As we aggressively pursue research to cure and prevent Alzheimer’s disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects’ death; the creation of cohorts of (...) ’study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants’ welfare if the information is obtained by insurance companies or long-term care providers; the use of study partners that creates unique risks of harm to the relationship of subject and study partner. We need greater attention, at all levels, to these complex ethical issues. Work on these issues should be included in research plans, from the federal to the local, and should be supported through NIH in the same way that it supported work on the ethical, legal and social implications of genetic research. (shrink)

There is a flood of papers being published on new ways to diagnose Alzheimer disease before it is symptomatic, involving a combination of invasive tests , and pen and paper tests. This changes the landscape with respect to genetic tests for risk of AD, making rational suicide a much more feasible option. Before the availability of these presymptomatic tests, even someone with a high risk of developing AD could not know if and when the disease was approaching. One could (...) lose years of good life by committing suicide too soon, or risk waiting until it was too late and dementia had already sapped one of the ability to form and carry out a plan. One can now put together what one knows about one's risk, with continuing surveillance via these clinical tests, and have a good strategy for planning one's suicide before one becomes demented. This has implications for how these genetic and clinical tests are marketed and deployed, and the language one uses to speak about them. The phrase ‘there is nothing one can do’ is insulting and disrespectful of the planned suicide option, as is the language of the Risk Evaluation and Education for Alzheimer's Disease studies and others that conclude that it is ‘safe’ to tell subjects their risk status for AD. Further, the argument put forward by some researchers that presymptomatic testing should remain within research protocols, and the results not shared with subjects until such time as treatments become available, disrespects the autonomy of people at high risk who consider suicide an option. (shrink)

Americans who are afraid of living for many years with Alzheimer's might seek a way to end their lives early, when their dementia has just entered the moderate phase. There is no legal process for doing so. In this paper I argue that advance directives, in particular, are not a legal solution for those who prefer to die rather than suffer years of dementia. The problem is that an advance directive only works to hasten death when there is a (...) life-threatening illness for which one can refuse treatment; more often than not, Alzheimer's kills the self long before it kills the body. (shrink)

This study explored possible deficits in selective attention brought about by Dementia of Alzheimer Type (DAT). In three experiments, we tested patients with early DAT, healthy elderly, and young adults under low memory demands to assess perceptual filtering, conflict resolution, and set switching abilities. We found no evidence of impaired perceptual filtering nor evidence of impaired conflict resolution in early DAT. In contrast, early DAT patients did exhibit a global cost in set switching consistent with an inability to maintain (...) the goals of the task (mental set). We discuss these findings in relation to the DAT literature on executive attention, dual-tasking, and working memory. Ó 2007 Elsevier Inc. All rights reserved. (shrink)

Patients with behavioral variant of frontotemporal dementia (FTD) have difficulties recognizing facial emotions, a deficit that may contribute to their impaired social skills. In three experiments, we investigated the FTD deficit in recognition of facial emotions, by comparing six patients with impaired social conduct, nine Alzheimer’s patients, and 10 age-matched healthy adults. Experiment 1 revealed that FTD patients were impaired in the recognition of negative facial emotions. Experiment 2 replicated these findings when participants had to determine whether two faces (...) were expressing the same or different emotions. Experiment 3 was a control study in which participants had to discriminate whether two faces were of the same sex. In this non-emotional processing task, both patient groups performed worse than normal participants, but FTD patients performed as well as Alzheimer’s patients. We conclude that FTD patients are impaired in the recognition of negative facial emotions. © 2005 Elsevier Ltd. All rights reserved. (shrink)

Impairment of the Self has been described in frontal–temporal dementia but little research has been carried out in patients with Alzheimer’s disease. Objective. The aim of this study was to explore changes in the self in patients with AD. Method. Forty-seven patients with mild to moderate AD were examined using a semi-structured scale designed to assess the self-concept along three dimensions, namely, the Material Self, the Social Self and the Spiritual Self. Results. The majority of patients presented impairment of (...) at least one dimension of the Self. When only one dimension was affected, it was always the Social Self. The severity of impairment of the Self was correlated to the impairment of the semantic autobiographical memory and apathy. The Self is impaired in AD and the Social Self dimension appears to be more vulnerable in AD than other dimensions. (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)

