The meaningful consideration of cultural practices, values and beliefs is a necessary component in the effective translation of advancements in neuroscience to clinical practice and public discourse. Society’s immense investment in biomedical science and technology, in conjunction with an increasingly diverse socio-cultural landscape, necessitates the study of how potential discoveries in neurodegenerative diseases such as Alzheimer disease are perceived and utilized across cultures. Building on the work of neuroscientists, ethicists and philosophers, we argue that the growing field of (...) neuroethics provides a pragmatic and constructive pathway to guide advancements in neuroscience in a manner that is culturally nuanced and relevant. Here we review a case study of one issue in culturally oriented neuroscience research where it is evident that traditional research ethics must be broadened and the values and needs of diverse populations considered for meaningful and relevant research practices. A global approach to neuroethics has the potential to furnish critical engagement with cultural considerations of advancements in neuroscience. (shrink)

The last year has seen major advances in the study of Alzheimer's disease (AD).† Four mutations involving amino acid substitutions in axons 16 and 17 of the amyloid precursor protein (APP) gene, have been identified which co‐segregate with the disease in some families multiply affected by early onset Alzheimer's disease. These mutations are strongly suggestive of a causative role for the amyloid preursor protein in Alzheimer's disease. Despite their rarity, these mutations (...) are important because they represent the first known cause of Alzheimer's disease. Processing of APP must be central to the pathogenesis of the disease although the precise effects of these amino acid substitutions are not understood. Work is now being undertaken to characterise the processing pathways of APP and to identify other causes of AD. The development of models of AD using the APP mutations offers the possibility of identifying drug targets and developing more effective treatments than are presently available. (shrink)

I note with interest the Controversy regarding a baby born free of an inherited predisposition to early onset Alzheimer’s disease through the use of preimplantation genetic diagnosis .1,2 As the medical geneticist for the PGD programme for single gene disorders in Melbourne, Australia, I have seen many couples who have considered PGD for a wide range of genetic conditions. My observation is that many couples look to PGD for “milder” conditions and adult onset conditions for (...) which they are not comfortable to have traditional prenatal diagnosis and termination of pregnancy.An example of this is that in the last 11 years our unit has undertaken 13 prenatal diagnoses for Huntington’s disease from nine couples, whereas in the two years that we have been offering it we have had six requests for PGD for Huntington’s disease and three couples …. (shrink)

Is it right to use pre-implantation genetic diagnosis to select an embryo free of the gene for early-onset Alzheimer’s disease?A 30 year old woman with the gene for early-onset Alzheimer’s disease, who seems certain to develop the disease by the time she is 40, has used IVF and preimplantation genetic diagnosis to select an embryo that is free of the mutant gene. The woman, a geneticist, has given birth to a mutation-free (...) child. This marks the first time that preimplantation genetic diagnosis has been used to “weed out” an embryo with the defect.1–3Early-onset Alzheimer’s is an inherited, incurable disease striking people …. (shrink)

Alzheimer disease is a huge and growing societal problem with upwards of 35% of the population over the age of 80 developing the disease. AD results in a loss of memory, the ability to make reasoned and sound decisions, and ultimately the inability to take care of oneself. AD has an impact not only on the sufferer, but their caretakers and loved ones, who must take on a costly and time-consuming burden of care. AD is found in (...) virtually all racial and ethnic groups. Genetic influences on AD are substantial, and there has been a 30 year history of both success and failure. Mutations for rare early onset forms of the disease have been identified, but this information has not yet led to an effective treatment. Multiple common genetic variations have also been identified, and have led to new insights into the potential role of microglia cells in addition to neuronal cells in the brain. Despite intensive efforts, a significant portion of the genetic etiology of AD remains unknown and must be identified. (shrink)

Only a few studies explore the lifeworld of the spouses of persons affected by early-onset Alzheimer disease. The aim of this study is to explore the lifeworld of spouses when their partners are diagnosed with AD, focusing on spouses’ lived experience. The study employs an interpretative phenomenological framework. Ten in-depth interviews are performed. The results show that spouses’ lifeworld changes with the diagnosis. They experience an imprisoned existence in which added obligations, fear, and worry keep them (...) trapped at home, both physically and mentally. In their longing for freedom, new strategies and attitudes helps the spouses to create an extended “lived space” with their partner. The findings stress the importance of paying attention to the lifeworld of spouses and making clinical recommendations on this basis. Most importantly, the lifeworld perspective has implications for how we understand what care is. We hope to challenge all different healthcare professionals and invite them to discuss the deep meaning of care and the definition of being professional in encounters with vulnerable others from a lifeworld perspective. (shrink)

