons, it is important (...) to classify memory loss and to know the patient at what level and his assessment of Alzheimer's disease through CT scans of the brain. In this thesis, we review ways and techniques to use deep learning classification to classifying the Alzheimer's Disease The proposed method used to improve patient care, reduce costs, and allow fast and reliable analysis in large studies. The model will be designed using Python language for implementing the system, which is very useful for doctors, classifying the Alzheimer's Disease, was used. The model used 70% from image for training and 30% from image for validation, our trained model achieved an accuracy of 100% on a held-out test set. (shrink)

Abstract: Alzheimer's disease (AD) is one of the most common types of dementia. Symptoms appear gradually and end with severe brain damage. People with Alzheimer's disease lose the abilities of knowledge, memory, language and learning. Recently, the classification and diagnosis of diseases using deep learning has emerged as an active topic covering a wide range of applications. This paper proposes examining abnormalities in brain structures and detecting cases of Alzheimer's disease especially in the early stages, using features derived from medical (...) images. The entire brain image was passed on through the transmission of Xception learning architectures. The Convolutional Neural Network (CNN) was constructed with the help of separable convolution layers that It can automatically learn general features from imaging data for classification. (shrink)

Loss of personal identity in dementia can raise a number of ethical considerations, including the applicability of advance directives and the validity of patient preferences that seem incongruous with a previous history of values. In this chapter, we first endorse the self-concept view as the most appropriate approach to personal continuity in healthcare. We briefly describe two different types of dementia, Alzheimer’s dementia (AD) and behavioral-variant frontotemporal dementia (bv-FTD). We identify elements considered important for the continuation of a self-concept, including (...) continuation of memories, consistency in personality traits and personal preferences, and continued endorsement of certain moral tenets. We show that, depending on which element is considered most important for personal identity, continuity of a self-concept for individuals with distinct types of dementia will be affected and assessed differently. Utilizing a variety of empirical evidence, we argue that persistence of memory, personality traits, and preferences are not the most important for the maintenance of personal identity. Instead, as studies aimed to capture the folk-psychological view of personal continuity demonstrate, judgements about continuity depend primarily on the persistent commitment to widely shared moral beliefs. Because of that, we argue that individuals with bv-FTD are more likely to lose their sense of self than individuals whose dementia primarily affects memory, such as Alzheimer’s disease. We end the chapter by showing how the importance of moral beliefs for continuity of self can be used to provide guidance to health-care professionals when considering changes in preference by individuals with dementia. (shrink)

Biomarker-based predictive tests for subjectively asymptomatic Alzheimer’s disease (AD) are utilized in research today. Novel applications of artificial intelligence (AI) promise to predict the onset of AD several years in advance without determining biomarker thresholds. Until now, little attention has been paid to the new ethical challenges that AI brings to the early diagnosis in asymptomatic individuals, beyond contributing to research purposes, when we still lack adequate treatment. The aim of this paper is to explore the ethical arguments put forward (...) for AI aided AD prediction in subjectively asymptomatic individuals and their ethical implications. The ethical assessment is based on a systematic literature search. Thematic analysis was conducted inductively of 18 included publications. The ethical framework includes the principles of autonomy, beneficence, non-maleficence, and justice. Reasons for offering predictive tests to asymptomatic individuals are the right to know, a positive balance of the risk-benefit assessment, and the opportunity for future planning. Reasons against are the lack of disease modifying treatment, the accuracy and explicability of AI aided prediction, the right not to know, and threats to social rights. We conclude that there are serious ethical concerns in offering early diagnosis to asymptomatic individuals and the issues raised by the application of AI add to the already known issues. Nevertheless, pre-symptomatic testing should only be offered on request to avoid inflicted harm. We recommend developing training for physicians in communicating AI aided prediction. (shrink)

Many models of cognitive ability and disability rely on the idea of cognition as abstract reasoning processes implemented in the brain. Research in cognitive science, however, emphasizes the way that our cognitive skills are embodied in our more basic capacities for sensing and moving, and the way that tools in the external environment can extend the cognitive abilities of our brains. This chapter addresses the implications of research in embodied cognition and extended cognition for how we think about cognitive impairment (...) and rehabilitation, how cognitive reserve mitigates neural impairment, and the distinction between medical and social models of disability. (shrink)

In this commentary, I critique three aspects of Emily Walsh's proposal to reduce the moral and legal weight of advance directives: (1) the ambiguity of its initial thesis, (2) its views about the ethics and legality of clinical practice, and (3) its interpretation and application of Ronald Dworkin’s account of advance directives and L.A. Paul's view on transformative experience. I also consider what Walsh’s proposal would mean for people facing the prospect of dementia. I conclude that our reasons to honor (...) many advance directives survive the move to a transformative experience framework. (shrink)