Some years ago I received a phone call telling me that my mother, then in her eighties, had been found wandering the street outside her home. It was the first indication my wife and I had of Alzheimer's disease. We arrived to discover that my mother was incoherent, with the house in disorder, bills unpaid, and perishable food in the night table rather than the refrigerator. Having spent much of my career trying to improve the assessment of decisional capacity, (...) in part to avoid unnecessary deprivation of decision-making rights, I did not take lightly the step to have my mother declared incompetent. But it was necessary. This episode has been on my mind since I returned recently from a conference in Paris devoted to the United Nations Convention on the Rights of Persons with Disabilities. (shrink)

We conducted a cross-sectional survey of a random sample of 1943 spouses of home-dwellers with Alzheimer’s disease (AD) to examine the prevalence of court-appointed guardians or financial powers of attorney for persons with AD, related factors and the need for information about these issues among caregiving families. The questionnaire consisted questions on variables of demographic characteristics, disability, symptoms and care needs of the person with dementia, the strain of caregiving, the use of court-appointed legal guardians or powers of attorney, (...) as well as discussions about these issues—and the need for them—with a doctor. The response rate was 77% and the mean ages of those with AD and caregivers were 80.2 and 78.2 years, respectively. The use of legal guardians was rare (4.3%), while the use of financial powers of attorney was more common (37.8%). Only 9.9% of the couples had discussed these issues with their doctor, whereas 47.9% expressed a need for it. The factors associated with the use of these legal arrangements were related to the severity of dementia, including experiencing dementia symptoms for more than 3 years, poor functioning, incontinence and behavioural symptoms. There is a clear need for information on medico-legal issues related to dementia among caregivers of AD patients. If held soon after the diagnosis, such discussions could support the autonomy of these persons in spite of AD and enable them to plan for the future as they wish. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The 2004 Meeting of the Society for Buddhist-Christian StudiesFrances S. AdeneyThe 2004 meeting of the Society for Buddhist-Christian Studies was held in San Antonio, Texas, 19–20 November 2004. This year's theme was "Dealing with Illness and Promoting Healing: Buddhist and Christian Resources." During the first session panelists Laura Habgood Arsta, Jay McDaniel, and Beth Blizman presented Christian views on dealing with illness, and Rita Gross responded from a Buddhist (...) perspective. The second session focused Buddhist resources for promoting healing by panelists Francis Tsio and Grace Buford, with Laurel Curran presenting a Christian response.Laura Habgood Arsta presented research done by undergraduate students in border communities between the United States and Mexico. The topic was the connection between the Pentecostal movement and environmental health. Pentecostal Christianity (250–400 million members worldwide) emphasizes the signs that accompany the presence of Christ, evidenced by experiences of spirit baptism and faith healing.Their sample indicated that poor and minority people don't identify with the environmental movement until personal health problems emerge. One possible reason for Pentecostal religion thriving, according to this research, might be that exposure to toxins and poverty draws people to healing, a theological pillar of Pentecostalism. Religious services provide an emotional outlet and inspire self-confidence, which can become a mental health component of a healing solution. Women are free to share and lead services, finding leadership opportunities and a social group in churches. As an inexpensive alternative to medical care, healing in the Pentecostal church provides a sense of physical healing as well as help in overcoming addictions.Beth Blizman informed the group of the toxicity of the Lake Erie area of northern Ohio. Cancer is becoming normalized in this region, which has the highest level of multiple cancers in the United States. Beth feels called to heal her own body and become part of the healing process of that region. She argued that an attitude that disrespects the earth leads to disrespect of one another. "How can healing be found?" she asked. She discussed many resources from ancient monastics to modern women religious, from process and feminist thought to new cosmologies. Finally she connected [End Page 149] Audre Lourde's work on the rejection of difference to the bioregional studies that she has been doing on toxicity and illness.Jay McDaniels followed by giving a Christian perspective on Alzheimer's disease as an ecumenical Christian influenced by Buddhism. He addressed three questions that Christians ask in this situation. The first question is "Where is God now? Is God inside my loved one? How?" In response to this question, Jay outlined an evangelical view of God that understands God as a transcendent being, "way up there, watching from a distance." He contrasted this view with a process view of God as an "umbrella of compassion that envelops the world without smothering it." In this view, God is the great companion, sharing the confusion and anxiety of the ill person.So where is the person as they experience personality changes caused by the disease? Jay addressed this second question through process theology, stating that in process theology the person is defined in Buddhist terms, inheriting from the past and contributing to the future. A person is constantly in flux or transformation, so the person with illness may be a different person than they once were but can be embraced as the person that they are now. The multidimensional universe of process theology allows for a person to live "with one foot on earth and one foot in heaven."Help for dealing with Alzheimer's disease, Jay's third question, can be found in the Benedictine vow of obedience, stability, and ongoing conversion. The deepest need for those with Alzheimer's is to be with them, being available to others to listen. Stability is the vow to stay with the relationship through these changes. Ongoing conversion can come through Alzheimer's as those with this disease invite us into a space of creative imagination and a new kind of respect.Rita Gross responded to the three presentations by arguing that how one perceives a situation changes it tremendously. Two Buddhist principles that apply here are... (shrink)

