Prendre soin d’un parent souffrant de la maladie d’Alzheimer place l’ensemble de la famille dans des circonstances complexes et difficiles. Cet article s’emploie à comprendre comment la maladie d’Alzheimer vient convoquer l’histoire familiale, ses conflits et ses traces du négatif, perturbant à la fois les liens familiaux et l’inscription des proches dans leur rôle d’aidant. Les auteures rendent compte d’entretiens cliniques à visée de recherche menés auprès d’une fratrie de quatre sœurs confrontées à la dépendance de (...) leur mère atteinte de la maladie d’Alzheimer. À partir d’une analyse phénoménologique, elles montrent l’importance de la désorganisation des liens familiaux et la réactivation des conflits dans l’organisation concrète des aidants autour du parent malade. Les enfants confrontés à la maladie grave d’un parent doivent non seulement réaliser un travail d’acceptation de la maladie, mais aussi réélaborer l’histoire familiale ainsi réactivée. (shrink)

We conducted a systematic analysis of conceptions of Alzheimer’s disease in the French specialized social workers press between 1990 and 2014, and compared these results to recent studies on autism and Attention Deficit Hyperactivity Disorder (ADHD) in the same field. Analysis of discourse about Alzheimer’s disease, and more generally on mental and psychosocial disorders in the specialized social workers press shows that social factors highly involved in these pathologies are never presented, as they are widely argued in the international literature, (...) and can be subject to specific socio-educational policies and practices. Most ways of Alzheimer’disease presented to French social workers belong to the therapeutic sphere, and reveal a growing medicalization of social work, allowing us to question the practice, institutional and training issues. (shrink)

propre vie, et à haut risque pathologique pour l’individu concerné, ce rôle parental, caractéristique de l’aide informelle d’aujourd’hui, est l’un des enjeux socio-écono-miques et de santé de la société de demain. Pour aider au maintien d’une écologie familiale stable et soutenir psychologiquement ces acteurs familiaux, essentiels au mieux-être de leurs parents malades, certaines capacités de résilience peuvent être mises au jour et utilisées avec discernement dans le cadre des dispositifs d’aide et de soins. Une vignette clinique expose la résilience d’une (...) famille touchée par la maladie d’Alzheimer et, plus spécifiquement, de ses « enfants-parents ». Une nouvelle forme de parentalité apparaît avec le vieillissement accru des populations et l’émergence de syndromes démentiels souvent associés : être le parent de son propre parent malade, en rupture d’autonomie, et totalement dépendant de son entourage à plus ou moins long terme. Spécifique, lourd de conséquences au quotidien et sur sa. (shrink)

Toute réalité dans la vie humaine est-elle réductible à une question philosophique? La maladie d’Alzheimer est une partie de la réalité humaine. On peut la décrire : la perte progressive de la mémoire, une identité personnelle de plus en plus rompue. Depuis Locke, la philosophie attache l’identité personnelle à la conscience. La conscience est un acte, elle n’est pas une substance. Comment penser cet acte comme une identité dans le temps? On invoque alors la mémoire. Mais la mémoire (...) ne donne pas la réponse, même lorsqu’on passe de la question psychologique de cette faculté à la question ontologique du temps. Comment dès lors reconnaître le patient atteint d'Alzheimer comme un être humain? (shrink)

La musique est actuellement utilisée pour la rééducation motrice de patients handicapés par la maladie de Parkinson ou l’âge. Elle facilite aussi la restauration des fonctions du langage chez les aphasiques. Elle permet d’améliorer la mémoire dans la maladie d’Alzheimer. Enfin, dans un cadre de normalité, elle facilite l’apprentissage des langues. La musique n’est qu’une expression particulière de l’expérience du temps décrite par Bergson sous le nom de durée. Celle-ci constitue la mémoire primitive, fonde le mouvement authentique, (...) instaure la fluidité du discours. C’est donc dans la perspective de la pensée bergsonienne que les données actuelles de la musicothérapie doivent être interprétées. (shrink)

