An integral concern across care settings is the prompt intervention for patients suffering with pain. Long-term care (LTC) settings present with unique challenges to assess and manage pain in resident populations. Pain assessment is especially challenging, because residents have varying degrees of cognition to communicate their pain, and clinician/staff knowledge of pain symptoms may be lacking. The purpose of this research was to improve the measurement of pain and outcomes of care for the elderly residing in skilled nursing care, especially those with cognitive-impairment. The specific aims of this study were to: 1) Determine the magnitude of the relationship between pain behaviors and a measurement model hypothesized for pain; 2) Test the construct validity of a pain measurement model; 3) Examine the concomitance of pain and cognition in a three-year longitudinal analysis. The research questions answered: 1) Is there a difference in the prevalence of pain in cognitively intact versus cognitively-impaired residents; 2) Can a theoretically derived model of pain aid in detecting pain across all cognitive levels; and 3) Do pain and cognitive status concomitantly correlate? The goal was to examine the covariance model of concomitance of pain and cognition to more accurately construct theoretical models of pain to then include additional resident care factors in future research. Traditional self-reports of pain are often under-assessed and under-treated in the cognitively-impaired (CI) elderly resident. Having additional measures to detect pain beyond self-reports of pain intensity and frequency increases the likelihood of detecting pain in populations with complex symptom presentation. Data collected from skilled nursing facilities offer exceptional opportunities to study resident demographics, characteristics, symptoms, medication use, quality indicators, and care outcomes. The Minimum Data Set-Resident Assessment Instrument (MDS-RAI) 2.0, a nationally required resident assessment tool, must be completed on every resident in a Medicare LTC facility within 14 days of admission, quarterly, annually and with significant changes in resident status. Because the MDS is widely used and recognized in LTC settings, core items from MDS [i.e., pain frequency (J2a) and pain intensity (J2b)] along with additional MDS items hypothesized to signify pain were analyzed in the pilot measurement model. Ten core items from MDS were used: 1) Inappropriate behavior frequency (E4da); 2) Repetitive physical movements; 3) Repetitive verbalizations (E1c); 4) Sad facial expressions (E1l); 5) Crying (E1m); 6) Change in mood (E3); 7) Negative statements (E1a); 8) Pain frequency (J2a); 9) Pain intensity (J2b); and 10) Cumulative pain sites scores. All indicators of pain were significant at the <.01 level. A longitudinal cohort design was used to answer if a concomitance exists between pain and cognition. Data were collected from MDS annual assessments from 2001, 2002 and 2003 for residents across the United States. The sample consisted of 56,494 residents age 65 years and older with an average age of 83 [plus or minus] 8.2 years. Descriptive statistics, ANOVA and a covariance model were used to evaluate cognition and pain at the three time intervals. ANOVA indicated a significant effect (<.01) for pain and cognition with protected t-tests indicating scores decreased significantly over time with resident measures of pain and cognition. Results from this study suggest that: 1) Using only pain intensity and frequency, pain prevalence was found in 30% of the pilot population, while 47.7% of cognitively intact residents had documented pain and only 18.2% of the severely CI had documented pain, supporting previous research that pain is potentially under-reported in the CI; 2) Parsimonious measurements models of pain should include dimensions beyond self-reports of pain (i.e., cognitive, affective, behavioral and inferred pain indicators); 3) Model fit was improved by using specific MDS items in the pain construct; 4) Longitudinal analysis revealed relative stability for pain and cognition measures over time (e.g., larger stability or consistency was found in cognitive measures than the measures of pain over the three-year period); 5) Crossed-legged effects between pain and cognition were not consistent; 6) A concomitant relationship was not found between pain and cognition. The relationship was significant (<.01), but associations were weak (r=0.03 to 0. 08). Pain or cognition should not be used as a predictor of the other in theoretical models for similar populations. The MDS is a reliable instrument to follow resident attributes, quality of care, and patient outcomes over time. The development of more accurate assessments of pain may improve resident care outcomes. Ineffectively intervening on the pain cycle is posited to cause secondary unmet needs that affect the resident's quality of life. Findings support the importance of improving clinical outcomes in the management of pain in the elderly residing in long-term care. Deficits in the treatment of pain highlight the impetus to support health policy change that includes pain treatment as a top health priority and a quality indicator for federally funded programs supporting eldercare.