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

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

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

By age 85, most adults manifest some degree of motor impairment. However, in most individuals a specific etiology for motor decline and treatment to modify its inexorable progression cannot be identified. Recent clinical-pathologic studies provide evidence that mixed-brain pathologies are commonly associated with late-life motor impairment. Yet, while nearly all older adults show some degree of accumulation of Alzheimer’s disease and related dementias pathologies, the extent to which these pathologies contribute to motor decline varies widely from person to person. (...) Slower or faster than expected motor decline in the presence of brain injury and/or pathology has been conceptualized as more or less “resilience” relative to the average person This suggests that other factors, such as lifestyles or other neurobiologic indices may offset or exacerbate the negative effects of pathologies via other molecular pathways. The mechanisms underlying neural motor resilience are just beginning to be illuminated. Unlike its cousin, cognitive resilience which is restricted to neural mechanisms above the neck, the motor system extends the total length of the CNS and beyond the CNS to reach muscle and musculoskeletal structures, all of which are crucial for motor function. Building on prior work, we propose that by isolating motor decline unrelated to neuropathologies and degeneration, investigators can identify genes and proteins that may provide neural motor resilience. Elucidating these molecular mechanisms will advance our understanding of the heterogeneity of late-life motor impairment. This approach will also provide high value therapeutic targets for drug discovery of therapies that may offset the negative motor consequences of CNS pathologies that are currently untreatable. (shrink)

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non‐coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the (...) in‐depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome‐editing techniques including CRISPR/Cas9. These approaches are also applicable to low‐frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. (shrink)

I review the recent case of Edna Folz, a 73 year-old woman who was suffering through the end stages of very advanced Alzheimer's dementia when her case was adjudicated by the Wisconsin Supreme Court. I consider this case as an example of how courts are increasingly misinterpreting the ethical and legal decision-making standards known as substituted judgment and best interests and thereby threatening individuals' treatment decision-making rights as developed by other courts over the past two decades and creating serious (...) roadblocks to health-care providers' ability to render appropriate patient care. The Wisconsin Supreme Court held that Edna's legal guardian could not authorize withdrawal of Edna's treatment, ruling that as a matter of law, if an incompetent person is not in a persistent vegetative state, it is not in his or her best interests for life-sustaining treatment to be withdrawn unless (s)he has executed an advance directive or other statement clearly indicating his or her desires. (shrink)

Older minority Americans experience worse health outcomes than their white counterparts, exhibiting the need for social justice in all areas of their health care. Justice, fairness, and equity are crucial to minimizing conditions that adversely affect the health of individuals and communities. In this paper, Alzheimer's disease (AD) is used as an example of a health care disparity among elderly Americans that requires social justice interventions. Cultural factors play a crucial role in AD screening, diagnosis, and access to care, (...) and are often a barrier to support and equality for minority communities. The “conundrum of health disparities” refers to the interplay between disparity, social justice, and cultural interpretation, and encourages researchers to understand both (1) disparity caused by economic and structural barriers to access, treatment, and diagnosis, and (2) disparity due to cultural interpretation of disease, in order to effectively address health care issues and concerns among elderly Americans. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

