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)

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical (...) desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts, ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective. (shrink)

That aluminum is fatally toxic is beyond doubt, demonstrated by mass human poisoning at Camelford in Cornwall in Britain in 1988 and by occasional fish kills. Aluminum may also be a contributing factor in a number of human diseases, in particular those involving brain and nerves — autism, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis. Aluminum salts used in kidney dialysis may be responsible for dialysis-related encephalopathy. Aluminum adjuvants in vaccine can cause macrophagic myofasciitis as well as such whole-body ailments as (...) chronic fatigue syndrome and marked cognitive deficits ; one middle-aged individual injected with five aluminum-adjuvanted vaccines within 4 weeks became work-disabled. Studying the possible dangers associated with aluminum adjuvants in vaccines is complicated by the fact that aluminum acts as an antigen as well as an adjuvant — the immune system generates antibodies against aluminum itself, so that later exposures to aluminum might produce an antibody cascade capable of damaging any of the tissues in which aluminum had accumulated. Christopher Exley has studied aluminum in relation to human health for some 35 years. This book summarizes his work and cites the pertinent primary publications in appropriate peer-reviewed journals. The book also offers quite convincing evidence of the determined efforts by a variety of vested interests to disparage and suppress Exley’s work and findings. In my opinion, the published work summarized in this book makes a plausible case based on empirical evidence that aluminum may be a contributing causative factor in neurological and nerve diseases. Further, Exley suggests fully detailed mechanisms and quite plausible for how that comes about. Beyond that, he points to a quite fundamental a priori reason why aluminum, among all the other elements and metals, might be so uniquely dangerous. It is the third most abundant element in the Earth’s crust, yet there are no known biological uses of aluminum. By contrast, several other metals and non-metals are essential components of some biological systems, for example, iron in hemoglobin in blood. Those two facts make it far from implausible that absorption of aluminum could be biologically harmful, by competing with or replacing other metals, or perhaps just because of its chemically oxidative properties. But if all that is so, how has the Earth’s biosphere flourished for billions of years without succumbing to the toxicity of the super-abundant aluminum? (shrink)

Patients with advanced dementia are less likely than those with other terminal illnesses to receive palliative care. Due to the nature and course of dementia, there may be a failure to recognize the terminal stage of the disease. A possible and under-investigated explanation for this healthcare disparity is the healthcare practitioner who plays a primary role in end-of-life decision-making. Two potential areas that might impact provider decision-making are cognitive biases and moral considerations. In this analysis, we demonstrate how the cognitive (...) biases and moral considerations of practitioners related to clinical decision-making are inherent in clinical practice and may impact on providers’ accuracy related to diagnostic and treatment related decision-making associated with patients with advanced dementia. Anchoring, default, availability, representativeness and framing biases are cognitive biases based on the "Two System Model" that relate to decision-making in end-of-life care. In patients with advanced dementia, those biases may result in a tendency to adhere to traditional mandatory care, involving an aggressive approach to care, which values saving lives at all costs, without taking into account the possible suffering and long-term consequences. Aspects such as moral sensitivity and moral courage play an important role in ethical decision-making related to advanced dementia. Investigations of clinical decision-making that include the cognitive biases and ethical considerations of practitioners might advance the comprehensive understanding of the clinical decision-making process related to care of patients with advanced dementia and promote the quality of care given to this population. (shrink)

In Gustavsson et al,1 we discussed the ethical issues that arise when identifying the relevant population for disease-modifying drugs targeting Alzheimer disease. More specifically, we focused on novel immunotherapies aimed at amyloid β and tau, two relevant biomarkers. The commentaries to our paper2 3 acknowledge our conclusion: screening for AD involve ethical costs that cannot be justified unless a drug with clinically relevant effect becomes available. Since Aduhelm is the only immunotherapy targeting AD currently approved by the Food and Drug (...) Administration, we use that as a …. (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)

ObjectiveCaring for patients with Alzheimer’s disease is a stressful situation and an overwhelming task for family caregivers. Therefore, these caregivers need to have their hardiness empowered to provide proper and appropriate care to these older adults. From the introduction of the concept of hardiness, few studies have been conducted to assess the hardiness of caregivers of patients with AD. Presumably, one reason for this knowledge gap is the lack of a proper scale to evaluate hardiness in this group. This study (...) was conducted to develop a reliable and valid Family Caregivers’ Hardiness Scale to measure this concept accurately among Iranian family caregivers sample.MethodsThis study is a cross-sectional study with a sequential-exploratory mixed-method approach. The concept of family caregivers’ hardiness was clarified using deductive content analysis, and item pools were generated. In the psychometric step, the samples were 435 family caregivers with a mean age of 50.26, and the data were gathered via an online form questionnaire. In this step, the items of the FCHS were evaluated using face and content validity. Then, the factor structure was determined and confirmed using exploratory factor analysis and confirmatory factor analysis followed by convergent and divergent validity, respectively. Finally, scale reliability, including stability, and internal consistency were evaluated.ResultsThe finding revealed that FCHS consists of five factors, namely, “Religious Coping”, “Self-Management”, “Empathic Communication”, “Family Affective Commitment”, and “Purposeful Interaction” that explained 58.72% of the total variance. The results of CFA showed a good model fit. Reliability showed acceptable internal consistency and stability.ConclusionBased on the results of the psychometric evaluation of the FCHS, turned out that the concept of hardiness in Iranian family caregivers is a multidimensional concept that is most focused on individual-cultural values, emotional family relationships, and social relationships. The designed scale also has acceptable validity and reliability features that can be used in future studies to measure this concept in family caregivers. (shrink)

