京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第24540号 / 人健博第111号 / 新制||人健||8(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 澤本 伸克, 教授 稲富 宏之, 教授 髙橋 良輔 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Le dé cit cognitif est une cause majeure de handicap de la personne âgée. Du fait de l’augmentation de la durée de vie, le nombre de personnes âgées qui pourraient béné cier d’une prise en charge spécialisée dans le but de ralentir leur perte fonctionnelle va croitre. En dépit de traitement validé qui stoppe le processus neurodégénératif, des interventions spéci ques peuvent en ralentir les manifestations. De nombreuses études expérimentales, neuroscienti ques et comportementales ont démontré la relation étroite entre cognition en motricité.Ce travail doctoral propose d’explorer si certaines caractéristiques de la marche sont des biomarqueurs non-invasifs d’un trouble cognitif et des chutes, et de mieux comprendre les relations entre la cognition et le contrôle de la marche. Le cadre théorique était l’hypothèse de la « Perte de Complexité ». Des analyses multivariées ont été appliquées aux critères de jugement dynamiques de marche en relation avec le statut cognitif-et-chute (Le Chapitre 1).Le Chapitre 2 est une revue systématique de la littérature. Nous avons recensé 20 études longitudinales de prédiction de trouble de la marche et de dé cit cognitif. La vitesse de marche était associée à la cognition, son ralentissement était un prédicteur de la perte cognitive. Cette revue a aussi mis en évidence la nécessité d’améliorer la mesure des phénomènes concernésL’objectif du Chapitre 3 était de déterminer ce qu’apportait l’évaluation cognitive (MMSE, mémoire et fonctions exécutives) et des paramètres dynamiques précis de la marche, au bilan habituel du risque de chute. La précision de la classi cation entre chuteurs et non- chuteurs a augmenté avec l’ajout de la cognition et des paramètres de marche de AUC=0.86 à AUC=0.93. La spéci cité du modèle de classi cation a, quant à elle, augmenté de 60% à 72% avec l’ajout des mesures cognitives, et de 72% à 80% avec l’ajout des paramètres dynamiques de la marche. Dans leur ensemble, ces résultats montrent l’intérêt d’une approche multidimensionnelle incluant l’évaluation des fonctions cognitives et de la marche, dans la prédiction du risque de chute chez la personne âgée.Le Chapitre 4 détermine les paramètres de marche les plus associés au déclin cognitif. La vitesse de marche, la régularité, la prévisibilité et la stabilité ont montré que les simples et doubles-tâches étaient les plus discriminantes (score VIP moyen de 1.12). La marche des patients avec troubles cognitifs est plus lente, moins régulière et moins stable que celle de personnes âgées saines. Cependant, les résultats montrent également que la discrimination des patients âgés avec et sans dé cit cognitif, fondée sur l’exploitation des paramètres de marche uniquement, est faible, avec 57% (simple tâche) et 64% (double-tâche) des patients classés de manière erronée.Le Chapitre 5 présente une étude pilote prospective dans laquelle les paramètres de marche les plus discriminants du Chapitre 4 ont été étudiés. Les résultats ont montré qu’un déclin cognitif signi catif observé après 14.4 mois en moyenne était corrélé avec une marche plus régulière (ρ=0.579*) et plus prévisible (ρ=0.486*) mesurée pendent les mesures de ligne de base, mais pas avec la vitesse de marche de la ligne de base (ρ=0.073). Une augmentationde la régularité et de la prévisibilité de la marche est le re et d’une perte de la complexité de la marche, témoin d’une détérioration future des fonctions cognitives chez les patients âgés.Les résultats de ce travail doctoral sont résumés et discutés dans le Chapitre 6. / The rising life expectancy will result in an increased number of ‘older old adults’ who will need specialized geriatric care to slow functional decline. Cognitive impairment is a major cause of disability in geriatric patients. Even though there is no cure yet to reverse neurodegeneration, tailored interventions can slow disease progression and reduce symptoms. Because of the abundant evidence from experimental, neuroscienti c, and behavioral studies that underscored the close link between motor- and cognitive function, the present thesis proposed to use gait characteristics as non-invasive indicators of cognitive impairment and falls in geriatric patients. The main objective therefore was to increase our understanding of the relationship between gait and cognition in this vulnerable population, in which gait outcomes were calculated from 3D-acceleration signals of the lower trunk that were collected with an iPod Touch 4G. The ‘Loss of Complexity’ hypothesis provided a theoretical framework. Multivariate analyses were applied to dynamic gait outcomes in relation to cognitive- and fall-status (Chapter 1).Chapter 2 presents a systematic literature review including 20 longitudinal studies that examined associations between baseline gait function and future cognitive decline. A slow gait speed was associated with future decline in global cognition and in speci c cognitive functions, and with an increased risk for Mild Cognitive Impairment (MCI) and dementia (maximal