As the global prevalence of Alzheimer’s disease increases, the need to understand family caregiving becomes increasingly pressing. I argue that there is an under-recognized form of caregiving for people with early to mid-stage Alzheimer’s disease. This type of caregiving involves, roughly, helping people reason through their values. It arises along with the loss of the capacity for executive functioning. Moreover, it is prone to give rise to moral distress, which is an under-recognized vulnerability in family (...) caregiving. Categories of family caregiving thus need to be expanded, and moral distress needs to be recognized not only in the context of nursing. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short (...) commentary offers a perspective on this debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

Advance patient directives are various forms of anticipatory medical directives made by competent individuals for the eventuality of future incompetence. They are therefore appropriate instruments for competent patients in the early stage of Alzheimer's disease to document their self-determined will in the advanced stages of dementia. Theoretical objections have been expressed against the concept of advance patient directives (problems of authenticity and identity) which, however, cannot negate the fundamental moral authority of advance patient directives. Therefore, patients, family (...) members, and physicians should make use of the appropriate form of advance directive as part of common treatment and care planning. Advance directives, when utilized intelligently, represent appropriate instruments for shared decision-making by patient, family members and physician. They should be utilized to a greater extent, particularly for the treatment planning of demented patients. (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)

The proposal of the new criteria for the diagnosis of Alzheimer’s disease based on biomarker data is making possible a diagnosis of AD at the mild cognitive impairment or predementia/prodromal– stage. Given the present lack of effective treatments for AD, the opportunity for the individuals to personally take relevant decisions and plan for their future before and if cognitive deterioration occurs is one the main advantages of an early diagnosis. Advance directives are largely seen as an effective (...) tool for planning medical care in the event the subject becomes incompetent. Nevertheless, their value has been questioned with regard to people with dementia by scholars who refer to the arguments of personal identity and of patient’s changing interests before and after the onset of dementia. In this paper, I discuss the value of advance directives in Alzheimer’s disease and other kind of dementia. Despite critics, I argue that advance directives are especially advisable in dementia and provide reasons in favor of their promotion at an early stage of the disease as a valuable tool to respect patients’ values and preferences on medical treatment, including participation in research and end of life decisions. I mainly support advance directives that include both decisions regarding health care and the appointment of an attorney in fact. I conclude that patients with AD at a prodromal or early stage should be offered the opportunity to execute an advance directive, and that not to honor a demented individual’s directive would be an unacceptable form of discrimination towards those patients. (shrink)

Background and Aims Progress towards validating amyloid beta as an early indicator of Alzheimer’s disease (AD) heightens the need for evaluation of stakeholders’ perspectives of the benefits and harms of preclinical testing in asymptomatic individuals. Methods Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD. Results Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, (...) and psychological harms. Nine participants reported either a “positive global perspective” or a “positive global perspective (qualified).” Conclusion Results from this study characterized stakeholders’ perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research. (shrink)

Over the last century, Alzheimer’s disease has proven a highly malleable concept. Initially an obscure diagnosis pertaining to rare cases of young onset dementia, by the latter half of the 20th cen...

The world population aged significantly over the twentieth century, leading to an increase in the number of individuals presenting progressive, incapacitating, incurable chronic-degenerative diseases. Advances in medicine to prolong life prompted the establishment of instruments to ensure their self-determination, namely the living will, which allows for an informed person to refuse a type of treatment considered unacceptable according to their set of values. From the knowledge on the progression of Alzheimer disease, it is possible to plan the medical (...) care, even though there is still no treatment available. Irreversible cognitive incapacity underlines the unrelenting loss of autonomy of the demented individual. Such a loss requires the provision of specific and permanent care. Major ethical issues are at stake in the physician–patient–family relationship, even when dementia is still at an early stage. The authors suggest that for an adequate health care planning in Alzheimer disease the living will can be presented to the patient in the early days of their geriatric care, as soon as the clinical, metabolic or even genetic diagnosis is accomplished. They also suggest that the appointment of a health care proxy should be done when the person is still in full enjoyment of his cognitive ability, and that the existence and scope of advance directives should be conveyed to any patient in the early stages of the disease. It follows that ethical guidelines should exist so that neurologists as well as other physicians that deal with these patients should discuss these issues as soon as possible after a diagnosis is reached. (shrink)

