Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

ObjectiveTo use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.MethodsRasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008–December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.ResultsThe Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.ConclusionsThese two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up.

Queering the web archive: A xenofeminist approach to gender, function, language and culture in the London French Special Collection

Based on the author’s experience of curating a collection of migrant community web objects within the UK Web Archive, this paper combines conceptual interrogation with empirical analysis. The central premise is that the incorporation of multilingual, diasporic micro-archives serves to queer the anglophone UK Web Archive, or “patriarchive”, by dismantling steadfast binaries and implicit postcolonial hegemonies. The article challenges Jacques Derrida’s contention that the mal d’archive is the result of the archive’s ‘troubling’ duality, and posits, on the contrary, that such boundary-crossings are the very incarnation of a positive, transgressive form of xenofeminism (XF). From the dualism at the origin of the archive itself, to that comprised in the concept of genre/gender, and from the spatiotemporal in-betweenness of the archived diasporic (web)site to the translanguaging present therein, the article demonstrates how the diasporic micro-archive is the embodiment of a non-binary, trans-inclusive XF ideology. Taking French migrant women’s blogs preserved in the London French Special Collection as a primary source and examining their transformation over time, the paper explores how blog repurposing can be apprehended as a technomaterialist XF act and how the blogs’ increasing multimodal translanguaging bears witness to a form of culturo-linguistic transitioning that transcends binary hybridity.

A Cognitive Archaeology of Writing: Concepts, Models, Goals

Complex systems like literacy and numeracy emerge through multigenerational interactions of brains, behaviors, and material forms. In such systems, material forms – writing for language and notations for numbers – become increasingly refined to elicit specific behavioral and psychological responses in newly indoctrinated individuals. These material forms, however, differ fundamentally in things like semiotic function: language signifies, while numbers instantiate. This makes writing for language able to represent the meanings and sounds of particular languages, while notations for numbers are semantically meaningful without phonetic specification. This representational distinction is associated with neurofunctional and behavioral differences in what neural activity and behaviors like handwriting contribute to literacy and numeracy. In turn, neurofunctional and behavioral differences place written representations for language and numbers under different pressures that influence the forms they take and how those forms change over time as they are transmitted across languages and cultures.

Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum

Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and communication/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and FASD. Oxidative and ER stresses are induced by thiamine deficiency, especially in alcohol abuse, and are exacerbated by neuroinflammation, particularly in fetal ethanol exposure. Furthermore, exposure to ethanol during the prenatal period interferes with neurotransmission, neurotrophic factors and retinoic acid-mediated signaling, and reduces the number of microglia, which diminishes expected cerebellar development. We highlight the spectrum of cerebellar damage induced by ethanol, emphasizing physiological-based clinical profiles and biological mechanisms leading to cell death and disorganized development.

Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer’s disease

Background Although few studies have shown that risk factors for Alzheimer’s disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer’s disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD. Methods We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories. Results APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD. Conclusions Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.

Executive Function, Language, and the Toddler’s Discovery of Representational Drawing

Working memory capacity and executive functions play important roles in the early development of drawing and language, but we lack models that specify the relationships among these representational systems and cognitive functions in toddlers. To respond to this need, the present study investigated the relations between drawing and language in very young children, and the role of working memory capacity, inhibition, and shifting in the association between these two representational systems. The participants were 80 children, 25–37 months old. The results revealed that in toddlers (a) all the measures of working memory, inhibition, and shifting loaded on a single factor of general executive functioning; (b) language and drawing are two distinct, but substantially correlated, representational systems; and (c) the development of executive function has a strong impact on language development, which in turn influences the development of drawing.

A Systematic Review of MRI Neuroimaging for Education Research

This study aims to disclose how the magnetic resonance imaging (MRI) neuroimaging approach has been applied in education studies, and what kind of learning themes has been investigated in the reviewed MRI neuroimaging research. Based on the keywords “brain or neuroimaging or neuroscience” and “MRI or diffusion tensor imaging (DTI) or white matter or gray matter or resting-state,” a total of 25 papers were selected from the subject areas “Educational Psychology” and “Education and Educational Research” from the Web of Science and Scopus from 2000 to 2019. Content analysis showed that MRI neuroimaging and learning were studied under the following three major topics and nine subtopics: cognitive function (language, creativity, music, physical activity), science education (mathematical learning, biology learning, physics learning), and brain development (parenting, personality development). As for the type of MRI neuroimaging research, the most frequently used approaches were functional MRI, followed by structural MRI and DTI, although the choice of approach was often motivated by the specific research question. Research development trends show that the neural plasticity theme has become more prominent recently. This study concludes that in educational research, the MRI neuroimaging approach provides objective and empirical evidence to connect learning processes, outcomes, and brain mechanisms.

537 Insomnia Symptoms and Subsequent Cognitive Performance in Older Adults: Are Depressive Symptoms and Vascular Disease Mediators?

Introduction Alzheimer’s disease and related dementias (ADRD) are growing public health concerns, and poor sleep may represent a modifiable risk factor. However, there is limited research on insomnia as a predictor of subsequent performance in different cognitive domains and mechanisms that might underlie domain-specific associations. The current study examined: (1) which insomnia symptoms predicted performance across five cognitive domains 14 years later, and (2) whether depressive symptoms and/or vascular diseases mediated these associations. Methods Participants included 2,496 adults aged 51+ in the Health and Retirement Study. Insomnia symptoms in 2002 (i.e., “baseline”) were quantified by four self-reported items on frequency of trouble falling asleep, nighttime awakenings, early awakenings, and feeling rested upon awakening. Cognition was assessed in 2016 as part of the Harmonized Cognitive Assessment Protocol and operationalized with five factor scores corresponding to episodic memory, executive function, language, visuoconstruction, and processing speed. Multiple regressions examined associations between baseline insomnia symptoms and subsequent cognitive performance, controlling for sociodemographics and baseline global cognitive performance. Mediation models tested whether associations were explained by self-reported depressive symptoms and/or vascular diseases (i.e., hypertension, heart disease, diabetes, and/or stroke) in 2014, controlling for baseline values. Results Only trouble falling asleep in 2002 was associated with cognition in 2016. Specifically, more frequent trouble falling asleep predicted poorer episodic memory, executive function, language and processing speed performance, but not visuoconstruction. These associations were mediated by depressive symptoms and vascular diseases in 2014 for all domains except episodic memory; only depressive symptoms mediated the association involving memory. After accounting for these mediators, direct effects of trouble falling asleep remained for episodic memory, executive function and language, but not processing speed. Conclusion Difficulty with sleep initiation may be more consequential for later-life cognition than other insomnia symptoms. Depressive symptoms and vascular diseases may partially drive these associations. We speculate that sleep-onset insomnia could mean less total sleep, immune dysfunction, or endocrine effects that worsen mood, vascular health, and cognition. Remaining associations indicate that additional research is needed to characterize other mechanisms through which sleep initiation problems could contribute to later impairments in frontal and temporal cognitive systems, which are implicated early in ADRD. Support (if any):

PROBLEMATIKA PENCAPAIAN KOMPETENSI KETERAMPILAN BERBICARA SISWADALAM PEMBELAJARAN BAHASA INDONESIA

Learning language skills in schools does not only emphasize theory, but students are required to be able to use language as its function. Language skills in listening, writing, reading, and speaking are a component that cannot be separated from language activities. The ability to speak must also be able to analyze and ensure that what is said can be received appropriately by the listener. In fact, there are still various obstacles in speaking, both internal and external factors. Evaluation of learning to speak is still guided by speaking theory, not emphasizing speaking practice.