odds and hazard ratios of 10.4 and 11.1, respectively) in 4.5 years on average. The review projected that future research could increase the speci city of the gait-cognition link by indexing gait and cognition in more detail.From this perspective, Chapter 3 examined whether an extensive cognitive evaluation (global cognition, memory, and executive functioning) and ne-grained, dynamic gait outcomes could add to a usual fall-risk screening. The overall classi cation accuracy of fallers and non-fallers increased from Area Under the Curve (AUC) =0.86 to AUC=0.93. The speci city of the fall-classi cation model increased from 60% to 72% when cognitive outcomes were added, and from 72% up to 80% when gait dynamics were added to the model. The results underscored the need for a multifactorial approach in fall risk assessment in geriatric patients, including a detailed evaluation of cognitive- and gait function.Chapter 4 explored what gait outcomes are most susceptible to change with cognitive decline, and examined multiple gait outcomes in relation to cognitive impairment. Outcomes related to gait speed, regularity, predictability, and stability revealed with the highest discriminative power, indicated by the Variable Importance in Projection (VIP)-values for single- and dual-tasking (average VIP-score of 1.12, with a VIP-score>1 indicating a high discriminative power). Geriatric patients walked slower, less regular, and less stable than healthy old controls. However, the discrimination of geriatric patients with- and without cognitive impairment based on gait outcomes alone was poor, with 57% (single-task) and 64% (dual-task) of the patients being misclassi ed.In Chapter 5, the gait outcomes with the highest discriminative power in chapter 4 were studied in a prospective pilot study. Signi cant cognitive decline (in global cognition, memory, and executive functioning) over 14.4 months on average correlated with a moreregular (ρ=0.579*) and more predictable (ρ=0.486*) gait at baseline, but not with baseline gait speed (ρ=0.073). The increased gait regularity and predictability re ected a loss of gait complexity and this loss of gait complexity may thus predict future cognitive decline in geriatric patients.The results are summarized and discussed in Chapter 6 of this thesis.

WEAVING IN WOOD  An architectural strategy in Umeå that strive to decrease loneliness and include elderly with physical and cognitive impairments A Master Thesis by Rebecka Littbrand                                                                                                   Spring 2020   Background Feelings of loneliness is common in the whole western world, especially among older people. Loneliness is of public health concerns as being a risk factor for many severe diseases and premature mortality. Scientists argues that an increase of social embeddedness is essential for improvements in well-being and quality of life. The focus group for this master thesis is elderly that lives in ordinary housing in Umeå, Sweden. Among elderly physical and cognitive impairments such as dementia are common, as well as getting help from the Home care service. Methodology This master thesis investigates different factors linked to loneliness, the current situation in Umeå regarding meeting places for elderly and architectural features to include elderly with impairments. Study visits to existing meeting places, interviews with local actors and experts within the field as well as reading literature have driven the project forward.   Findings Most districts in Umeå have no meeting place where elderly with impairments easily can participate. To include elderly with physical and cognitive impairments there are important to counteract 5 barriers: Long distance, Hidden placement, Need to plan and sign up in advance to participate, Insecurity if there will be someone there who can support you and Cost for participating.        To ease for people with dementia and to create a meeting place that feels welcoming and secure there are several architectural features that should be taken into consideration, e.g. arrange the rooms around a central common space, highlight functions by using powerful colours, being on ground floor and visual connections between certain spaces, which the “Open meeting places” provided by the municipality in Umeå have problems in fulfilling.    Conclusion  An architectural strategy in Umeå to reduce loneliness among elderly living in ordinary housing and that counteracts the barriers to include elderly with physical and cognitive impairments is needed. By placing New open meeting places next to the local food stores in the different districts of Umeå the barriers Hidden placement and Long distance are counteracted, enabling the Home care service to guide elderly to the places. The meeting places will consider important architectural features to include people with dementia and create a place that feels welcoming and secure.      The New open meeting places will collaborate with local actors, strive to highlight the importance of social interaction, take away the stigma related to loneliness as well as give the elderly population more prominent and visible places in society.