Successful preimplantation genetic diagnosis to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the chance that (...) the parents will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing”, PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant. (shrink)

Successful preimplantation genetic diagnosis to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the chance that (...) the parents will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing”, PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant. (shrink)

Successful preimplantation genetic diagnosis (PGD) to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization (IVF) to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the (...) chance that the parents will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing” (rather than to avoid a sex-linked disorder), PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant. (shrink)

It may soon be possible to diagnose neurodegenerative disorders, such as early onset Alzheimer's disease, with a high degree of accuracy well before these conditions become symptomatic. In a carefully argued and thought-provoking piece, Dena Davis maintains that preemptive suicide may be a rational option for those confronted with a preclinical diagnosis of impending dementia, and consequently that withholding the results of dementia research until effective treatments become available constitutes an unjustified infringement on patient autonomy. If (...) suicide is indeed a rational course of action for some people diagnosed with dementia, then contrary to received wisdom, biomarker information indicating a high risk of dementia may be ‘actionable’ even if there is no known treatment for the condition. Preemptive suicide, Davis argues, may be motivated and justified by a mixture of other-regarding and self-regarding considerations. These include, inter alia, the wish to avoid imposing significant financial or psychological hardships on one's family, the unwillingness to live without the capacities for meaningful independence or agency, and the desire to write a final chapter that is consistent with one's stable values and that does not distort or eclipse the overarching narrative of one's life. Dementia raises an ethical dilemma that does not arise in connection with other diseases with respect to which many believe suicide is a rational course of action. This dilemma arises from the fact that a person with impending dementia cannot wait until the disease takes hold to issue and carry out a decision to end his or her life, since dementia destroys the capacities that underpin rational decision-making. Because jurisdictions permitting suicide require, quite reasonably, that a …. (shrink)

With more people in the world living into older age, Alzheimer's and other Dementias: The Facts takes a comprehensive look at the spread of dementia, and provides authoritative information and practical advice for sufferers, their families, and the medical professionals who care for them. -/- Written by a consultant in old age psychiatry, the book provides an overview of all the different types of dementia (including younger-onset dementias), from the most-recognized - Alzheimer's - to the less-frequent types, (...) such as those caused by inherited metabolic disorders or HIV. The book guides the reader step-by-step through how the brain works, and explains in clear and simple language the effect of dementias on the brain, and the impact on an individual's cognitive function. -/- A dedicated chapter explains how a diagnosis is reached, including the different modes of assessment, from blood tests carried out by a GP, to specialist scans, highlighting how the brain actually works. Detailed sections cover the latest treatments available, including the controversial use of antipsychotic medication, and the possibility of disease-modifying treatments in the future. -/- The book also explains how the multi-disciplinary team works together to look after the sufferer's social needs, such as bathing and washing, as well as their spiritual and palliative needs. Alzheimer's and other Dementias: The Facts provides all the relevant information and guidance for sufferers, family and their care-givers to choose the right intervention at the right time, to create - as the book advocates - a unique and personalized management plan. (shrink)

Detection of Alzheimer’s disease in an early stage is receiving increasing attention for a number of reasons, such as the failure of drug trials in more advanced disease stages, the demographic evolution, the financial impact of AD, and the approval of amyloid tracers for clinical use. Five focus group interviews with stakeholders were conducted.. The verbatim transcripts were analysed via the Nvivo 11 software. Most stakeholder groups wanted to know their own amyloid PET scan result. However, (...) differences occurred between FGs: two groups wanted to know, whilst in the three other groups FG members opted not to know or were still in doubt about their decision. Stakeholders provided insight into their reasons for wanting to know their amyloid PET scan result, for not wanting to know their result, or why they were in doubt about their decision. Several advantages and disadvantages were mentioned as part of knowing their amyloid PET scan result. Certain considerations were clustered in a grey zone, in between advantage and disadvantage, such as the emotional consequences. Clinicians, researchers, and policymakers ought to be aware of the diversity of reasons for wanting to know their result and how possible benefits and risks can be viewed differently. The current findings are of importance for future early diagnosis and disclosure of results in the research setting. (shrink)