Les troubles de mémoire sont un motif fréquent de consultation dans les services de gériatrie, psychiatrie ou neurologie. Ils sont pour beaucoup synonymes d’un mot terrible : Alzheimer. Dès l’apparition de troubles mnésiques, chacun s’interroge : « Est-ce l’âge, ou bien la maladie? Puis-je panser ma mémoire, ou vais-je dériver avec elle? » Les docteurs Emmanuelle Candas et Bruno Le Dastumer, gériatres, spécialistes des troubles de la mémoire, font un état des lieux de la maladie d’Alzheimer et (...) répondent à ces interrogations : comment faire la différence entre le vieillissement naturel du cerveau et les troubles mnésiques pathologiques? Existe-t-il un traitement pour soigner la maladie d’Alzheimer? Et surtout, comment accompagner le malade, dès le diagnostic établi? (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (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)

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)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (shrink)

In this paper, we suggest some of the dimensions of the problematic concept of Alzheimer Disease as a natural disease discerned by increasingly sophisticated medical scientific progress. Taking a page from Max Weber concerning unique events, we show some of the conceptual building blocks and social processes that have coalesced into the perception of certain phenomena as abnormalities that are seen as implicated in the development of a degenerative disease distinct from the process of normal, but variable, brain aging. We (...) note some of the decisions and social forces pushing for particular conceptualizations, interpretations, and reifications of brain alterations. In so doing, we suggest that the mystery of the "there" may not be much different from, and probably is, the mystery of the "everywhere". (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)

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)

Early last year, the GenEthics Consortium (GEC) of the Washington Metropolitan Area convened at George Washington University to consider a complex case about genetic testing for Alzheimer disease (AD). The GEC consists of scientists, bioethicists, lawyers, genetic counselors, and consumers from a variety of institutions and affiliations. Four of the 8 co-authors of this paper delivered presentations on the case. Supplemented by additional ethical and legal observations, these presentations form the basis for the following discussion.

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (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)

Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma cells treated with FITC conjugated Abeta1-40 (...) localized Abeta to the nucleus in the presence of H2O2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Abeta peptides and/or H2O2. Abeta treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Abeta peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD. (shrink)

En novembre 1984, Christa Wolf ouvrait la première conférence de l'association des gynécologues psy-chosomaticiens de RDA réunis à Mag-Debourg. Dans son discours intitulé "Maladie et privation d'amour", elle s'interrogeait sur l'évolution de la médecine moderne dont les progrès en matière d'appareils médicaux éloignaient toujours davantage les praticiens de leurs patients. Par-delà son regard sur la relation entre l'âme et le corps, Christa Wolf informait aussi des attentes des femmes qui avaient pris au mot les promesses d'égalité des sexes en (...) régime "socialiste réel". Quelques années plus tôt Georges Canguilhem, résistant au scientisme triomphant, se proposait de continuer à penser la médecine comme un art qui devait s'adapter à chaque individu malade. Déplorant la disparition progressive de la clinique, il plaidait pour un dialogue continu entre le patient et le médecin Tandis que Sonia Combe s'appuie sur le discours de Christa Wolf pour appréhender l'expérience communiste à partir de l'étude de genre, revenant sur la double leçon de Christa Wolf et de Canguilhem, Antoine Spire se demande dans quelles conditions un retour de la médecine à la pratique clinique pourrait se faire et répondre à la demande des malades. (shrink)

Cognitive deficits were produced in rats by different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate, and AMPA) of the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of the neurotoxin, (...) colchicine) of the granule cells of the dentate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex and/or hippocampus) restored performance almost to control levels, with a time course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. After ischaemic damage, however, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage it was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft functional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Because the different types of brain damage studied provide analogues of human alcoholic dementia, Alzheimer's disease, and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans. (shrink)

Shift work is a fixture of our 24-hour economy, with approximately 18 per cent of workers in the USA engaging in shift work, many overnight. Since shift work has been linked to an increased risk for an array of serious maladies, including cardiometabolic disorders and cancer, and is done disproportionately by the poor and by minorities, shift work is a highly prevalent economic and occupational health disparity. Here we draw primarily on the state of science around shift work and breast (...) cancer to argue that shift work represents a public health threat serious enough to warrant a precautionary stance. We use the precautionary principle to advance our case and view it as a moral compass for shift work research, empowering public health to cast shift work within the domain of health disparities deserving action despite scientific uncertainty. With the precautionary principle, we call for a deliberative decision-making process and formation of a broad shift work research collaboration to protect the health of many millions who work at night. (shrink)

Les utopies se situent souvent dans des futurs où le handicap et la maladie n’existent plus. À rebours de ces rêves d’éradication, les SF crip spéculent sur les manières dont les vies handies permettent d’imaginer d’autres mondes. Ni des métaphores, ni des idéaux, ni des super-pouvoirs ou des vies improbables, les expériences crip deviennent des occasions de penser nos rapports à la terre, au corps et aux technologies qui les traversent.

