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)

Given the past two decades of over 40 failed trials of amyloid-lowering therapies in Alzheimer’s Disease (AD), many of which succeeded in lowering amyloid as designed, we present an ethical argument for emptying the drug pipeline of tests of amyloid-lowering agents so as to end the historical dominance of the amyloid-reducing therapeutic approach in AD.

While Alzheimer's might be associated with a difficulty to express oneself, Ana Paula Barbosa-Fohrmann addresses this topic by examining experiences with Alzheimer's based on narratives. In this original contribution, she studies the nexus of life stories, subjectivity, fragmentation, and fiction. The philosophical basis of this research is phenomenology from the end of the 19th century to the middle of the 20th century, specifically that of Husserl and above all that of Merleau-Ponty. This work also draws on Proust's and Camus' literature (...) as well as Beckett's dramaturgy. (shrink)

Philosophers have debated whether the advance directives of Alzheimer’s patients should be enforced, even if patients seem content in their demented state. The debate raises deep questions about the nature of human autonomy and personal identity. But it tends to proceed on the assumption that the advance directive’s terms are clear, whereas in practice they are often vague or ambiguous, requiring the patient’s healthcare proxy to make difficult judgment calls. This practical wrinkle raises its own, distinct but related, philosophical question: (...) what criteria may the proxy bring to bear when making such interpretive judgments on which the patient’s life may depend? After defending a general policy of enforcing advance directives on normative (rather than metaphysical) grounds, I argue that when advance directives are vague, a patient’s proxy may permissibly make her own fresh evaluation of the patient’s life as a whole and, in so doing, consider how the patient’s character as a demented person contributes or fails to contribute to that life. (shrink)

Peterson et al. (2023) identify two potential uses of psychedelic drugs in Alzheimer’s disease and related disorders (AD/ADRD). The first is to treat depression and anxiety that commonly occur afte...

It is a tale of two Pfizers. In 2018 they abandoned research into the leading cause of dementia, Alzheimer’s Disease (AD) (Hawkes 2018). In 2021, they developed the first vaccine for Covid-19 to re...

In “Journeying to Ixtlan,” Peterson and colleagues (2023) evaluate some of the potential ethical implications of treating Alzheimer’s disease (AD) with psychedelic medicines. In this commentary, I...

BackgroundThe UN Convention on the Rights of Persons with Disabilities, and the reformed guardianship law in Germany, require that persons with a disability, including people with dementia in Alzheimer’s disease (PwAD), are supported in making self-determined decisions. This support is achieved through communication. While content-related communication is a deficit of PwAD, relational aspects of communication are a resource. Research in supported decision-making (SDM) has investigated the effectiveness of different content-related support strategies for PwAD but has only succeeded in improving understanding, (...) which, although one criterion of capacity to consent, is not sufficient to ensure overall capacity to consent. The aim of the ‘spatial intervention study’ of the DECIDE project is to examine an innovative resource-oriented SDM approach that focuses on relational aspects. We hypothesise that talking to PwAD in their familiar home setting (as opposed to a clinical setting) will reduce the complexity of the decision-making process and enhance overall capacity to consent. MethodsPeople with a suspected or confirmed diagnosis of dementia in Alzheimer’s disease will be recruited from two memory clinics (N = 80). We will use a randomised crossover design to investigate the intervention effect of the decision-making place on capacity to consent. Besides reasoning capacity, which is part of overall capacity to consent and will be the primary outcome, various secondary outcomes (e.g., other aspects of capacity to consent, subjective task complexity, decisional conflict) and suspected moderating or mediating variables (e.g., meaning of home, demographic characteristics) will be assessed.DiscussionThe results of the study will be used to develop a new SDM strategy that is based on relational resources for PwAD. If a change in location achieves the anticipated improvement in capacity to consent, future research should focus on implementing this SDM strategy in a cost-effective manner in clinical practice.Trial registration: DRKS00030799. (shrink)

The dominant discourse on dementia promotes a view that as individuals progress with the disease, they experience a neurological decline causing a loss of self. This notion, grounded in a Cartesian representation of selfhood, associates a loss of self as directly related to cognition. This paper presents an alternative anthropological framework, embodied selfhood, that challenges this representation. It then examines a potential tool, graphic medicine, to translate this theory into caregiving practice. Through analyzing three graphic novels—Wrinkles, Tangles, and Aliceheimer’s—this paper (...) demonstrates how tension exists between different conceptions of selfhood and associated implications for caregivers and patients alike. (shrink)