Syfte: Syftet med denna studie var att beskriva arbetsterapeuters erfarenheter av digitalisering i arbetet med klienter med kognitiva funktionsnedsättningar. Metod: För att besvara studiens syfte användes kvalitativ metod. Data samlades in genom åtta semistrukturerade intervjuer med yrkesverksamma legitimerade arbetsterapeuter från olika verksamhetsområden inom offentlig sektor. Insamlade data analyserades genom kvalitativ innehållsanalys med induktiv ansats. Resultat: Analysen av den insamlade data resulterade i fyra kategorier: Att motivera till delaktighet i en alltmer komplex digital vardag, Att mötas digitalt medför för- och nackdelar, Pedagogiska interventioner utifrån digitala förutsättningar samt Behov av att följa med i utvecklingen. Resultatet beskriver nya arbetssätt som arbetsterapeuterna inkorporerat för att stödja klienternas delaktighet i samhället och hantering av digitala verktyg och tjänster. Resultatet beskriver även faktorer som inverkat på arbetsterapeuternas förvärvande av digital kompetens i syfte att bistå med digitala lösningar till sina klienter, då den digitala omställningen påskyndats av Covid-19 pandemin. Slutsats: Studien visade att arbetsterapeuterna tog stort ansvar att förvärva egen digital kompetens för att kunna stödja klienterna till delaktighet, samt att interventioner och mötesformer har behövts anpassas ur ett klientcentrerat perspektiv utifrån digitala förutsättningar. Vidare forskning behövs gällande digitala videomöten som alternativ till fysiska möten och hur de inverkar på arbetsterapeutisk bedömning samt intervention. / Aim: The purpose of this study was to describe the experience of digitalization for occupational therapists in their work with cognitive impairment clients. Method: To answer the purpose of the study, a qualitative method was used. Data was collected through eight semi-structured interviews with professional licensed occupational therapists from different areas within the public sector. The collected data was analyzed through qualitative content analysis with an inductive approach. Results: The analyzed collected data resulted in four categories: Motivating participation in an increasingly complex digital everyday life, Digital meetings entails pros and cons, Pedagogical interventions based on digital conditions and The need to follow the development. The result describes new ways of working incorporated by occupational therapists to support clients' participation in society as well as the management of digital tools and services. The result also describes factors that have influenced occupational therapists' acquisition of digital skills in order to provide their clients with digital solutions as the digitalization transition has been accelerated by the Covid-19 pandemic. Conclusion: The study showed that occupational therapists took great responsibility to acquire their own digital skills to support their client’s participation, and that interventions and meeting forms have had to be adapted from a client-centred perspective based on digital conditions. Further research is needed regarding digital video meetings as an alternative to physical meetings and the influence on occupational therapy assessment and intervention.

Bakgrund: Antalet äldre i världen ökar ständigt. Åtta procent av Sveriges befolkning, som är 65 år och äldre, har någon form av kognitiv svikt. Med åldern ökar risken för mild kognitiv svikt, vilket påverkar alla områden i människans liv. Mild kognitiv svikt är ett tillstånd som kan leda till mer omfattande kognitiv nedsättning om det inte åtgärdas i ett tidigt skede. Det är därför viktigt att tidigt upptäcka och åtgärda de första symtomen på mild kognitiv svikt.  Syfte: Syftet med studien var att undersöka vilka interventioner som kan förbättra livskvaliteten hos äldre personer med mild kognitiv svikt. Metod: Systematisk blandad litteratur översikt (Systematic mixed studie review) med narrativ sammanfattning (narrativ summary) enligt Ryan (2013) valdes som studiedesign. Artiklar söktes systematiskt i databaserna Cinahl, PubMed och PsycINFO. Följande kategorier fastställdes vid analysen: fysisk aktivitet, kognitiv stimulans, kombinerade fysiska och kognitionsstimulerande interventioner och estetiska aktiviteter. Resultat: Studiens resultat baserades på en analys av elva kvantitativa och tre kvalitativa studier som omfattade äldre personer i ålder 65+ med MCI. Dessa artiklar publicerades mellan åren 2019 och 2023 och omfattade länderna Italien (1), Kanada (1), Kina (6), Mexiko (1), Nederländerna (1), Sverige (1), Tyskland (1) och USA (2). Interventioner som inkluderades i studien omfattade: fysiska aktiviteter som Tai Chi, måttlig aerob träning och squaredans; interventioner för kognitiv stimulans med hjälp av modern teknink; fysiska aktiviteter kombinerade med kognitiv träning; samt estetiska aktiviteter som stråkkonst, akvarell och akrylmålning. Interventionerna visade varierande