In Alzheimer's disease (AD), pathological processes start in the brain long before clinical dementia. Biomarkers reflecting brain alterations may therefore indicate disease at an early stage, enabling early diagnosis. This raises several ethical questions and the potential benefits of early diagnosis must be weighted against possible disadvantages. Currently, there are few strong arguments favouring early diagnosis, due to the lack of disease modifying therapy. Also, available diagnostic methods risk erroneous classifications, with potentially (...) grave consequences. However, a possible benefit of early diagnosis even without disease modifying therapy is that it may enable early decision making when patients still have full decision competence, avoiding problems of hypothetical consents. It may also help identifying patients with cognitive dysfunction secondary to other diseases that may be responsive to treatment already today. (shrink)

Alzheimer’s disease (AD) in its most common form results in cognitive changes in memory function leading to dementia due to underlying neurodegenerative disease. Recent research advancements in AD...

Background: Today, many healthcare or dementia organizations, clinicians, and companies emphasize the importance of detection of Alzheimer’s disease in an early phase. This idea has gained considerable momentum due to the development of biomarkers, the recent FDA and EMA approval of three amyloid tracers, and the failure of a number of recent therapeutic trials conducted in the early dementia phase. On the one hand, an early etiological diagnosis can lead to early and more efficacious (...) intervention. On the other hand, it is questioned how early an etiological diagnosis is beneficial to the patient. Here we consider ethical issues related to the process of biomarker testing and the impact on the diagnostic disclosure to patients with mild cognitive impairment due to prodromal Alzheimer’s disease. Methods: A systematic review of the theoretical bioethics literature was performed by using electronic databases. The review was limited to articles published in English between 2003 and 2016. Results: A total of twenty articles were included in our effort to make an analysis of the ethical challenges. One of the biggest challenges was the uncertainty and the predictive value of the biomarker-based diagnosis where patients can be amyloid positive without full certainty whether or when they will develop symptomatic decline due to Alzheimer’s disease. Another challenge was the tension between the right to know versus the wish not to know, the limited efficacy of currently available treatment options, and the opportunities and consequences after receiving such an early diagnosis. Conclusion: Based on the results and the additional comments in the discussion, several unanswered questions emerged. Therefore, careful consideration of all these ethical issues is required before the disclosure of a biomarker-based diagnosis to the patient with mild cognitive impairment due to Alzheimer’s disease. (shrink)

It's not unusual to hear someone say, ‘I'd rather be dead than have Alzheimer's’. In ‘Alzheimer Disease and Preemptive Suicide’,1 Dena Davis explains why this is a reasonable position. People taking this position will welcome the discovery of biomarkers permitting very early AD diagnosis, Davis suggests, for this will enable more of them to end their lives while they remain motivated and able to do so. At the same time, Davis observes, people would have less reason (...) to resort to the drastic remedy of pre-emptive suicide if they had absolute authority over the medical treatment they received as patients with dementia; but the threat of pre-emptive suicide is not, in my view, a sufficient reason to grant competent individuals that authority.If preclinical diagnosis of AD becomes possible, some pre-emptive suicides will probably occur. There would be no ethical or practical way to ban such suicides, and it would be silly to try. Clinicians will undoubtedly try to discourage people seeking biomarker information in furtherance of a suicide plan, but savvy individuals will simply conceal their true motivation for having the tests. The real problem for people intent on self-destruction is that biomarkers are unlikely to deliver a clear suicide signal.First, as Davis notes, work on biomarkers remains in the research stage. No one yet knows whether biomarker tests will prove accurate enough to warrant clinical use. Second, even clinically accepted biomarker tests will generate imperfect information about future disease. Biomarkers may produce more accurate estimates of a person's risk of developing AD, but like all predictive tests, they will also yield false positive and negative results. The …. (shrink)

Background: Although genetic research into Alzheimer disease (AD) is increasing, the ethical aspects of this kind of research and the differences between ethical issues related to genetic and non-genetic research into AD have not yet received much attention. Objectives: (1) To identify and compare the five ethical issues considered most important by surveyed expert panellists in non-genetic and genetic AD research and (2) to compare our empirical findings with ethical issues in genetic research in general as described in (...) the literature. Method: A modified Delphi study in two rounds Results: Genetic and non-genetic research into AD generated an approximately equal number of topics with a considerable overlap. Different priorities in the ethics of both types of research were found. Genetic research raised new topics such as “confidentiality of genetic information” and “implications of research for relatives” which changes the impact and application of existing ethical topics such as “informed consent” and is judged to have more impact on both individuals and society. A difference with the results of more theoretical approaches on ethical aspects related to AD research was also found. Conclusions: Different priorities are given to ethical issues in genetic and non-genetic research. These arise partly because genetic research causes unique and new questions, mostly related to the position of family members and the status of and access to genetic information. Differences found between the results of our empirical study and the more theoretical literature, suggest an additional value for empirical research in medical ethics. (shrink)