BackgroundThis study aimed to elucidate the influence of dementia etiologies on the degree of caregiver burden and determine which factors predict a high caregiving burden.MethodsThis 18-month retrospective cohort study enrolled 630 patients and their caregivers from the Dementia Center of Changhua Christian Hospital. The care team performed face-to-face interviews every 6 months, for 18 months from when a diagnosis of dementia was made. The primary outcome was the change in Zarit Burden Interview scores. Generalized estimating equations were used for the (...) longitudinal data analysis.ResultsParticipants with Lewy body disease had a significantly higher caregiving burden compared with those with Alzheimer's disease after adjusting for patient and caregiver features. Caregivers of mixed-type dementia and frontotemporal dementia experienced a greater burden than caregivers of AD, at 6- and 18-month follow-up. Patients with more severe dementia, neuropsychiatric symptoms, being cared for by more than two caregivers, or utilizing social resources were associated with higher ZBI scores; the depressive mood of caregiver also predicted higher ZBI scores.ConclusionThis longitudinal study demonstrated that caregiver burden was influenced by the underlying dementia etiology of patients. The dementia care team should provide personalized education and transfer patients and caregivers to appropriate resources, especially for high-risk populations. (shrink)

An association between age-related hearing loss and Alzheimer's Disease has been widely reported. However, the nature of this relationship remains poorly understood. Quantification of hearing loss as it relates to AD is imperative for the creation of reliable, hearing-related biomarkers for earlier diagnosis and development of ARHL treatments that may slow the progression of AD. Previous studies that have measured the association between peripheral hearing function and AD have yielded mixed results. Most of these studies have been small and underpowered (...) to reveal an association. Therefore, in the current report, we sought to estimate the degree to which AD patients have impaired hearing by performing a meta-analysis to increase statistical power. We reviewed 248 published studies that quantified peripheral hearing function using pure-tone audiometry for subjects with AD. Six studies, with a combined total of 171 subjects with AD compared to 222 age-matched controls, met inclusion criteria. We found a statistically significant increase in hearing threshold as measured by pure tone audiometry for subjects with AD compared to controls. For a three-frequency pure tone average calculated for air conduction thresholds at 500–1,000–2,000 Hz, an increase of 2.3 decibel hearing level was found in subjects with AD compared to controls. Likewise, for a four-frequency pure tone average calculated at 500–1,000–2,000–4,000, an increase of 4.5 dB HL was measured, and this increase was significantly greater than that seen for 0.5–2 kHz PTA. There was no difference in the average age of the control and AD subjects. These data confirm the presence of poorer hearing ability in AD subjects, provided a quantitative estimate of the magnitude of hearing loss, and suggest that the magnitude of the effect is greater at higher sound frequencies.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42021288280. (shrink)

My mother died within the first few months of the pandemic. Her sudden and rapid decline from Alzheimer's disease is difficult to separate from the COVID-19 restrictions put in place by her nursing home just two months prior. We went from visiting her daily to not at all, then to a strictly enforced twenty-minute hospice visit to say goodbye. After her passing, and still amidst the pandemic, I could not write. The conventional methods and outputs of bioethics inquiry felt impossible.Making (...) art is the only thing that felt possible then. Perhaps that's the function of art, to make things feel more possible. I began by collecting materials from work—package inserts, empty prescription bottles and gelatin capsules—to... (shrink)

IntroductionDementia diseases, especially Alzheimer’s disease, 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 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)

“Readiness cohorts” are an innovation in clinical trial design to tackle the scarcity of time and people in drug studies. This has emerged in response to the challenges of recruiting the “right” research participants at the “right time” in the context of precision medicine. In this paper, we consider how the achievement of “readiness” aligns temporalities, biologies, and market processes of pharmaceutical innovation: how the promise of “willing bodies” in research emerges in relation to intertwined economic and biological time imperatives. (...) Drawing on long-term engagement with the field of Alzheimer’s disease prevention and interviews with researchers from academia and the pharmaceutical industry, we describe the discursive construction and practical arrangement of readiness. This paper contributes to understandings of temporal specificity, or “timing,” within prevention research and casts critical light on the way this specificity—the threshold for “trial readiness”—relates to an opaque and highly speculative drug development pipeline. Extending the study of biomedical potential, as that which holds promise but may not yet exist, we consider how absences operate in adaptive trials. By highlighting these absences, we outline an opportunity for socio-ethical research to intervene in the speculative gaps of drug development. (shrink)

The capacity to designate a surrogate is not simply another kind of medical decision-making capacity. A patient with DMC can express a preference, understand information relevant to that choice, appreciate the significance of that information for their clinical condition, and reason about their choice in light of their goals and values. In contrast, a patient can possess the CDS even if they cannot appreciate their condition or reason about the relative risks and benefits of their options. Patients who lack DMC (...) for many or most kinds of medical choices may nonetheless possess the CDS, particularly since the complex means-ends reasoning required by DMC is one of the first capacities to be lost in progressive cognitive diseases. That is, patients with significant cognitive decline or mental illness may still understand what a surrogate does, express a preference about a potential surrogate, and be able to provide some kind of justification for that selection. Moreover, there are many legitimate and relevant rationales for surrogate selection that are inconsistent with the reasoning criterion of DMC. Unfortunately, many patients are prevented from designating a surrogate if they are judged to lack DMC. When such patients possess the CDS, this practice is ethically wrong, legally dubious and imposes avoidable burdens on healthcare institutions. There are no data in this work. (shrink)