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

Research on dyscalculia in neurodegenerative diseases is still scarce, despite high impact on patients’ independence and activities of daily living function. Most studies address Alzheimer’s Disease; however, patients with Parkinson’s Disease also have a higher risk for cognitive impairment while the relation to arithmetic deficits in financial contexts has rarely been studied. Therefore, the current exploratory study investigates deficits in two simple arithmetic tasks in financial contexts administered within the Clinical Dementia Rating in a sample of 100 PD patients. Patients (...) were classified as cognitively normal or mildly impaired according to Level I consensus criteria, and assessed using a comprehensive neuropsychological test battery, neurological motor examination, and sociodemographic and clinical questionnaires. In total, 18% showed arithmetic deficits: they were predominately female, had longer disease duration, more impaired global cognition, but minor signs of depression compared to PD patients without arithmetic deficits. When correcting for clinical and sociodemographic confounders, greater impairments in attention and visuo-spatial/constructional domains predicted occurrence of arithmetic deficits. The type of deficit did not seem to be arbitrary but seemed to involve impaired place × value processing frequently. Our results argue for the importance of further systematic investigations of arithmetic deficits in PD with sensitive tests to confirm the results of our exploratory study that a specific subgroup of PD patients present themselves with dyscalculia. (shrink)

Le don d’ovocytes est une technique d’assistance médicale à la procréation dont peuvent parfois bénéficier des femmes qui souhaitent ne pas prendre le risque de transmettre une maladie génétique. Aucune étude ne s’étant spécifiquement intéressée à ces dernières, l’auteur de cet article a souhaité mieux connaître la façon dont elles se préparent à devenir mères dans ce contexte singulier. Les pistes de réflexion proposées sont issues d’entretiens cliniques menés auprès de deux femmes enceintes souffrant d’une maladie génétique. Ces (...) dernières doivent s’engager dans un processus d’élaboration des angoisses suscitées par la figure de la donneuse, notamment celle de ne pas être reconnue comme mère par leur enfant et que celui-ci veuille retrouver la donneuse. De plus, le choix de recourir à un don d’ovocytes les conduit à réinterroger l’histoire de leur maladie et peut réactiver l’hostilité à l’égard des parents qui ont transmis les gènes de la maladie. L’engagement dans un processus de renoncement de la transmission de leur filiation génétique sera étroitement lié au destin de cette hostilité. (shrink)

Cet article a pour but de montrer la proximité importante de deux auteurs, a priori très différents, au sujet de la question de la santé et de la maladie : Georges Canguilhem et Oliver Sacks. Ils se sont tous deux efforcés de critiquer une conception naturaliste et objectiviste de la santé et de la maladie, le premier en forgeant et en travaillant le concept de norme vitale, le deuxième en décrivant des patients atteints de troubles neurologiques. Ils se (...) rejoignent pour soutenir que la maladie n’est pas une réalité antinaturelle ou aberrante, mais une façon de vivre, une forme d’équilibre physiologique. Toutefois, leurs façons de concevoir la santé vont s’avérer très différentes, pour ne pas dire antinomiques. Canguilhem se reconnaît très influencé par Nieztsche : la santé, c’est la grande santé, la capacité à surmonter les maladies et les épreuves. Il s’ensuit un dualisme entre les héros de la grande santé et la vie plus faible et plus fragile de tous les autres, un dualisme que Sacks remet radicalement en cause lorsqu’il montre que la maladie est aussi une expérience qui nous ouvre à des possibilités nouvelles. Le dialogue qui peut s’ouvrir entre ces deux penseurs permet de problématiser des enjeux essentiels de la question de la santé et de la maladie. (shrink)

A scholarly and imaginative contribution to ethics and aesthetics. The author sees in certain types of abstract art an affectation of austerity which he interprets as compensation in the aesthetic realm for moral lassitude, and a symptom of the decadence which characterizes our age. Decadence is natural and inevitable; in fact, everything is decadence, but in some ages, notably ours, decadence becomes monstrous. The author distinguishes two types of austerity: the limited and rational, and the infinite. Rational austerity is the (...) austerity of the scientist, who denies himself everything but abstract relationships. Through this austerity, the aesthetic and moral realms are joined, in a Platonic fashion; but when this sort of austerity is applied to ethics, it results in a stylized and unproductive ethics. It is necessary to turn to infinite austerity, in which it is seen that the moral "cure" is itself a further "malady," but a malady which is a continuous cure. Even infinite austerity, however, is not enough; in the end, "C'est l'amour qui importe, non l'austérité."--D. S. (shrink)