Current debate and policy surrounding the use of genetic editing in humans often relies on a binary distinction between therapy and human enhancement. In this paper, we argue that this dichotomy fails to take into account perhaps the most significant potential uses of CRISPR-Cas9 gene editing in humans. We argue that genetic treatment of sporadic Alzheimer’s disease, breast- and ovarian-cancer causing BRCA1/2 mutations and the introduction of HIV resistance in humans should be considered within a new category of genetic (...) protection treatments. We find that if this category is not introduced, life-altering research might be unnecessarily limited by current or future policy. Otherwise ad hoc decisions might be made, which introduce a risk of unforeseen moral costs, and might overlook or fail to address some important opportunities. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for (...) the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing (...) the 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Loss of insight is a prominent clinical manifestation of behavioral variant frontotemporal dementia , but its characteristics are poorly understood. Twelve bvFTD patients were compared with 12 Alzheimer’s disease patients on a structured insight interview of cognitive insight and emotional insight . Compared to the AD patients, the bvFTD patients were less aware and less concerned about their disorder, and they had less appreciation of its effects on themselves and on others. After corrective feedback , the bvFTD patients were (...) just as aware of their disorder as the AD patients but remained unconcerned and unappreciative of its effects. These findings suggest that lack of insight in bvFTD is not due to “anosognosia,” or impaired cognitive and executive awareness of disease, but to “frontal anosodiaphoria,” or lack of emotional concern over having bvFTD and its impact on themselves and others. (shrink)

Accelerated approval of aducanumab for mild Alzheimer's by the U.S. Food and Drug Administration on June 7, 2021, has generated substantial medical, scientific, and ethical controversy. That approval was contrary to the nearly unanimous judgment of the FDA's Advisory Committee that little reliable evidence existed of significant benefit, even though the drug did reduce β‐amyloid. Three major ethical problems were created by this approval: (1) Medicare resources would be unjustly squandered, given the drug's $56,000 annual price and the 3.1 (...) million older potential American patients needing the drug; (2) physicians will feel ethically compelled to provide the drug to desperate, insistent patients, given FDA approval and in spite of side effects of brain bleeds and brain swelling; (3) and false hopes are generated for patients. A needed corrective by the federal government would reduce reimbursement to the bare cost of producing the drug (plus only a modest profit) until a phase IV trial has been successfully completed. (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)

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology (...) including β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)