grad av påverkan på livskvalitet för äldre personer med MCI, men samtliga visade positiv effekt på livskvaliteten. Slutsatser: Det finns evidens som tyder på att användandet av moderna teknologier kan förbättra äldre personernas med MCI livskvalitet. Interventioner som mindfulness, reminiscens, estetiska och fysiska aktiviteter kan också ge en positiv effekt på livskvalitet hos äldre personer med MCI. / Background: The number of elderly people in the world is constantly increasing. Eight percent of Sweden's population, who are 65 years and older, have some form of cognitive impairment. With age, the risk of mild cognitive impairment increases, which affects all areas of a person's life. Mild cognitive impairment is a condition that can lead to more extensive cognitive impairment if not addressed in its early stages. It is therefore important to detect and address the first symptoms of mild cognitive impairment at an early stage.  Aim: The aim of this study was to investigate which interventions can improve the quality of life in older people with mild cognitive impairment. Method: Systematic mixed study review with narrative summary according to Ryan (2013) was chosen as the study design. Articles were systematically searched in the databases Cinahl, PubMed and PsycINFO. The following categories were established in the analysis: physical activity, cognitive stimulation, combined physical and cognition-stimulating interventions, and aesthetic activities. Results: The results of the study were based on an analysis of eleven quantitative and three qualitative studies that included older people aged 65+ with MCI. These articles were published between the years 2019 and 2023 and covered the countries Italy (1), Canada (1), China (6), Mexico (1), the Netherlands (1), Sweden (1) Germany (1), and the United States (2). Interventions in the study included: physical activities such as Tai Chi, moderate aerobic, and square dancing; interventions for cognitive stimulation using modern technology; physical activities combined with cognitive training; as well as aesthetic activities such as string art, watercolor, and acrylic painting. The interventions showed varying degrees of impact on quality of life for older people with MCI, but all showed a positive effect on quality of life.  Conclusions: There is evidence to suggest that the use of modern technologies can improve the quality of life of older people with MCI. Interventions such as mindfulness, reminiscence, aesthetic and physical activities can also have a positive effect on quality of life in older people with MCI.

Alzheimer's disease (AD) is neurodegenerative disorder that causes memory loss and cognitive dysfunction. It affects one in five people over the age of 80 and is distressing for both sufferers and their families. A transitional stage between normal ageing and dementia including AD is termed a mild cognitive impairment (MCI). Recent studies have shown that people with MCI may convert to AD over time although not all MCI cases progress to AD. Much research is now focussing on early detection of AD and diagnosing an MCI that will progress to AD to allow prompt treatment and disease management before the neurons degenerate to a stage beyond repair. Hence, the ability to obtain a method of identifying MCI is of great importance. Virtual reality plays an important role in healthcare and offers opportunities for detection of MCI. There are various studies that have focused on detection of early AD using virtual environments, although results remain limited. One significant drawback of these studies has been their limited capacity to incorporate levels of difficulty to challenge users' capability. Furthermore, at best, these studies have only been able to discriminate between early AD and healthy elderly with about 80% of overall accuracy. As a result, a novel virtual simulation called Virtual Reality for Early Detection of Alzheimer's Disease (VREAD) was developed. VREAD is a quick, easy and friendly tool that aims to investigate cognitive functioning in a group of healthy elderly participants and those with MCI. It focuses on the task of following a route, since Topographical Disorientation (TD) is common in AD. An investigation was set up with two cohorts: non-elderly and elderly participants. The findings with regard to the non-elderly are important as they represent a first step towards implementation with elderly people. The results with elderly participants indicate that this simulation based assessment could provide a method for the detection of MCI since significant correlations between the virtual simulation and existing neuropsychological tests were found. In addition, the results proved that VREAD is comparable with well-known neuropsychological tests, such as Cambridge Neuropsychological Automated Test Battery, Paired Associate Learning (CANTAB PAL) and Graded Naming Test (GNT). Furthermore, analysis through the use of machine learning techniques with regard to the prediction of MCI also obtained encouraging results. This novel simulation was able to predict with about 90% overall accuracy using weighting function proposed to discriminate between MCI and healthy elderly. / Ministry of Higher Education, Malaysia and University Sultan Zainal Abidin, Malaysia (UNisZa)