Mild Cognitive Impairment (MCI) is a diagnostic category indicating cognitive impairment which does not meet diagnostic criteria for dementia such as Alzheimer’s disease. There are public health concerns about Alzheimer’s disease (AD) prompting intervention strategies to respond to predictions about the impacts of ageing populations and cognitive decline. This relationship between MCI and AD rests on three interrelated principles, namely, that a relationship exists between AD and MCI, that MCI progresses to AD, and that there is a reliable system of (...) classification of MCI. However, there are also several ethical issues and problems arising in the AD/MCI relationship. These include early diagnosis and interventions, the effects on people with MCI, and the newer neuroimaging and neuropharmacological approaches used in diagnosis and treatment. All these issues pose questions about the principles of MCI in relation to AD, with implications for how MCI is understood, diagnosed, treated, and experienced by patients. This article analyses four challenging areas for neuroethics: the definition and diagnosis of MCI; MCI in relation to AD; clinical implications of MCI for ethical disclosure, diagnosis, and treatment; and the research implications of MCI. The significant connections between these areas are often overlooked, together with uncertainties overall. Patients, healthcare systems and society are best served by informed clinicians, academics and researchers. After 35 years, the store of MCI knowledge is expanding and evolving. (shrink)

Currently, the number of individuals affected by Alzheimer’s disease is rapidly increasing, expected to reach 14 million in the United States within 30 years. In spite of this impending crisis, less than 50 percent of primary care physicians disclose the diagnosis of dementia to their patients. This failure negatively impacts not only patients but also caregivers, whom dementia patients require to help them meet their needs and who often serve as important decision makers, either as surrogates or as designated healthcare (...) agents for the patient. If caregivers are not informed about and prepared to deal with the challenges they face, their health, both emotional and physical, is put at risk. We will argue that both patient and caregiver have the right to be informed of the diagnosis, as their interests are intertwined, especially as the disease progresses and the caregiver becomes the primary advocate for the patient. The caregiver of an individual with dementia therefore becomes intimately connected to the patient’s autonomy in a way few caregivers of other diseases do. In this article, we will show that a timely and thorough disclosure of the diagnosis is morally obligated by the core principles of medical ethics. As the population ages, primary care physicians must see themselves in a triadic relationship with both the dementia patient and caregiver, recognizing that the interests of both are deeply interdependent. (shrink)

In their target article, Peterson et al. discuss the intriguing prospect of using psychedelics as a treatment for patients with Alzheimer’s Disease and Related Dementias (AD/ADRD) (Peterson et al....

In this paper, we examine the case of psychedelic medicine for Alzheimer’s disease and related dementias (AD/ADRD). These “mind-altering” drugs are not currently offered as treatments to persons with AD/ADRD, though there is growing interest in their use to treat underlying causes and associated psychiatric symptoms. We present a research agenda for examining the ethics of psychedelic medicine and research involving persons living with AD/ADRD, and offer preliminary analyses of six ethical issues: the impact of psychedelics on autonomy and consent; (...) the impact of “ego dissolution” on persons experiencing a pathology of self; how psychedelics might impact caregiving; the potential exploitation of patient desperation; institutional review boards’ orientation to psychedelic research; and methods to mitigate inequity. These ethical issues are magnified for AD/ADRD but bear broader relevance to psychedelic medicine and research in other clinical populations. (shrink)

While the developers of the “Ixtlan Basic Kit” promise a curative treatment taking advantage of increased neuroplasticity for targeting the underlying neurological causes of Alzheimer's disease and...

Dementia is an ever-growing public health concern with significant impact on the quality of life of older adults and their families (Aranda et al. 2021). Research continues to investigate treatment...