Αντικρουόμενα συμπεράσματα παρουσιάζονται στη βιβλιογραφία σχετικά με την υγεία των καλλιεργητών. Στην παρούσα μελέτη η επίδραση της ενασχόλησης με τις αγροτικές καλλιέργειες διερευνήθηκε με κλινικά και εργαστηριακά ευρήματα, συγκρίνοντας αγρότες με μη αγρότες που διαμένουν στις ίδιες αγροτικές περιοχές. Δείγμα 328 αγροτών και 347 μη αγροτών, σταθμισμένα κατά ηλικία και φύλο, επελέγησαν με τυχαίο τρόπο σε αγροτικές περιοχές του νομού Αιτωλοακαρνανίας στη Δυτική Ελλάδα. Στα μέλη και των δύο ομάδων έγινε αιμοληψία για διενέργεια γενικής εξέτασης αίματος και βιοχημικών εξετάσεων ενώ εφαρμόστηκαν δύο νευροψυχιατρικές δοκιμασίες, η MMSE και η MADRS για την εκτίμηση της μνήμης και της διάθεσης αντίστοιχα και δύο νευρομυϊκές δοκιμασίες, η MRCS και η MAS για την εκτίμηση του μυϊκού τόνου και της μυϊκής κινητικότητας αντίστοιχα. Έγινε καταγραφή των δημογραφικών στοιχείων, διατροφικών και άλλων συνηθειών και του ατομικού ιατρικού ιστορικού. Από τους αγρότες ζητήθηκαν πληροφορίες σχετικά με τις καλλιέργειες, τα χρησιμοποιούμενα φυτοφάρμακα και τα λαμβανόμενα προστατευτικά μέσα. Οι αγρότες ανέφεραν συχνότερα αρτηριακή υπέρταση και κάποιες καρδιαγγειακές νόσους, ορθοπεδικά και ΩΡΛ προβλήματα. Στους αγρότες παρατηρήθηκαν χαμηλότερες τιμές αιματοκρίτη, αιμοσφαιρίνης και χολινεστεράσης πλάσματος και υψηλότερες τιμές καλίου, ασβεστίου, SGOT, LDH, χολερυθρίνης, ολικών λευκωμάτων, CRP και τριγλυκεριδίων. Στους αγρότες νεότερων ηλικιών παρατηρήθηκαν χαμηλότερες τιμές αρτηριακής υπέρτασης και καλύτερες επιδόσεις στις δοκιμασίες MMSE και MADRS σε σχέση με τους μη αγρότες, ενώ στις μεγαλύτερες ηλικίες συνέβαινε το αντίθετο. Κανένας νέος αγρότης δεν εμφάνιζε παθολογικά αποτελέσματα στις δοκιμασίες MRCS και MAS, ενώ οι ηλικιωμένοι αγρότες είχαν μεγαλύτερη συχνότητα παθολογικών αποτελεσμάτων σε σχέση με τους ηλικιωμένους μη αγρότες. Οι αγρότες είναι περισσότερο ευάλωτοι σε διάφορα προβλήματα υγείας. Οι παράγοντες που σχετίζονται με αυτή την τάση δεν είναι απολύτως σαφείς. Χρειάζονται περισσότερες αποδείξεις για να συνδεθεί η έκθεση στα φυτοφάρμακα με τα παρατηρούμενα προβλήματα υγείας. / Contradictory outcomes concerning the farmers’ health are reported in the literature. In this study the effect of “farming” is investigated by comparing farmers versus non-farmers living in the same rural area with regard to certain clinical and neurobehavioral health outcomes. 328 farmers and 347 non-farmers, matched per age and sex, were selected randomly in an agricultural area in West Greece. Both groups underwent haematological and biochemical examinations and were administered two neurobehavioral tests, namely the Mini-Mental State Examination (MMSE) and the Montgomery-Åsberg Depression Rating Scale (MADRS) as well as two neuromuscular tests, the Medical Research Council Scale (MRCS) and the Modified Ashworth Scale (MAS). Sociodemographic, personal medical, nutritional data and lifestyle were recorded. Farmers also gave details concerning cultivations, application of pesticides and protective measures taking. According to personal statements, farmers suffered from hypertension, cardiovascular, orthopaedic and ENT problems in higher frequency. Haematocrit, haemoglobin and serum cholinesterase’s activity were found to be lower among farmers. Potassium, calcium, SGOT, LDH, bilirubin, albumin, CRP and triglycerides levels are higher among farmers. Lower prevalence of hypertension and better performances on MMSE and MADRS tests were recorded in young farmers in relation to young non farmers, while these findings were reversed in older ages. Noone young farmer has abnormal results in MRCS and MAS tests, while in older ages farmers present abnormal results in higher frequency than non farmers in those scales. Farmers are susceptible to potential impairments on their health status. Factors affecting these impairments remain to be clarified. The pesticides’ exposure needs further investigation and evidence in order to be correlated with the observed effects.