IntroductionThis study aimed to evaluate, in adults with mild cognitive impairment, the brain atrophy that may distinguish between three AT biomarker-based profiles, and to determine its clinical value.MethodsStructural MRI was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT profiles, namely, A−T−−: normal AD biomarkers; A+T−−: AD pathologic change; and A+T++: prodromal AD. Sensitivity and specificity of these changes were also estimated.ResultsAn initial atrophy in medial temporal lobe areas was found in the A+T−− and (...) A+T++ groups, spreading toward the parietal and frontal regions in A+T++ patients. These structural changes allowed distinguishing AT profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status.ConclusionsMRI is useful in the determination of the specific brain structural changes of AT profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkers. (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)

The semantic fluency task is a widely used clinical tool in the diagnostic process of Alzheimer's disease. The task requires efficient mapping of the semantic space to produce as many items as possible within a semantic category. We examined whether healthy volunteers and patients with early Alzheimer's disease take advantage of and travel in the semantic space differently. With focus on the animal fluency task, we sought to emulate the detailed structure of the multidimensional semantic space by utilizing word2vec-method from (...) the natural language processing domain. To render the resulting multidimensional semantic space visually comprehensible, we applied a dimensionality reduction algorithm, which enabled a straightforward division of the semantic space into sub-categories. Moving in semantic space was quantified with the number of items created, sub-categories visited, and switches and returns to these sub-categories. Multinomial logistic regression models were used to predict the diagnostic group with these independent variables. We found that returning to a sub-category provided additional information, besides the number of words produced in the task, to differentiate patients with Alzheimer's dementia from both amnestic Mild Cognitive Impairment patients and healthy controls. The results suggest that the frequency of returning to a sub-category may serve as an additional aid for clinicians in diagnosing early Alzheimer's disease. Moreover, our results imply that the combination of word2vec and subsequent t-SNE-visualization may offer a valuable tool for examining the semantic space and its sub-categories. (shrink)

Dementia has rapidly become a major global health crisis. As the aging population continues to increase, the burden increases commensurately on both individual and societal levels. The behavioral and psychological symptoms of dementia are a prominent clinical feature of Alzheimer’s disease and related dementias. BPSD represent a myriad of manifestations that can create significant challenges for persons living with dementia and their care providers. As such, BPSD can result in detriments to social interaction with others, resulting in harm to the (...) psychosocial health of the person with dementia. While brain deterioration can contribute to BPSD as the disease progresses, it may be confounded by language and communication difficulties associated with ADRD. Indeed, when a person with dementia cannot effectively communicate their needs, including basic needs such as hunger or toileting, nor symptoms of pain or discomfort, it may manifest as BPSD. In this way, a person with dementia may be attempting to communicate with what little resources are available to them in the form of emotional expression. Failing to recognize unmet needs compromises care and can reduce quality of life. Moreover, failing to fulfill said needs can also deteriorate communication and social bonds with loved ones and caregivers. The aim of this review is to bring the differential of unmet needs to the forefront of BPSD interpretation for both formal and informal caregivers. The overarching goal is to provide evidence to reframe the approach with which caregivers view the manifestations of BPSD to ensure quality of care for persons with dementia. Understanding that BPSD may, in fact, be attempts to communicate unmet needs in persons with dementia may facilitate clinical care decisions, promote quality of life, reduce stigma, and foster positive communications. (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)

Dementia, a prevalent disorder of the brain, has negative effects on individuals and society. This paper concerns using Spontaneous Speech Challenge of Interspeech 2020 to classify Alzheimer's dementia. We used VGGish, a deep, pretrained, Tensorflow model as an audio feature extractor, and Scikit-learn classifiers to detect signs of dementia in speech. Three classifiers were 59.1% accurate, which was 3% above the best-performing baseline models trained on the acoustic features used in the challenge. We also proposed DemCNN, a new PyTorch raw (...) waveform-based convolutional neural network model that was 63.6% accurate, 7% more accurate then the best-performing baseline linear discriminant analysis model. We discovered that audio transfer learning with a pretrained VGGish feature extractor performs better than the baseline approach using automatically extracted acoustic features. Our DepCNN exhibits good generalization capabilities. Both methods presented in this paper offer progress toward new, innovative, and more effective computer-based screening of dementia through spontaneous speech. (shrink)