Objectives: To examine the experiences of spousal care givers of Alzheimer patients to disclosure of dementia diagnosis and subsequent care.Methods: A random sample of 1943 spousal care givers of people receiving medication for Alzheimer disease was sent a cross-sectional postal survey about their opinions on the disclosure of dementia and follow-up care. A smaller qualitative study included open-ended questions concerning their experiences of the same topics.Results: The response rate for the survey was 77%. Of the respondents, 1214 (...) of 1434 acknowledged themselves as their spouse’s care giver. The mean age of the care givers was 78.2 years, and that of demented spouses, 80.5 years. Of the care givers, 63% were women. The couples had long-lasting marriages. Of the care givers, 93% reported that dementia had been disclosed openly to their spouse; 97% also preferred that physicians openly inform the patients of the dementia diagnosis, although 55% of their spouses with AD had developed depressive symptoms after the disclosure. Of the care givers, 71% felt they had received sufficient information about dementia. However, only 50% estimated that their spouses’ follow-up care had been well organised. The responses in the qualitative study indicated that many care givers felt grief and anxiety. They also expressed feelings of loneliness and uncertainty about how to deal with follow-up care for dementia.Conclusions: Elderly spousal care givers were quite satisfied with the information given them about dementia. However, the support with regard to the follow-up care of care-giving families failed to meet their needs adequately. (shrink)

This paper analyses self-declared aims and representation of dementia patient organizations and advocacy groups in relation to two recent upheavals: the critique of social stigmatization and biomedical research focusing on prediction. Based on twenty-six semi-structured interviews conducted in 2016–2017 with members, service recipients, and board representatives of POs in Germany and Israel, a comparative analysis was conducted, based on a grounded theory approach, to detect emerging topics within and across the POs and across national contexts. We identified a heterogeneous landscape, (...) with the only Israeli PO focusing strongly on caretakers, whereas in Germany several POs claim to represent this patient collective. Shared aims of all POs were fighting social stigma, balancing the loss of patients’ individual autonomy, and the well-being of caretakers. By highlighting the emergence of new groups of dementia self-advocacy against the more traditional advocacy by others, this study highlights how advocacy and representation in the context of AD are embedded in the discursive context of stigmatization and revised disease conception. Future developments in early diagnosis and prediction of dementia, with more affected people likely to conduct dementia self-advocacy, might challenge existing representation structures even more. (shrink)

Alzheimer’s disease is a very common, progressive and still incurable disease. Future possibilities for its cure lie in the promotion of research that will increase our knowledge of the disorder’s causes and lead to the discovery of effective remedies. Such research will necessarily involve individuals suffering from Alzheimer’s disease. This raises the controversial issue of whether patients with Alzheimer’s disease are competent to give their consent for research participation.

If you developed Alzheimer disease, would you want to go all the way to the end of what might be a decade‐long course? Some would; some wouldn't. Options open to those who choose to die sooner are often inadequate. Do‐not‐resuscitate orders and advance directives depend on others' cooperation. Preemptive suicide may mean giving up years of life one would count as good. Do‐it‐yourself methods can fail. What we now ask of family and clinicians caring for persons with dementia, (...) and of patients given no better option than to go on with lives they may not want, is unacceptable. To explore how one might better control one's own dying and avoid burdening others with overwhelming care and morally painful choices, we propose a thought experiment: an advance directive implant that would enable persons with early dementia, while competent, to arrange their own deaths without the subsequent intervention of anyone else. (shrink)

The purpose of this study was to explore how one person experienced the early years of dementia as she was living through the pre-clinical and earlyclinical stages of Alzheimer’s disease. Interviews were held onfour occasions over a period of three years. The data were analyzed usingthe descriptive phenomenological psychological method, in which theresearcher approached the data from a caring perspective. The livedexperience of early-stage Alzheimer’s disease showed to be acomplex transitional phenomenon that involves a (...) dynamic process of personaladjustment. The process is set in motion as the participant receives thediagnosis and will eventually lead her towards a state of increased opennessand receptiveness toward the disease. The results describe this process asit unfolds in the context of the overall experience, and the variousadjustments that the participant undertakes. Some reflections concerning theplausible needs of patients with early-stage Alzheimer’s diseaseare included in the discussion. (shrink)