This thesis contains an overview of the mechanisms of addiction as well as a description of the impairments related to drug abuse. The general view of addiction is that it depends on three characteristics that have separate neural mechanisms, called “wanting”, liking and learning. “Wanting” is described as a desire evoked by reward cues, liking refers to the pleasure of getting a reward and learning is described in terms of classical conditioning. “Wanting” and liking are usually in agreement but in addiction they are dissociable, that is, wanting a drug but getting no pleasure from it. Reward cues, acquired through learning, awakes the motivation to obtain the drug again. This can be problematic when trying to cease drug taking. The dopamine system in the brain is much discussed in relation to addiction and its neural correlates. The prefrontal cortex (PFC) is suggested to be altered in addiction, and this may underlie some of the impairments discussed. Addiction is also strongly related to cognitive impairments such as working memory problems, impulsivity, attentional problems and decision-making impairments. Affective impairments, such as empathy problems, may also to have some connection to addiction, although this is less clear.

Digitalisation in today’s society is constantly evolving. Research shows the positive effects of apps for people with cognitive impairments by enabling meaningful activities as well as increasing independence. The purpose of this study was to describe the occupational therapist's professional reasoning regarding the recommendation and use of apps to enable activity for people with a cognitive impairment. The study adopted a qualitative approach to capture the participants' reasoning whilst working with apps. The selection was carried out with purposeful selection based on the criteria set. A total of ten participants participated. Data was collected via semi-structured interviews with open-ended questions and then analysed with a qualitative content analysis. The analysis resulted in three categories; Identify the client's needs and prerequisites to promote activity, Match and customize the app for a sustainable use and The Occupational Therapist's prerequisites for using apps as an intervention. The results shows that the occupational therapist works closely with the client and its social network to match the appropriate app based on needs and conditions in activity. Furthermore, the occupational therapists see great benefits of using apps, primarily for the supportive features that can increase independence as well as the freedom of movement the app can contribute to. However, problem areas are in the form of uncertainty in app updates and difficulties in having sufficient knowledge of the available apps. The conclusion is that Occupational therapists in this study use a wide breadth in their reasoning. Where several aspects of the client's needs and prerequisites as well as the occupational therapist's own prerequisites are weighed together to use apps as intervention. This showed great complexity, as apps are a new and large area for the occupational therapists and therefore further studies are needed for more knowledge within the subject.

Education reform in schools has focused on inclusion of all students in general education environments and accountability measures. Students with cognitive impairments are mandated to participate in standards-based alternate assessments. Special education teachers in a school district in a southeastern state in this study have been faced with the challenge of implementing these assessments. A bounded case study design was used to examine their perceptions of the use of standards-based alternate assessments for students with cognitive impairments. Guiding research questions focused on the nature and process of implementing alternate assessments. Resistance to change was the conceptual framework. The bounded case included 3 elementary, 1 middle school, and 4 high school special education teachers who have taught students with mild to moderate cognitive disabilities in self-contained classrooms in the district. Teachers were interviewed and data were coded and analyzed for common themes. Results included implementation concerns such as time for administration, scoring issues, lack of usefulness of assessment results, inappropriate expectations for performance, and lack of validity of assessments for cognitively impaired students. Recommendations included decision makers' reconsideration of the procedures for implementation and establishing validity and usefulness of standards-based alternate assessments. Findings in this study reflected teachers' resistance to change, but were informative in providing local decision makers with an opportunity for social change that includes examination of where current policy fails to accommodate students with cognitive impairments and creation of appropriate policy and assessments that actually benefit those students.