Photo by Jr Korpa on Unsplash INTRODUCTION The moral authority of advance directives is contingent on one of two metaphysical concepts of personhood common in the West. The first tradition originated in the ideas of David Hume and Jeremy Bentham. Hume asserts that the idea of personhood is socially fabricated and that we are nothing more than “bundles” of sensations.”[1] Bentham is famous for developing a utilitarian ethical approach predicated on Hume’s reductionist theory, a person who asserts the morally right (...) act is the one which maximizes pleasure and minimizes pain.[2] The second metaphysical tradition, which grants moral authority to ADs, stems from the work of John Locke[3] and John Stuart Mill.[4] Locke conceived of persons as beings that are “rational, concerned, continuing, and self-conscious,”[5] and Mill understood that persons act in a manner that maximizes their holistic goods, not only the sum of their experience of pleasure or pain.[6] In the 1980s, this metaphysical divergence on personhood materialized in a debate between Ronald Dworkin, whose reasoning parallels that of Locke and Mill, and Rebecca Dresser, who employs an approach that comports with that of Hume and Bentham. The debate focused on the real case of an incompetent patient named Margo who developed early-onset Alzheimer’s and, despite her condition, “or maybe somehow because of it,”[7] led a remarkably cheerful life. She no longer identified with the provision in her AD to forgo any life-sustaining medical treatment after she could no longer recognize her loved ones. When she contracted pneumonia, an ethical dilemma emerged as her prior preferences recorded when she was competent conflicted with her contemporary preferences regarding her end-of-life care. Dworkin argues that Margo’s precedent autonomy, i.e., her past ability to govern her future self through a directive and the corresponding obligation of her current self to follow the directive, has moral authority over her current treatment, but Dresser objects, asserting that because Margo is now a “new person”[8] the AD is no longer relevant.[9] In this essay, I argue that precedent autonomy morally authorizes ADs when dementia renders patients medically incompetent because it respects their dignity as persons, not merely pleasure-seeking creatures. The Case: Margo, ‘the Happy Alzheimer’s Patient’ In Margo’s Logo, Dr. Andrew Firlik describes the life of an Alzheimer’s patient he visited frequently while interning in gerontology.[10] Because she developed the disease at a relatively young age, Margo had virtually no physiological problems and lived a “carefree” life consisting of flipping through mystery novels and painting the same image every day during art class.[11] Firlik describes her life almost romantically, commenting that “there is something graceful about the degeneration her mind is undergoing, leaving her carefree, always cheerful.”[12] He does not mention Margo’s early stages of dementia which were perhaps characterized by confusion, anxiety, and existential fear, as is often the case with diseases that erode mental capacity.[13] Still, arguably in her current state Margo is happy and therefore should be given non-invasive treatments, like oral antibiotics, to extend her life if she contracts pneumonia. The argument to adhere to her previous wishes against such life-prolonging treatments may seem cruel. However, Dworkin argues that to ignore her AD would compromise her autonomy and dignity and constitute the greater cruelty. Dworkin contra Dresser Dworkin uses the framework of experiential and critical interests to defend the moral authority of precedent autonomy. Experiential interests roughly parallel Bentham’s conception of pursuing pleasure and avoiding pain, whereas critical interests are focused on the actions that lend “genuine meaning and coherence to our lives.”[14] Critical interests comport with Locke’s valuing rationality and with Mills’ appreciation of the big picture taken holistically. Dworkin’s conception of personhood emphasizes our pursuit of critical interests over and above our pursuit of experiential interests, indicating that there is a moral superiority to critical interests. For example, parents willingly give up sleep to sustain the critical interest of raising children and athletes endure pain to improve their odds of victory. The pursuit of critical interests lends genuine meaning to our lives. In contrast, a life characterized by the constant pursuit of experiential interests is often meaningless. Dworkin’s dichotomy of interests grounds his view of precedent autonomy because the critical interests encoded in ADs represent the “whole person”[15] - all the relationships, values, and narrative richness of personhood before the onset of late-stage dementia. If we ignore the AD, we disregard the autonomy of Margo’s “whole person” in favor of her immediate preferences. Dworkin’s view of autonomy argues that we should honor Margo’s precedent autonomy even if we believe it conflicts with her best interest because persons have the right to act “out of a distinctive sense of their own character”[16] in writing the narrative of their life. Ignoring her AD would be "an unacceptable form of moral paternalism”[17] because it effectively authors a conclusion to the story of Margo’s life that she explicitly wished to avoid, ignoring the strongest living articulation of her autonomy. Dworkin further argues the moral authority of Margo’s precedent autonomy through the principle of beneficence, the ethical obligation to promote the patient’s welfare.[18] It would be cruel to subject Margo to a chapter of life that she did not want to lead, a life that conflicts with her critical interests, even if she no longer remembers those interests. Thus, to genuinely act in the best interest of the patient, the doctor must adhere to her competent conception of what is best for her “whole person”, not merely her current experiential interests. Dresser argues that when patients with incurable dementia lead enjoyable lives, we should ignore their previous wishes. She raises an epistemic and a moral objection to Dworkin’s argument in favor of precedent autonomy. Her epistemic argument points out that when she wrote the AD, Margo did not know what quality her life would have with dementia, therefore carrying out a preference based on such limited information would not respect autonomy.[19] This argument fails to recognize that individuals make decisions all the time without knowledge of the outcome, so to disregard Margo’s AD because she did not know whether her experiential interests would be fulfilled is unjustifiably paternalistic. Furthermore, Dresser implicitly asserts that if Margo were to know the quality of her life with dementia in advance, she would not have authored the same AD. However, this removes the possibility of Margo autonomously prioritizing her critical interests regardless of the experiential outcomes. Margo likely did know that people can lead enjoyable lives with dementia yet she still chose to word the AD to not prolong life once her critical interests could not be satisfied. Dresser’s moral argument against precedent autonomy contends that because Margo can no longer recognize her previous preferences, she is a metaphysically distinct person, and that the AD is therefore not applicable. Dresser claims that the “drastic psychological alteration that has occurred” to Margo has “produce[d] a new person.”[20] This metaphysical assertion carries significant moral weight. If we consider Margo the Alzheimer’s patient to be a distinct individual from the woman who wrote the AD, then executing an AD is akin to sentencing an innocent person to death. However, Dresser’s claim is predicated on the flawed assertion that dramatic psychological changes over time produce an entirely new individual. Children, for example, undergo substantial psychological changes from infancy to adolescence, yet we regard them as continuous individuals.