Abstract2020 saw the rapid onset of a global pandemic caused by the SARS‐CoV‐2 virus. For healthcare systems worldwide, the pandemic called upon quick organization ensuring treatment and containment measures for the new virus disease. Nurses were seen as constituting a vital instrumental professional component in this study. Due to the pandemic's unpredictable and potentially dangerous nature, nurses have faced unprecedented risks and challenges. Based on interviews and free text comment from a survey, this study explores how ethical challenges (...) related to “being a nurse” during the COVID‐19 pandemic was experienced and understood by Danish hospital‐based nurses. Departing from anthropologist Jarett Zigon's notion of moral breakdown, the study demonstrates how the rapid onset of the pandemic constitutes a moral breakdown raising ethical demands for nurses. Analytically we identify three different ethical demands experienced by the nurses. These ethical demands are Nursing and societal ethical demands, Nursing and personal ethical demands, and Nursing and conflicting ethical demands. These demands represent not only very different understandings of ethical demands but also different understandings of ethical acts that are seen as necessary to respond to these demands. (shrink)

Recent advances in biomarkers may soon make it possible to identify persons at high risk for late-onset Alzheimer’s disease at a presymptomatic stage. Popular demand for testing is increasing despite the lack of cure and effective prevention options and despite uncertainties regarding the predictive value of biomarker tests. This underscores the relevance of the ethical, cultural and social implications of predictive testing and the need to advance the bioethical debate beyond considerations of clinical consequences. Our qualitative study (...) included three groups of affected persons: People with mild neurocognitive disorder, their relatives and family caregivers of people with dementia. We explored their moral motivations regarding predictive, biomarker-based testing and preclinical diagnostics. We interviewed affected individuals in Germany and Israel. Transcripts of 12 focus groups and 12 semistructured interviews were content analysed with a focus on the moral motivations of affected persons in their justification of why they accept or reject predictive testing and early diagnosis. We grouped the underlying aspects of moral motivation into four ethical categories: beneficence as a form of personal utility focusing on well-being, the ties of responsibility linking families and their individual members, the importance of self-determination by later life planning and notions of a good life. In general, cultural parallels among these motives were very obvious. Cultural variation occurred mainly in openness to suicide, scepticism about test validity and emphasis on personal autonomy. The study underscores the importance of counselling for life-planning issues and of informing test candidates about problems with test validity and about the ambiguity of test results. All data relevant to the study are included in the article or uploaded as supplementary information. (shrink)

Existing accounts of the early history of Alzheimer’s disease have focused on Alois Alzheimer’s (1864–1915) publications of two ‘peculiar cases’ of middle-aged patients who showed symptoms associated with senile dementia, and Emil Kraepelin’s (1856–1926) discussion of these and a few other cases under the newly introduced name of ‘Alzheimer’s disease’ in his Textbook of Psychiatry. This article questions the underpinnings of these accounts that rely mainly on publications and describe ‘presenility’ as a defining characteristic (...) of the disease. Drawing on archival research in the Munich psychiatric clinic, in which Alzheimer and Kraepelin practised, this article looks at the use of the category as a diagnostic label in practice. It argues that the first cases only got their exemplary status as key referents of Alzheimer’s disease in later readings of the original publications. In the 1900s, the published cases rather functioned as material to think about the limits of the category of senile dementia. The examination of paper technologies in the Munich psychiatric clinic reveals that the use of the clinical diagnosis of Alzheimer’s disease was not limited to patients of a certain age and did not exclude ‘senile’ cases. Moreover, the archival records reflect that many diagnoses of Alzheimer’s disease were noted in the medical records as suspicions rather than conclusions. Against this background, the article argues that in theory and practice, Alzheimer’s disease was not treated as a well-defined disease entity in the Munich clinic, but as an exploratory category for the clinical and histopathological investigation of varieties of organic brain diseases. (shrink)