Alzheimer’s Disease (AD) provides an excellent case study to investigate emerging conceptions of health, disease, pre-disease, and risk. Two scientific working groups have recently reconceptualized AD and created a new category of asymptomatic biomarker positive persons, who are either said to have preclinical AD, or to be at risk for AD. This article examines how prominent theories of health and disease would classify this condition: healthy or diseased? Next, the notion of being “at risk”—a state somewhere in-between health and disease—is (...) considered from various angles. It is concluded that medical-scientific developments urge us to let go of dichotomous ways of understanding disease, that the notion of “risk,” conceptualized as an increased chance of getting a symptomatic disease, might be a useful addition to our conceptual framework, and that we should pay more attention to the practical usefulness and implications of the ways in which we draw lines and define concepts. (shrink)

Peterson et al. (2023) outline a broad ethics agenda for imminent research on psychedelic agents for Alzheimer’s disease and related dementias (AD/ADRD) by acknowledging the therapeutic promise of...

Alzheimer’s disease (AD), the devastating and most prevailing underlying cause for age-associated dementia, has no effective disease-modifying treatment. The last approved drug for the relief of AD symptoms was in 2003. The recent approval of sodium oligomannate (GV-971, 2019) in China and the human antibody aducanumab in the USA (ADUHELM, 2021) therefore represent significant breakthroughs, albeit ones that are fraught with controversy. Here, we explore potential scientific ethics issues associated with GV-971 and aducanumab’s development and approval. While these issues may (...) be belied by socioeconomic and political complexities in the heady business of commercial drug development, they are of fundamental importance to scientific integrity and ultimately, welfare of patients. We posit that the push for approval of both AD drugs based on incomplete research and unconvincing marginal effectiveness is ethically unsound. Regardless of how both these drugs shall perform in the market for the years to come, the scientific ethics issues and potentially questionable research practices should therefore be duly noted and lessons learned. (shrink)

In this article, caring, remembering and sharing memory are presented as moral responses, the case study being Alzheimer’s disease (AD). Memory connects memories and images, while care connects individuals, which is an ethical issue. When a person’s memory is lost, the care of others becomes the only thread connecting them to the world. AD deprives a person of memories, body control, makes it impossible to remember, communicate, move, recognize the environment, and disrupts consciousness. Caring for a patient with a neurodegenerative (...) brain disease requires constant reminding and reiteration; the presence of a caring person reminds of what the patient themselves can no longer remember. Lost memories do not mean that life or relational values have also lost their meaning. The description of the memory movement emphasizes the importance of repetition in the moral act. Highlighting the matter of care, also in scientific work, is the aim of this text. To care is to remember, on behalf of the AD patient, about the patient’s life. Within bioethical research, moral responses are an important point for projects which seek to improve the condition of patients—not only the condition of health but also the comfort of life. This improvement will not be possible without attentive, committed caregivers and their responsible attitude in the face of the phenomenon of memory loss. (shrink)

That aluminum is fatally toxic is beyond doubt, demonstrated by mass human poisoning at Camelford in Cornwall in Britain in 1988 (chapter 18) and by occasional fish kills (p. 49). Aluminum may also be a contributing factor in a number of human diseases, in particular those involving brain and nerves (p. 124) — autism, Alzheimer’s disease (AD) (chapter 14), Parkinson’s disease, multiple sclerosis. Aluminum salts used in kidney dialysis may be responsible for dialysis-related encephalopathy (pp. 38, 79). Aluminum adjuvants in (...) vaccine can cause macrophagic myofasciitis (MMF: inflammation and associated microscopic muscle necrosis at the injection site) as well as such whole-body ailments as chronic fatigue syndrome and marked cognitive deficits (Rigolet et al. 2014); one middle-aged individual injected with five aluminum-adjuvanted vaccines within 4 weeks became work-disabled (pp. 72-73). 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 (pp. 73-76). 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 (some 200) 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 (after oxygen and silicon), 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 (pp. 5-6, 11). 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)

In this paper, we examine the practice and promises of digital phenotyping. We build on work on the ‘data self’ to focus on a medical domain in which the value and nature of knowledge and relations with data have been played out with particular persistence, that of Alzheimer's disease research. Drawing on research with researchers and developers, we consider the intersection of hopes and concerns related to both digital tools and Alzheimer's disease using the metaphor of the ‘data shadow’. We (...) suggest that as a tool for engaging with the nature of the data self, the shadow is usefully able to capture both the dynamic and distorted nature of data representations, and the unease and concern associated with encounters between individuals or groups and data about them. We then consider what the data shadow ‘is’ in relation to ageing data subjects, and the nature of the representation of the individual's cognitive state and dementia risk that is produced by digital tools. Second, we consider what the data shadow ‘does’, through researchers and practitioners’ discussions of digital phenotyping practices in the dementia field as alternately empowering, enabling and threatening. (shrink)