[21]Ultimately, we must consider persons rather than pleasure-seeking subjects to be the locus of autonomous decision making, therefore moral authority is granted to precedent autonomy in cases like Margo’s. Locke’s emphasis on rationality also supports following the AD. Personal identity, in Locke’s view, is meaningfully linked to persistence over time and the ability to rationally self-reflect – abilities which Margo presently lacks. He writes in An Essay Concerning Human Understanding, “a thinking intelligent Being, … has reason and reflection, and can consider itself as itself, the same thinking thing in different times and places.”[22] From this diachronic view of identity, Locke characterizes persons as agents. Margo, in contrast, no longer has these abilities and has lost her sense of personhood and agency. It is only through our ability to self-reflect and project our values onto the current situation that we can be said to be persons. Dresser makes an erroneous metaphysical assertion in saying that the late-stage Alzheimer’s patient is a new person due to “substantial memory loss and other psychological changes.” It is exactly these changes which rob late-stage Alzheimer’s patients of their personhood. Utilitarianism and Advance Directives The two founding figures of Utilitarian ethics, Jeremy Bentham and John Stuart Mill, agreed that the ‘right’ action is the one which maximizes utility in a given situation, but they disagreed on what sorts of consequences constitute utility. Bentham focused merely on the quantity of pleasures, asserting that the right action would result in the most favorable balance between pleasure and pain.[23] Pursuant to this hedonistic calculus which disregards the quality of pleasure, the right action is to ignore Margo’s AD by providing the life-saving treatment. This would be the most ethical choice according to Bentham because it produces a greater sum of pleasure than her death, regardless of her prior critical interests. Hume’s view of experiences also overvalues pleasure as opposed to cognition. When applied to Margo, who essentially experiences a bundle of sensations without the ability to rationally appreciate them, Hume’s viewpoint would negate the AD vis a vis Bentham’s calculus. Yet, Margo’s AD concerned ranking the characteristics of life that would justify prolonging it which included experiences like remembering one’s narrative and having meaningful relationships with friends and loved ones. These values transcend the immediate sense data that Bentham factors into the utilitarian sum. The philosophies of Hume and Bentham not only impede dignity, and negate autonomy, they impose a limited, outside view on what persons value. Mill criticized Bentham’s approach to utilitarianism because it was indiscriminate in its valuation of different pleasures, implicitly leading to the conclusion that distinctly human pleasures “of the intellect, of the feelings and imagination and of the moral sentiments” are no more valuable than animal pleasures “of mere sensation.”[24] In Mill’s view this degrades the moral status of humans. If our pleasures are no different, then Bentham suggests that our moral status is equivalent to that of animals, which is clearly problematic. In an example of the flaws of utilitarian applications, in a purely quantitative utilitarian calculus, the life of an immortal oyster is more desirable after a certain amount of time than the life of the jovial and accomplished composer, Joseph Hayden.[25] If given the choice, I suspect an overwhelming majority of people would prefer to live as a human being that feels pain over an animal that feels only simple pleasures. Even though human life is often characterized by stress, uncertainty, and vulnerability, the profound heights of the human condition justify life according to Mill’s philosophy. Mill’s utilitarianism focused on the quality rather than the quantity of pleasures, and thus he would argue that following Margo’s AD will result in the outcome with the greatest utility because she is no longer capable of pursuing higher pleasures.[26] Her current existence is characterized only by experiential pleasures, which according to Mill, is not a life worth living.[27] CONCLUSION A consequence of the reductionist view of personhood endorsed by Hume, Bentham, and Dresser is an erroneous moral equivalence between animals and humans and a disregard for human dignity. Dworkin’s framework of critical interests and Mill’s version of Utilitarian ethics support the moral authority of precedent autonomy by defending the narrative quality of life, the important pursuit of higher pleasures, and a dignified characterization of humanity. [1] Hume, D. & P. H. Nidditch.. A Treatise of Human Nature. Oxford: Clarendon Press. Hume posits a distinct ontology of self: “each of us is nothing but a bundle or collection of different perceptions that follow each other enormously quickly and are in a perpetual flux and movement” [2] Bentham, J.. An Introduction to the Principles of Morals and Legislation. Oxford: Clarendon Press. [3] Locke, J.. An essay concerning human understanding, 1690. [4] Mill, J. S.. Utilitarianism, Roger Crisp, Oxford: Oxford University Press. [5] Rich, B. A.. Prospective autonomy and critical interests: A narrative defense of the moral authority of advance directives. Cambridge Quarterly of Healthcare Ethics, 6, 138-147. Chicago [6] Mill, J. S.. Utilitarianism, Roger Crisp, Oxford: Oxford University Press. [7] Firlik, A. D.. Margo's logo. JAMA, 265, 201-201. [8] Dresser, R.. Dworkin on dementia: elegant theory, questionable policy. Hastings Center Report, 25, 32-38. [9] Dresser, R.. Dworkin on dementia: elegant theory, questionable policy. Hastings Center Report, 25, 32-38. [10] Firlik, A. D.. Margo's logo. JAMA, 265, 201-201. [11]Firlik, A. D.. Margo's logo. JAMA, 265, 201-201. [12]Firlik, A. D.. Margo's logo. JAMA, 265, 201-201. [13] Menzel, P. T., & Steinbock, B.. Advance Directives, Dementia, and Physician‐Assisted Death. The Journal of Law, Medicine & Ethics, 41, 484-500. [14] Dresser, R.. Dworkin on dementia: elegant theory, questionable policy. Hastings Center Report, 25, 32-38. [15] Dworkin, R.. Life’s dominion. An argument about abortion, euthanasia and individual freedom. New York: Books V, 69-101. [16] Dworkin, R.. Life’s dominion. An argument about abortion, euthanasia and individual freedom. New York: Books V, 69-101. [17] Dworkin, R.. Life’s dominion. An argument about abortion, euthanasia and individual freedom. New York: Books V, 69-101. [18] Dworkin, R.. Life’s dominion. An argument about abortion, euthanasia and individual freedom. New York: Books V, 69-101. [19] Dresser, R.. Dworkin on dementia: elegant theory, questionable policy. Hastings Center Report, 25, 32-38. [20] Dresser, R.. Dworkin on dementia: elegant theory, questionable policy. Hastings Center Report, 25, 32-38. [21] Rich, B. A.. Prospective autonomy and critical interests: A narrative defense of the moral authority of advance directives. Cambridge Quarterly of Healthcare Ethics, 6, 138-147. Chicago [22] Locke, J.. An essay concerning human understanding, 1690. [23] Bentham, J.. An Introduction to the Principles of Morals and Legislation. Oxford: Clarendon Press. [24] Mill, J. S.. Utilitarianism, Roger Crisp, Oxford: Oxford University Press. [26] Mill, J. S.. Utilitarianism, Roger Crisp, Oxford: Oxford University Press. [27] Mill, J. S.. Utilitarianism, Roger Crisp, Oxford: Oxford University Press. (shrink)