Consumer demand for health information and health services has rapidly evolved to capture and even propel the movement to online health information seeking. Seventeen percent of health information internet users will look for information about memory loss, dementia and Alzheimer’s disease. We examined the content of the 25 most frequently retrieved websites marketing AD dietary supplements. We found that the majority of websites and their products claimed AD-related benefits, including improvement and enhancement of function, treatment for AD, prevention of (...) AD, maintenance of function, delayed progression of AD, and decreased symptoms. Supplements were described as effective, natural, powerful or strong, dependable and pure or of high quality. Peer reviewed references to proper scientific studies were infrequent on websites. Statements highlighting the risks of dietary supplements were as common as statements mitigating or minimizing these risks. Different strategies were used to promote supplements such as popular appeals and testimonials. Further enforcement of relevant policy is needed and preparation of clinicians to deal with requests of patients and caregivers is indicated. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Aging, Chance, and RaceAtwood D. Gaines (bio)KeywordsAlzheimer’s disease, chance, mild cognitive impairment, racism, social constructionsThomas Kirkwood's comments are a welcome, articulate detailing of how and why we age with special reference to the brain. As well, his paper indicates clearly that processes reified as pathology and disease, such as Alzheimer's disease (AD), are in fact common and inevitable as the human brain ages. Doubtless, this (...) is the reason that aging is by far the greatest risk factor for the development of AD. A key notion, briefly mentioned by Kirkwood, is that of chance. He points out that, "cells (will be) burdened with protein aggregates and similar materials that will increase with aging. Once again, which cells will experience this fate and which will continue to function healthily is strongly influenced by chance" (Kirkwood 2006, 80–81). This mention of chance is most important for our paper, "Building a Mystery," and for an understanding of science as well. In "Building a Mystery," Peter Whitehouse and I sought to show that the history of AD was not inevitable and demonstrates a variety of chance and singular decisive occurrences of encounters, interpretations, social movements, government initiatives, and technological developments. Such decisive moments do not occur by virtue of some (natural) lawful process that is unfolding, but rather, these are chance events that could have happened in other ways. Indeed, science has been viewed as human attempts to "tame chance" (Hacking 1990). However, it often does so by sleight of hand, misinterpretation, and the biomedical discourse of hope. Increasingly, we are learning that chance is a commonality, not a rarity, in social and biological domains. The biomedical approach assumes the opposite. For example, it seeks to tame the chance appearance of AD in the case of Auguste D, and does so in part by reifying differences that exist, as Kirkwood notes, along a continuum rather than as the discrete entities implied by the labels Alzheimer's disease or mild cognitive impairment (MCI).We thus stand with Kirkwood's bold recognition of chance (see also Kirkwood 2003) in the biological domain and have applied the same idea to the social domain in which we consider the practice of biomedical science. We have elsewhere emphasized consensus statements in the making of AD (Gaines and Whitehouse 1998). In the present article, we add a number of other chance, decisive sociocultural moments to the mix of social processes producing AD and MCI. We have not considered in detail here a host of cultural features in the theory and practice of biomedicine with respect to AD. These include implicit, yet highly [End Page 83] implicative, cultural notions of bilateral kinship employed in genetic research on AD considered elsewhere (Gaines 1998).Bavidge's comments are cogent as well. With respect to the notion of my concept of the local biology of "race" (Gaines 2005), it is germane to point out here that such culturally constructed biologies are relevant to a discussion of AD and other dementias. Such constructions represent culture in science. We used the dramatic example of "race" in US biomedicine because it is experiencing a resurgence as an explanatory tool. For example, recently Haiman et al. (2006) presented research that suggests that "Among cigarette smokers, African Americans and native Hawaiians are more susceptible to lung cancer than whites, Japanese Americans and Latinos." The authors assert, as have many US studies, that their findings show differences relate to the alleged biology of the social groups concerned. Their problem and that of others, is that the groups are social, not biological, and most have mixed ancestry and do not stem from distinct groups. This is particularly true of African Americans and Latinos; both groups are substantially composed of individuals with European, West African, and Native American ancestry in widely varying proportions (Gaines 2005). Thus, they are different only in terms of their classification. Such work regularly overlooks influences, such as environmental racism, discrimination, poverty, and a lack of medical care, as well as other practices. These might include, in a study of smoking, pakalolo smoking (local marijuana) among Hawaiians, who themselves are usually part Portuguese, Japanese, Chinese, and or European... (shrink)

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

The leading accounts of the ethics of proxy decision making implicitly draw on internalist conceptions of the philosophy of mind, or so this essay tries to demonstrate. Using the views of Ronald Dworkin as its jumping‐off point, the essay argues that accepting the sort of externalism associated with writers such as Putnam and Burge would alter Dworkin's conclusions concerning how we should respond to the current or precedent decisions of people suffering from dementia. Building on the views of Agnieszka Jawarska, (...) it argues that accepting “active” externalism à la Clark and Chambers would provide currently competent people with new resources for establishing the authority of their present values over inconsistent values they might come to entertain should they become demented. (shrink)

The rate of individuals diagnosed with Alzheimer’s disease is expected to increase significantly in the coming decades. As more attention is paid to end-of-life care for these patients, questions about the use of assisted nutrition and hydration will become more prevalent. Two recent articles that discuss the use of ANH in patients suffering from advanced Alzheimer’s disease are discussed. The author argues that Pope John Paul II’s designation of medically assisted nutrition and hydration as “ordinary care” does not (...) alleviate the ethical necessity of discerning the benefits and burdens of the procedure for these patients. He argues that tube feeding of patients with advanced Alzheimer’s disease should be considered extraordinary, non-obligatory treatment, but future research is still needed to assess the objective and subjective criteria for making this judgment. National Catholic Bioethics Quarterly 13.3 (Autumn 2013): 469–482. (shrink)

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

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

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

This chapter contains sections titled: Semantic Externalism: A Rough Sketch and a Gesture at Motivation Interests, Values, and the Mind's End Beyond Externalism About Mental Contents Acknowledgments References.