While cognitive impairment is common in peripheral diseases such as chronic kidney disease (CKD), mechanistic insights and effective therapies are lacking. Multiple toxins accumulating as a consequence of CKD have been identified, yet the consequences for cellular crosstalk in the brain and the mechanisms underlying the associated neuronal dysfunction remain largely elusive. In the case of CKD, more than 100 uremic toxins have been identified. Renal transplantation largely reverses the cognitive impairment associated with CKD, demonstrating that cognitive impairment in CKD can be reversed. This indicates that pharmaceutical approaches to target cognitive impairment in association with CKD may be feasible. However, it is unlikely that targeting a single toxin will be sufficient to combat neuronal dysfunction associated with peripheral diseases such as CKD, given the large number of toxins involved and since the pattern of accumulating toxins varies among affected patients. Rather than identifying single toxins, identifying a common mechanism inducing neuronal dysfunction and thus impairing cognition may identify new and feasible therapeutic approaches. One commonality of peripheral diseases such as liver or renal failure is sterile inflammation. Sterile inflammation has been linked with neurodegenerative diseases and associated cognitive impairment and inflammasome activation is one hallmark of chronic pathologies in the brain. Mutations in the inflammasome component NLRP3 show clinical manifestations of cryopyrin- associated periodic syndromes (CAPS), which are characterized by skin rash, fever and joint pain. Further, abnormal and constant NLRP3 signaling has been associated with some chronic and degenerative diseases such as Alzheimer’s disease (AD), atherosclerosis, arthritis or cancer. A causative function of the NLRP3 inflammasome for neurodegenerative processes is supported by preclinical studies. These pre-clinical studies used whole body knock out mice to demonstrate that deficiencies of NLRP3, caspase-1 or the primary receptor for IL-1β, IL-1R1, protect mice from neurodegenerative processes. While providing important insights into the role of the NLRP3-inflammasome in neurodegenerative processes, these studies did not identify the relevant cell types in which the inflammasome is activated, the mechanisms underlying inflammasome activation and the consequences thereof, e.g. for intracerebral cross-talk. In addition, whether sterile inflammation triggered by the NLRP3 inflammasome impairs cognition in the setting of primarily peripheral diseases such as CKD remains unknown. To address these open questions, I used a mouse model of CKD, in which I detected NLRP3 inflammasome in brains. Interestingly, despite inflammasome activation in the brain, microglial caspase-1 deficiency did not improve cerebral inflammation and cognition in CKD mice. I identified noncanonical IL-1β maturation in microglia in CKD conditions, which was cathepsin c – caspase-8 mediated. Restoring K+ homeostasis in microglia or genetic inhibition of neuronal IL-1R1 signaling abolished CKD-induced cognitive impairment. Mechanistically, noncanonical IL-1β maturation and secretion from microglia promotes via IL-1R signaling cognitive impairment in neurons. This identifies a molecular mechanism of sterile CNS inflammation and the associated intercellular signaling pathway, which may be therapeutically amendable. Microglial K+ dyshomeostasis and noncanonical microglial IL-1β maturation may be druggable targets in some forms of cognitive impairment.:Content 2 List of abbreviations 5 Graphical abstract 8 2 Introduction 9 2.1 Chronic kidney disease and cognition 11 2.2 Microglia cells 13 2.3 The inflammasome, potassium dyshomeostasis in brain cells and thallium autometallography 15 2.4 Sterile inflammation in neurodegenerative diseases 17 3 Aims of the study 19 4 Materials and Methods 20 4.1 Reagents 20 4.2 Mice 27 4.3 CKD mouse model (5/6 nephrectomy model) 30 4.4 Evans Blue extravasation assay 32 4.5 2-photon microscopy 32 4.6 Analysis of mice 33 4.7 In vivo interventions 33 4.8 Histology and immunohistochemical analysis 34 4.9 Cell culture 34 4.10 Dextran permeability assay 35 4.11 Thallium-AMG (TlAMG), ex vivo and in vitro 36 4.12 Protein extraction and Western blotting 38 4.13 IL-1β ELISA 38 4.14 Reverse Transcriptase Polymerase Chain Reaction (RT–PCR) 38 4.15 Proximity ligation assay (PLA) 39 4.16 Behavioral analysis 39 4.17 Cathepsin c substrate assay 40 4.18 snRNA-Seq 41 4.19 Statistical Analysis 42 5 Results 