The article by Gustavsson et al 1 addresses the important question how to handle new medications with focus on drug candidates that reduce Aβ or tau in the brain, for individuals with Alzheimer’s disease, where the need for a disease-modifying drug is enormous. There are several ethical issues to deal with. The challenges and ethical implications associated with whom should be eligible for treatment are thoroughly discussed in the article. Should treatment only be available to those with mild symptoms and/or (...) to those with no symptoms but with risk for AD? Where do we draw the line between who will be eligible for treatment and who will not? Who will be responsible for the prioritisation? There are many ethical problems with both population screening and screening of those with high risk well discussed in the article. Indeed, the first immunotherapy drug Aducanumab was approved by the US Food and Drug Administration in …. (shrink)

The stressful nature of caring for an older adult with a chronic disease, such as Alzheimer’s disease, can create barriers between the caregiver-care recipient, as they try to navigate their continuously changing social relationship. Interpersonal synchrony, is an innovative approach that could help to sustain caregiving relationship dynamics by promoting feelings of connection and empathy through shared behavior and experiences. This review investigates the current literature on interpersonal synchrony from an interdisciplinary perspective by examining interpersonal synchrony through psychological, neural, and (...) hormonal measures across the adult lifespan. We then present a case for examining the degree to which interpersonal synchrony can be used to facilitate affiliation and well-being in the caregiver-care recipient relationship. We find that there is significant evidence in healthy adult populations that interpersonal synchrony can support affiliative feelings, prosocial behavior, and well-being. Characterizing the psychological, neural, and hormonal mechanisms of interpersonal synchrony is a first step towards laying the groundwork for the development of tools to support relational closeness and empathy in the caregiving context. Finally, we explore the strengths and limitations of using interpersonal synchrony to support relational well-being, and discuss possible avenues for future research. (shrink)

Bioethics, Volume 36, Issue 1, Page 25-41, January 2022.

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)

In this article, I consider my relationship with my father who developed Alzheimer's disease and criticize dominant models of social interactions and relationships. I argue that the point of a relationship is not what we exchange or achieve within it. The point is not even that we depend on others for our vital needs. The point is simply that a relationship is valuable in and of itself.

Intensive research is carried out to develop a disease-modifying drug for Alzheimer’s disease. The development of drug candidates that reduce Aß or tau in the brain seems particularly promising. However, these drugs target people at risk for AD, who must be identified before they have any, or only moderate, symptoms associated with the disease. There are different strategies that may be used to identify these individuals. Each of these strategies raises different ethical challenges. In this paper, we analyse these challenges (...) in relation to the risk stratification for AD necessary for using these drugs. We conclude that the new drugs must generate large health benefits for people at risk of developing AD to justify the ethical costs associated with current risk stratification methods, benefits much larger than current drug candidates have. This conclusion raises a new set of ethical questions that should be further discussed. No data are available. (shrink)

Alzheimer's Disease is a form of dementia that affects the memory, cognition, and motor skills of patients. Extensive research has been done to develop accessible, cost-effective, and non-invasive techniques for the automatic detection of AD. Previous research has shown that speech can be used to distinguish between healthy patients and afflicted patients. In this paper, the ADReSS dataset, a dataset balanced by gender and age, was used to automatically classify AD from spontaneous speech. The performance of five classifiers, as well (...) as a convolutional neural network and long short-term memory network, was compared when trained on audio features and text features. The same audio and text features were used to train five regression models to predict the Mini-Mental State Examination score for each patient, a score that has a maximum value of 30. The top-performing classification models were the support vector machine and random forest classifiers trained on BERT embeddings, which both achieved an accuracy of 85.4% on the test set. The best-performing regression model was the gradient boosting regression model trained on BERT embeddings and CLAN features, which had a root mean squared error of 4.56 on the test set. The performance on both tasks illustrates the feasibility of using speech to classify AD and predict neuropsychological scores. (shrink)

Background: The field of voice and speech analysis has become increasingly popular over the last 10 years, and articles on its use in detecting neurodegenerative diseases have proliferated. Many studies have identified characteristic speech features that can be used to draw an accurate distinction between healthy aging among older people and those with mild cognitive impairment and Alzheimer's disease. Speech analysis has been singled out as a cost-effective and reliable method for detecting the presence of both conditions. In this research, (...) a systematic review was conducted to determine these features and their diagnostic accuracy.Methods: Peer-reviewed literature was located across multiple databases, involving studies that apply new procedures of automatic speech analysis to collect behavioral evidence of linguistic impairments along with their diagnostic accuracy on Alzheimer's disease and mild cognitive impairment. The risk of bias was assessed by using JBI and QUADAS-2 checklists.Results: Thirty-five papers met the inclusion criteria; of these, 11 were descriptive studies that either identified voice features or explored their cognitive correlates, and the rest were diagnostic studies. Overall, the studies were of good quality and presented solid evidence of the usefulness of this technique. The distinctive acoustic and rhythmic features found are gathered. Most studies record a diagnostic accuracy over 88% for Alzheimer's and 80% for mild cognitive impairment.Conclusion: Automatic speech analysis is a promising tool for diagnosing mild cognitive impairment and Alzheimer's disease. The reported features seem to be indicators of the cognitive changes in older people. The specific features and the cognitive changes involved could be the subject of further research. (shrink)

Lynch et al.’ s work “Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?” is an essential c...