Definition of the problemThe concept of privacy has been astonishingly absent in the discussion about dementia care. In general, questions of privacy receive a lot of attention in nursing ethics; however, when it comes to dementia care, hardly any systematic ethical debate on the topic can be found. It almost seems as though people with dementia had lost any comprehensible interest in privacy and no longer had any private sphere that needed to be considered or protected. However, this not only (...) contradicts widespread moral intuitions but also ignores the views and needs of those affected.ArgumentsWe first outline the origins and dimensions of the concept of privacy and point out problems and limitations in the context of dementia. Especially the prevalent liberal conceptions’ dependence on the idea of autonomy poses significant challenges to an adequate conceptualization of the moral significance of privacy for people with dementia. Therefore, we subsequently explore alternative ways of conceptualizing the “value of privacy” in the context of dementia care.ConclusionAutonomy-based concepts of privacy may still be valid in the early stages of dementia. However, in the further course of the syndrome, the relevance of other normative aspects comes to the fore, especially respect for remaining personal preferences as well as objective criteria of dignity and well-being. Thus, we outline in a differentiated manner how and to what extent privacy can be of normative importance beyond the purview of autonomy and should consequently be taken into consideration in dementia care. (shrink)

A través del presente trabajo se aborda el papel de la musicoterapia en la enfermedad de alzheimer (EA) desde el ámbito del trabajo social. Para ello, se lleva a cabo una revisión bibliográfica y se identifican conceptos claves como musicoterapia, EA e intervención del trabajo social. La información recogida lleva a considerar la musicoterapia como tratamiento coadyuvante en la enfermedad de Alzheimer a través de áreas como la integración social, la autoestima, la comunicación o la reducción del estrés. Por ello, (...) se concluye que la estimulación musical mejora la calidad de vida en pacientes con EA. (shrink)

Robert George and Christopher Tollefsen argue that human beings have fundamental dignity and basic rights (“human rights”) in virtue of the kind of entity they are—creatures bearing a rational nature. The indicia of a rational nature are the basic natural capacities—which obtain from the point a rational creature comes into existence—for thinking, deliberating, and choosing, whether or not these capacities are immediately exercisable. All human beings, including those who are asleep, or under general anesthesia, or who are in deep comas (...) or persistent minimally conscious states, are bearers of a rational nature. The same is true of those suffering even severe cognitive disabilities. A person with advanced Alzheimer’s disease, for example, has not undergone a change of nature—he is not a creature different in species or otherwise different in kind from what he was before the onset of the disease. Bearers of fundamental dignity and basic rights, which includes all human beings, must not be treated as mere objects or instruments by, for example, subjecting them to damaging or deadly experimentation designed for the benefit of others. So the question at the heart of debates over human embryo research is the empirical one, fully accessible to inquiry using scientific methods of analysis: Is the human embryo, from the formation of the zygote forward, a human being, viz., a living member of the species Homo sapiens. George and Tollefsen assess the evidence and conclude that the answer to that question is unambiguously yes. (shrink)

A general obligation to make aggregate research results available to participants has been widely supported in the bioethics literature. However, dementia research presents several challenges to this perspective, particularly because of the fear associated with developing dementia. The authors argue that considerations of respect for persons, beneficence, and justice fail to justify an obligation to make aggregate research results available to participants in dementia research. Nevertheless, there are positive reasons in favor of making aggregate research results available; when the decision (...) is made to do so, it is critical that a clear strategy for communicating results is developed, including what support will be provided to participants receiving aggregate research results. (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)