No description available.

The increased understanding of underlying neurobiological processes and their connections to cognitive performance has opened new doors for novel therapeutic strategies that aim to prevent, and even reverse the effects of memory disorders, neurodegenerative diseases and other cognitive impairments. One of the new and exciting drug targets that has emerged as a result of this research is insulin-regulated aminopeptidase (IRAP). While the research is still in its early stages, inhibition of IRAP have promising therapeutic potential and several small molecule and peptidomimetic candidates that act as inhibitors of IRAP have been synthesized. Analysis of in vivo performed novel object recognition tests, in vitro cell viability and morphology assays were conducted in this study to further investigate the cognitive effects and other effects of an IRAP-inhibitor called HA08. Recorded novel object recognition test previously performed on rats were scored and analysed with statistical software. Primary cortical and hippocampal cells harvested from rat fetuses were treated with increasing concentrations of HA08 and oxytocin. The cell viability assays consisted of LDH assays to analyse HA08’s effect on the cells membrane integrity and MTT assays to analyse its effect on mitochondrial function. Immunocytochemistry was used to assess the difference in neurite length in cortical cells and the number of dendritic spines in hippocampal cells. No increases in recognition were found in HA08 treated rats. HA08 did not seem to affect the membrane integrity at concentrations used. Further research is needed to improve the accuracy of the results and to fully unlock the potential of IRAP-inhibitor HA08.

Background: Technology can provide efficient and accessible solutions to manage private economy, taking into account user needs and experiences. People with disability are most likely to encounter challenges related to financial literacy and lack of access to their own money. The project God man i fickan in Sweden aims to develop an accessible application that supports people with difficulties handling their private economy. Purpose: The purpose of this study was to investigate basic functions and interactions in a digital tool used by people who cannot manage their own economy without some kind of assistance. Method: Participatory design activities involving people with cognitive impairments were utilized. The qualitative data collection included discussions, storyboarding and an online design session. Due to Covid- 19 we had to modify one workshop for online environments. The collected data was analyzed with a content theme analysis which then was visualized and refined iteratively through wireframes and a lo-fi prototype. Results: The study revealed a number of user values, reflecting user needs, and a number of key features that should be supported by the application. A heuristic evaluation of the lo-fi prototype showed that using a provocative object engaged the participants in critical reflections and discussions. Discussion: By involving people with cognitive impairments in the design process through participatory design activities, the methodology used in this study allowed them to influence the design and application functionalities. / Bakgrund: Teknik kan bidra med effektiva och tillgängliga lösningar för att hantera privatekonomi, med hänsyn till användarens behov och erfarenheter. Personer med funktionsnedsättningar är den grupp som möter störst utmaningar relaterade till ekonomisk förståelse och bristande tillgång till sina egna pengar. Syftet med projektet God man i fickan är att utveckla en applikation som stödjer personer med svårigheter att hantera sin privatekonomi. Syfte: Syftet med denna studie var att undersöka grundläggande funktionalitet och interaktion i ett digitalt verktyg för personer som inte kan hantera sin ekonomi utan någon form av assistans. Metoder: För att genomföra studies syfte användes deltagande design aktiviteter med personer med kognitiva funktionsnedsättningar. Kvalitativa data samlades in genom diskussioner, storyboarding och en designsession. På grund av Covid-19 var vi tvungna att anpassa en workshop för miljöer online. Data som samlades in analyserades i olika teman som visualiserades och gradvis förfinades genom wireframes och en lo-fi prototyp. Resultat: Studien kunde urskilja ett antal användarvärden, som reflekterar användarbehov, och ett antal nyckelfunktioner som borde vara inkluderade i applikationen. En heuristisk utvärdering av lo-fi prototypen visade på att användningen av ett provokativt objekt engagerade användarna i kritiska reflektioner och diskussioner. Diskussion: Genom att involvera personer med kognitiva funktionsnedsättningar i designprocessen och i deltagande design aktiviteter kunde studie ge dessa personer ett inflytande över designen och applikationens funktionalitet.