Cognitive symptoms after COVID-19 have been increasingly recognized several months after the acute infection and have been designated as “brain fog.” We report a patient with cognitive symptoms that started immediately after COVID-19, in which cerebrospinal fluid biomarkers were highly suggestive of Alzheimer’s disease. Our case highlights the need to examine patients with cognitive symptoms following COVID-19 comprehensively. A detailed assessment combining clinical, cognitive, and biomarker studies may help disentangle the underlying mechanisms associated with cognitive dysfunction in each case. The (...) investigation of neurodegenerative processes in an early stage, especially in older patients, is probably warranted. (shrink)

Given the lack of effective curative treatment options and in light of a significant reconceptualization of Alzheimer’s disease, the focus of dementia research has shifted towards prevention, risk prediction, and detection in very early disease stages. In the context of these shifts, the edited volume Preventing Dementia?: Critical Perspectives on a New Paradigm of Preparing for Old Age collects critical and insightful positions on the new paradigm of dementia prevention from an interdisciplinary and international perspective. The editors introduce the overarching (...) topic of prevention by reflecting on the optimistic framing of modifiable risk factors and their novelty in the dementia context. Leibing and Schicktanz call for a cautious reception of the findings in the Lancet report and draw attention to epistemic, ethical, and socio-political issues of what the editors term the contested “new dementia” and to the effect that this might have on rethinking individual and societal perceptions of aging. The contributions of the anthology depict the social and cultural dimensions of dementia discourses and consider the ethical implications of the changing conceptions of Alzheimer’s disease as well as the shift towards early disease stages and prevention. With this, the anthology initiates a debate about the often implicit unresolved social, ethical, and political implications and preconditions of the medical understanding and handling of cognitive disorders. (shrink)

Despite severe amnesia, some studies showed that Alzheimer Disease patients with moderate to severe dementia keep a consistent, but impoverished representation of themselves, showing preservation of the sense of identity even at severe stages of the illness. Some studies suggest that listening to music can facilitate the reminiscence of autobiographical memories and that stimulating autobiographical memory would be relevant to support the self of these patients. Consequently, we hypothesized that repeated participation to reminiscence workshops, using excerpts of familiar songs as (...) prompts would participate to the enrichment of autobiographical memories, self-representation and sense of identity. We included a group of 20 AD patients with severe dementia residing in nursing homes. Their performances were compared to a control group of 20 matched healthy residents living in the same institutions. The experiment was conducted in three phases over a 2-week period. On phase 1, an individual assessment of sense of identity was proposed to each participant. On phase 2, participants joined musical reminiscence workshops. During the third phase, individual evaluation of autobiographical memory and a second assessment of sense of identity were proposed. Our results showed that, despite their massive amnesia syndrome, autobiographical memories of AD reached at the end of the 2 weeks the number and quality of those of matched controls. Moreover, we confirmed a continuity of self-representation in AD patients with a stable profile of the answers between the first and second individual assessments of sense of identity. However, the increase in number and episodic quality of autobiographical memories was not accompanied by an enrichment of the sense of identity. In a complementary study, new patients participated in the same paradigm, but using movie extracts as prompts, and showed very similar effects. We discuss all of these results with regard to the literature showing the significant impact of repetition on the reactivation of memory traces even in very amnestic AD patients at severe stages of the disease. (shrink)

The Alzheimer field is in desperate need for an effective treatment. After decades of research, the available drugs treat only symptoms, and even their effectiveness is disputed. Because brain changes precede the clinical symptoms by years to decades, disease-modifying treatments should probably be started early, when the first symptoms occur—or even before. But how to determine who to treat? In this issue, Erik Gustavsson c.s. approach this question by addressing the benefits, harms and ethical issues encountered when using different modes (...) of screening for ‘preclinical’ or early symptomatic Alzheimer disease.1 Their overall conclusion is clear—screening for high risk of developing AD dementia to select those who are eligible for treatment is ethically problematic, unless extremely effective treatment becomes available. An additional major challenge is that diagnostic test accuracy is generally poor, with a particularly high risk of false-positive results, that is, biological evidence of Alzheimer pathology in persons who will never develop dementia. The risk of overmedicalisation is serious, and the potential harms of screening for AD should not be ignored, as Le Couteur c.s. previously argued.2 In short, there is no evidence base for any form of screening for AD whether in a preclinical stage (an …. (shrink)

Background: In Quebec, medical aid in dying is legal under certain conditions. Access is currently restricted to patients who are able to consent at the time of the act, which excludes most people with dementia at an advanced stage. However, recent legislative and political developments have opened the door to an extension of the legislation that could give them access to MAiD. Our study aimed to explore the attitudes of people with early-stage dementia toward MAiD should it become accessible to (...) them. Methods: We used a qualitative descriptive design consisting of eight face-to-face semi-structured interviews with persons living with early-stage Alzheimer’s disease, followed by a thematic analysis of the contents of the interviews. Results and Interpretations: Analysis revealed three main themes: 1) favourable to MAiD; 2) avoiding advanced dementia; and 3) disposition to request MAiD. Most participants anticipated dementia to be a painful experience. The main reasons for supporting MAiD were to avoid cognitive loss, dependence on others for their basic needs, and suffering for both themselves and their loved ones. Every participant said that they would ask for MAiD at some point should it become available to incompetent patients and most wished that it would be legal to access it through a request written before losing capacity. Conclusion: The reasons for which persons with Alzheimer’s disease want MAiD are related to the particular trajectory of the disease. Any policy to extend MAiD to incompetent patients should take their perspective into account. (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 prevalence of negative representations of Alzheimer’s disease reinforces the stigma and negative attitudes toward this dementia. To mitigate these negative views, campaigns have been launched by several organizations. This study aims to explore the effect of framing in AD campaigns on attitude change. For this purpose, several posters were designed with framed messages defining dementia and 189 participants were shown the posters. In order to analyze the effect of the different frames, a repeated-measures design was used, in which attitudes (...) toward dementia were measured three times. The impact of the campaign and the emotions it produced were recorded as well as the effects of the participants’ experience with AD and the importance they attached to it. Posters with unity-framed messages produced a positive and lasting change in attitudes toward dementia and higher levels of happiness, while dualism-framed messages had a greater impact and produced feelings of sadness, anger, and fear but did not change the audience’s attitude. Although more research is needed on persuasion in campaigns, the findings can serve to guide the design of AD campaigns. (shrink)