As in the United States, the Dutch conversation about assisted suicide emerged primarily in the context of cancer. At least in that context, before acceding to a request for assistance in dying, caregivers must be sure that the person has made a voluntary and carefully considered request, and that her suffering is unbearable and without prospect of improvement. The Dutch have recently been trying to use those criteria in the context of Alzheimer's disease. Given the wave of (...) class='Hi'>Alzheimer's cases poised to crash onto wealthy countries, along with emerging technology to detect the disease process before symptoms appear, we should be grateful to the Dutch for that attempt. As a newcomer to this discussion, however, I was struck that those criteria may have a somewhat odd result. A patient with Alzheimer's disease can easily meet the conditions in the early stage of the disease, when one usually has the mental capacity to request assistance in dying and to make the case that one's existential suffering is unbearable. If one is in the late stage, though, it can be much harder to get such assistance because one does not have that capacity. (shrink)

In the hope of future treatments to prevent or slow down the disease, there is a strong movement towards an ever-earlier detection of Alzheimer's disease. In conjunction with scientific developments, this has prompted a reconceptualization of AD, as a slowly progressive pathological process with a long asymptomatic phase. New concepts such as "preclinical" and "prodromal" AD have been introduced, raising a number of conceptual and ethical questions. We evaluate whether these new concepts are theoretically defensible, in light (...) of theories of health and disease, and whether they should be understood as disease or as an at-risk state. We introduce a pragmatic view on disease concepts and argue that an evaluation of the reconceptualization of AD should also take its aims and effects into account, and assess their ethical acceptability. The reconceptualization of AD is useful to coordinate research into preventive strategies, and may potentially benefit future patients. However, in the short term, early detection and labelling of "preclinical AD" can potentially harm people. Since there is no treatment available and the predictive value is unclear, it may only create a group of "patients in waiting" who may suffer from anxiety, uncertainty and stigmatization, but will never actually develop dementia. We conclude that only if the promise of preventive medication materializes, will the reconceptualization of AD turn out unequivocally to be for the better. Otherwise, the reconceptualization may do more harm than good. (shrink)

Dementia accompanies aging in certain susceptible individuals. The chemical function of the brain remains normal, but certain neurotransmitter-selective diseases, such as Parkinson's disease, Huntington's disease, and Alzheimer's disease occur more commonly with age.There are at least two issues troubling researchers of senile dementia at the moment. One is the contribution of cell death, as opposed to selective neuronal atrophy, to the pathology of degenerative disorders. The other is how early the onset of dementia might (...) be detected. The resolution of such issues is important for the design of therapies for the common and most serious chronic, rather than acute, neurodegenerative disease.Alzheimer's disease is one of the most devastating neurological disorders. The ethical debate is often related to when human biological life ceases or when a person ceases to exist. If the elder is still a person, he/she is no more the same person. Huntington's disease is inherited as a highly penetrant, autosomal dominant neuronal disorder. A genetic test can accurately predict a person's risk and that of the children. As the knowledge of the genetic basis is increasing and prenatal diagnosis gets easier, the possibilities to avoid child disorders will become greater, but genetic testing raises problematic ethical issues. Ethical action involves the right to know and the right not to know, it involves freedom of choice and freedom implies knowledge. It is ethical that relatives in age of procreation should be informed. In any case, efficacy and safety of the procedure, the risk-benefit ratio for a particular disease must be judged to be acceptable and understood through informed consent by the patient or the family or both. (shrink)

Dementia accompanies aging in certain susceptible individuals. The chemical function of the brain remains normal, but certain neurotransmitter-selective diseases, such as Parkinson's disease, Huntington's disease, and Alzheimer's disease occur more commonly with age.There are at least two issues troubling researchers of senile dementia at the moment. One is the contribution of cell death, as opposed to selective neuronal atrophy, to the pathology of degenerative disorders. The other is how early the onset of dementia might (...) be detected. The resolution of such issues is important for the design of therapies for the common and most serious chronic, rather than acute, neurodegenerative disease.Alzheimer's disease is one of the most devastating neurological disorders. The ethical debate is often related to when human biological life ceases or when a person ceases to exist. If the elder is still a person, he/she is no more the same person. Huntington's disease is inherited as a highly penetrant, autosomal dominant neuronal disorder. A genetic test can accurately predict a person's risk and that of the children. As the knowledge of the genetic basis is increasing and prenatal diagnosis gets easier, the possibilities to avoid child disorders will become greater, but genetic testing raises problematic ethical issues. Ethical action involves the right to know and the right not to know, it involves freedom of choice and freedom implies knowledge. It is ethical that relatives in age of procreation should be informed. In any case, efficacy and safety of the procedure, the risk-benefit ratio for a particular disease must be judged to be acceptable and understood through informed consent by the patient or the family or both. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated (...) in aged monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The paper outlines the policy context and summarizes the numerous policy issues that AD raises from the more generic to the unique. It posits that strong public fears of AD and its future prevalence projections and costs, raise increasingly difficult policy dilemmas. After reviewing the costs in human lives and money and discussing the latest U.S. policy initiatives, the paper presents two policy areas as examples the demanding policy decisions we face. The first focuses on the basic regulatory function of (...) protecting the public from those who would exploit these fears. The second centers on the well-debated issues of advance directives and euthanasia that surround AD. Although more dialogue, education and research funding are needed to best serve the interests of AD patients and families as well as society at large, this will be challenging because of the strong feelings and divisions AD engenders. (shrink)