In this paper, I answer the following question: suppose that two individuals, C and D, have been in a long-term committed relationship, and D now has dementia, while C is competent; if D agrees to have sex with C, is it permissible for C to have sex with D? Ultimately, I defend the view that, under certain conditions, D can give valid consent to sex with C, rendering sex between them permissible. Specifically, I argue there is compelling reason to endorse (...) the following thesis: -/- Prior Consent Thesis: D, when competent, can give valid prior consent to sex with her competent partner (C) that will take place after she has dementia, assuming that D is the same person as she was when she gave prior consent, meaning that, if D, when competent, gave prior consent to sex with C, then C may permissibly have sex with D. In section I, I explain both the background and the existing literature on this issue. In section II, I outline relevant stipulations about the kinds of cases I will be examining. In section III, I defend the Prior Consent Thesis. And, in section IV, I address objections to the Prior Consent Thesis. (shrink)

This paper takes a novel approach to the active bioethical debate over whether advance medical directives have moral authority in dementia cases. Many have assumed that advance directives would lack moral authority if dementia truly produced a complete discontinuity in personal identity, such that the predementia individual is a separate individual from the postdementia individual. I argue that even if dementia were to undermine personal identity, the continuity of the body and the predementia individual’s rights over that body can support (...) the moral authority of advance directives. I propose that the predementia individual retains posthumous rights over her body that she acquired through historical embodiment in that body, and further argue that claims grounded in historical embodiment can sometimes override or exclude moral claims grounded in current embodiment. I close by considering how advance directives grounded in historical embodiment might be employed in practice and what they would and would not justify. (shrink)

Cerebrospinal fluid (CSF) is a fluidic part of the brain’s microenvironment that isolates the brain from the rest of the body. CSF dilutes metabolites from neuronal activities and removes them from the brain. Its production and resorption are regulated dynamically and are central to maintaining brain homeostasis. We discovered that the major CSF source, the choroid plexus (CP), harbors the brain’s strongest circadian clock. Here, we consider some implications of the CP circadian clock for metabolite clearance in the brain. If (...) the circadian clock contributes to timed production of the CSF, its synchronization with sleep timing can maximize clearance efficiency and help prevent neurodegenerative diseases such as Alzheimer’s disease. (shrink)

This book analyses three of the most prevalent illnesses of late modernity: anxiety, depression and Alzheimer’s disease, in terms of their relation to cultural pathologies of the social body. Usually these conditions are interpreted clinically in terms of individualized symptoms and responded to discretely, as though for the most part unrelated to each other. However, these diseases also have a social and cultural profile that transcends their particular symptomologies and etiologies. Anxiety, depression and Alzheimer’s are diseases related to disorders of (...) the collective esprit de corps of contemporary society. Multidisciplinary in approach, the book addresses questions of how these conditions are manifest at both the individual and collective levels in relation to hegemonic biomedical and psychologistic understandings. Rejecting such reductive diagnoses, the authors argue that anxiety, depression and Alzheimer’s disease, as well as other contemporary epidemics, are to be analysed in the light of individual and collective experiences of profound and radical changes in our civilization. A diagnosis of our times, Late Modern Subjectivity and its Discontents will appeal to a broad range of scholars with interests in health and illness, the sociology of medicine and contemporary life. (shrink)

This study aimed to understand the preserved elements of self-identity in persons with moderate to severe dementia attributable to Alzheimer’s disease. A semi-structured interview was developed to explore the narrative self among residents with dementia in a residential care facility and residents without dementia in an independent living setting. The interviews were transcribed verbatim from audio recordings and analyzed for common themes, while being sensitive to possible differences between the groups. The participants with dementia showed evidence of self-reference even though (...) losses in explicit memory were evident. The most noticeable difference between the two groups was time frame reference. Nonetheless, all participants showed understanding of their role in relationships and exhibited concrete preferences. Our findings suggest that memory loss and other cognitive deficits associated with moderate to severe dementia do not necessarily lead to a loss of “self.”. (shrink)

Philosophers concerned with what would be good for a person sometimes consider a person’s past desires. Indeed, some theorists have argued by appeal to past desires that it is in the best interests of certain dementia patients to die. I reject this conclusion. I consider three different ways one might appeal to a person’s past desires in arguing for conclusions about the good of such patients, finding flaws with each. Of the views I reject, the most interesting one is the (...) view that prudential value is, at least partly, concerned with the shape of a life as a whole. (shrink)

The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, as these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focussed on marker development and cellular stress as well as on diseases, in particular on diseases of kidney (...) and skin. (shrink)

We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) (...) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer’s disease, multiple sclerosis, and stroke. (shrink)