BackgroundSubjective cognitive decline, non-amnestic mild cognitive impairment, and amnestic mild cognitive impairment are regarded to be at high risk of converting to Alzheimer’s disease. Amplitude of low-frequency fluctuations can reflect functional deterioration while diffusion tensor imaging is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 and slow-5 bands and white matter (...) fiber integrity among normal controls, SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus and superior frontal gyrus within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus in aMCI patients and within the superior longitudinal fasciculus in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression. (shrink)

With the development of artificial intelligence technologies, it is possible to use computer to read digital medical images. Because Alzheimer’s disease has the characteristics of high incidence and high disability, it has attracted the attention of many scholars, and its diagnosis and treatment have gradually become a hot topic. In this paper, a multimodal diagnosis method for AD based on three-dimensional shufflenet and principal component analysis network is proposed. First, the data on structural magnetic resonance imaging and functional magnetic resonance (...) imaging are preprocessed to remove the influence resulting from the differences in image size and shape of different individuals, head movement, noise, and so on. Then, the original two-dimensional ShuffleNet is developed three-dimensional, which is more suitable for 3D sMRI data to extract the features. In addition, the PCANet network is applied to the brain function connection analysis, and the features on fMRI data are obtained. Next, kernel canonical correlation analysis is used to fuse the features coming from sMRI and fMRI, respectively. Finally, a good classification effect is obtained through the support vector machines method classifier, which proves the feasibility and effectiveness of the proposed method. (shrink)

Alzheimer’s disease is an insidious onset neurodegenerative syndrome without effective treatment or cure. It is rapidly becoming a global health crisis that is overwhelming healthcare, society, and individuals. The clinical nature of neurocognitive decline creates significant challenges in bidirectional communication between caregivers and persons with Alzheimer’s disease that can negatively impact quality-of-life. This paper sought to understand how and to what extent would awareness training about the levels of consciousness in AD influence the quality-of-life interactions in the caregiver-patient dyad. A (...) literature review of multiple databases was conducted utilizing a transdisciplinary approach. The sum of findings indicates a positive relationship between enhanced caregiver awareness and training, positive interactions, and improved QOL measures among patients and caregivers. A multidirectional relationship was found among healthcare policies, training and education resources, caregivers, and persons with AD. Specifically, the current lack of policy and inadequate training and educational resources has various detrimental effects on patients and caregivers, while improvements in training and education of caregivers yields positive outcomes in communication and QOL. Furthermore, evidence of preserved consciousness in persons with AD was demonstrated from multiple disciplines, including neurobiological, psychological, and biopsychosocial models. The literature further revealed several methods to access the preserved consciousness in persons with AD and related dementias, including sensory, emotional, and cognitive stimulations. The evidence from the literature suggests a reframed approach to our understanding and treatment of persons with AD is not only warranted, but crucial to address the needs of those affected by AD. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD underwent surgery (...) for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

Background Biomarker research is gaining increasing attention focusing on the preclinical stages of the disease. Such interest requires special attention for communication and disclosure in clinical contexts. Many countries give dementia a high health policy priority by developing national strategies and by improving guidelines addressing disclosure of a diagnosis; however, risk communication is often neglected. Main text This paper aims to identify the challenges of disclosure in the context of dementia prediction and to find out whether existing clinical guidelines sufficiently (...) address the issues of disclosing a dementia diagnosis and of disclosing the risk of developing dementia in asymptomatic and MCI stage. We will examine clinical guidelines and recommendations of three countries regarding predictive testing and diagnostic disclosure in dementia and Mild Cognitive Impairment to show their potentials and limits. This will provide a background to address ethical implications of predictive information and to identify ways how to proceed further. We will start by examining the guidelines and recommendations by focusing on what there is already and what is missing regarding the challenges of disclosing dementia prediction and MCI. Then, we will highlight the novel ethical issues generated by the shift to identify preclinical stages of the disease by biomarkers. We will argue for the need to develop guidelines for disclosing a risk status, which requires different considerations then disclosing a diagnosis of dementia. Finally, we will make some suggestions on how to address the gap and challenges raised by referring to German Stakeholder Conference, which presents us a good starting point to the applicability of involving stakeholders. Conclusions This paper underlines the need to develop empirically based guidelines that address the ethical and social strategies for risk communication of dementia prediction by genetic as well as non-genetic biomarkers. According to our analysis, the guidelines do not address the new developments sufficiently. International efforts should aim for specific guidelines on counseling, communicating risk and disclosing results. We argue that guidelines on disclosure should be developed by involving various stakeholders and should be informed by socio-empirical studies involving laypersons’ needs and wishes regarding risk communication. (shrink)