BackgroundDespite severe cognitive dysfunction in Alzheimer's disease, aesthetic preferences in AD patients seem to retain some stability over time, similarly to healthy controls. However, the underlying mechanisms of aesthetic preference stability in AD remain unclear. We therefore aimed to study the role of emotional valence of stimuli for stability of aesthetic preferences in patients with AD compared to cognitively unimpaired elderly adults.MethodsFifteen AD patients score 12–26) without visual impairment and/or psychiatric disorder, as well as 15 healthy controls without cognitive impairment (...) matched in age, sex, art interest and highest level of education were included in this study. All participants were asked to rank-order eight artworks per stimulus category according to their preference twice with a 2-week span in-between. Based on these two rankings a preference change score was calculated. In order to assess explicit recognition memory of the artworks in the second testing session, four artworks of each stimulus category used in the preference ranking task were presented together with a content-matched distractor artwork painted by the same artist. Participants had to indicate which of the stimuli they had seen 2 weeks previously.ResultsAD patients [MMSE = 18.9 ± 3.6; Age = 85.4 ± 6.9; 33.3% male] had no explicit recognition memory of the artworks, whereas healthy controls [MMSE = 27.7 ± 1.4; Age = 84.3 ± 6.7; 33.3% male] correctly recognized 85% of stimuli after 2 weeks. AD patients had equally stable preferences compared to the control group for negative artworks, but less stable preferences for positive and neutral images.ConclusionEven in cognitively impaired AD patients, aesthetic preference for negatively-valenced artworks remains relatively stable. Our study provides novel evidence that AD patients may have a somewhat preserved implicit valence system for negative compared to neutral or positive visual information, especially in the domain of aesthetics. However, more studies need to further uncover the details of the underlying neurocognitive mechanisms of preference stability in pathological aging. (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)

There are at least three related issues that need to be resolved in this case: Who should be the patient’s medical decision-maker?, Should the patient be treated and possibly admitted?, and...

ObjectiveStatic regional homogeneity based on the resting-state functional magnetic resonance imaging has been used to study intrinsic brain activity in Alzheimer’s disease. However, few studies have examined dynamic ReHo in AD. In this study, we used rs-fMRI and dReHo to investigate the alterations in dynamic IBA in patients with AD to uncover dynamic imaging markers of AD.MethodIn total, 111 patients with AD, 29 patients with mild cognitive impairment, and 73 healthy controls were recruited for this study ultimately. After the rs-fMRI (...) scan, we calculated the dReHo values using the sliding window method. ANOVA and post hoc two-sample t-tests were used to detect the differences among the three groups. We used the mini-mental state examination and Montreal Cognitive Assessment to evaluate the cognitive function of the subjects. The associations between the MMSE score, MoCA score, and dReHo were assessed by the Pearson correlation analysis.ResultsSignificant dReHo variability in the right middle frontal gyrus and right posterior cingulate gyrus was detected in the three groups through ANOVA. In post hoc analysis, the AD group exhibited significantly greater dReHo variability in the right MFG than the MCI group. Compared with the HC group, the AD group exhibited significantly increased dReHo variability in the right PCG. Furthermore, dReHo variability in the right PCG was significantly negatively correlated with the MMSE and MoCA scores of patients with AD.ConclusionDisrupted dynamic IBA in the DMN might be an important characteristic of AD and could be a potential biomarker for the diagnosis or prognosis of AD. (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)

Elucidating distinct morphological atrophy patterns of Alzheimer’s disease and its prodromal stage, namely, mild cognitive impairment helps to improve early diagnosis and medical intervention of AD. On that account, we aimed to obtain distinct patterns of voxel-wise morphological atrophy and its further perturbation on structural covariance network in AD and MCI compared with healthy controls. T1-weighted anatomical images of matched AD, MCI, and HCs were included in this study. Gray matter volume was obtained using voxel-based morphometry and compared among three (...) groups. In addition, structural covariance network of identified brain regions exhibiting morphological difference was constructed and compared between pairs of three groups. Thus, patients with AD have a reduced hippocampal volume and an increased rate of atrophy compared with MCI and HCs. MCI exhibited a decreased trend in bilateral hippocampal volume compared with HCs and the accelerated right hippocampal atrophy rate than HCs. In AD, the hippocampus further exhibited increased structural covariance connected to reward related brain regions, including the anterior cingulate cortex, the putamen, the caudate, and the insula compared with HCs. In addition, the patients with AD exhibited increased structural covariance of left hippocampus with the bilateral insula, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum than MCI. These results reveal distinct patterns of morphological atrophy in AD and MCI, providing new insights into pathology of AD. (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)