There’s a possibly more interesting general question: does technology transform and extend the mind and our mental powers? In a widely discussed 1998 paper titled “The Extended Mind”, Andy Clark and David Chalmers argue that mind and cognition can extend outside the head and can include items and processes in the world. In their thought experiment, Otto has alzheimer’s syndrome but does not lose his ability to function because he records information he learns in a notebook that he always carries. (...) Thus, C&C claim, Otto continues to have beliefs. The notebooks function as his memory. C&C propose a "parity principle": a part of the world is part of a cognitive process if it "functions as a process which, were it done in the head, we would have no hesitation in recognizing [it] as part of the cognitive process .... Cognitive processes ain't (all) in the head!" (in Menary p. 29, original emphasis). (shrink)

Le don d’ovocytes est une technique d’assistance médicale à la procréation dont peuvent parfois bénéficier des femmes qui souhaitent ne pas prendre le risque de transmettre une maladie génétique. Aucune étude ne s’étant spécifiquement intéressée à ces dernières, l’auteur de cet article a souhaité mieux connaître la façon dont elles se préparent à devenir mères dans ce contexte singulier. Les pistes de réflexion proposées sont issues d’entretiens cliniques menés auprès de deux femmes enceintes souffrant d’une maladie génétique. Ces (...) dernières doivent s’engager dans un processus d’élaboration des angoisses suscitées par la figure de la donneuse, notamment celle de ne pas être reconnue comme mère par leur enfant et que celui-ci veuille retrouver la donneuse. De plus, le choix de recourir à un don d’ovocytes les conduit à réinterroger l’histoire de leur maladie et peut réactiver l’hostilité à l’égard des parents qui ont transmis les gènes de la maladie. L’engagement dans un processus de renoncement de la transmission de leur filiation génétique sera étroitement lié au destin de cette hostilité. (shrink)

Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, (...) and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind–body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person’s sense of presence and agency in the world. (shrink)

BackgroundSexual minority (SM) older adults experience mental health disparities. Psychiatric disorders and neuropsychiatric symptoms (NPS) are risk factors for cognitive decline. Although older people in same-sex (SSR) compared to mixed-sex relationships (MSR) perform more poorly on cognitive screening tests, prior studies found no differences in rates of dementia diagnosis or neuropsychological profiles. We sought to explore the role of NPS on neurocognitive outcomes for SM populations. We compared cognitive performance and structural brain parameters of older adults in SSR and MSR.MethodsData (...) were originally collected at Alzheimer's Disease Research Centers (ADRCs). Inclusion criteria were: age of 55+ years, a study partner identified as a spouse/partner, and availability of T1-MRI brain volumes/thickness. Participants were labeled as either SSR or MSR based on their/their co-participant's reported sex. We identified 1,073 participants (1,037 MSR−555 cognitively unimpaired [CU]; 36 SSR−23 CU) with structural MRI data, Mini-Mental State Exam (MMSE), and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores. A subset of the overall sample completed comprehensive neuropsychological assessment (n = 939; 908 MSR−494 CU; 31 SSR−22 CU). Covariates included in statistical models were age, sex, education, total intracranial volume, and apolipoprotein E genotype.ResultsMultivariate general linear models showed significant diagnosis-by-relationship interaction effects on the left parahippocampal gyrus volume. After stratification by relationship group, only cognitively impaired (CI) MSR had significantly smaller left parahippocampal volumes than MSR-CU. The SSR group showed better episodic memory performance. Severity of neuropsychiatric symptoms was negatively associated with volume/thickness of bilateral fronto-temporal areas and with MMSE scores, predominantly in the MSR group.ConclusionIn our study, MSR participants presented with a more compromised cognitive profile than SSR participants. MSR-CI participants showed significantly smaller left medio-temporal volumes, a neural signature of AD. Neuropsychiatric symptoms predicted smaller fronto-temporal volumes in the MSR more consistently than in the SSR group. These findings may be due to unexplored protective factors against cognitive decline in SM elders. Indeed, social support has been proposed as a protective factor warranting future investigation. (shrink)