This paper first considers why it is important to give children genetic information about hereditary conditions in the family, which will go on to affect their lives in a salient way. If it is important to inform children that they are at risk for an adult-onset disease that exists in the family, why should they not also grow up knowing whether they actually carry the genetic mutation? Central to this discussion is the importance of the process of disclosure (...) and the environment in which genetic information is divulged. It is concluded that the reasons given for defending disclosure of genetic conditions in the family to children are also important reasons to cautiously defend predictive genetic testing of children for adult-onset diseases. (shrink)

IntroductionDementia diseases, especially Alzheimer’s disease (AD), are of considerable importance in terms of social policy and health economics. Moreover, against the background of the current Karlsruhe judgement on the legalisation of assisted suicide, there are also questions to be asked about medical humanities in AD.MethodologyRelevant literature on complementary forms of therapy and prognosis was included and discussed.ResultsCreative sociotherapeutic approaches (art, music, dance) and validating psychotherapeutic approaches show promise for suitability and efficiency in the treatment of dementia, but in (...) some cases still need to be scientifically tested. Biomarker-based early diagnosis of dementia diseases is increasingly becoming a subject of debate against the background of the Karlsruhe ruling.DiscussionNeeds-oriented and resource-enhancing approaches can make a significant contribution to improving the quality of life of people with dementia. The discussion on the issue of “assisted suicide” should include questions of the dignity and value of a life with dementia.OutlookThe integrative dementia therapy model can be complemented by a religion- and spirituality-based approach. Appropriate forms of psychotherapy should be scientifically evaluated. (shrink)

In the United States alone, the prevalence of AD is expected to more than double from six million people in 2019 to nearly 14 million people in 2050. Meanwhile, the track record for developing treatments for AD has been marked by decades of failure. But recent progress in genetics, neuroscience and gene editing suggest that effective treatments could be on the horizon. The arrival of such treatments would have profound implications for the way we diagnose, triage, study, and allocate resources (...) to Alzheimer’s patients. Because the disease is not rare and because it strikes late in life, the development of therapies that are expensive and efficacious but less than cures, will pose particular challenges to healthcare infrastructure. We have a window of time during which we can begin to anticipate just, equitable and salutary ways to accommodate a disease-modifying therapy Alzheimer’s disease. Here we consider the implications for caregivers, clinicians, researchers, and the US healthcare system of the availability of an expensive, presymptomatic treatment for a common late-onset neurodegenerative disease for which diagnosis can be difficult. (shrink)

Cognitive dysfunction in Alzheimer’s disease is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulation, via activation of the locus coeruleus, results in the release of catecholamines in the hippocampus and neocortex, which can enhance synaptic plasticity and reduce inflammatory signalling. Vagal nerve stimulation has shown (...) promise to enhance cognitive ability in animal models. Research in rodents has shown that VNS can have positive effects on basal synaptic function and synaptic plasticity, tune inflammatory signalling, and limit the accumulation of amyloid plaques. Research in humans with invasive and non-invasive VNS devices has shown promise for the modulation of cognition. However, the direct stimulation of the vagus nerve afforded with the invasive procedure carries surgical risks. In contrast, non-invasive VNS has the potential to be a broadly available therapy to manage cognitive symptoms in early AD, however, the magnitude and specificity of its effects remains to be elucidated, and the non-inferiority of the effects of non-invasive VNS as compared with invasive VNS still needs to be established. Ongoing clinical trials with healthy individuals and patients with early AD will provide valuable information to clarify the potential benefits of non-invasive VNS in cognition and AD. Whether invasive or non-invasive VNS can produce a significant improvement on memory function and whether its effects can modify the progression of AD will require further investigation. (shrink)