BackgroundStory recall tests have shown variable sensitivity to rate of cognitive decline in individuals with Alzheimer’s disease biomarkers. Although SR tasks are typically scored by obtaining a sum of items recalled, item-level analyses may provide additional sensitivity to change and AD processes. Here, we examined the difficulty and discrimination indices of each item from the Logical Memory SR task, and determined if these metrics differed by recall conditions, story version, lexical categories, serial position, and amyloid status.Methodsn = 1,141 participants from (...) the Wisconsin Registry for Alzheimer’s Prevention longitudinal study who had item-level data were included in these analyses, as well as a subset of n = 338 who also had amyloid positron emission tomography imaging. LM data were categorized into four lexical categories, and by serial position. We calculated difficulty and discriminability/memorability by item, category, and serial position and ran separate repeated measures ANOVAs for each recall condition, lexical category, and serial position. For the subset with amyloid imaging, we used a two-sample t-test to examine whether amyloid positive and amyloid negative groups differed in difficulty or discrimination for the same summary metrics.ResultsIn the larger sample, items were more difficult in the delayed recall condition across both story A and story B. Item discrimination was higher at delayed than immediate recall, and proper names had better discrimination than any of the other lexical categories or serial position groups. In the subsample with amyloid PET imaging, proper names were more difficult for Aβ+ than Aβ−; items in the verb and “other” lexical categories and all serial positions from delayed recall were more discriminate for the Aβ+ group compared to the Aβ− group.ConclusionThis study provides empirical evidence that both LM stories are effective at discriminating ability levels and amyloid status, and that individual items vary in difficulty and discrimination by amyloid status, while total scores do not. These results can be informative for the future development of sensitive tasks or composite scores for early detection of cognitive decline. (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. (shrink)

Anticipation of future decisions can be important for individuals at risk for diseases to maintain autonomy over time. For future treatment and care decisions, advance care planning is accepted as a useful anticipation tool. As research with persons with dementia seems imperative to develop disease-modifying interventions, and with changing regulations regarding research participation in Germany, advance research directives (ARDs) are considered a solution to include persons with dementia in research in an ethically sound manner. However, little is known about what (...) affected people deem anticipatable.This contribution provides a critical reflection of the literature on anticipation and of a qualitative study on the assessment of ARDs with persons with cognitive impairment in Germany. It combines theoretical and empirical reflections to inform the ethical-legal discourse.Anticipation involves the conceptual separation of the past, the present, and the future. Including dimensions such as preparedness, injunction, and optimization helps in establishing a framework for anticipatory decision-making. While dementia may offer a window of time to consider future decisions, individual beliefs about dementia including fears about stigma, loss of personhood, and solitude strongly impact anticipating sentiments. Concepts of anticipation can be useful for the examination of uncertainty, changing values, needs, and preferences interconnected with the dementia trajectory and can serve as a means to make an uncertain future more concrete. However, fears of losing one’s autonomy in the process of dementia also apply to possibilities of anticipation as these require cognitive assessment and reassessment of an imagined future with dementia. (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)

This paper provides an overview of the societal impact of a rising dementia population and examines the legal and ethical implications posed by voluntary registries as a community-oriented solution to improve interactions between law enforcement and individuals with dementia. It provides a survey of active voluntary registries across the United States, with a focus on Arizona, which has the highest projected growth for individuals living with dementia in the country.

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)

Mental time travel and language enable us to go back and forth in time and to organize and express our personal experiences through time reference. People with Alzheimer’s disease have both mental time travel and time reference impairments, which can greatly impact their daily communication. Currently, little is known about the potential relationship between time conceptualization and time reference difficulties in this disease. A systematic review of the literature was performed to determine if this link had already been investigated. Only (...) three articles integrated both time conceptualization and time reference measures. However, the link between the two was not systematically analyzed and interpreted. This review highlights the lack of research addressing the question of the influence of time conceptualization impairments in Alzheimer’s disease on other cognitive domains, and especially language. (shrink)

2020 was a year of global crisis. During this time, I experienced crisis on a very personal level. For me this coincided with the beginning of the pandemic, when my older brother developed a kind of dementia. In this text, I briefly explore a few philosophical issues relating both to the spread of COVID-19 and to my brother’s disease. Reflecting on themes such as anxiety, uncertainty, grief, privilege, vulnerability, social distancing, and misfit bodies—mainly through critical phenomenology—I attempt to give sense (...) to the experience of personal crisis in times of global crisis. I conclude by embracing “misfit bodies” in a sincere attempt to recognize the pervasiveness of sickness and absurdity—but also in hope for solidarity and empathy to persist. (shrink)