43 5.1 Chronically impaired renal function leads to cognitive decline 43 5.2 Blood brain barrier (BBB) disruption in chronic kidney disease 44 5.3 Potassium dyshomeostasis in brain cells in CKD 45 5.4 CKD leads to microglia activation 46 5.5 Priming of microglia in CKD depends on potassium dyshomeostasis and its restoration improves cognition in CKD 49 5.6 TRAM34 ameliorates potassium dyshomeostasis and behavior in CKD 51 5.7 Uremia-induced cognitive impairment depends on microglia- neuron crosstalk via IL-1R1 52 5.8 Deciphering the microglial molecular pathway in CKD 56 5.9 Microglia activation in CKD is independent of NLRP3 56 5.10 Microglial IL-1β maturation occurs independently of the NLRP3-Caspase-1 inflammasome in CKD 57 5.11 The role of caspase- 8 in microglia activation in CKD 60 5.12 Lysosomal cathepsin c promotes microglia activation pivotal for caspase-8 activation 62 5.13 Broader implication of the pathway in other chronic peripheric diseases 63 5.14 Microglia inflammasome activation and IL-1β release is sufficient to induce cognitive impairment 64 5.15 Tables 66 6 Discussion 69 7 Summary 75 8 Zusammenfassung 80 9 References 86 10 Declaration about the independent preparation of the work 97 11 Presentation of own contribution 98 12 Curriculum vitae 99 13 Publications 104 14 Acknowledgments 106

OBJECTIVE: Everyday tasks, such as meal preparation and bill paying, require the coordination of multiple cognitive processes and are essential for independent living. In dementia, cognitive impairment disrupts the ability to perform everyday tasks, though subtle difficulties occur prior to the onset of a frank dementia and predict risk of further decline. Current clinical methods of assessing everyday functioning fail to elucidate the reasons people experience mild functional difficulties, but new sensitive and objective measures of mild functional difficulties may advance our understanding of the cognitive mechanisms associated with very early functional decline. In separate paradigms, prior work has identified two markers of mild functional difficulties that distinguish healthy older adults from younger adults: (1) micro errors, inefficient reaching movements (e.g., reaching for but not using a distractor object) and (2) inefficient eye movements during verbal description of common everyday activities (e.g., making coffee). The present study used a novel single, streamlined paradigm that integrates analysis of inefficient eye movements with inefficient reaching to increase sensitivity for early detection and advance our understanding of mild functional difficulties. METHODS: Thirty-four older adults with healthy cognition (n = 28) or mild cognitive impairment (n = 6) completed a novel, non-immersive virtual reality (VR) test involving two everyday tasks (Breakfast and Lunch) during which both eye movements and reaching movements were measured. Participants also completed clinical questionnaires and a performance-based test (with real objects) of everyday functioning as well as cognitive testing. Analyses examined whether eye movements are (1) associated with precision of reaching movements during the VR task (Aim 1); (2) associated with clinical measures of everyday function (Aim 2); and (3) show meaningful patterns across the VR tasks (beginning vs. end; between vs. within subtask) that are differentially associated with cognitive measures (Aim 3). RESULTS: Within the VR task, participants spent the highest proportion of time viewing objects necessary for completion of the current task step (target objects) compared to distractor objects or objects not needed at the current task step. Relations between efficiency of eye movements and reaching movements during the VR task were not statistically significant (Aim1). Time spent viewing non-target objects in the VR task was moderately correlated with errors on the performance-based test, but not with clinical questionnaires of everyday functioning (Aim 2). Participants spent a greater proportion of time viewing non-target objects at the beginning of the task sequence compared to later in the task sequence, as well as between sub-tasks compared to within sub-tasks, but correlation coefficients between these viewing patterns and cognitive tests failed to reach statistical significance (Aim 3). CONCLUSIONS: Results provide preliminary evidence that eye movements during execution of a VR task of everyday functioning involving reaching movements may be a reliable and sensitive measure of subtle, real-world functional difficulties. Eye movement patterns suggest premature decay of task goals and interference from competing task goals are mechanisms that may contribute to early functional decline in older adults. Further study is required to demonstrate the utility of eye movements in predicting cognitive and functional decline in older adults. / Psychology

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